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H. pylori is classified as a group I carcinogen by WHO because of its involvement in gastric cancer development. Several reports have suggested anti-bacterial effects of menadione, although the effect of menadione on major virulence factors of H. pylori and H. pylori-induced inflammation is yet to be elucidated. In this study, therefore, we demonstrated that menadione has anti-H. pylori and anti-inflammatory effects. Menadione inhibited growth of H. pylori reference strains and clinical isolates. Menadione reduced expression of vacA in H. pylori, and translocation of VacA protein into AGS (gastric adenocarcinoma cell) was also decreased by menadione treatment. This result was concordant with decreased apoptosis in AGS cells infected with H. pylori. Moreover, cytotoxin-associated protein A (CagA) translocation into H. pylori-infected AGS cells was also decreased by menadione. Menadione inhibited expression of several type IV secretion system (T4SS) components, including virB2, virB7, virB8, and virB10, that are responsible for translocation of CagA into host cells. In particular, menadione inhibited nuclear factor kappa-light-chain-enhancer of activated B cell (NF-B) activation and thereby reduced expression of the proinflammatory cytokines such as IL-1, IL-6, IL-8, and TNF- in AGS as well as in THP-1 (monocytic leukemia cell) cell lines. Collectively, these results suggest the anti-bacterial and anti-inflammatory effects of menadione against H. pylori. | [
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Here we show a constructed wetland (CW), a viable alternative wastewater treatment system, be used to produce biofuels from biomass by using nitrogen contained in domestic wastewater. We summarize the potential biomass yield evaluated as cellulosic ethanol bioenergy production, and combine the life cycle analysis with a mass balance approach to estimate the energetic, environmental, and economic performance of a CW biofuel system. The results showed that the annual aboveground biomass yield of a CW in Zhoushan, Zhejiang Province, China, averaged 37,813 kg ha-1 year-1 as the by-product of treating waste N, which is about one order of magnitude larger than traditional biofuel production systems. The biomass yield in the Zhoushan CW system had life cycle environment benefits of 8.8 Mg (1 Mg = 10⁶ g) CO₂ equivalent ha-1 year-1 of greenhouse gas emission reduction. The CW in Zhoushan had a net energy gain of 249.9 GJ (1 GJ = 10⁸ J) ha-1 year-1 while the wastewater treatment plant (WTP) consumes 7442.5 GJ ha-1 year-1. Moreover, the CW reduced greenhouse gas emissions to 2714 times less than that of the WTP. The CW also provided various ecosystem services, such as regional climate regulation and habitat conservation. We suggest that the potential use of a CW as biofuel production and carbon sequestration via nitrogen-negative input can be explored more widely in the future. | [
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] |
The aim of this study was to investigate the effects of resistance exercise training on hypothalamic GLP-1R levels and its related signaling mechanisms in T2DM. The animals were separated into three groups: a non-diabetic control (CON), diabetic control (DM), and diabetic with resistance exercise (DM + EXE) group. The resistance exercise training group performed ladder climbing (eight repetitions, three days per week for 12 weeks). Body weight was slightly lower in the DM + EXE group than the DM group, but difference between the groups was not significant. Food intake and glucose were significantly lower in the DM + EXE group than in the DM group. The blood insulin concentration was significantly higher and glucagon was significantly lower in the DM + EXE group. The DM + EXE group in the hypothalamus showed significant increases in GLP-1R mRNA, protein kinase A (PKA), glucose transporter 2 (GLUT2), and protein kinase B (AKT) and significant decrease in protein kinase C-iota (PKC-iota). Antioxidant enzymes and apoptosis factors were significantly improved in the DM + EXE group compared with the DM group in the hypothalamus. The results suggest that resistance exercise contributes to improvements the overall health of the brain in diabetic conditions. | [
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] |
Background: The objective of this study was to compare conventional versus digital impressions for Full-Arch maxillary rehabilitations. Methods: Patients selected for this study were treated with full-arch screw-retained rehabilitations supported by six immediately loaded dental implants. Patients have been scheduled randomly into control (conventional impression group, CIG) and test (digital impression group, DIG) groups respectively for a fully conventional workflow and a fully digital workflow. In both groups, within 24 h, temporary prostheses were delivered. Four months after the implant positioning, the two groups dealt with the fabrication of definitive restorations: conventional pick-up was performed in the control group, and definitive digital impressions were carried out in the test group. The time involved following these two procedures was recorded. Patients underwent intraoral digital radiographs to evaluate the accuracy of the framework-implant connection, check for the presence of voids at the bar-implant connection and measure bone level. Criteria used to assess success at the prosthetic level were the occurrence of prosthetic maintenance, the absence of fractures of the acrylic resin superstructure and voids. Results: A total of 50 patients received immediately loaded prostheses supported by six implants (total 300 implants). A fixture and prosthetic survival rate of 100% was observed. All digital X-ray examinations revealed a bar-implant connection accuracy and no voids. Differences that were not statistically significant (p > 0.05) in marginal bone loss were found between control and test groups. Significantly less time was spent to perform digital impression procedure (p < 0.05). Conclusions: Clinical and radiological results of the test group advocate a satisfactory accuracy and predictability of the intraoral scanner (IOS) to be a reliable alternative in clinical practice for implant full-arch rehabilitations and suggest fabrication of definitive restorations with a successful marginal fit precision. | [
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Red coleoptiles can help crops to cope with adversity and the key genes that are responsible for this trait have previously been isolated from Triticum aestivum, Triticum urartu, and Aegilops tauschii. This report describes the use of transcriptome analysis to determine the candidate gene that controls the trait for white coleoptiles in T. monococcum by screening three cultivars with white coleoptiles and two with red coleoptiles. Fifteen structural genes and two transcription factors that are involved in anthocyanin biosynthesis were identified from the assembled UniGene database through BLAST analysis and their transcript levels were then compared in white and red coleoptiles. The majority of the structural genes reflected lower transcript levels in the white than in the red coleoptiles, which implied that transcription factors related to anthocyanin biosynthesis could be candidate genes. The transcript levels of MYC transcription factor TmMYC-A1 were not significantly different between the white and red coleoptiles and all of the TmMYC-A1s contained complete functional domains. The deduced amino acid sequence of the MYB transcription factor TmMYB-A1 in red coleoptiles was homologous to TuMYB-A1, TaMYB-A1, TaMYB-B1, and TaMYB-D1, which control coleoptile color in corresponding species and contained the complete R2R3 MYB domain and the transactivation domain. TmMYB-a1 lost its two functional domains in white coleoptiles due to a single nucleotide deletion that caused premature termination at 13 bp after the initiation codon. Therefore, TmMYB-A1 is likely to be the candidate gene for the control of the red coleoptile trait, and its loss-of-function mutation leads to the white phenotype in T. monococcum. | [
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MYB proteins play important roles in the regulation of plant growth, development, and stress responses. Overexpression of BplMYB46 from Betula platyphylla improved plant salt and osmotic tolerances. In the present study, the interaction of eight avian myeloblastosis viral oncogene homolog (MYB) transcription factors with BplMYB46 was investigated using the yeast two-hybrid system, which showed that BplMYB46 could form homodimers and heterodimers with BplMYB6, BplMYB8, BplMYB11, BplMYB12, and BplMYB13. Relative beta-glucuronidase activity and chromatin immunoprecipitation assays showed that the interaction between BplMYB46 and the five MYBs increased the binding of BplMYB46 to the MYBCORE motif. A subcellular localization study showed that these MYBs were all located in the nucleus. Real-time fluorescence quantitative PCR results indicated that the expressions of BplMYB46 and the five MYB genes could be induced by salt and osmotic stress, and the BplMYB46 and BplMYB13 exhibited the most similar expression patterns. BplMYB46 and BplMYB13 co-overexpression in tobacco using transient transformation technology improved tobacco's tolerance to salt and osmotic stresses compared with overexpressing BplMYB13 or BplMYB46 alone. Taken together, these results demonstrated that BplMYB46 could interact with five other MYBs to form heterodimers that activate the transcription of target genes via an enhanced binding ability to the MYBCORE motif to mediate reactive oxygen species scavenging in response to salt and osmotic stresses. | [
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Instrumental activities of daily living (IADL) represent the most relevant action capacity in older people with regard to independent living. Previous studies have reported that there are geographical disparities in IADL decline. This study examined the associations between each element of community-level social capital (SC) and IADL disability. This prospective cohort study conducted between 2010 and 2013 by the Japan Gerontological Evaluation Study (JAGES) surveyed 30,587 people aged 65 years or older without long-term care requirements in 380 communities throughout Japan. Multilevel logistic-regression analyses were used to determine whether association exists between community-level SC (i.e., civic participation, social cohesion, and reciprocity) and IADL disability, with adjustment for individual-level SC and covariates such as demographic variables, socioeconomic status, health status, and behavior. At three-year follow-up, 2886 respondents (9.4%) had suffered IADL disability. Residents in a community with higher civic participation showed significantly lower IADL disability (odds ratio: 0.90 per 1 standard deviation increase in civic participation score, 95% confidence interval: 0.84⁻0.96) after adjustment for covariates. Two other community-level SC elements showed no significant associations with IADL disability. Our findings suggest that community-based interventions to promote community-level civic participation could help prevent or reduce IADL disability in older people. | [
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The two-component system (TCS) is a significant signal transduction system for bacteria to adapt to complicated and variable environments, and thus has recently been regarded as a novel target for developing antibacterial agents. The natural product luteolin (Lut) can inhibit the autophosphorylation activity of the typical histidine kinase (HK) HK853 from Thermotoga maritime, but the inhibition mechanism is not known. Herein, we report on the binding mechanism of a typical flavone with HK853 by using solution NMR spectroscopy, isothermal titration calorimetry (ITC), and molecular docking. We show that luteolin inhibits the activity of HK853 by occupying the binding pocket of adenosine diphosphate (ADP) through hydrogen bonds and - stacking interaction structurally. Our results reveal a detailed mechanism for the inhibition of flavones and observe the conformational and dynamics changes of HK. These results should provide a feasible approach for antibacterial agent design from the view of the histidine kinases. | [
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The 2014⁻2016 Ebola Virus Disease (EVD) epidemic outbreak reached over 28,000 cases and totaled over 11,000 deaths with 4 confirmed cases in the United States, which sparked widespread public concern about nationwide spread of EVD. Concern was elevated in locations connected to the infected people, which included Kent State University in Kent, Ohio. This threat of exposure enabled a unique opportunity to assess self-reported knowledge about EVD, risk perception, and behavior response to EVD. Unlike existing studies, which often survey one point in time across geographically coarse scales, this work offers insights into the geographic context of risk perception and behavior at finer-grained spatial and temporal scales. We report results from 3138 respondents comprised of faculty, staff, and students at two time periods. Results reveal increased EVD knowledge, decreased risk perception, and reduction in protective actions during this time. Faculty had the lowest perceived risk, followed by staff and then students, suggesting the role of education in this outcome. However, the most impactful result is the proof-of-concept for this study design to be deployed in the midst of a disease outbreak. Such geographically targeted and temporally dynamic surveys distributed during an outbreak can show where and when risk perception and behaviors change, which can provide policy-makers with rapid results that can shape intervention practices. | [
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To supplement a special edition of the journal Viruses, entitled "What's New with Flu?", influenza virus researchers have worked together to generate simple educational material to communicate their science to school students. Educational materials suitable for a range of ages are included, from coloring exercises for younger students through to explanations of cutting-edge science in straightforward language for older students. This article contains a handout with influenza facts, a coloring page, a glossary and word find and a connect-the-dots exercise explaining the ideas behind recently published scientific papers. Together, these materials are intended to make research on influenza viruses more accessible to students and teachers. | [
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India, the second largest agro-based economy with year-round crop cultivation, generates a large amount of agricultural waste, including crop residues. In the absence of adequate sustainable management practices, approximately 92 seems a very small number of metric tons of crop waste is burned every year in India, causing excessive particulate matter emissions and air pollution. Crop residue burning has become a major environmental problem causing health issues as well as contributing to global warming. Composting, biochar production and mechanization are a few effective sustainable techniques that can help to curtail the issue while retaining the nutrients present in the crop residue in the soil. The government of India has attempted to curtail this problem, through numerous measures and campaigns designed to promote sustainable management methods such as converting crop residue into energy. However, the alarming rise of air pollution levels caused by crop residue burning in the city of Delhi and other northern areas in India observed in recent years, especially in and after the year of 2015, suggest that the issues is not yet under control. The solution to crop residue burning lies in the effective implementation of sustainable management practices with Government interventions and policies. This manuscript addresses the underlying technical as well as policy issues that has prevented India from achieving a long-lasting solution and also potential solutions that have been overlooked. However, effective implementation of these techniques also requires us to look at other socioeconomic aspects that had not been considered. This manuscript also discusses some of the policy considerations and functionality based on the analyses and current practices. The agricultural waste sector can benefit immensely from some of the examples from other waste sectors such as the municipal solid waste (MSW) and wastewater management where collection, segregation, recycling and disposal are institutionalized to secure an operational system. Active stakeholder involvement including education and empowerment of farmers along with technical solutions and product manufacturing can also assist tremendously. Even though the issue of crop residue burning touches many sectors, such as environment, agriculture, economy, social aspects, education, and energy, the past governmental efforts mainly revolved around agriculture and energy. This sectorial thinking is another barrier that needs to be broken. The government of India as well as governments of other developing countries can benefit from the emerging concept of nexus thinking in managing environmental resources. Nexus thinking promotes a higher-level integration and higher level of stakeholder involvement that goes beyond the disciplinary boundaries, providing a supporting platform to solve issues such as crop residue burning. | [
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Sugarcane (Saccharum officinarum L.) is an important perennial grass in the Poaceae family cultivated worldwide due to its economical and medicinal value. In this study, a combined approach using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy was employed for the large-scale metabolite profiling of sugarcane juice and its by-product molasses. The polyphenols were analysed via UPLC-UV-ESI-MS, whereas the primary metabolites such as sugars and organic and amino acids were profiled using NMR spectroscopy and gas chromatography/mass spectrometry (GC/MS). UPLC/MS was more effective than NMR spectroscopy or GC/MS for determining differences among the metabolite compositions of the products. Under the optimized conditions, UPLC/MS led to the identification of 42 metabolites, including nine flavonoids, nine fatty acids, and two sterols. C/O Flavone glycosides were the main subclass detected, with tricin-7-O-deoxyhexosyl glucuronide being detected in sugarcane and molasses for the first time. Based on GC/MS analysis, disaccharides were the predominant species in the sugarcane juice and molasses, with sucrose accounting for 66% and 59%, respectively, by mass of all identified metabolites. The phenolic profiles of sugarcane and molasses were further investigated in relation to their in vitro antioxidant activities using free radical scavenging assays such as 2,2-Diphenyl-1-picrylhydrazyl free radical-scavenging ability (DPPH), Trolox equivalent antioxidant capacity (TEAC) and ferric reducing antioxidant power (FRAP). In view of its higher total phenolic content (TPC) (196 2.1 mg GAE/100 g extract) compared to that of sugarcane juice (93 2.9 mg GAE/100 g extract), molasses exhibited a substantially higher antioxidant effect. Interestingly, both extracts were also found to inhibit -glucosidase and -amylase enzymes, suggesting a possible antihyperglycaemic effect. These findings suggest molasses may be a new source of natural antioxidants for functional foods. | [
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Recent animal studies found the potential of a collagen peptide derived from skate skin to have anti-obesity effects through the suppression of fat accumulation and regulation of lipid metabolism. However, no studies have yet been performed in humans. Here, this very first human randomized, placebo-controlled, and double-blinded study was designed to investigate the efficacy and tolerability of skate skin collagen peptides (SCP) for the reduction of body fat in overweight adults. Ninety healthy volunteers (17 men) aged 41.2 10.4 years with a mean body mass index of 25.6 1.9 kg/m were assigned to the intervention group (IG), which received 2000 mg of SCP per day or to the control group (CG) given the placebo for 12 weeks and 81 (90%) participants completed the study. Changes in body fat were evaluated using dual energy X-ray absorptiometry as a primary efficacy endpoint. After 12 weeks of the trial, the percentage of body fat and body fat mass (kg) in IG were found to be significantly better than those of subjects in CG (-1.2% vs. 2.7%, p = 0.024 and -1.2 kg vs. 0.3 kg, p = 0.025). Application of SCP was well tolerated and no notable adverse effect was reported from both groups. These results suggest the beneficial potential of SCP in the reduction of body fat in overweight adults. | [
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Parent-teen discussions about sexual and reproductive health (SRH) are associated with delayed sex and higher contraceptive use among teens. Using the National Survey of Family Growth, we conducted bivariate and multivariate analyses of different types of parent-teen SRH discussions among two cohorts of teens. We describe differences in patterns for males and females by race/ethnicity and nativity, and test for racial/ethnic interactions within each cohort. Analyses found that the prevalence of parent-teen discussions about SRH increased across cohorts. For males and females, there were increases in parent-teen discussions about condoms, and for males only, there were increases in any SRH discussions and discussions about contraception and STIs. Based on interactions, parent-teen discussions and STI discussions increased most for Hispanic females, and among Hispanics, increased most for the foreign-born. These data indicate increases in different types of parent-teen SRH discussions, particularly for males and foreign-born teens overall, and for Hispanic teen females regarding condom use. Future research should examine what factors are driving these changes, including changes in the structure of U.S. Hispanic communities and expansion of evidence-based teen pregnancy prevention programs. | [
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Cell⁻cell communication is vital to multicellular organisms, and distinct types of cellular protrusions play critical roles during development, cell signaling, and the spreading of pathogens and cancer. The differences in the structure and protein composition of these different types of protrusions and their specific functions have not been elucidated due to the lack of a method for their specific isolation and analysis. In this paper, we described, for the first time, a method to specifically isolate distinct protrusion subtypes, based on their morphological structures or fluorescent markers, using laser capture microdissection (LCM). Combined with a unique fixation and protein extraction protocol, we pushed the limits of microproteomics and demonstrate that proteins from LCM-isolated protrusions can successfully and reproducibly be identified by mass spectrometry using ultra-high field Orbitrap technologies. Our method confirmed that different types of protrusions have distinct proteomes and it promises to advance the characterization and the understanding of these unique structures to shed light on their possible role in health and disease. | [
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Maternal hypercaloric exposure during pregnancy and lactation is a risk factor for developing diseases associated with inflammation such as obesity, diabetes and, neurological diseases in the offspring. Neuroinflammation might modulate neuronal activation and flavonoids are dietary compounds that have been proven to exert anti-inflammatory properties. Thus, the aim of the present study is to evaluate the effect of maternal supplementation with flavonoids (kaempferol-3-O-glucoside and narirutin) on the prevention of depression-like behaviour in the female offspring of dams fed with an obesogenic diet during the perinatal period. Maternal programming was induced by high fat (HFD), high sugar (HSD), or cafeteria diets exposure and depressive like-behaviour, referred to as swimming, climbing, and immobility events, was evaluated around postnatal day 56⁻60 before and after 30 mg/kg i.p. imipramine administration in the female offspring groups. Central inflammation was analyzed by measuring the TANK binding kinase 1 (TBK1) expression. We found that the offspring of mothers exposed to HSD programming failed to show the expected antidepressant effect of imipramine. Also, imipramine injection, to the offspring of mothers exposed to cafeteria diet, displayed a pro-depressive like-behaviour phenotype. However, dietary supplementation with flavonoids reverted the depression-like behaviour in the female offspring. Finally, we found that HSD programming increases the TBK1 inflammatory protein marker in the hippocampus. Our data suggest that maternal HSD programming disrupts the antidepressant effect of imipramine whereas cafeteria diet exposure leads to depressive-like behaviour in female offspring, which is reverted by maternal flavonoid supplementation. | [
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OBJECTIVES: To assess the cost-effectiveness of workplace-delivered interventions designed to reduce sitting time as primary prevention measures for cardiovascular disease (CVD) in Australia.METHODS: A Markov model was developed to simulate the lifetime cost-effectiveness of a workplace intervention for the primary prevention of CVD amongst office-based workers. An updated systematic review and a meta-analysis of workplace interventions that aim to reduce sitting time was conducted to inform the intervention effect. The primary outcome was workplace standing time. An incremental cost-effectiveness ratio (ICER) was calculated for this intervention measured against current practice. Costs (in Australia dollars) and benefits were discounted at 3% annually. Both deterministic (DSA) and probabilistic (PSA) sensitivity analyses were performed.RESULTS: The updated systematic review identified only one new study. Only the multicomponent intervention that included a sit-and-stand workstation showed statistically significant changes in the standing time compared to the control. The intervention was associated with both higher costs ($6820 versus $6524) and benefits (23.28 versus 23.27, quality-adjusted life year, QALYs), generating an ICER of $43,825/QALY. The DSA showed that target age group for the intervention, relative risk of CVD relative to the control and intervention cost were the key determinants of the ICER. The base case results were within the range of the 95% confidence interval and the intervention had a 85.2% probability of being cost-effective.CONCLUSIONS: A workplace-delivered intervention in the office-based setting including a sit-and-stand desk component is a cost-effective strategy for the primary prevention of CVD. It offers a new option and location when considering interventions to target the growing CVD burden. | [
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Prostate cancer (PCa) is a clinically heterogeneous disease and currently, accurate diagnostic and prognostic molecular biomarkers are lacking. This study aimed to identify novel DNA hypermethylation markers for PCa with future potential for blood-based testing. Accordingly, to search for genes specifically hypermethylated in PCa tissue samples and not in blood cells or other cancer tissue types, we performed a systematic analysis of genome-wide DNA methylation data (Infinium 450K array) available in the Marmal-aid database for 4072 malignant/normal tissue samples of various types. We identified eight top candidate markers (cg12799885, DOCK2, FBXO30, GRASP, HIF3A, MOB3B, PFKP, and TPM4) that were specifically hypermethylated in PCa tissue samples and hypomethylated in other benign and malignant tissue types, including in peripheral blood cells. Potential as diagnostic and prognostic biomarkers was further assessed by the quantitative methylation specific PCR (qMSP) analysis of 37 nonmalignant and 197 PCa tissue samples from an independent population. Here, all eight hypermethylated candidates showed high sensitivity (75⁻94%) and specificity (84⁻100%) for PCa. Furthermore, DOCK2, GRASP, HIF3A and PKFP hypermethylation was significantly associated with biochemical recurrence (BCR) after radical prostatectomy (RP; 197 patients), independent of the routine clinicopathological variables. DOCK2 is the most promising single candidate marker (hazard ratio (HR) (95% confidence interval (CI)): 1.96 (1.24⁻3.10), adjusted p = 0.016; multivariate cox regression). Further validation studies are warranted and should investigate the potential value of these hypermethylation candidate markers for blood-based testing also. | [
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Rumex japonicus Houtt. (RJ) is traditionally used in folk medicines to treat patients suffering from skin disease in Korea and other parts of East Asia. However, the beneficial effect of RJ extract on atopic dermatitis (AD) has not been thoroughly examined. Therefore, this study aimed to investigate the anti-inflammatory effects of RJ on AD in vitro and in vivo. Treatment with RJ inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) as well as the activation of nuclear factor-kappa B (NF-B) in tumor necrosis factor- (TNF-) stimulated in HaCaT cells. The five-week-old Balb/c mice were used as an AD-like mouse model by treating them with 1-chloro-2, 4-dinitrobenzene (DNCB). Topical administration of RJ to DNCB-treated mice significantly reduced clinical dermatitis severity, epidermal thickness, and decreased mast cell and eosinophil infiltration into skin and ear tissue. These results suggest that RJ inhibits the development of AD-like skin lesions by regulating the skin inflammation responses in HaCaT cells and Balb/c mice. Thus, RJ may be a potential therapeutic agent for AD. | [
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A series of novel 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-diones were designed and synthesized by using 4-aminophenol and -glycolic acid or lactic acid as starting materials in three or four steps. The key step is the metal-catalyzed oxidative cyclization of the amide to 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-diones (10a and 10b), the reaction conditions of which are investigated and optimized. The anticancer activity of 17 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-dione derivatives was evaluated. Preliminary results showed that 15 compounds have moderate to potent activity against human lung cancer A549, human breast cancer MDA-MB-231, and human cervical cancer HeLa cancer cell lines. Among them, compounds 11b and 11h were the most potent against A549 cell line with 0.18 and 0.19 M of IC50, respectively; compounds 11d, 11h, and 11k showed the most potent cytotoxicity against MDA-MB-231 cell line with 0.08, 0.08, and 0.09 M of IC50, respectively, while the activities of 11h, 11k, and 12c against HeLa cell line were the most potent with 0.15, 0.14, and 0.14 M of IC50, respectively. Compound 11h is a promising candidate for further development, which emerged as the most effective compound overall against the three tested cancer cell lines. | [
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] |
The GABAB receptor (GABAB-R) is a heterodimeric class C G protein-coupled receptor comprised of the GABAB1a/b and GABAB2 subunits. The endogenous orthosteric agonist -amino-butyric acid (GABA) binds within the extracellular Venus flytrap (VFT) domain of the GABAB1a/b subunit. The receptor is associated with numerous neurological and neuropsychiatric disorders including learning and memory deficits, depression and anxiety, addiction and epilepsy, and is an interesting target for new drug development. Ligand- and structure-based virtual screening (VS) are used to identify hits in preclinical drug discovery. In the present study, we have evaluated classical ligand-based in silico methods, fingerprinting and pharmacophore mapping and structure-based in silico methods, structure-based pharmacophores, docking and scoring, and linear interaction approximation (LIA) for their aptitude to identify orthosteric GABAB-R compounds. Our results show that the limited number of active compounds and their high structural similarity complicate the use of ligand-based methods. However, by combining ligand-based methods with different structure-based methods active compounds were identified in front of DUDE-E decoys and the number of false positives was reduced, indicating that novel orthosteric GABAB-R compounds may be identified by a combination of ligand-based and structure-based in silico methods. | [
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] |
A mild rhodium-catalyzed annulation of Boc-protected benzamides with diazo compounds via C-C/C-O bond formation has been explored. In the presence of [Cp*RhCl₂]₂, AgSbF₆ and Cs₂CO₃, Boc-protected benzamides can be effectively annulated to yield isocoumarins in 0.5⁻2 h. | [
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] |
Aspalathin, the main polyphenol of rooibos (Aspalathus linearis), is associated with diverse health promoting properties of the tea. During fermentation, aspalathin is oxidized and concentrations are significantly reduced. Standardized methods for quality control of rooibos products do not investigate aspalathin, since current techniques of aspalathin detection require expensive equipment and expertise. Here, we describe a simple and fast thin-layer chromatography (TLC) method that can reproducibly visualize aspalathin in rooibos herbal tea and plant extracts at a limit of detection (LOD) equal to 178.7 ng and a limit of quantification (LOQ) equal to 541.6 ng. Aspalathin is a rare compound, so far only found in A. linearis and its (rare) sister species A. pendula. Therefore, aspalathin could serve as a marker compound for authentication and quality control of rooibos products, and the described TLC method represents a cost-effective approach for high-throughput screening of plant and herbal tea extracts. | [
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This paper intends to use data to verify the correlation between safety culture, safety management system and safety knowledge, safety awareness, and safety habits, which is the correlation between the various parts of the behavior safety "2-4" model. Due to data limitations, the results are limited to the study of safety culture related relationships in coal mining enterprises. This paper first designed a questionnaire containing 30 questions, of which 1⁻5 questions represent safety culture, 6⁻22 questions represent safety management system, and 23⁻30 questions represent safety knowledge, safety awareness and safety habits. Employees of 27 coal mining enterprises in Shandong, Henan, Hunan and other places in China were surveyed and sampled by stratified random sampling, and 1514 valid questionnaires were obtained. After item analysis and correlation analysis, and it was found that, within the data of 1514 questionnaires, the item total correlation coefficients of questions 6, 9, 19 and 28 were all less than 0.2, indicating that the identification degree of these four items was poor, which was deleted. Using the data analysis of the remaining 26 questions in the questionnaire, it was found that the relationship between safety culture and the safety management system, the safety management system and safety knowledge, and safety awareness and safety habits is moderately related; safety culture and safety knowledge, safety awareness and safety habits are weakly related. The conclusion shows that the safety culture directly affects the safety management system; the safety management system directly affects the safety knowledge, safety awareness and safety habits; the safety culture indirectly affects safety knowledge, safety awareness and safety habits. However, why the expected strong correlation is not achieved, and whether the same conclusion can be obtained if the data scale is expanded or other types of enterprises are added for questionnaire measurement, these are questions worthy of further study, which is also the author's next research content. | [
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] |
Nearly one-third of patients with high-grade serous ovarian cancer (HGSC) do not respond to initial treatment with platinum-based therapy. Genomic and clinical characterization of these patients may lead to potential alternative therapies. Here, the objective is to classify non-responders into subsets using clinical and molecular features. Using patients from The Cancer Genome Atlas (TCGA) dataset with platinum-resistant or platinum-refractory HGSC, we performed a genome-wide unsupervised cluster analysis that integrated clinical data, gene copy number variations, gene somatic mutations, and DNA promoter methylation. Pathway enrichment analysis was performed for each cluster to identify the targetable processes. Following the unsupervised cluster analysis, three distinct clusters of non-responders emerged. Cluster 1 had overrepresentation of the stage IV disease and suboptimal debulking, under-expression of miRNAs and mRNAs, hypomethylated DNA, "loss of function" TP53 mutations, and the overexpression of genes in the PDGFR pathway. Cluster 2 had low miRNA expression, generalized hypermethylation, MUC17 mutations, and significant activation of the HIF-1 signaling pathway. Cluster 3 had more optimally cytoreduced stage III patients, overexpression of miRNAs, mixed methylation patterns, and "gain of function" TP53 mutations. However, the survival for all clusters was similar. Integration of genomic and clinical data from patients that do not respond to chemotherapy has identified different subgroups or clusters. Pathway analysis further identified the potential alternative therapeutic targets for each cluster. | [
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Chemerin, a novel adipokine, has been associated with metabolic, inflammatory, and atherosclerotic diseases. We aimed to determine the genetic basis of chemerin levels by conducting a genome-wide association study (GWAS) and to investigate the role of RARRES2 polymorphisms and circulating chemerin levels in the long-term outcome of coronary artery disease (CAD). A total of 2197 participants from the Taiwan Biobank (TWB) were recruited for the GWAS analysis, and 481 patients with angiographically confirmed CAD were enrolled for long-term outcome analysis. One locus of genome-wide significance with a single independent association signal was identified in the GWAS for chemerin levels with the peak association at the RARRES2 gene promoter region polymorphism rs3735167 (p = 2.35 ? 10-21). In the CAD population, borderline significance was noted between RARRES2 polymorphisms and chemerin levels, whereas high chemerin levels were associated with obesity, female sex, diabetes mellitus, hypertension, current smoking, high platelet and leukocyte counts, anemia, impaired renal function, high C-reactive protein (CRP) levels, and multi-vessel disease. Kaplan⁻Meier survival curves indicated that the patients with high chemerin and CRP levels, but not those with RARRES2 polymorphisms, had a lower survival rate and higher combined cerebral and cardiovascular event rates. Combined chemerin and CRP levels further revealed a stepwise increase in poor clinical outcomes from low- to high-risk subgroups. In conclusion, rs3735167 is the lead RARRES2 polymorphism for chemerin levels in Taiwanese. Chemerin levels, but not the rs3735167 genotypes, predicted the long-term outcome of CAD, especially when combined with CRP levels. | [
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] |
Viral metagenomics and high throughput sequence mining have revealed unexpected diversity, and the potential presence, of parvoviruses in animals from all phyla. Among arthropods, this diversity highlights the poor knowledge that we have regarding the evolutionary history of densoviruses. The aim of this study was to explore densovirus diversity in a small arthropod pest belonging to Acari, the two-spotted spider mite Tetranychus urticae, while using viral metagenomics based on virus-enrichment. Here, we present the viromes obtained from T. urticae laboratory populations made of contigs that are attributed to nine new potential viral species, including the complete sequence of a novel densovirus. The genome of this densovirus has an ambisens genomic organization and an unusually compact size with particularly small non-structural proteins and a predicted major capsid protein that lacks the typical PLA2 motif that is common to all ambidensoviruses described so far. In addition, we showed that this new densovirus had a wide prevalence across populations of mite species tested and a genomic diversity that likely correlates with the host phylogeny. In particular, we observed a low densovirus genomic diversity between the laboratory and natural populations, which suggests that virus within-species evolution is probably slower than initially thought. Lastly, we showed that this novel densovirus can be inoculated to the host plant following feeding by infected mites, and circulate through the plant vascular system. These findings offer new insights into densovirus prevalence, evolution, and ecology. | [
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Auricularia cornea var. Li. is an edible fungi and polysaccharides in Auricularia cornea var. Li. may have bioactive activities. Polysaccharides from Auricularia cornea var. Li. (ACP) was extracted using ultrasound-assisted extraction (UAE) method and compared with hot water extraction (HWE) for extraction yield, extraction rate, purity of polysaccharides, microstructure of residues after extraction, preliminary structure and rheological properties of polysaccharides. Optimum conditions for UAE (particle size of 150⁻200 mesh, water to raw material ratio of 70:1, extraction temperature at 70 C for 40 min, ultrasonic amplitude of 40%) and HWE (particle size of 150⁻200 mesh, water to raw material ratio of 60:1, extraction temperature at 90 C for 3.0 h) were obtained via single-factor experiment. Under optimum conditions, extraction yield of polysaccharides by UAE was 30.99 1.93% which showed no significant difference with that by HWE (30.35 1.67%) (P > 0.05). Extraction rate (29.29 1.41%) and purity (88.62 2.80%) of polysaccharides by UAE were higher than those by HWE (extraction rate of 24.95 2.78% and purity of 75.33 6.15%) (P < 0.05). Scanning Electron Microscopy (SEM) images of residues by UAE showed more broken cells than those by HWE. Fourier Transform Infrared (FTIR) spectra showed that the dialyzed ACP extracted by HWE and UAE (DACP-HWE and DACP-UAE) had similar characteristic absorption peaks of polysaccharides. Both DACP-HWE and DACP-UAE solutions showed typical shear thinning and temperature-independent behaviors (25⁻90 C) and UAE resulted in polysaccharides with remarkably lower viscosity in comparison with HWE. DACP-UAE solutions exhibited more liquid-like state while DACP-HWE solutions solid-like system. Data indicated that ultrasound treatment may be a useful means for extraction of polysaccharides from Auricularia cornea var. Li. | [
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he effect of docosahexaenoic acid (DHA, an omega-3 polyunsaturated fatty acid) upon the proliferation of EoL-1 (Eosinophilic leukemia) cell line was assessed, while additional cellular events during the antiproliferative action were recorded. DHA inhibited EoL-1 cells growth dose-dependently by inducing growth arrest at G0/1 phase of the cell cycle. After DHA addition to the cells, the expression of MYC oncogene was decreased, PTAFR-mRNA overexpression was observed which was used as a marker of differentiation, and PLA2G4A-mRNA increase was recorded. The enzymatic activities of phospholipase A₂ (PLA₂), a group of hydrolytic enzymes, whose action precedes and leads to PAF biosynthesis through the remodeling pathway, as well as platelet activating factor acetylhydrolase (PAFAH) which hydrolyses and deactivates PAF, were also measured. DHA had an effect on the levels of both the intracellular and secreted activities of PLA₂ and PAFAH. The inflammatory cytokines IL-6 and TNF- were also detected in high levels. In conclusion, DHA-induced EoL-1 cells differentiation was correlated with downregulation of MYC oncogene, overexpression of PTAFR and PLA2G4A-mRNAs, increase of the inflammatory cytokines production, and alteration of the enzymatic activities that regulate PAF levels. DHA is a natural substance and the understanding of its action on EoL-1 cells on molecular level could be useful in further investigation as a future therapeutic tool against F/P ⁺ hypereosinophilic syndrome. | [
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] |
Baizhu Shaoyao San (BSS) is a crucial traditional Chinese medicinal formula widely applied for the treatment of painful diarrhea, diarrhea-predominant irritable bowel syndrome, ulcerative colitis, and some other gastrointestinal diseases. Corresponding to the clinical medication, the three medicinal herbs (Atractylodis Macrocephalae Rhizoma, Paeoniae Radix Alba, and Citri Reticulatae Pericarpium) included in BSS should be processed using some specific methods of stir-frying. To find the underlying correlations between serum chemical profiles and curative effects of crude and processed BSS on ulcerative colitis rats, and further explore for the effective material basis of processing, an UHPLC/Q-TOF-MS/MS technique coupled with gray correlation analysis (GCA) was developed. A total of 134 compounds were identified in rat sera after oral administration of BSS, among which 24 compounds were prototypes and 110 compounds were metabolites. Meanwhile, an ulcerative colitis model was established in rats by enema with 2,4,6-trinitrobenzene sulfonic acid, and the pharmacodynamic indicators for drug efficacies were evaluated as well. According to the results, processed BSS showed better efficacy than crude BSS. The top 10 potential effective components with high degree of correlation were identified based on GCA results, which were thought to be the crucial compounds that contributed to the enhancement of therapeutic effects in BSS after processing. | [
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With the aim to discuss the similarities and differences of phytochemicals in Moringa oleifera leaves collected from China (CML) and India (IML) in mind, comparative ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS) analysis was performed in this study. A screening analysis based on a UNIFI platform was first carried out to discuss the similarities. Next, untargeted metabolomic analysis based on multivariate statistical analysis was performed to discover the differences. As a result, a total of 122 components, containing 118 shared constituents, were characterized from CML and IML. The structure types included flavonoids, alkaloids, glyosides, organic acids and organic acid esters, iridoids, lignans, and steroids, etc. For CML, 121 compounds were characterized; among these, 18 potential biomarkers with higher contents enabled differentiation from IML. For IML, 119 compounds were characterized; among these, 12 potential biomarkers with higher contents enabled differentiation from CML. It could be concluded that both CML and IML are rich in phytochemicals and that CML is similar to IML in the kinds of the compounds it contains, except for the significant differences in the contents of some compounds. This comprehensive phytochemical profile study provides a basis for explaining the effect of different growth environments on secondary metabolites and exists as a reference for further research into or applications of CML in China. | [
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Melatonin (MT; N-acetyl-5-methoxytryptamine) is a pleiotropic signaling molecule that has been demonstrated to play an important role in plant growth, development, and regulation of environmental stress responses. Studies have been conducted on the role of the exogenous application of MT in a few species, but the potential mechanisms of MT-mediated stress tolerance under salt stress are still largely unknown. In this study, naked oat seedlings under salt stress (150 mM NaCl) were pretreated with two different concentrations of MT (50 and 100 M), and the effects of MT on the growth and antioxidant capacity of naked oat seedlings were analyzed to explore the regulatory effect of MT on salt tolerance. The results showed that pretreating with different concentrations of MT promoted the growth of seedlings in response to 150 mM NaCl. Different concentrations of MT reduced hydrogen peroxide, superoxide anion, and malondialdehyde contents. The exogenous application of MT also increased superoxide dismutase, peroxidase, catalase, and ascorbate peroxide activities. Chlorophyll content, leaf area, leaf volume, and proline increased in the leaves of naked oat seedlings under 150 mM NaCl stress. MT upregulated the expression levels of the lipid peroxidase genes lipoxygenase and peroxygenase, a chlorophyll biosynthase gene (ChlG), the mitogen-activated protein kinase genes Asmap1 and Aspk11, and the transcription factor genes (except DREB2), NAC, WRKY1, WRKY3, and MYB in salt-exposed MT-pretreated seedlings when compared with seedlings exposed to salt stress alone. These results demonstrate an important role of MT in the relief of salt stress and, therefore, provide a reference for managing salinity in naked oat. | [
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Catechins and rutin are among the main metabolites found in apple fruit. Sixty apple genotypes, harvested in 2016 and 2017, were analyzed for their phenolic content and antioxidant activity. The HPLC analysis showed that the catechin concentration ranged from 109.98 to 5290.47 g/g, and the rutin concentration ranged from 12.136 to 483.89 g/g of apple fruit. The level of DPPH activity ranged from 9.04% to 77.57%, and almost half of the 15 genotypes showed below 30⁻40% DPPH activity. The apple genotypes 'Lal Ambri', 'Green Sleeves', and 'Mallus floribunda' showed the highest DPPH activity of between 70% and 80%, while 'Schlomit', 'Luxtons Fortune', 'Mayaan', 'Ananas Retrine', and 'Chaubatia ambrose' showed the lowest ferric reducing antioxidant power (FRAP) activity (0.02⁻0.09%). Statistical analysis showed a correlation between DPPH activity and catechin content (r = 0.7348) and rutin content (r = 0.1442). Regarding antioxidant activity, fractionated samples of apple genotypes revealed significant activity comparable to that of ascorbic acid. There was also a consistent trend for FRAP activity among all apple genotypes and a significant positive correlation between FRAP activity and rutin content (r = 0.244). Thus, this study reveals a significant variation in antioxidant potential among apple genotypes. This data could be useful for the development of new apple varieties with added phytochemicals by conventional and modern breeders. | [
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Neuronal nicotinic acetylcholine receptors are cell membrane-bound ion channels that are widely distributed in the central nervous system. The 42 subtype of neuronal nicotinic acetylcholine receptor plays an important role in modulating the signaling pathways for pain. Previous studies have shown that agonists, partial agonists, and positive allosteric modulators for the 42 receptors are effective in relieving pain. Desformylflustrabromine is a compound that acts as an allosteric modulator of 42 receptors. The aim of this study was to assess the effects of desformylflustrabromine on chemically induced pain. For this purpose, the formalin-induced pain test and the acetic acid-induced writhing response test were carried out in CD-1 mice. Both tests represent chemical assays for nociception. The results show that desformylflustrabromine is effective in producing an analgesic effect in both tests used for assessing nociception. These results suggest that desformylflustrabromine has the potential to become a clinically used drug for pain relief. | [
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BACKGROUND: Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are closely related members of the Semliki Forest complex within the genus alphavirus and are transmitted by arthropods, causing acute febrile illness in humans. CHIKV has spread to almost all continents, whereas autochthonous MAYV infections have been reported in South America and in the Caribbean. Nevertheless, there was concern about potential spread of MAYV to other regions similar to CHIKV in the past. The risk for transmission of emerging viruses by blood transfusion and the safety of plasma-derived medicinal products (PDMPs) are constant concerns. The manufacturing processes of PDMPs include procedures to inactivate/remove viruses.METHODS: In this study, we investigated the reduction of MAYV and CHIKV by heat inactivation in various matrices, solvent/detergent treatment and nanofiltration.RESULTS: Unexpectedly, MAYV was significantly more resistant to heat and solvent/detergent treatment compared to CHIKV. However, being similar in size, both MAYV and CHIKV were removed below the detection limit by 35 nm virus filters.CONCLUSIONS: The inactivation profiles of different alphavirus members vary considerably, even within the Semliki Forest Complex. However, robust dedicated viral inactivation/removal procedures commonly used in the plasma product industry are effective in inactivating or removing MAYV and CHIKV. | [
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The different geographical contexts seen in European metropolitan areas are reflected in the uneven distribution of health risk factors for the population. Accumulating evidence on multiple health determinants point to the importance of individual, social, economic, physical and built environment features, which can be shaped by the local authorities. The complexity of measuring health, which at the same time underscores the level of intra-urban inequalities, calls for integrated and multidimensional approaches. The aim of this study is to analyse inequalities in health determinants and health outcomes across and within nine metropolitan areas: Athens, Barcelona, Berlin-Brandenburg, Brussels, Lisbon, London, Prague, Stockholm and Turin. We use the EURO-HEALTHY Population Health Index (PHI), a tool that measures health in two components: Health Determinants and Health Outcomes. The application of this tool revealed important inequalities between metropolitan areas: Better scores were found in Northern cities when compared with their Southern and Eastern counterparts in both components. The analysis of geographical patterns within metropolitan areas showed that there are intra-urban inequalities, and, in most cities, they appear to form spatial clusters. Identifying which urban areas are measurably worse off, in either Health Determinants or Health Outcomes, or both, provides a basis for redirecting local action and for ongoing comparisons with other metropolitan areas. | [
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A museum is an important place for science education for children. The learning method in the museum is reading exhibits and explanations. Museums are investing efforts to quantify interests using questionnaires and sensors to improve their exhibitions and explanations. Therefore, even in places where many people gather, such as in museums, it is necessary to quantify people's interest by sensing behavior of multiple people. However, this has not yet been realized. We aim to quantify the interest by sensing a wide range of human behavior for multiple people by coordinating multiple noncontact sensors. When coordinating multiple sensors, the coordinates and the time of each sensor differ. To solve these problems, coordinates were transformed using a simultaneous transformation matrix and time synchronization was performed using unified time. The effectiveness of this proposal was verified through experimental evaluation. Furthermore, we evaluated the actual museum content. In this paper, we describe the proposed method and the results of the evaluation experiment. | [
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Epidemic thunderstorm asthma (ETA) is an emerging public health threat in Australia, highlighted by the 2016 event in Melbourne, Victoria, that overwhelmed health services and caused loss of life. However, there is limited understanding of the regional variations in risk. We evaluated the public health risk of ETA in the nearby state of Tasmania by quantifying the frequency of potential ETA episodes and applying a standardized natural disaster risk assessment framework. Using a case⁻control approach, we analyzed emergency presentations in Tasmania's public hospitals from 2002 to 2017. Cases were defined as days when asthma presentations exceeded four standard deviations from the mean, and controls as days when asthma presentations were less than one standard deviation from the mean. Four controls were randomly selected for each case. Independently, a meteorologist identified the dates of potential high-risk thunderstorm events. No case days coincided with thunderstorms during the study period. ETA was assessed as a very low risk to the Tasmanian population, with these findings informing risk prioritization and resource allocation. This approach may be scaled and applied in other settings to determine local ETA risk. Furthermore, the identification of hazards using this method allows for critical analysis of existing public health systems. | [
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Fucoxanthin has interesting anticancer activity, but is insoluble in water, hindering its use as a drug. Microencapsulation is used as a technique for improving drug delivery. This study aimed to formulate fucoxanthin-loaded microspheres (F-LM) for anticancer treatment of H1299 cancer cell lines and optimize particle size (PS) and encapsulation efficiency (EE). Using response surface methodology (RSM), a face centered central composite design (FCCCD) was designed with three factors: Polyvinylalcohol (PVA), poly(d,l-lactic-co-glycolic acid) (PLGA), and fucoxanthin concentration. F-LM was produced using a modified double-emulsion solvent evaporation method. The F-LM were characterized for release profile, release kinetics, and degradation pattern. Optimal F-LM PS and EE of 9.18 m and 33.09%, respectively, with good surface morphology, were achieved from a 0.5% (w/v) PVA, 6.0% (w/v) PLGA, 200 g/mL fucoxanthin formulation at a homogenization speed of 20,500 rpm. PVA concentration was the most significant factor (p < 0.05) affecting PS. Meanwhile, EE was significantly affected by interaction between the three factors: PVA, PLGA, and fucoxanthin. In vitro release curve showed fucoxanthin had a high burst release (38.3%) at the first hour, followed by a sustained release stage reaching (79.1%) within 2 months. Release kinetics followed a diffusion pattern predominantly controlled by the Higuchi model. Biodegradability studies based on surface morphology changes on the surface of the F-LM, show that morphology changed within the first hour, and F-LM completely degraded within 2 months. RSM under FCCCD design improved the difference between the lowest and highest responses, with good correlation between observed and predicted values for PS and EE of F-LM. | [
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Morbidity prediction can be useful in improving the effectiveness and efficiency of medical services, but accurate morbidity prediction is often difficult because of the complex relationships between diseases and their influencing factors. This study investigates the effects of food contamination on gastrointestinal-disease morbidities using eight different machine-learning models, including multiple linear regression, a shallow neural network, and three deep neural networks and their improved versions trained by an evolutionary algorithm. Experiments on the datasets from ten cities/counties in central China demonstrate that deep neural networks achieve significantly higher accuracy than classical linear-regression and shallow neural-network models, and the deep denoising autoencoder model with evolutionary learning exhibits the best prediction performance. The results also indicate that the prediction accuracies on acute gastrointestinal diseases are generally higher than those on other diseases, but the models are difficult to predict the morbidities of gastrointestinal tumors. This study demonstrates that evolutionary deep-learning models can be utilized to accurately predict the morbidities of most gastrointestinal diseases from food contamination, and this approach can be extended for the morbidity prediction of many other diseases. | [
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] |
Preschool children in Addis Ababa, Ethiopia, are highly exposed to influenza viruses. Factors related to infections, nutrition, and environmental conditions that might explain the burden of influenza among these children were investigated. Ninety-five preschool children, 48 girls and 47 boys, were followed clinically for 12 months. Illness and immune responses to influenza; three other respiratory viruses; five airway pathogenic bacteria; and levels of vitamins D, A, and B12 were assessed. Most of the children had antibodies to numerous respiratory viral and bacterial agents at study start, and many were infected during follow-up. Twenty-five girls and 25 boys fell ill during the study, and were treated with one or more courses of systemic antimicrobials. Ninety percent of both girls and boys had 25-hydroxyvitamin D [25(OH)D] levels below the recommended levels. While there was no overall difference in the levels of vitamins D, A, and B12 between girls and boys, treated girls had significantly lower 25(OH)D levels than non-treated girls and treated boys. There was a considerable number of short for age children, but only the short treated girls had significantly lower 25(OH)D levels than the non-treated children. Preschool girls with low 25(OH)D levels were more vulnerable to pathogenic microbes than boys. | [
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There is limited evidence from epidemiological studies for the inflammatory or anti-inflammatory properties of fatty acids in blood cell membranes. Therefore, this study examined associations between baseline (n = 282) and 1-year (n = 143) changes in the levels of fatty acids in blood cell membranes with circulating inflammatory markers in older adults at high cardiovascular risk. The data for this cross-sectional analysis was obtained from a case-control study within the PREDIMED study. Linear regression with elastic net penalty was applied to test associations between measured fatty acids and inflammatory markers. Several fatty acids were associated with interferon- (IFN) and interleukins (ILs) IL-6, IL-8, and IL-10 at baseline and additionally also with IL-1b at 1 year. Omega-6 fatty acids were consistently positively associated with pro-inflammatory IL-6 and IL-8 at baseline. Omega-3 fatty acids including C20:5n3 and C18:3n3 were negatively associated with IFN- at 1 year. It is interesting to note that the cis and trans forms of C16:1n7 at 1 year were oppositely associated with the inflammatory markers. C16:1n7trans was negatively associated with IFN-, IL-6, IL-8, IL-10, and IL-1b, whereas C16:1n7cis was positively associated with IL-1b. This study adds to the growing body of evidence suggesting potential differences in inflammatory or anti-inflammatory properties of fatty acids in blood cell membranes. | [
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] |
Background and objective: The increased participation in endurance sports such as marathon running has attracted scientific interest especially with regard to adult athletes. However, few studies have examined the impact of a marathon race on children and adolescents. Therefore, the aim of the present case study was two-fold: first, to describe pacing during a marathon race, and second, to examine acute responses of blood physiology and biochemistry parameters during the race (i.e., pre- and post-race) as well as five consecutive days after the race. Materials and Methods: Participant was a 15-year-old boy who completed a self-paced marathon attempt for the first time and finished in 5 h 19 m 53 s. Positive pacing (i.e., a running speed that decreased throughout race) with a final end spurt was observed. Results: An increase in fluid intake across race was shown. Exercise-associated hyponatremia (EAH, i.e., plasma sodium concentration <135 mmol/L) was found post-race. C-reactive protein (CRP) did not correlate either with creatine kinase (CK) (r = 0.457, p = 0.302) or with lactate dehydrogenase (LDH) (r = 0.156, p = 0.739); however, leukocytes correlated very largely with LDH (r = 0.889, p = 0.007) but not with CK (r = 0.696, p = 0.082). CK and LDH related almost perfectly with creatinine (r = 0.937, p = 0.002 and r = 0.959, p = 0.001, respectively); also, creatinine clearance correlated very largely with CK (r = -0.782, p = 0.038) but not with LDH (r = -0.733, p = 0.061). Leukocytes, aspartate aminotransferase, LDH, and CK deviated from physiological range post-race, but returned to normal values during the five-day recovery period. Conclusions: In summary, a male teenager at the age of 15 years was able to run a marathon in under 6 h without significant harmful effects on health. He developed mild and asymptomatic EAH and an increase in leucocytes, CRP, CK, and LDH as markers of inflammation and skeletal muscle damage. EAH after the marathon was resolved within one day of recovery. | [
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Oxidative stress resulting from decreased antioxidant protection and increased reactive oxygen and nitrogen species (RONS) production may contribute to muscle mass loss and dysfunction during aging. Curcumin is a phenolic compound shown to upregulate antioxidant defenses and directly quench RONS in vivo. This study determined the impact of prolonged dietary curcumin exposure on muscle mass and function of aged rats. Thirty-two-month-old male F344xBN rats were provided a diet with or without 0.2% curcumin for 4 months. The groups included: ad libitum control (CON; n = 18); 0.2% curcumin (CUR; n = 18); and pair-fed (PAIR; n = 18) rats. CUR rats showed lower food intake compared to CON, making PAIR a suitable comparison group. CUR rats displayed larger plantaris mass and force production (vs. PAIR). Nuclear fraction levels of nuclear factor erythroid-2 related-factor-2 were greater, and oxidative macromolecule damage was lower in CUR (vs. PAIR). There were no significant differences in measures of antioxidant status between any of the groups. No difference in any measure was observed between CUR and CON rats. Thus, consumption of curcumin coupled with reduced food intake imparted beneficial effects on aged skeletal muscle. The benefit of curcumin on aging skeletal muscle should be explored further. | [
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] |
Tears are exceptionally rich sources of information on the health status of the eyes, as well as of whole body functionality, due to the presence of a large variety of salts and organic components whose concentration can be altered by pathologies, eye diseases and/or inflammatory processes. Surface enhanced Raman spectroscopy (SERS) provides a unique method for analyzing low concentrations of organic fluids such as tears. In this work, a home-made colloid of gold nanoparticles has been used for preparing glass substrates able to efficiently induce an SERS effect in fluid samples excited by a He⁻Ne laser ( = 633 nm). The method has been preliminary tested on Rhodamine 6G aqueous solutions at different concentrations, proving the possibility to sense substance concentrations as low as few M, i.e., of the order of the main tear organic components. A clear SERS response has been obtained for human tear samples, allowing an interesting insight into tear composition. In particular, aspartic acid and glutamic acid have been shown to be possible markers for two important human tear components, i.e., lactoferrin and lysozyme. | [
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] |
Trypanosoma brucei is a unicellular eukaryotic parasite, which causes the African sleeping sickness in humans. The recently discovered trypanosomal protein Parvulin 42 (TbPar42) plays a key role in parasite cell proliferation. Homologues of this two-domain protein are exclusively found in protozoa species. TbPar42 exhibits an N-terminal forkhead associated (FHA)-domain and a peptidyl-prolyl-cis/trans-isomerase (PPIase) domain, both connected by a linker. Using NMR and X-ray analysis as well as activity assays, we report on the structures of the single domains of TbPar42, discuss their intra-molecular interplay, and give some initial hints as to potential cellular functions of the protein. | [
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Although research on children of parents with mental illness is growing, few researchers have examined the long-term impact of parental mental illness on adult children. This study explored the potential impact of growing up with a parent with a mental illness on the parenting role assumed by adult children. The qualitative study included ten participants, who were individually interviewed using a semi-structured interview schedule. Interpretative phenomenological analysis (IPA) along with member checks were utilised to derive themes from participants' narratives. Three main themes were identified, including: 'this is me', 'a whole new world', and 'because of you'. 'This is me' consisted of narratives highlighting how adult children intentionally went about parenting in ways different from their parents, and 'a whole new world' captured the salient identity that parenthood served for adult children. The third theme, 'because of you' highlighted the challenges adult children faced in their parenting roles as a result of their childhood experience living with a parent with mental illness. Participants highlighted the main challenges to be an absence of a reference point and lack of informal social supports. Recommendations for mental health practitioners and future research are presented in order to develop better ways to support adult children and their families. | [
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Square dancing is a popular music-related group physical exercise for health benefits in China mainly participated by mid-aged women and elderly people. This paper investigates the soundscape and enjoyment of the square dancing in urban streets through a case study in Lichuan, a county level city in southwest China, in December 2017. It examines the impact of gender, age, participation and places on perceptions of square dancing soundscape. Two sites along two main urban streets in the city were selected to conduct onsite investigations where residents spontaneously perform square dancing on a daily basis. Ethnographical observations were conducted to identify the social-physical features and sounds of both sites during the dance and without dance. Sound pressure measurements (LAeq and LAmax) were also conducted under the two conditions. An off-site survey was distributed through the local social media groups to understand residents' everyday experiences and perceptions of square dancing in the city; 106 responses were received for the off-site survey. T-tests and Chi-squared tests were used for statistical analysis of the survey data. The results show gender does appear to be a factor influencing the regularity of participation in square dancing, with a bias towards more female participants. Participation frequency of square dance has an impact on the enjoyment of square dancing. There is no correlation between the dislike of watching square dancing, or dislike of the music and a desire to restrict locations for square dancing. | [
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This contribution outlines the design and manufacturing of a microfluidic device implemented as a biosensor for retrieval and detection of bacteria RNA. The device is fully made of Cyclo-Olefin Copolymer (COC), which features low auto-fluorescence, biocompatibility and manufacturability by hot-embossing. The RNA retrieval was carried on after bacteria heat-lysis by an on-chip micro-heater, whose function was characterized at different working parameters. Carbon resistive temperature sensors were tested, characterized and printed on the biochip sealing film to monitor the heating process. Off-chip and on-chip processed RNA were hybridized with capture probes on the reaction chamber surface and identification was achieved by detection of fluorescence tags. The application of the mentioned techniques and materials proved to allow the development of low-cost, disposable albeit multi-functional microfluidic system, performing heating, temperature sensing and chemical reaction processes in the same device. By proving its effectiveness, this device contributes a reference to show the integration potential of fully thermoplastic devices in biosensor systems. | [
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] |
The maturation of mammalian oocytes in vitro can be stimulated by gonadotropins (follicle-stimulating hormone, FSH) or their intrafollicular mediator, epidermal growth factor (EGF)-like peptide-amphiregulin (AREG). We have shown previously that in pig cumulus-oocyte complexes (COCs), FSH induces expression and the synthesis of AREG that binds to EGF receptor (EGFR) and activates the mitogen-activated protein kinase 3/1 (MAPK3/1) signaling pathway. However, in this study we found that FSH also caused a rapid activation of MAPK3/1 in the cumulus cells, which cannot be explained by the de novo synthesis of AREG. The rapid MAPK3/1 activation required EGFR tyrosine kinase (TK) activity, was sensitive to SRC proto-oncogene non-receptor tyrosine kinase (SRC)-family and protein kinase C (PKC) inhibitors, and was resistant to inhibitors of protein kinase A (PKA) and metalloproteinases. AREG also induced the rapid activation of MAPK3/1 in cumulus cells, but this activation was only dependent on the EGFR TK activity. We conclude that in cumulus cells, FSH induces a rapid activation of MAPK3/1 by the ligand-independent transactivation of EGFR, requiring SRC and PKC activities. This rapid activation of MAPK3/1 precedes the second mechanism participating in the generation and maintenance of active MAPK3/1-the ligand-dependent activation of EGFR depending on the synthesis of EGF-like peptides. | [
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A set of overall 40 carboxamides was prepared from five different natural occurring triterpenoids including oleanolic, ursolic, maslinic, betulinic, and platanic acid. All of which were derived from ethylene diamine holding an additional substituent connected to the ethylene diamine group. These derivatives were evaluated regarding their inhibitory activity of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) employing Ellman's assay. We further determined the type of inhibition and inhibition constants. Carboxamides derived from platanic acid have been shown to be potent and selective BChE inhibitors. Especially the mixed-type inhibitor (3)-N-(2-pyrrolidin-1-ylethyl)-3-acetyloxy-20-oxo-30-norlupan-28-amide (35) showed a remarkably low Ki of 0.07 0.01 M (Ki' = 2.38 0.48 M) for the inhibition of BChE. | [
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] |
Background/aim: The aim of this study was to determine the usefulness of tigecycline in combination treatment of Stenotrophomonas
maltophilia infections by evaluating the in vitro synergistic effects of tigecycline with various antibiotics using the E-test method.Materials and methods: Synergy testing by E-test was performed with various antibiotic combinations in 10 S. maltophilia isolates
identified as a cause of infection. The antibiotics used in the study included tigecycline (TGC), cefoperazone-sulbactam (CPS),
ceftazidime (TZ), levofloxacin (LEV), and trimethoprim-sulfamethoxazole (cotrimoxazole) (TS). Four different combinations (TGCCPS,
TGC-TZ, TGC-LEV, TGC-TS) were studied with the E-test synergy method.Results: S. maltophilia isolates were found to have the highest level of susceptibility to trimethoprim-sulfamethoxazole, tigecycline, and
levofloxacin. The fractional inhibitory concentration (FIC) index was calculated as FIC = MICAB/MICA + MICBA/MICB. The FIC
index values were calculated and classified as synergistic (FIC < 0.5), additive (FIC = 0.5–1), indifferent (FIC = 1–4), and antagonistic
(FIC > 4). According to FIC index values, synergy was found with the highest rate with TGC-CPS and TGC-LEV combinations (20%).
Antagonistic activity was not found in any combination.Conclusion: When trimethoprim-sulfamethoxazole cannot be used because of resistance or allergy, tigecycline alone or in combination
may be included as an alternative option. Although in vitro results are promising, clinical data are required. | [
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] |
Background/aim: Genetic aspects play a role in insulin resistance in children. In this study, for the first time, the association of LRP5
(rs556442) polymorphism and insulin resistance in Iranian children and adolescents was investigated.Materials and methods: The study population comprises children and adolescents aged 9–18 years. Anthropometric and biochemical
parameters were assessed. Insulin resistance/sensitivity was determined by the quantitative insulin sensitivity check index (QUICKI),
homeostasis model assessment-insulin resistance (HOMA-IR), insulin-to-glucose ratio, McAuley index, revised McAuley index, fasting
insulin resistance index (FIRI), and Bennett’s index. LRP5 (rs566442) single nucleotide polymorphism (SNP) was identified using
restriction fragment length polymorphism (RFLP). Linear regression analysis was used to determine the association between the LRP5
polymorphism (rs556442) and insulin sensitivity indexes.Results: Significant differences were found between GG genotype vs. AG/AA genotypes for McAuley index (P = 0.049) and revised
McAuley index (P = 0.044) when adjusted for interaction factors (age, sex, and puberty) in regression models. No significant association
was found between LRP5 (rs566442) and other insulin resistance indexes. Also, LRP5 (rs566442) did not show a significant impact on
biochemical parameters.Conclusion: This study showed that LRP5 polymorphism (rs556442) was associated with insulin resistance in Iranian children and
adolescents. | [
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] |
Background/aim: The aim of the study is to examine the relationship among bone density, adipose tissue, and muscle mass with
abdominal CT in geriatric patients.Materials and methods: The study is a retrospective cohort study of patients 65 years and over who underwent abdominal CT for any
reason between October 2017 and July 2018. Third lumbar vertebra density, fatty degeneration of the paraspinal muscle, subcutaneous
adipose tissue, and mesenteric adipose tissue ratio were evaluated.Results: A total of 312 patients, 144 females and 168 males, were included in the study. Reduced bone density was found in 237 (76%)
patients. Reduced bone density and muscle atrophy was more frequent in females (P < 0.001). Muscle atrophy was found to occur
5.7 times more frequently in cases of reduced bone density (OR, 95% CI = 5.74 (3.27–10.09), P < 0.001). There was no significant
relationship found between reduced bone density and subcutaneous adipose tissue thickness or mesenteric adipose tissue ratio (P =
0.073, P = 0.939, respectively).Conclusion: In the geriatric age group, reduced bone density and muscle atrophy were quite common and were significantly more
frequent in women. Furthermore, a strong association between reduced bone density and muscle atrophy was found. No relationship
was found between reduced bone density and subcutaneous adipose tissue thickness–mesenteric adipose ratio. | [
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] |
Background/aim: The KCNQ1 gene has a significant role in long QT syndrome, Jervell and Lange-Nielsen syndrome, familial
atrial fibrillation, and short QT syndrome. Analyzing such heterogeneous disorders, six novel short tandem repeat (STR) markers
around the KCNQ1 gene were found and evaluated in a healthy population, and other statistical traits of the markers were detected.Materials and methods: Using Tandem Repeats Finder (TRF) and Sequence-Based Estimation of Repeat Variability (SERV) software,
STR markers were detected with valid tetra- and pentanucleotide repeats. The markers were investigated for a total of 60 unrelated
Iranian healthy individuals and analyzed using GenAlEx 6.502 and Cervus 3.0.7.Results: A total of 77 haplotypes was detected, of which 25 haplotypes were unique and the others occurred at least two times. The
number of haplotypes per locus ranged from 7 to 18 with the highest frequency of 69.2%, and the observed heterozygosity was calculated
as 0.589. The power of discrimination ranged from 0.70 to 0.96. Five of the markers meet Hardy–Weinberg equilibrium.Conclusion: A novel panel of STR markers was described with high allele heterozygosity and segregation in every locus, which may
lead to faster and more credible recognition of the disease-inducing KCNQ1 gene and allow it to be used for human identity testing and
prenatal diagnosis. | [
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] |
Background/aim: Gastric cancer (GC) is one of the major causes of cancer mortality worldwide. As a novel type of endogenous
noncoding RNAs, circular RNAs (circRNAs) are formed by a covalent link between 5’ and 3’ ends. They are very stable and abundant
in eukaryotes. As there were no reported studies on the expression profiles of circular RNA ITCH (cir-ITCH) and circHIPK3 in GC, in
the current study, we aimed to delineate the expression profiles and clinicopathological relevance of these two circRNAs in GC tissues
compared to their paired adjacent noncancerous tissues.Materials and methods: Quantitative real-time polymerase chain reaction was performed to evaluate cir_ITCH and circHIPK3
expression in 30 paired gastric cancer tissues. The clinicopathological relevance of these two circular RNAs’ expression levels with
gastric cancer was further examined.Results: Our results showed that the expression of cir_ITCH and circHIPK3 were significantly downregulated in GC tumoral tissues
compared with their paired adjacent nonneoplastic counterparts. Further analyses showed that cir_ITCH and circHIPK3 expression
levels were related with numerous clinicopathological features of tumoral tissues.Conclusion: Cir_ITCH and circHIPK3 may have imperative roles in GC and serve in the future as potential prognostic biomarkers in GC. | [
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] |
Two OBP genes, BodoOBP1 and BodoOBP2, were cloned from Bradysia odoriphaga, a major agricultural pest of Chinese chives. The amino acid sequence alignment of both BodoOBPs showed high similarity. Fluorescence competitive binding assays revealed that both BodoOBPs have a moderate binding affinity to dipropyl trisulfide. Tissue expression profiles indicated that both BodoOBPs are antennae-specific and more abundant in the male antennae than in the female antennae. Developmental expression profile analysis indicated that expression levels of both BodoOBPs were higher in the male adult stage than in the other developmental stages. Both BodoOBPs also showed differential expression in pre- and postmating adults. RNAi assays indicated that ability of dsOBPs-treated males to detect females was significantly reduced compared to controls. Attraction of plant volatile dipropyl trisulfide to dsOBPs-treated adults was also significantly lower than in the control. Our findings indicate that both BodoOBPs are involved in host-seeking behavior and in detecting sex pheromones. | [
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Bacillus amyloliquefaciens NX-2S154 is a promising poly(-glutamic acid) (-PGA) producing strain discovered in previous studies. However, the wild-type strain contains an unknown endogenous plasmid, p2Sip, which causes low transformation efficiency and instability of exogenous plasmids. In our study, p2Sip is 5622 bp with 41% G+C content and contains four putative open reading frames (ORFs), including genes repB, hsp, and mobB and -PGA-synthesis regulator, pgsR. Elimination of p2Sip from strain NX-2S154 delayed -PGA secretion and decreased production of -PGA by 18.1%. Integration of a pgsR expression element into the genomic BamHI locus using marker-free manipulation based on pheS* increased the -PGA titer by 8%. pgsR overexpression upregulated the expression of -PGA synthase pgsB, regulator degQ, and glutamic acid synthase gltA, thus increasing the -PGA production in B. amyloliquefaciens NB. Our results indicated that pgsR from p2Sip plays an important regulatory role in -PGA synthesis in B. amyloliquefaciens. | [
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Introduction: Introduction: the study during adolescence of adherence to the Mediterranean diet, alcohol consumption, weight status as well as the practice of physical activity is fundamental to promote healthy habits conducive to a better quality of life in adulthood. Objectives: to know the adherence to the Mediterranean diet (DM) in the adolescent population, the weight status, the consumption of alcohol and the practice of physical activity (AF); and to analyze if in the studied sample there is an association between the motivation towards the realization of physical and sports practice and sex, age, body mass index (BMI), DM, the consumption of alcohol and the practice of FA. Methods: transversal descriptive study of 648 adolescents aged between 12 and 16 years. Adherence to the Mediterranean diet was analyzed with the KIDMED test; alcohol consumption, with the alcohol consumption scale; physical activity, with the IPAQ-A; and physical-sport motivation, with the CSAPPA scale. Results: according to the results, 17.6% of school children are overweight, 73.4% have high adherence to DM, and most do not consume or make moderate alcohol consumption and practice vigorous intensity AF within the recommended ranges. Men have a higher BMI (20.86 vs 20.67) and practice more days per week vigorous AF than women (3.16 vs 2.45). Schoolchildren who enjoy more the practice of AF have a better diet, spend more time doing AF and consume less alcohol. Conclusion: adolescents who do more physical activity have greater adherence to the Mediterranean diet, reduce alcohol consumption, have better weight status and increase physical-sports motivation. | [
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Introduction: Introduction: the use of real images of food portions constitutes a useful and effective tool to help measure the amount of food consumed. Objective: to validate content and visual perception of the images of a photographic atlas of food portions designed for Ecuador. Methods: first, eight experts assessed the content in an atlas of food portions, using the Delphi technique. Then, 56 adults (aged 18-59) gave an assessment of their visual perception of about 35 portions of nine selected products. The concordance in the estimation using the atlas versus an estimation without the atlas was evaluated through the intra-class correlation coefficient (ICC), the Bland-Altman graphical method, and a hypothesis contrast. The differences between the real amounts and the estimation were assessed using the Wilcoxon test (p < 0.05). For each of the food items, the percentage of participants who chose the correct photograph, the one directly above or below was calculated. Results: the assessment carried out by experts showed that this instrument is relevant and appropriate. ICC values of between 0.576 and 0.956 were obtained using the atlas, as well as significant differences between the real amounts and the estimation without the atlas (p < 0.001). There was a sufficient correlation between the actual image and its perception for all food items except mayonnaise. The correct photograph was chosen in 66% of 500 estimations. Conclusions: the photographic atlas of food portions for Ecuador is an appropriate tool for helping to estimate the amount of food consumed by adults. | [
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Introduction: Background and objective: hemodynamically significant patent ductus arteriosus (HS-PDA) is associated with an increased risk of necrotizing enterocolitis (NEC) and worse enteral tolerance in preterm newborns (PN). An association has been demonstrated between brain natriuretic propeptide (proBNP) and HS-PDA. Our objective was to analyze the relationship between proBNP levels and enteral tolerance, NEC risk and weight gain in PN. Material and methods: a retrospective study was performed in neonates born before 32 weeks' gestation or with birth weight below 1500 grams, in whom proBNP determination and echocardiography were performed at 48 to 72 h of life. Results: 117 patients were included. 65.8% had a HS-PDA and 9.4% had an outcome of NEC. HS-PDA was associated with longer duration of parenteral nutrition (p < 0.001), a confirmed NEC (p = 0.006) and worse weight gain during admission (p < 0.001). ProBNP levels were associated to NEC (no NEC 12189.5 pg / mL, range 654-247986; NEC 41445 pg/mL, range 15275-166172, p < 0.001). No association was found with the rest of gastrointestinal outcomes. Multivariate logistic regression analysis showed a significant association of NEC with gestational age and proBNP above 22,400 pg/mL (OR 13,386, 95% CI 1,541-116,262, p = 0.019). Conclusions: proBNP could be an early marker of severe digestive pathology in PN. Increased proBNP levels could be associated with a significant increased risk of NEC in very immature newborns. | [
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Introduction: Introduction: obesity and breast cancer (BC) are two diseases with known symptoms; however, the association of both and its impact on the respiratory system is poorly investigated. Objective: to describe the effects of overweight and obesity on the pulmonary volumes of patients with breast cancer from the city of Talca. Method: forty-one women diagnosed with BC were divided into three groups: nine patients with breast cancer and normal weight (BC + NW), 18 with breast cancer and overweight (BC + OW) and 14 with breast cancer and obesity (BC + O). Forced vital capacity and lung volumes were measured, ANOVA or Kruskal-Wallis was used for the statistical analysis, and for the Pearson or Spearman correlations, a level of significance of p < 0.05 was considered. Results: patients with BC + NW had a greater residual volume than those with BC + OW and BC + O (both p < 0.05). Functional residual capacity (FRC) was significantly higher in patients with BC + NP versus patients with BC + OW and BC + O (both p < 0.05). The total lung capacity was significantly higher in patients with BC + NW versus BC + OW and BC + O (p < 0.01 and p < 0.001, respectively). Between the BMI and FRC, a negative and significant correlation was found in the patients with BC + O (p = 0.049). Finally, in patients with BC + O a positive and significant correlation was observed between height and FRC (p = 0.01). Conclusions: the decrease in pulmonary volumes is exacerbated when patients with BC present malnutrition by excess. In addition, it is negatively correlated with the BMI in patients with BC + O. | [
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Introduction: Introduction: the increase in prevalence of eating disorders in the population has brought with it an interest in evaluating the nutritional patterns of the adult population in order to increase individual health and wellbeing. Objectives: to analyze the Three Factor Eating Questionnaire (TFEQ) in order to find out if it is a valid model for adult populations without any eating pathology in different cultures and societies by analyzing its psychometric properties and structure and proposing the best version or model for application to healthcare professionals, specifically in nursing. Methods: a cross-sectional descriptive analysis was done in a sample of adult nurses with no food pathology. Nine hundred and eighty-three working nurses aged 22 to 57 were selected. The 18-item version of the TFEQ was used. Results: the 18-item model with three factors showed the best fit (2/gl = 4,594; CFI = 0.945; TLI = 0.935; RMSEA = 0.061). The CFI between model 1 (whole base model) and the rest of the models was 0.004, so configural, metric, scalar and strict invariance is accepted. Conclusions: the results described show the validity and consistency of the TFEQ as an instrument in the scope of adults with no pathology working in healthcare, specifically nursing, for evaluating eating behavior, and not exclusively for diagnosis, but also for intervention at the governmental and organizational level. | [
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BACKGROUND: Despite the nationwide micronutrient powder (MNP) supplementation, the Philippines only saw limited success in reducing the prevalence of anemia-a condition that has remained a public health concern among young children.OBJECTIVE: To assess and explore the acceptability and compliance to MNP and Bigas-Mongo (BigMo) complementary food blend among mothers/caregivers of children aged 6 to 23 months and the promotion of these products by community health workers (CHWs).METHODS: This study was part of the randomized controlled trial involving 3 methods of data collection: (1) bimonthly visits to mothers and caregivers for 6 months to determine the level of acceptability and compliance of the 4 intervention groups; (2) initial and final interviews with mothers/caregivers (initial = 141; final = 130) to gather their experiences and difficulties in MNP and BigMo preparation and feeding; and (3) focus group discussion (n = 4) among CHWs (n = 13) to understand their perceptions and difficulties in promoting MNP and BigMo.RESULTS: The overall compliance to MNP consumption was 74.7%, with some difference between the groups. Analysis of the information received from mothers/caregivers showed that maternal adaptive strategies in preparing and feeding MNP to their children could affect MNP use, while nonreceptiveness of mothers to integrating MNP into the child's feeding routine, perceived side effects, and perceived unfavorable taste and smell were key factors considered to limit MNP use.CONCLUSION: This study provides insights into MNP and BigMo acceptability and compliance by mothers and their promotion by CHWs, which may be useful in improving MNP program and complementary feeding projects and programs in similar settings. | [
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Tryptophan, an aromatic amino acid, has been widely used in food industry because it participates in the regulation of protein synthesis and metabolic network in vivo. In this study, we obtained a strain named TRP03 by enhancing the tryptophan synthesis pathway, which could accumulate tryptophan at approximately 35g/L in a 5L bioreactor. We then modified the central metabolic pathway of TRP03, to increase the supply of the precursor phosphoenolpyruvate (PEP), the genes related to PEP were modified. Furthermore, citric acid transport system and TCA were upregulated to effectively increase cell growth. We observed that strain TRP07 that could accumulate tryptophan at approximately 49g/L with a yield of 0.186g tryptophan/g glucose in a 5L bioreactor. By-products such as glutamate and acetic acid were reduced to 0.8g/L and 2.2g/L, respectively. | [
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One of the most important tasks in forensic medicine is differentiating between a homicide and a suicide, especially in cases where more than one self-inflicted gunshot wound is present. The significance is even greater when the victim's ability to act after the first gunshot is questionable. In these cases, the only way to determine the sequence of the shots is to consider the severity of the injuries and their disabling effect. Therefore, the importance of previously mentioned facts is even greater, not only in everyday forensic practice but also in court. The questions dealing with the crime scene and interpretation of the wounds' trajectories are of the utmost importance. | [
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We investigated the variability of strength trained athletes' self-selected rest periods between sets of heavy squat training. Sixteen strength-trained male athletes (Mage = 23, SD = 3 years) completed two squat training sessions 48 hours apart. Each training session consisted of five sets of 5RM squats, interspersed with self-selected interset rest periods. A Gymaware linear optical encoder collected kinetic data for each squat and temporal data for each interset rest period. The participants' subjective ratings of the experience were taken before (Readiness to Lift [RTL]) and after (Rating of Perceived Effort [RPE]) each set. Mean total rest time and mean power output differed significantly between sessions. For both sessions, interset rest period increased, and power output decreased between Sets 3, 4, and 5 (95% CI range [-101, -17]) compared with Set 1. In both sessions, RPE increased significantly in Set 3 compared with Set 1 (95% CI range = [0.68, 2.19]), while RTL decreased significantly from Set 3 (95% CI range [-2.99, -0.58]) compared to Set 1. Interset rest period and power output demonstrated fair reliability between sessions (mean intraclass correlation coefficient = 0.55), while RPE and RTL demonstrated good and excellent reliability, respectively (mean intraclass correlation coefficient = 0.63 and 0.80). In conclusion, highly trained strength athletes demonstrated a significant difference in their between session power output and total rest time when using self-selected interset rest periods, despite stability in their subjective ratings of fatigue and effort. Interset rest periods can be self-selected reliably to complete strength training in heavy squat protocol; however, power output may decline during the set. | [
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] |
We describe a case of concomitant fibromuscular dysplasia (FMD) and atherosclerotic internal carotid artery (ICA) disease in a symptomatic patient. Sixty-eight-year-old female presented for evaluation of a transient ischemic attack. Imaging revealed severe proximal >80% ICA stenosis with severe FMD to mid and distal ICA. Planned hybrid approach with left carotid endarterectomy (CEA) and balloon angioplasty was aborted intraoperatively due to lack of back bleeding. Open gradual rigid dilation was then performed with resumption of back bleeding. Completion angiogram revealed widely patent flow through CEA patch with no residual defects. Patient awoke from operation neurologically intact. At 6-month follow-up, carotid duplex revealed severe recurrent ICA stenosis. Endovascular intervention was performed with balloon dilation to the proximal and mid-ICA with stenting of a moderate 60% ostial common carotid stenosis. She recovered well from procedure with 3-month carotid duplex showing widely patent common carotid stent and ICA with no areas of stenosis. Informed consent has been obtained from the patient for publication of the case report and accompanying images. | [
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BACKGROUND:: Thoracic endovascular aortic repair (TEVAR) is associated with several short-term benefits, including reduced morbidity and mortality; however, the long-term durability of TEVAR and the need for secondary aortic reintervention remain unclear. We aimed to determine the adverse outcomes, including aortic reintervention, after TEVAR for thoracic aortic aneurysms and dissection.METHODS:: Between October 2009 and July 2016, 130 patients underwent TEVAR at Kyungpook National University Hospital. We excluded 35 patients with traumatic injury and included the remaining 95 patients in our study after TEVAR. The patients included in this study were categorized into 2 groups (reintervention [R] and nonintervention [N] groups) according to the need for reintervention. The mean follow-up period for all 95 patients was 22.4 (20.6) months.RESULTS:: The overall actuarial survival rates were 83.7% (4.1%) and 63.6% (8.8%) at 1 and 5 years, respectively. The rates of freedom from aortic reintervention after TEVAR were 94.0% (3.5%), 72.8% (8.2%), and 48.9% (10.5%) at 2, 3, and 5 years, respectively. The independent risk factors for aortic reintervention were endoleaks after TEVAR (odds ratio [OR] 6.13, P = .017), increase in aortic size by over 5% per year (OR 20.40, P = .001), and peripheral vascular occlusive disease (PVOD; OR 13.62, P = .007). Patients with preoperative hemoptysis tended to show a greater need for aortic reintervention ( P = .059). Increase in aortic size by over 5% per year and PVOD were the primary risk factors for endoleaks (OR 3.82, P = .013 and OR 4.37, P = .021, respectively).CONCLUSION:: Survival after TEVAR for thoracic aortic pathologies was satisfactory in most of the patients chosen as candidates for the procedure. However, the occurrence of endoleaks, increase in aortic size by over 5% per year, and PVOD were the primary causes of aortic reintervention. | [
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] |
Acquired heart diseases (AHD) cause significant morbidity and mortality in children. There are limited studies on their burden in children. We conducted a retrospective study of 85 consecutive children diagnosed with AHD using clinical evaluation and echocardiography at Medical College, Kanpur, India to determine the aetiology and outcome of AHD in children. We found rheumatic heart disease (RHD) in one-third, cardiomyopathies or myocarditis combined in a further third and the remaining third were other causes, including pericardial diseases and metabolic or genetic disorders. These latter diseases were frequently misdiagnosed, causing significant morbidity and mortality. Hence, in children of all age groups presenting with unexplained shock, dyspnoea, hepatomegaly and ascites, cardiac status should be carefully and critically evaluated so that non-rheumatic AHD may not be missed. | [
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Zika virus (ZIKV) is a historically neglected mosquito-borne flavivirus that has caused recent epidemics in the western hemisphere. ZIKV has been associated with severe symptoms including infant microcephaly and Guillain-Barr? syndrome, stimulating interest in understanding factors governing ZIKV infection. Heat shock protein 70 (Hsp70) has been shown to be an infection factor for multiple viruses, leading us to investigate the role of Hsp70 in the ZIKV infection process. ZIKV infection induced Hsp70 expression in host cells 48-h post-infection. Inducing Hsp70 expression in mammalian cells increased ZIKV production, whereas inhibiting Hsp70 activity reduced ZIKV viral RNA production and virion release from the cell. Hsp70 was localized both on the cell surface where it could interact with ZIKV during the initial stages of the infection process, and intracellularly where it localized with viral RNA. Blocking cell surface-localized Hsp70 using antibodies decreased ZIKV cell infection rates and production of infectious virus particles, as did competition with recombinant Hsp70 protein. Overall, Hsp70 was found to play a functional role in both the pre- and post-ZIKV infection processes affecting viral entry, replication, and egress. Understanding the interactions between Hsp70 and ZIKV may lead to novel therapeutics for ZIKV infection. | [
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] |
An outbreak with a remarkable Listeria monocytogenes clone causing 163 cases of non-invasive listeriosis occurred in Germany in 2015. Core genome multi locus sequence typing grouped non-invasive outbreak isolates and isolates obtained from related food samples into a single cluster, but clearly separated genetically close isolates obtained from invasive listeriosis cases. A comparative genomic approach identified a premature stop codon in the chiB gene, encoding one of the two L. monocytogenes chitinases, which clustered with disease outcome. Correction of this premature stop codon in one representative gastroenteritis outbreak isolate restored chitinase production, but effects in infection experiments were not found. While the exact role of chitinases in virulence of L. monocytogenes is still not fully understood, our results now clearly show that ChiB-derived activity is not required to establish L. monocytogenes gastroenteritis in humans. This limits a possible role of ChiB in human listeriosis to later steps of the infection. | [
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] |
Emergence of multidrug-resistant (MDR) Salmonella enterica serovar Indiana (S. Indiana), a dominant Salmonella serovar in China, has raised global awareness because the MDR S. Indiana also was rapidly emerged in other countries recently. To improve our understanding of underlying MDR mechanism and evolution of this emerging zoonotic pathogen, here we examined the standard ATCC51959 strain together with 19 diverse and representative Chinese S. Indiana strains by performing comprehensive microbiological, molecular, and comparative genomics analyses. The findings from S1-PFGE, plasmid origin analysis and Southern blotting suggested the MDR phenotype in the majority of isolates was associated with large integron-carrying plasmids. Interestingly, further in-depth analyses of two recently isolated, plasmid-free MDR S. Indiana revealed a long chromosomal class I integron (7.8 kb) that is not linked to the Salmonella Genome Island 1 (SGI1), which is rare. This unique chromosomal integron shares extremely high similarity to that identified in a MDR E. coli plasmid pLM6771 with respect to both genomic organization and sequence identity. Taken together, both plasmid and chromosomal integron I exist in the examined MDR S. Indiana strains. This timely study represents a significant step toward the understanding of molecular basis of the emerging MDR S. Indiana. | [
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Current influenza vaccines provide hemagglutinin strain-specific protection, but rarely provide cross-protection against divergent strains. It is, therefore, particularly important to develop a universal vaccine against conserved proteins or conserved regions of the virus. In this study, we used N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen and constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion. Both vaccines induced high M2e-specific humoral and cellular immune responses in the vaccinated mice. These two vaccines also conferred protection against a lethal infection of homo-subtypic H1N1 virus, with p-tPA-p3M2e being the most effective. In addition, p-tPA-p3M2e also showed cross-protection against different subtypes of the influenza virus (H9N2, H6N6, and H10N8) at varying rates (80%, 40%, and 20%, respectively). After passive immunization, M2e DNA vaccine-induced antibodies in the sera provided complete protection against homologous virus challenge. An analysis of the mechanism underlying this immunization-mediated protection indicates that M2e-specific IgG and T-cell immune responses may play critical roles in the prevention of infection and viral clearance. Taken together, our results indicate that this optimized M2e DNA vaccine is a promising candidate for the development of a universal, broad-spectrum influenza virus vaccine. | [
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Accumulating evidence indicates that bacterial metabolism plays an important role in virulence. Acetyl phosphate (AcP), the high-energy intermediate of the phosphotransacetylase-acetate kinase pathway, is the major acetyl donor in E. coli. PhoP is an essential transcription factor for bacterial virulence. Here, we show in Salmonella typhimurium that PhoP is non-enzymatically acetylated by AcP, which modifies its transcriptional activity, demonstrating that the acetylation of Lysine 102 (K102) is dependent on the intracellular AcP. The acetylation level of K102 decreases under PhoP-activating conditions including low magnesium, acid stress or following phagocytosis. Notably, in vitro assays show that K102 acetylation affects PhoP phosphorylation and inhibits its transcriptional activity. Both cell and mouse models show that K102 is critical to Salmonella virulence, and suggest acetylation is involved in regulating PhoP activity. Together, the current study highlights the importance of the metabolism in bacterial virulence, and shows AcP might be a key mediator. | [
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Chikungunya virus (CHIKV) is a mosquito-borne pathogen that causes an acute febrile syndrome and severe, debilitating rheumatic disorders in humans that may persist for months. CHIKV's presence in Asia dates from at least 1954, but its epidemiological profile in the region remains poorly understood. We systematically reviewed CHIKV emergence, epidemiology, clinical features, atypical manifestations and distribution of virus genotypes, in 47 countries from South East Asia (SEA) and the Western Pacific Region (WPR) during the period 1954-2017. Following the Cochrane Collaboration guidelines, Pubmed and Scopus databases, surveillance reports available in the World Health Organisation (WHO) and government websites were systematically reviewed. Of the 3504 records identified, 461 were retained for data extraction. Although CHIKV has been circulating in Asia almost continuously since the 1950s, it has significantly expanded its geographic reach in the region from 2005 onwards. Most reports identified in the review originated from India. Although all ages and both sexes can be affected, younger children and the elderly are more prone to severe and occasionally fatal forms of the disease, with child fatalities recorded since 1963 from India. The most frequent clinical features identified were arthralgia, rash, fever and headache. Both the Asian and East-Central-South African (ECSA) genotypes circulate in SEA and WPR, with ECSA genotype now predominant. Our findings indicate a substantial but poorly documented burden of CHIKV infection in the Asia-Pacific region. An evidence-based consensus on typical clinical features of chikungunya could aid in enhanced diagnosis and improved surveillance of the disease. | [
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Influenza A virus (IAV) is a common pathogen of respiratory disease. The IAV-induced seasonal epidemics and the sporadic pandemics are associated with high morbidity and mortality. Therefore, effective protection and therapy for IAV infections is an important challenge in countering this public health threat. Because vaccinations only protect against known circulating strains, and the currently available antivirals pose the risk of resistance formation, drugs targeting host cell factors needed for viral replication offer a promising therapeutic approach. In this study, we describe the use of the antifungal therapeutics posaconazole and itraconazole in the therapy of IAV. We show that both drugs efficiently inhibit the propagation of IAV in the cell culture model without being cytotoxic. The mode of action is probably based on several targets and includes both a priming of the interferon response and the induced imbalance of cellular cholesterol. The antiviral effect of itraconazole could be confirmed in the mouse model, where the administration of itraconazole led to a drastic reduction in mortality and a significant increase in the survival rate. Thus, our data indicate a promising therapeutic potential of at least itraconazole in influenza therapy. | [
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There was a substantial increase with infections of H7N9 avian influenza virus (AIV) in humans during Wave 5 (2016-2017). To investigate whether H7N9 had become more infectious/transmissible and pathogenic overall, we characterized the receptor binding and experimentally infected ferrets with highly pathogenic (HP)- and low pathogenic (LP)-H7N9 isolates selected from Wave 5, and compared their pathogenicity and transmissibility with a Wave 1 isolate from 2013. Studies show that A/Anhui/1/2013 (LP) and A/Chicken/Heyuan/16876/2016 (HP) were highly virulent in ferrets, A/Guangdong/Th008/2017 (HP) and A/Chicken/Huizhou/HZ-3/2017 (HP) had moderate virulence and A/Shenzhen/Th001/2016 (LP) was of low virulence in ferrets. Transmission was observed only in ferrets infected with A/Anhui/1/2013 and A/Chicken/Heyuan/16876/2016, consistent with the idea that sicker ferrets had a higher probability to transmit virus to naive animals. Given the Varied virulence and transmissibility observed in circulating H7N9 viruses from Wave 5, we conclude that the current public health risk of H7N9 has not substantially increased compared to 2013 and the circulating viruses are quite diverse. | [
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Dromedary camels are natural host of the Middle East respiratory syndrome coronavirus (MERS-CoV). However, there are limited studies of MERS-CoV infection of other domestic mammals exposed to infected dromedaries. We expanded our surveillance among camels in Egypt, Tunisia, and Senegal to include other domestic mammalian species in contact with infected camels. A total of 820 sera and 823 nasal swabs from cattle, sheep, goats, donkeys, buffaloes, mules, and horses were collected. Swabs were tested using RT-PCR and virus RNA-positive samples were genetically sequenced and phylogenetically analysed. Sera were screened using virus microneutralization tests and positive sera (where available) were confirmed using plaque reduction neutralization tests (PRNT). We detected 90% PRNT confirmed MERS-CoV antibody in 35 (55.6%) of 63 sera from sheep collected from Senegal, two sheep (1.8%) of 114 in Tunisia and a goat (0.9%) of 107 in Egypt, with titres ranging from 1:80 to ?1:320. We detected MERS-CoV RNA in swabs from three sheep (1.2%) of 254 and five goats (4.1%) of 121 from Egypt and Senegal, as well as one cow (1.9%) of 53 and three donkeys (7.1%) of 42 from Egypt. Partial sequences of the RT-PCR amplicons confirmed specificity of the results. This study showed that domestic livestock in contact with MERS-CoV infected camels may be at risk of infection. We recommend expanding current MERS-CoV surveillance in animals to include other livestock in close contact with dromedary camels. The segregation of camels from other livestock in farms and live animal markets may need to be considered. | [
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] |
Genotypic diversity and fluconazole susceptibility of 82 Cryptococcus neoformans and Cryptococcus gattii isolates from 60 renal transplant recipients in Brazil were characterized. Clinical characteristics of the patients and prognostic factors were analysed. Seventy-two (87.8%) isolates were C. neoformans and 10 (12.2%) were C. gattii. VNI was the most common molecular type (40 cases; 66.7%), followed by VNII (9 cases; 15%), VGII (6 cases; 10%), VNB (4 cases; 6.7%) and VNI/II (1 case; 1.7%). The isolates showed a high genetic diversity in the haplotype network and six new sequence types were described, most of them for VNB. There was a bias towards skin involvement in the non-VNI population (P = .012). VGII isolates exhibited higher fluconazole minimum inhibitory concentrations compared to C. neoformans isolates (P = 0.008). The 30-day mortality rate was 38.3%, and it was significantly associated with fungemia and absence of headache. Patients infected with VGII had a high mortality rate at 90 days (66.7%). A variety of molecular types produce disease in renal transplant recipients in Brazil and highlighted by VGII and VNB. We report the clinical appearance and impact of the molecular type, fluconazole susceptibility of the isolates, and clinical characteristics on patient outcome in this population. | [
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Seasonal outbreaks of acute encephalitis syndrome (AES) at Gorakhpur, India have been recognized since 2006. So far, the causative agent has not been identified. Use of next generation sequencing identified human parvovirus 4 (HPARV4) sequences in a CSF/plasma pool. These sequences showed highest identity with sequences earlier identified in similar patients from south India. Real-time PCR detected HPARV4 DNA in 20/78 (25.6%) CSF and 6/31 (19.3%) plasma of AES patients. Phylogenetic analysis classified three almost complete genomes and 24 partial NS1 sequences as genotype 2A. The observed association of HPARV4 with AES needs further evaluation. ELISAs for the detection of IgM and IgG antibodies against scrub typhus (Orientia tsutsugamushi, OT) showed ?70% IgM/IgG positivity suggestive of etiologic association. Prospective, comprehensive studies are needed to confirm association of these agents, singly or in combination with AES in Gorakhpur region. | [
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Respiratory viruses of human origin infect wild apes across Africa, sometimes lethally. Here we report simultaneous outbreaks of two distinct human respiratory viruses, human metapneumovirus (MPV; Pneumoviridae: Metapneumovirus) and human respirovirus 3 (HRV3; Paramyxoviridae; Respirovirus, formerly known as parainfluenza virus 3), in two chimpanzee (Pan troglodytes schweinfurthii) communities in the same forest in Uganda in December 2016 and January 2017. The viruses were absent before the outbreaks, but each was present in ill chimpanzees from one community during the outbreak period. Clinical signs and gross pathologic changes in affected chimpanzees closely mirrored symptoms and pathology commonly observed in humans for each virus. Epidemiologic modelling showed that MPV and HRV3 were similarly transmissible (R0 of 1.27 and 1.48, respectively), but MPV caused 12.2% mortality mainly in infants and older chimpanzees, whereas HRV3 caused no direct mortality. These results are consistent with the higher virulence of MPV than HRV3 in humans, although both MPV and HRV3 cause a significant global disease burden. Both viruses clustered phylogenetically within groups of known human variants, with MPV closely related to a lethal 2009 variant from mountain gorillas (Gorilla beringei beringei), suggesting two independent and simultaneous reverse zoonotic origins, either directly from humans or via intermediary hosts. These findings expand our knowledge of human origin viruses threatening wild chimpanzees and suggest that such viruses might be differentiated by their comparative epidemiological dynamics and pathogenicity in wild apes. Our results also caution against assuming common causation in coincident outbreaks. | [
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Influenza viruses of the H4 subtype are widespread in wild birds, circulate in domestic poultry, readily infect mammals, and tolerate the insertion of a polybasic cleavage site. In addition, serological evidence suggests that humans working with poultry are exposed to these viruses. While H4 viruses are not of immediate pandemic concern, there is a lack of knowledge regarding their antigenicity. In order to study viruses of the H4 subtype, we generated and characterized a panel of antibodies that bind a wide variety of H4 hemagglutinins from avian and swine isolates of both the Eurasian and North American lineage. We further characterized these antibodies using novel recombinant H4N6 viruses that were found to be lethal in DBA/2J mice. Non-neutralizing antibodies, which had activity in an antibody dependent cell-mediated cytotoxicity reporter assay in vitro, protected mice against challenge in vivo, highlighting the importance of effector functions. Our data suggest a high degree of antigenic conservation of the H4 hemagglutinin. | [
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Protective immunity wanes rapidly after immunization of children with acellular pertussis (aP) vaccines and these vaccines do not prevent nasal colonization or transmission of Bordetella pertussis in baboons. In this study, we examined the role of tissue-resident memory T (TRM) cells in persistent protective immunity induced by infection or immunization with aP and whole-cell pertussis (wP) vaccines in mice. Immunization of mice with a wP vaccine protected against lung and nasal colonization, whereas an aP vaccine failed to protect in the nose. IL-17 and IFN--secreting CD69+CD4+ TRM cells were expanded in the lung and nasal tissue after B. pertussis challenge of mice immunized with wP, but not aP vaccines. However, previous infection induced the most persistent protection against nasal colonization and this correlated with potent induction of nasal tissue TRM cells, especially IL-17-secreting TRM cells. Blocking T cell migration to respiratory tissue during immunization with a wP vaccine impaired bacterial clearance, whereas transfer of TRM cells from convalescent or wP-immunized mice conferred protection to na?ve mice. Our findings reveal that previous infection or wP vaccination are significantly more effective than aP vaccination in conferring persistent protective immunity against B. pertussis and that this is mediated by respiratory TRM cells. | [
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] |
BACKGROUND.: Stroke has long-term consequences for functional performance of daily activities. Evaluating client-perceived occupational performance provides insight for designing stroke-specific programs supporting home and community participation.PURPOSE.: This study describes the personal characteristics and self-perceived occupational performance in community-dwelling adults with stroke.METHOD.: A retrospective chart review was undertaken of 25 stroke survivors who sought services at a community-based centre. The outcome measures were the Canadian Occupational Performance Measure (COPM) to evaluate self-perceived occupational performance and the Montreal Cognitive Assessment (MoCA) to screen for cognitive impairment. The analysis used descriptive statistics.FINDINGS.: Mean participant age was 64 years, and most participants were Caucasian males (72%). The mean cognitive function score was 22.1 on MoCA, and the mean COPM performance and satisfaction subscores were 4.1 and 3.9, respectively. The top three challenging daily activities were driving, seeking employment, and functional mobility.IMPLICATIONS.: Stroke-specific community programs should emphasize the diverse performance concerns important to stroke survivors. | [
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] |
BACKGROUND.: The written languages and handwriting acquisition stages place different demands on the writer. Therefore, the relationship between body functions and handwriting performance may vary in different languages and acquisition stages; yet these demands have not been studied in the Arabic language.PURPOSE.: We examined the relationship between linguistic, visual-motor integration (VMI), and motor coordination (MC) functions and Arabic handwriting at two handwriting acquisition stages.METHOD.: This study used a cross-sectional and correlative design. Second- ( n = 54) and fourth-grade ( n = 59) students performed tasks examining reading, handwriting automaticity, VMI, MC, and copying a text.FINDINGS.: Handwriting automaticity significantly explained the variance in handwriting speed in both grades, in addition to the VMI in second grade and the MC in fourth grade. Enhanced performance in the VMI increased the likelihood of having good legibility in second but not in fourth grade.IMPLICATIONS.: Similar to other languages, the body functions related to Arabic handwriting vary at the different acquisition stages. Handwriting evaluation should be adjusted to students' acquisition stage. | [
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] |
Hollow mesoporous structures with interior cavities and expanded surface area have attracted considerable interest as drug delivery systems. In this study, a multifunctional nanotheranostic agent was developed by conjugating indocyanine green (ICG) and loading doxorubicin (DOX) onto the surfaces or within the cavities of hollow mesoporous Prussian blue (HMPB) nanoparticles, known as HMPB@PEI/ICG/DOX or simply HPID NPs, which were investigated as phototheranostic agents for in vivo fluorescence imaging and light-induced chemotherapy, photothermal therapy (PTT) and photodynamic therapy (PDT). These original HPID NPs exhibited strong near infrared (NIR) absorbance, reactive oxygen species (ROS) yield, and controlled chemotherapeutic drug release behavior. After intravenous injection of HPID NPs, highly efficient solid tumor ablation effects were observed in 4T1 tumor-bearing mouse models under NIR laser irradiation. Additionally, there was insignificant low-term toxicity or damage to normal tissues, as evidenced by histopathological and hemocompatibility analyses, suggesting that this agent has reliable biosafety for systemic applications. Taken together, the results of this study suggest that HPID NPs can produce tumor-specific and stimuli-triggered theranostic effects under tri-modal combination therapy. These HPID NPs advantageously provide traceable accumulation and activation and therefore could be a capable mediator in nanomedicines for eliminating solid tumors. | [
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Background: The polymorphism in FTO gene (rs9939609) is known to be associated with higher BMI and body fat mass content. However, environmental factors can modify this effect. The purpose of the present study was to investigate an association between sport specialization and the rs9939609 SNP in FTO gene in the cohort of professional and amateur young athletes. Methods: A total number of 250 young individuals 8-18 years old living in Moscow or Moscow district participated in the study. Individuals were divided into 3 groups in accordance with their physical activity level: control group (n = 49), amateurs (n = 67) and professionals (n = 137). Amateur and professional athletes were subdivided into groups according to their sport specialization. Quantile regression was used as a regression model, where the dependent (outcome) variable was BMI, along with percentage of body fat mass, and the independent variables (predictors) were the rs9939609 SNP in FTO gene, physical activity (active versus inactive), sport specialization (aerobic, intermittent sports and martial arts), nationality, level of sport experience (in years), gender and percentage of free fat mass content. Results: The regression analysis revealed that physical activity and sport specialization had greater impact compared to FTO allele in the group of physically active individuals. Physical activity, in particular aerobic, had negative associations with body fat mass and BMI. The rs9939609 SNP in FTO gene is associated with physical activity and aerobic activity. The magnitude of association becomes significantly larger at the upper quantiles of the body fat mass distribution. Conclusion: Physical activity and sport specialization explained more variance in body composition of physically active young individuals compared to the FTO polymorphism. Effect of interaction of physical activity, in particular aerobic, with the FTO polymorphism on body composition of young athletes was found. | [
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Since Hobbes' dictum of "homo homini lupus" in 17th century the tenor in European philosophy was the one of human nature in need of strong external rules to restrain from mutual aggression, inter-personal and inter-group. Behavioral measures and rules limiting a presumably aggressive human nature were perceived as purely moral and cultural. Evolutionary theory in the 19th century seemed to confirm the notion of a self-interested individual, at least in parts. By contrast, new models of cooperation later on modified the concept of a selfish human nature. Under conditions of reciprocity, immediate or delayed, cooperative behaviors tend to function better than egoistic ones. According to Human Ethology, comparable conditions are found in the first nuclear small group that is the extended family. Kin-based societies hence shape the original form of sociability. The key for understanding the ambivalence of pro-social and asocial behaviors, trust and mistrust, is the evolution of parental care and individual bonding. With parental care friendly dispositions and signals came into being, already in vertebrate sociability, but the differentiation of "we and the others" as well. The appetence to bond is opposed by dispositions of mistrust that tend to keep a distance and defend primary resources. Hence, small-group sociability could be handled quite well. Rituals of appeasement and the leveling of dominance were cultural means that evolved to nurture group cohesion. As for the rise of Neolithic larger groups of heterogeneous populations living together, new cultural rules had to arise. This process includes forms of customs, of religion, monuments and sacred objects. We may observe comparable phenomena in traditional cultures that exist today. The construction of group identity depends on myths that explain the group's identity by means of the cultural creation of common ancestors. The earlier kinship-relations of group members are extended to become culturally co-defined relations. Materially, these myths are made manifest by sacred objects. Through such symbols, the group communicates its "identity". The small-group ethos is thereby transferred to a larger group. On another level, artifacts and monuments that derive their expression from the repertoire of ritual "hostility displays" are used to secure the group's territory. Both forms of symbolic practice serve to maintain group identity internally by binding through common descent and externally by territorial demarcation through agonistic symbols. | [
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Elevated levels of non-accidental fractures in different populations, regions, and time periods are considered an indicator for violence within a population. Whilst soldiers from a mass grave contribute unambiguously to the bioarchaeological evidence for the presence of warfare in medieval England, we aim to further analyse the absence of temporal variation in the general population-wide fracture distribution pattern. A detailed study, consisting only of clearly dated and aged male individuals was conducted to investigate the impact of prolonged warfare and general instability by means of blunt force fracture distribution patterns in early (AD 1066-1100), middle (AD 1100-1380) and late (AD 1380-1558) medieval England. Statistically significant differences were only observed between the 26-35 years age group of the middle period (AD 1100-1380) vs the 18-25 year age group of the late period (AD 1380-1558). The latter included many individuals from Towton, North Yorkshire, and therefore battle-related injuries are reflected in the pattern. The former presented inconclusive causal effects, none of them could be reliably linked to warfare. It was concluded that aside from the inclusion of battle-related graves no evidence for the impact of prolonged warfare and economic instability could be observed in medieval England. | [
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] |
This article describes the agent-based modelling of catastrophic events using skeletal data from archaeological excavations with special regard to massacres and inter-personal violence. It is well-known, that the age and sex distributions of massacre sites and normal cemeteries formed over an extended period of use show drastic differences (Margerison & Kn?sel 2002). Living populations and cemetery populations have different distributions of the average ages of the individuals living in the group/ interred in the cemetery. However, the problems of correctly ageing skeletal human remains and mixed contexts, in which both attritional and catastrophic influences can be found, require an analytical tool which allows researchers to try out and play through different scenarios. The Population & Cemetery Simulator (PCS) allows researchers to model massacres. The Neolithic massacre of Talheim and a possible Late Neolithic war grave in central Iberia are presented as examples. | [
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Holotrichia parallela damages seriously on peanut (Arachis hypogaea) pods. Elucidation of its flight and walking performance in the presence of different plants may provide an insight in its host selection process and an explanation to its strong olfactory preference to an attractive nonhost, castor bean (Ricinus communis). We determined the relationships among flight performance, mate choice, and body weight of H. parallela beetles, and then investigated their flight and walking patterns in the presence of known hosts and attractive nonhost plants using a flight mill and a locomotion compensator, respectively. Body weights were not related to mating success, regardless of sex. The flight proportion of selected females drastically decreased compared with nonselected females, nonselected males, and selected males. Within mated males, heavier individuals exhibited poorer flight performance than lighter ones. In flight bioassay, peanut showed an arrestment effect on virgin females. For walking activity factors (distance, time, and speed), the host plants velvetleaf (Abutilon theophrasti) and Siberian elm (Ulmus pumila) elicited the strongest responses in females and males, respectively. Interestingly, the most preferred adult host, Siberian elm, and the nonhost, castor bean, elicited the highest values of two orientation factors (orientation and upwind length) in females. The chemical similarity hypothesis, which states that feeding or oviposition of insects mistakenly on nonhost can be traced to their chemical similarity to actual hosts, could explain the attraction of H. parallela to castor bean. | [
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] |
INTRODUCTION: Laparoscopic ventral hernia repair is a commonly performed procedure with a variety of mesh options. A relatively new mesh option is a non-woven polypropylene mesh with a silicone barrier designed for intraabdominal placement. This non-woven randomly oriented polypropylene microfiber hernia mesh may have benefits with potentially better biocompatibility compared with other ventral hernia repair mesh options.MATERIALS AND METHODS: A clinical quality improvement (CQI) program was initiated for ventral hernia patients to better measure and improve outcomes. From March 2013 to September 2015, 62 laparoscopic ventral hernia repairs were performed with this non-woven polypropylene mesh on 61 patients (one patient had two separate hernia repairs). Attempts were made to obtain long-term (> 2 years) follow up.RESULTS: There were 36 females and 25 males. The average age was 58.7 years (range 21-85). The average body mass index (BMI) was 36.2 (range 21.4-62.4). There were 51 (82%) incisional hernias and 11 (18%) primary hernias. There were 29 (47%) recurrent hernias. Mean hernia size was 83.4cm2 (range 1-400) and mean mesh size was 508.5cm2 (range 144-936). The mean operating room (OR) time was 108.2 minutes (range 38-418). The mean length of hospital stay was 2.7 days (range 0-13). There was one intraoperative complication-an injury to an inferior epigastric vessel that had a minor postoperative bleed that was self-limiting and required no treatment. There was one postoperative death due to aspiration on postoperative day #4. There has been one recurrence (1.6%) with long-term follow up. There were two patients (3.2%) with suture site pain postoperatively that resolved with suture site injections of local anesthetic in the clinic. There were no patients that required rehospitalization within 30 days after surgery. There were no mesh-related complications and no incidence of mesh removal was required.CONCLUSION: The results for laparoscopic ventral hernia repair, using a relatively new non-woven randomly oriented polypropylene microfiber mesh, are good with long-term follow up completed in the majority of patients. More experience with this type of mesh could generate evidence for the benefits of this mesh material in laparoscopic ventral hernia repair. | [
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BACKGROUND: Cohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health Organization (WHO) in 2011.METHODS: We conducted a phase 3 noninferiority trial in participants with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides. Participants were randomly assigned, in a 2:1 ratio, to receive a short regimen (9 to 11 months) that included high-dose moxifloxacin or a long regimen (20 months) that followed the 2011 WHO guidelines. The primary efficacy outcome was a favorable status at 132 weeks, defined by cultures negative for Mycobacterium tuberculosis at 132 weeks and at a previous occasion, with no intervening positive culture or previous unfavorable outcome. An upper 95% confidence limit for the between-group difference in favorable status that was 10 percentage points or less was used to determine noninferiority.RESULTS: Of 424 participants who underwent randomization, 383 were included in the modified intention-to-treat population. Favorable status was reported in 79.8% of participants in the long-regimen group and in 78.8% of those in the short-regimen group - a difference, with adjustment for human immunodeficiency virus status, of 1.0 percentage point (95% confidence interval [CI], -7.5 to 9.5) (P = 0.02 for noninferiority). The results with respect to noninferiority were consistent among the 321 participants in the per-protocol population (adjusted difference, -0.7 percentage points; 95% CI, -10.5 to 9.1). An adverse event of grade 3 or higher occurred in 45.4% of participants in the long-regimen group and in 48.2% in the short-regimen group. Prolongation of either the QT interval or the corrected QT interval (calculated with Fridericia's formula) to 500 msec occurred in 11.0% of participants in the short-regimen group, as compared with 6.4% in the long-regimen group (P = 0.14); because of the greater incidence in the short-regimen group, participants were closely monitored and some received medication adjustments. Death occurred in 8.5% of participants in the short-regimen group and in 6.4% in the long-regimen group, and acquired resistance to fluoroquinolones or aminoglycosides occurred in 3.3% and 2.3%, respectively.CONCLUSIONS: In persons with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides, a short regimen was noninferior to a long regimen with respect to the primary efficacy outcome and was similar to the long regimen in terms of safety. (Funded by the U.S. Agency for International Development and others; Current Controlled Trials number, ISRCTN78372190; ClinicalTrials.gov number, NCT02409290.). | [
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] |
BACKGROUND: Tuberculosis is the leading killer of patients with human immunodeficiency virus (HIV) infection. Preventive therapy is effective, but current regimens are limited by poor implementation and low completion rates.METHODS: We conducted a randomized, open-label, phase 3 noninferiority trial comparing the efficacy and safety of a 1-month regimen of daily rifapentine plus isoniazid (1-month group) with 9 months of isoniazid alone (9-month group) in HIV-infected patients who were living in areas of high tuberculosis prevalence or who had evidence of latent tuberculosis infection. The primary end point was the first diagnosis of tuberculosis or death from tuberculosis or an unknown cause. Noninferiority would be shown if the upper limit of the 95% confidence interval for the between-group difference in the number of events per 100 person-years was less than 1.25.RESULTS: A total of 3000 patients were enrolled and followed for a median of 3.3 years. Of these patients, 54% were women; the median CD4+ count was 470 cells per cubic millimeter, and half the patients were receiving antiretroviral therapy. The primary end point was reported in 32 of 1488 patients (2%) in the 1-month group and in 33 of 1498 (2%) in the 9-month group, for an incidence rate of 0.65 per 100 person-years and 0.67 per 100 person-years, respectively (rate difference in the 1-month group, -0.02 per 100 person-years; upper limit of the 95% confidence interval, 0.30). Serious adverse events occurred in 6% of the patients in the 1-month group and in 7% of those in the 9-month group (P = 0.07). The percentage of treatment completion was significantly higher in the 1-month group than in the 9-month group (97% vs. 90%, P<0.001).CONCLUSIONS: A 1-month regimen of rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing tuberculosis in HIV-infected patients. The percentage of patients who completed treatment was significantly higher in the 1-month group. (Funded by the National Institute of Allergy and Infectious Diseases; BRIEF TB/A5279 ClinicalTrials.gov number, NCT01404312.). | [
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] |
BACKGROUND: Surgical intervention is needed in some cases of spontaneous abortion to remove retained products of conception. Antibiotic prophylaxis may reduce the risk of pelvic infection, which is an important complication of this surgery, particularly in low-resource countries.METHODS: We conducted a double-blind, placebo-controlled, randomized trial investigating whether antibiotic prophylaxis before surgery to complete a spontaneous abortion would reduce pelvic infection among women and adolescents in low-resource countries. We randomly assigned patients to a single preoperative dose of 400 mg of oral doxycycline and 400 mg of oral metronidazole or identical placebos. The primary outcome was pelvic infection within 14 days after surgery. Pelvic infection was defined by the presence of two or more of four clinical features (purulent vaginal discharge, pyrexia, uterine tenderness, and leukocytosis) or by the presence of one of these features and the clinically identified need to administer antibiotics. The definition of pelvic infection was changed before the unblinding of the data; the original strict definition was two or more of the clinical features, without reference to the administration of antibiotics.RESULTS: We enrolled 3412 patients in Malawi, Pakistan, Tanzania, and Uganda. A total of 1705 patients were assigned to receive antibiotics and 1707 to receive placebo. The risk of pelvic infection was 4.1% (68 of 1676 pregnancies) in the antibiotics group and 5.3% (90 of 1684 pregnancies) in the placebo group (risk ratio, 0.77; 95% confidence interval [CI], 0.56 to 1.04; P = 0.09). Pelvic infection according to original strict criteria was diagnosed in 1.5% (26 of 1700 pregnancies) and 2.6% (44 of 1704 pregnancies), respectively (risk ratio, 0.60; 95% CI, 0.37 to 0.96). There were no significant between-group differences in adverse events.CONCLUSIONS: Antibiotic prophylaxis before miscarriage surgery did not result in a significantly lower risk of pelvic infection, as defined by pragmatic broad criteria, than placebo. (Funded by the Medical Research Council and others; AIMS Current Controlled Trials number, ISRCTN97143849.). | [
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BACKGROUND: Short-term studies have shown that bempedoic acid, an inhibitor of ATP citrate lyase, reduces levels of low-density lipoprotein (LDL) cholesterol. Data are limited regarding the safety and efficacy of bempedoic acid treatment in long-term studies involving patients with hypercholesterolemia who are receiving guideline-recommended statin therapy.METHODS: We conducted a randomized, controlled trial involving patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both. Patients had to have an LDL cholesterol level of at least 70 mg per deciliter while they were receiving maximally tolerated statin therapy with or without additional lipid-lowering therapy. (Maximally tolerated statin therapy was defined as the highest intensity statin regimen that a patient was able to maintain, as determined by the investigator.) Patients were randomly assigned in a 2:1 ratio to receive bempedoic acid or placebo. The primary end point was safety, and the principal secondary end point (principal efficacy end point) was the percentage change in the LDL cholesterol level at week 12 of 52 weeks.RESULTS: The trial involved 2230 patients, of whom 1488 were assigned to receive bempedoic acid and 742 to receive placebo. The mean (SD) LDL cholesterol level at baseline was 103.229.4 mg per deciliter. The incidence of adverse events (1167 of 1487 patients [78.5%] in the bempedoic acid group and 584 of 742 [78.7%] in the placebo group) and serious adverse events (216 patients [14.5%] and 104 [14.0%], respectively) did not differ substantially between the two groups during the intervention period, but the incidence of adverse events leading to discontinuation of the regimen was higher in the bempedoic acid group than in the placebo group (162 patients [10.9%] vs. 53 [7.1%]), as was the incidence of gout (18 patients [1.2%] vs. 2 [0.3%]). At week 12, bempedoic acid reduced the mean LDL cholesterol level by 19.2 mg per deciliter, representing a change of -16.5% from baseline (difference vs. placebo in change from baseline, -18.1 percentage points; 95% confidence interval, -20.0 to -16.1; P<0.001). Safety and efficacy findings were consistent, regardless of the intensity of background statin therapy.CONCLUSIONS: In this 52-week trial, bempedoic acid added to maximally tolerated statin therapy did not lead to a higher incidence of overall adverse events than placebo and led to significantly lower LDL cholesterol levels. (Funded by Esperion Therapeutics; CLEAR Harmony ClinicalTrials.gov number, NCT02666664.). | [
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BACKGROUND: ATP citrate lyase is an enzyme in the cholesterol-biosynthesis pathway upstream of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the target of statins. Whether the genetic inhibition of ATP citrate lyase is associated with deleterious outcomes and whether it has the same effect, per unit decrease in the low-density lipoprotein (LDL) cholesterol level, as the genetic inhibition of HMGCR is unclear.METHODS: We constructed genetic scores composed of independently inherited variants in the genes encoding ATP citrate lyase (ACLY) and HMGCR to create instruments that mimic the effect of ATP citrate lyase inhibitors and HMGCR inhibitors (statins), respectively. We then compared the associations of these genetic scores with plasma lipid levels, lipoprotein levels, and the risk of cardiovascular events and cancer.RESULTS: A total of 654,783 participants, including 105,429 participants who had major cardiovascular events, were included in the study. The ACLY and HMGCR scores were associated with similar patterns of changes in plasma lipid and lipoprotein levels and with similar effects on the risk of cardiovascular events per decrease of 10 mg per deciliter in the LDL cholesterol level: odds ratio for cardiovascular events, 0.823 (95% confidence interval [CI], 0.78 to 0.87; P = 4.0?10-14) for the ACLY score and 0.836 (95% CI, 0.81 to 0.87; P = 3.9?10-19) for the HMGCR score. Neither lifelong genetic inhibition of ATP citrate lyase nor lifelong genetic inhibition of HMGCR was associated with an increased risk of cancer.CONCLUSIONS: Genetic variants that mimic the effect of ATP citrate lyase inhibitors and statins appeared to lower plasma LDL cholesterol levels by the same mechanism of action and were associated with similar effects on the risk of cardiovascular disease per unit decrease in the LDL cholesterol level. (Funded by Esperion Therapeutics and others.). | [
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] |
BACKGROUND: The United States is undergoing a crippling opioid epidemic, spurred in part by overuse of prescription opioids by adults 25 to 64 years of age. Of concern are long-duration and high-dose initial prescriptions, which place the patients and their friends and relatives at heightened risk for long-term opioid use, misuse, overdose, and death.METHODS: We estimated the incidence of initial opioid prescriptions in each month between July 2012 and December 2017 using administrative-claims data from across the United States (accessed through Blue Cross-Blue Shield [BCBS] Axis); monthly incidence was estimated as the percentage of enrollees who received an initial opioid prescription among those who had not used opioids (i.e., no opioid prescription or a diagnosis of opioid use disorder in the 6 months before a given month). We then estimated the percentage of enrollees initiating opioid therapy who received a long-duration or high-dose initial opioid prescription in each month during this period. We also calculated the number of providers who initiated opioid therapy in any patient who had not used opioids in each month and examined monthly trends in the duration and dose of initial opioid prescriptions in prescriber and patient subgroups. Our study sample included 63,817,512 enrollees who had not used opioids (mean, 15,897,673 per month).RESULTS: The monthly incidence of initial opioid prescriptions among enrollees who had not used opioids declined by 54%, from 1.63% in July 2012 to 0.75% in December 2017. This decline was accompanied by a decreasing number of providers (from 114,043 in July 2012 to 80,462 in December 2017) who initiated opioid therapy in any patient who had not used opioids. Nonetheless, among the shrinking subgroup of physicians who initiated opioid therapy in such patients, high-risk prescribing (i.e., prescriptions for more than a 3-day supply or for a dose of 50 morphine milligram equivalents per day or higher) persisted at a monthly rate of 115,378 prescriptions per 15,897,673 enrollees who had not used opioids.CONCLUSIONS: As the opioid crisis progressed between July 2012 and December 2017, many providers stopped initiating opioid therapy. Although the number of initial opioid prescriptions declined, a subgroup of providers continued to write high-risk initial opioid prescriptions. (Funded by the National Institute on Aging and a gift from Owen and Linda Robinson.). | [
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] |
The temperature dependence of the conformational properties in simulations of the intrinsically disordered model protein histatin 5 has been investigated using different combinations of force fields, water models, and atomistic and coarse-grained methods. The results have been compared to experimental data obtained from NMR, SAXS, and CD experiments to assess the accuracy and validity of the simulations. The results showed that neither simulations completely agreed with the experimental data, nor did they agree with each other. It was however possible to conclude that the observed conformational changes upon variations in temperature were not at all driven by electrostatic interactions. The final conclusion was that none of the simulations that were investigated in this study was able to accurately capture the temperature induced conformational changes of our model IDP. | [
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Subsets and Splits