Targeted alveolar regeneration with Frizzled-specific agonists.

Wnt ligands oligomerize Frizzled (Fzd) and Lrp5/6 receptors to control the specification and activity of stem cells in many species. How Wnt signaling is selectively activated in different stem cell populations, often within the same organ, is not understood. In lung alveoli, we show that distinct Wnt receptors are expressed by epithelial (Fzd5/6), endothelial (Fzd4), and stromal (Fzd1) cells. Fzd5 is uniquely required for alveolar epithelial stem cell activity, whereas fibroblasts utilize distinct Fzd receptors. Using an expanded repertoire of Fzd-Lrp agonists, we could activate canonical Wnt signaling in alveolar epithelial stem cells via either Fzd5 or, unexpectedly, non-canonical Fzd6. A Fzd5 agonist (Fzd5ag) or Fzd6ag stimulated alveolar epithelial stem cell activity and promoted survival in mice after lung injury, but only Fzd6ag promoted an alveolar fate in airway-derived progenitors. Therefore, we identify a potential strategy for promoting regeneration without exacerbating fibrosis during lung injury.

A molecular cell atlas of the human lung from single-cell RNA sequencing.

Although single-cell RNA sequencing studies have begun to provide compendia of cell expression profiles1-9, it has been difficult to systematically identify and localize all molecular cell types in individual organs to create a full molecular cell atlas. Here, using droplet- and plate-based single-cell RNA sequencing of approximately 75,000 human cells across all lung tissue compartments and circulating blood, combined with a multi-pronged cell annotation approach, we create an extensive cell atlas of the human lung. We define the gene expression profiles and anatomical locations of 58 cell populations in the human lung, including 41 out of 45 previously known cell types and 14 previously unknown ones. This comprehensive molecular atlas identifies the biochemical functions of lung cells and the transcription factors and markers for making and monitoring them; defines the cell targets of circulating hormones and predicts local signalling interactions and immune cell homing; and identifies cell types that are directly affected by lung disease genes and respiratory viruses. By comparing human and mouse data, we identified 17 molecular cell types that have been gained or lost during lung evolution and others with substantially altered expression profiles, revealing extensive plasticity of cell types and cell-type-specific gene expression during organ evolution including expression switches between cell types. This atlas provides the molecular foundation for investigating how lung cell identities, functions and interactions are achieved in development and tissue engineering and altered in disease and evolution.

Investigating attention toward pain-related cues in an Arabic-speaking population with and without chronic pain.

There is some evidence for attentional biases in individuals with chronic pain (CP). Cultural and linguistic differences might affect the manifestation of these processes across populations. However, such attentional biases have not been explored in the Arabic-speaking population. The current study investigated these attentional biases and possible associations with resilience. Two matched groups of Arabic-speaking participants with (58) and without (58) CP were recruited from Jordan and the United Kingdom. They completed emotionally modified versions of the Posner cueing and Stroop tasks, alongside questionnaires. Significant group differences were found for the Posner task, with the CP group exhibiting disengagement revealed by the inhibition of return (IOR) effect for sensory pain-related cues compared to delayed disengagement for the other cue types. The control group showed IOR across cue types. No group differences were found on the Stroop task. The CP group had lower resilience scores than healthy controls, and resilience moderated performance on the Posner task. The study provides preliminary evidence about the attentional processes in the Arabic population; the speed of disengagement is affected in the CP group with early disengagement for sensory pain-related information compared to affect pain and neutral stimuli. Furthermore, resilience levels in the CP and control group moderated the performance on the Posner task, suggesting that it influences attentional allocation. This study can help in understanding how the phenomenon of attention bias intertwines with the cultural and linguistic factors. Future research should further explore attentional dynamics across different time points in this population and the modulatory effect of resilience.

The effect of C2 screw type on perioperative outcomes and long-term stability after C2-T2 posterior cervical decompression and fusion.

PURPOSE: To determine if C2 pedicle versus pars screw type predicts change in fusion status, C2 screw loosening, cervical alignment, and patient-reported outcomes measures (PROMs) after C2-T2 posterior cervical decompression and fusion (PDCF). METHODS: All adult patients who underwent C2-T2 PCDF for myelopathy or myeloradiculopathy between 2013-2020 were retrospectively identified. Patients were dichotomized by C2 screw type into bilateral C2 pedicle and bilateral C2 pars screw groups. Preoperative and short- and long-term postoperative radiographic outcomes and PROMs were collected. Univariate and multivariate analysis compared patient factors, fusion status, radiographic measures, and PROMs across groups. RESULTS: A total of 159 patients met the inclusion/exclusion criteria (76 bilateral pedicle screws, 83 bilateral pars screws). Patients in the C2 pars relative to C2 pedicle screw group were on average more likely to have bone morphogenic protein (p = 0.001) and four-millimeter diameter rods utilized intraoperatively (p = 0.033). There were no significant differences in total construct and C2-3 fusion rate, C2 screw loosening, or complication and revision rates between C2 screw groups in univariate and regression analysis. Changes in C2 tilt, C2-3 segmental lordosis, C0-2 Cobb angle, proximal junctional kyphosis, atlanto-dens interval, C1 lamina-occiput distance, C2 sagittal vertical axis, C2-7 lordosis, and PROMs at all follow-up intervals did not vary significantly by C2 screw type. CONCLUSION: There were no significant differences in fusion status, hardware complications, and radiographic and clinical outcomes based on C2 screw type following C2-T2 PCDF. Accordingly, intraoperative usage criteria can be flexible based on patient vertebral artery positioning and surgeon comfort level.

Unilateral versus bilateral pedicle screw fixation with anterior lumbar interbody fusion: a comparison of postoperative outcomes.

PURPOSE: To determine of the impact of ALIF with minimally invasive unilateral pedicle screw fixation (UPSF) versus bilateral pedicle screw fixation (BPSF) on perioperative outcomes, radiographic outcomes, and the rates of fusion, subsidence, and adjacent segment stenosis. METHODS: All adult patients who underwent one-level ALIF with UPSF or BPSF at an academic institution between 2015 and 2022 were retrospectively identified. Postoperative outcomes including length of hospital stay (LOS), wound complications, readmissions, and revisions were determined. The rates of fusion, screw loosening, adjacent segment stenosis, and subsidence were assessed on one-year postoperative CT. Lumbar alignment including lumbar lordosis, L4-S1 lordosis, regional lordosis, pelvic tilt, pelvic incidence, and sacral slope were assessed on standing x-rays at preoperative, immediate postoperative, and final postoperative follow-up. Univariate and multivariate analysis compared outcomes across posterior fixation groups. RESULTS: A total of 60 patients were included (27 UPSF, 33 BPSF). Patients with UPSF were significantly younger (p = 0.011). Operative time was significantly greater in the BPSF group in univariate (p < 0.001) and multivariate analysis (ß=104.1, p < 0.001). Intraoperative blood loss, LOS, lordosis, pelvic parameters, fusion rate, subsidence, screw loosening, adjacent segment stenosis, and revision rate did not differ significantly between fixation groups. Though sacral slope (p = 0.037) was significantly greater in the BPSF group, fixation type was not a significant predictor on regression. CONCLUSIONS: ALIF with UPSF relative to BPSF predicted decreased operative time but was not a significant predictor of postoperative outcomes. ALIF with UPSF can be considered to increase operative efficiency without compromising construct stability.

Framework for developing cost-effectiveness analysis threshold: the case of Egypt.

BACKGROUND: Cost-effectiveness analyses rarely offer useful insights to policy decisions unless their results are compared against a benchmark threshold. The cost-effectiveness threshold (CET) represents the maximum acceptable monetary value for achieving a unit of health gain. This study aimed to identify CET values on a global scale, provide an overview of using multiple CETs, and propose a country-specific CET framework specifically tailored for Egypt. The proposed framework aims to consider the globally identified CETs, analyze global trends, and consider the local structure of Egypt's healthcare system. METHODS: We conducted a literature review to identify CET values, with a particular focus on understanding the basis of differentiation when multiple thresholds are present. CETs of different countries were reviewed from secondary sources. Additionally, we assembled an expert panel to develop a national CET framework in Egypt and propose an initial design. This was followed by a multistakeholder workshop, bringing together representatives of different governmental bodies to vote on the threshold value and finalize the recommended framework. RESULTS: The average CET, expressed as a percentage of the gross domestic product (GDP) per capita across all countries, was 135%, with a range of 21 to 300%. Interestingly, while the absolute value of CET increased with a country's income level, the average CET/GDP per capita showed an inverse relationship. Some countries applied multiple thresholds based on disease severity or rarity. In the case of Egypt, the consensus workshop recommended a threshold ranging from one to three times the GDP per capita, taking into account the incremental relative quality-adjusted life years (QALY) gain. For orphan medicines, a CET multiplier between 1.5 and 3.0, based on the disease rarity, was recommended. A two-times multiplier was proposed for the private reimbursement threshold compared to the public threshold. CONCLUSION: The CET values in most countries appear to be closely related to the GDP per capita. Higher-income countries tend to use a lower threshold as a percentage of their GDP per capita, contrasted with lower-income countries. In Egypt, experts opted for a multiple CET framework to assess the value of health technologies in terms of reimbursement and pricing.

Comprehensive interpretation of single-nucleotide substitutions in GJB2 reveals the genetic and phenotypic landscape of GJB2-related hearing loss.

Genetic variants in GJB2 are the most frequent cause of congenital and childhood hearing loss worldwide. The purpose of this study was to delineate the genetic and phenotypic landscape of GJB2 SNV variants. All possible single-nucleotide substitution variants of the coding region of GJB2 (N = 2043) were manually curated following the ACMG/AMP hearing loss guidelines. As a result, 60 (2.9%), 177 (8.7%), 1499 (73.4%), 301 (14.7%) and 6 (0.3%) of the variants were classified as pathogenic, likely pathogenic, variant of uncertain significance, likely benign, and benign, respectively. 53% (84/158) of the pathogenic/likely pathogenic missense variants were not present in ClinVar. The second transmembrane domain and the 310 helix were highly enriched for pathogenic missense variants, while the intracellular loops were tolerant to variation. The N-terminal tail and the extracellular loop showed high clustering of variants that are associated with syndromic or dominant non-syndromic hearing loss. In conclusion, our study interpreted all possible single-nucleotide substitution coding variants, characterized novel clinically significant variants in GJB2, and revealed significant genotype-phenotype correlations at this common hearing loss locus. Our work provides a prototype for other genes with similarly high genetic and phenotypic heterogeneity.

Shared signatures and divergence in skin microbiomes of children with atopic dermatitis and their caregivers.

BACKGROUND: Atopic dermatitis (AD) is a common chronic skin condition in children (15-20%) that can significantly impair their quality of life. As a result of its relapsing nature and enrichment of Staphylococcus aureus during flares, clinical management can include eradicating S aureus from the skin of children; however, this does not extend to their healthy caregivers, who are potential reservoirs. OBJECTIVE: Our aim was to understand skin microbiome sharing and microbial features in children with AD and their healthy adult caregivers. METHODS: We utilized whole-metagenome profiling at 4 body sites (volar forearm, antecubital fossae, cheeks, and lesions) in combination with sequencing of S aureus isolates to characterize a cohort of children with AD and their healthy caregivers (n = 30 families) compared to matched pairs from control households (n = 30 families). RESULTS: Metagenomic analysis revealed distinct microbiome configurations in the nonlesional skin of AD children and their healthy caregivers versus controls, which were sufficient to accurately predict case-control status (area under the receiver operating characteristic curve > 0.8). These differences were accompanied by significant microbiome similarity between children and their caregivers, indicating that microbiome sharing may play a role in recurrent disease flares. Whole-genome comparisons with high-quality S aureus isolate genomes (n = 55) confirmed significant strain sharing between AD children and their caregivers and AD-specific enrichment of strains expressing enterotoxins Q and K/K2. CONCLUSION: Our results highlight the distinctive skin microbiome features of healthy caregivers for children with AD and support their inclusion in strategies for the treatment of recurrent pediatric AD.

AN EVALUATION OF ANTIBIOTIC PRESCRIPTION PRACTICES: PERSPECTIVES OF VETERINARY TRAINEES AND PRACTICING VETERINARIANS.

Antibiotic resistance is a major worldwide problem that has an impact on the well-being of humans as well as animals. Antibiotic resistance is caused by the misuse and excessive use of antibiotics. The key to reducing this issue lies in educating veterinary medical learners on the proper and accountable utilization of antibiotics for the care of animals. Objective - using awareness-raising and instruction as the foundation, this research of Indian veterinary learners can help resolve the issue of antibiotic resistance throughout the care of animals. The questionnaire survey was taken between June and July 2022 and it was aimed at learners registered in veterinary medical studies at academic and research institutions in India. The study included 500 pupils overall. The purpose of the survey was to gather information about students' knowledge of antibiotics, including antibiotic resistance, as well as their feelings on the consequences of antibiotic resistance on the globe at large and their acquaintance with the one health ideology. According to this study's findings, 83.3 percent of respondents thought antibiotic resistance was a serious problem. 57.92 percent of respondents understood the issue's worldwide consequences and its one health ideology. The study emphasizes the significance of expanding the veterinary educational program to include thorough instruction on prudent antibiotic usage and the concepts of one health.

UNDERSTANDING THE ADAPTATION AND SENSITIVITY OF THE MICROBIOME: MICROBIAL RESILIENT AND HUMAN WELL-BEING.

The term microbiome describes the assortment of microbes that dwell in and on a person's body, particularly in the gut, comprising fungi, bacteria, infectious agents and additional microbes. According to research, numerous elements of human well-being, such as digestion, immunological response and psychological well-being, have been linked to the microbiome. Preserving human wellness requires knowledge of the microbiome's stability and how it reacts to perturbations. According to preliminary research, adults' microbial ecosystems are considered stable with no signs of significant disturbances. This stability is not preserved by inertia and the system's interaction with restorative forces keeps the processes stable. Short antibiotic doses can result in quick and substantial microbiome alterations. However, there is confirmation that the taxonomic structure of the microbiome has at least recovered after such disruptions. The effect of antibiotics is individualized and can be altered by earlier exposure to a similar drug, which is a crucial aspect to remember. These results suggest that the individual's microbiome has adaptable qualities. Examining the microbiome's reactions to perturbations might be helpful in the prediction of potential instabilities and illness by revealing important features of function, microbial connections, and important species in the native microbiota. This information can benefit the management of the individual microbial community and the promotion of better health conditions.

Social Vulnerability and Premature Cardiovascular Mortality Among US Counties, 2014 to 2018.

BACKGROUND: Substantial differences exist between United States counties with regards to premature (<65 years of age) cardiovascular disease (CVD) mortality. Whether underlying social vulnerabilities of counties influence premature CVD mortality is uncertain. METHODS: In this cross-sectional study (2014-2018), we linked county-level CDC/ATSDR SVI (Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index) data with county-level CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research) mortality data. We calculated scores for overall SVI and its 4 subcomponents (ie, socioeconomic status; household composition and disability; minority status and language; and housing type and transportation) using 15 social attributes. Scores were presented as percentile rankings by county, further classified as quartiles on the basis of their distribution among all US counties (1st [least vulnerable] = 0 to 0.25; 4th [most vulnerable = 0.75 to 1.00]). We grouped age-adjusted mortality rates per 100 000 person-years for overall CVD and its subtypes (ischemic heart disease, stroke, hypertension, and heart failure) for nonelderly (<65 years of age) adults across SVI quartiles. RESULTS: Overall, the age-adjusted CVD mortality rate per 100 000 person-years was 47.0 (ischemic heart disease, 28.3; stroke, 7.9; hypertension, 8.4; and heart failure, 2.4). The largest concentration of counties with more social vulnerabilities and CVD mortality were clustered across the southwestern and southeastern parts of the United States. The age-adjusted CVD mortality rates increased in a stepwise manner from 1st to 4th SVI quartiles. Counties in the 4th SVI quartile had significantly higher mortality for CVD (rate ratio, 1.84 [95% CI, 1.43-2.36]), ischemic heart disease (1.52 [1.09-2.13]), stroke (2.03 [1.12-3.70]), hypertension (2.71 [1.54-4.75]), and heart failure (3.38 [1.32-8.61]) than those in the 1st SVI quartile. The relative risks varied considerably by demographic characteristics. For example, among all ethnicities/races, non-Hispanic Black adults in the 4th SVI quartile versus the 1st SVI quartile exclusively had significantly higher relative risks of stroke (1.65 [1.07-2.54]) and heart failure (2.42 [1.29-4.55]) mortality. Rural counties with more social vulnerabilities had 2- to 5-fold higher mortality attributable to CVD and subtypes. CONCLUSIONS: In this analysis, US counties with more social vulnerabilities had higher premature CVD mortality, varied by demographic characteristics and rurality. Focused public health interventions should address the socioeconomic disparities faced by underserved communities to curb the growing burden of premature CVD.

Elevated ASCL1 activity creates de novo regulatory elements associated with neuronal differentiation.

BACKGROUND: The pro-neural transcription factor ASCL1 is a master regulator of neurogenesis and a key factor necessary for the reprogramming of permissive cell types to neurons. Endogenously, ASCL1 expression is often associated with neuroblast stem-ness. Moreover, ASCL1-mediated reprogramming of fibroblasts to differentiated neurons is commonly achieved using artificially high levels of ASCL1 protein, where ASCL1 acts as an "on-target" pioneer factor. However, the genome-wide effects of enhancing ASCL1 activity in a permissive neurogenic environment has not been thoroughly investigated. Here, we overexpressed ASCL1 in the neuronally-permissive context of neuroblastoma (NB) cells where modest endogenous ASCL1 supports the neuroblast programme. RESULTS: Increasing ASCL1 in neuroblastoma cells both enhances binding at existing ASCL1 sites and also leads to creation of numerous additional, lower affinity binding sites. These extensive genome-wide changes in ASCL1 binding result in significant reprogramming of the NB transcriptome, redirecting it from a proliferative neuroblastic state towards one favouring neuronal differentiation. Mechanistically, ASCL1-mediated cell cycle exit and differentiation can be increased further by preventing its multi-site phosphorylation, which is associated with additional changes in genome-wide binding and gene activation profiles. CONCLUSIONS: Our findings show that enhancing ASCL1 activity in a neurogenic environment both increases binding at endogenous ASCL1 sites and also results in additional binding to new low affinity sites that favours neuronal differentiation over the proliferating neuroblast programme supported by the endogenous protein. These findings have important implications for controlling processes of neurogenesis in cancer and cellular reprogramming.

Network Analysis of Postoperative Surgical Complications in a Cohort of Children Reported to the National Surgical Quality Improvement Program: Pediatric.

OBJECTIVE: To understand the temporal relationships of postoperative complications in children and determine if they are related to each other in a predictable manner. SUMMARY OF BACKGROUND DATA: Children with multiple postoperative complications have increased suffering and higher risk for mortality. Rigorous analysis of the temporal relations between complications, how complications might cluster, and the implications of such clusters for children have not been published. Herein, we analyze the relationships between postoperative complications in children. METHODS: Data source: Surgical operations included in the National Surgical Quality Improvement Program Pediatric Participant Use Data File from 2013 to 2017. The main outcomes measure was presence of 1 or more postoperative complications within 30 days of surgery. Operations followed by multiple complications were analyzed using network analysis to study prevalence, timing, and co-occurrences of clusters of complications. RESULTS: This study cohort consisted of 432,090 operations; 388,738 (89.97%) had no postoperative complications identified, 36,105 (8.35%) operations resulted in 1 postoperative complication and 7247 (1.68%) operations resulted in 2 or more complications. Patients with multiple complications were more likely to be younger, male, African American, with a higher American Society of Anesthesiologists score, and to undergo nonelective operations (P < 0.001). More patients died with 2 complication versus 1 complication vs no complication (5.3% vs 1.5% vs 0.14%, P < 0.001). Network analysis identified 4 Louvain clusters of complications with dense intracluster relationships. CONCLUSIONS: Children with multiple postoperative complications are at higher risk of death, than patients with no complication, or a single complication. Multiple complications are grouped into defined clusters and are not independent.

Genetic variant pathogenicity prediction trained using disease-specific clinical sequencing data sets.

Recent advances in DNA sequencing have expanded our understanding of the molecular basis of genetic disorders and increased the utilization of clinical genomic tests. Given the paucity of evidence to accurately classify each variant and the difficulty of experimentally evaluating its clinical significance, a large number of variants generated by clinical tests are reported as variants of unknown clinical significance. Population-scale variant databases can improve clinical interpretation. Specifically, pathogenicity prediction for novel missense variants can use features describing regional variant constraint. Constrained genomic regions are those that have an unusually low variant count in the general population. Computational methods have been introduced to capture these regions and incorporate them into pathogenicity classifiers, but these methods have yet to be compared on an independent clinical variant data set. Here, we introduce one variant data set derived from clinical sequencing panels and use it to compare the ability of different genomic constraint metrics to determine missense variant pathogenicity. This data set is compiled from 17,071 patients surveyed with clinical genomic sequencing for cardiomyopathy, epilepsy, or RASopathies. We further use this data set to demonstrate the necessity of disease-specific classifiers and to train PathoPredictor, a disease-specific ensemble classifier of pathogenicity based on regional constraint and variant-level features. PathoPredictor achieves an average precision >90% for variants from all 99 tested disease genes while approaching 100% accuracy for some genes. The accumulation of larger clinical variant training data sets can significantly enhance their performance in a disease- and gene-specific manner.

Evaluating the impact of in silico predictors on clinical variant classification.

PURPOSE: According to the American College of Medical Genetics and Genomics/Association of Medical Pathology (ACMG/AMP) guidelines, in silico evidence is applied at the supporting strength level for pathogenic (PP3) and benign (BP4) evidence. Although PP3 is commonly used, less is known about the effect of these criteria on variant classification outcomes. METHODS: A total of 727 missense variants curated by Clinical Genome Resource expert groups were analyzed to determine how often PP3 and BP4 were applied and their impact on variant classification. The ACMG/AMP categorical system of variant classification was compared with a quantitative point-based system. The pathogenicity likelihood ratios of REVEL, VEST, FATHMM, and MPC were calibrated using a gold standard set of 237 pathogenic and benign variants (classified independent of the PP3/BP4 criteria). RESULTS: The PP3 and BP4 criteria were applied by Variant Curation Expert Panels to 55% of missense variants. Application of those criteria changed the classification of 15% of missense variants for which either criterion was applied. The point-based system resolved borderline classifications. REVEL and VEST performed best at a strength level consistent with moderate evidence. CONCLUSION: We show that in silico criteria are commonly applied and often affect the final variant classifications. When appropriate thresholds for in silico predictors are established, our results show that PP3 and BP4 can be used at a moderate strength.

Lactobacilli reduce recurrences of vaginal candidiasis in pregnant women: a randomized, double-blind, placebo-controlled study.

AIMS: The aim of this study was to investigate the effects of lactobacilli strains in preventing the recurrences of vaginal candidiasis (VC) in 78 pregnant women with VC (lactobacilli, n = 39; placebo, n = 39) and the potential benefits on quality of life. METHODS AND RESULTS: The lactobacilli putative probiotic (SynForU-HerCare; two capsules/day of 9·5 log CFU per capsule) or placebo was administered for 8-weeks in a randomized, double-blind, placebo-controlled study. Subjects were assessed for vaginal and gut health conditions at baseline, week-4 and week-8 via questionnaires. The vulvovaginal symptom questionnaire not only covered aspects pertaining to vulvovaginal symptoms but also the quality of life impacts such as emotional, social and sexual. The administration of lactobacilli reduced symptoms of irritation (P = 0·023) and discharge (P = 0·011) starting week-4 and continued after week-8 (P < 0·05), accompanied by reduced symptoms for burning after week-8 (P = 0·046) as compared to the placebo. Patients consuming lactobacilli also showed reduced concern about symptoms after week-4 (P = 0·010) and continued after week-8 (P = 0·001), accompanied by reduced impairment of daily activities attributed to vulvovaginal symptoms (P = 0·012) and continued after week-8 (P = 0·026). Insignificant differences were observed for sexual impacts between treatment groups. The administration of lactobacilli also reduced recurrences of both emotional and social stress as compared to the placebo at both week-4 and week-8 (P < 0·05). Patients consuming lactobacilli showed higher defecation times per week at week-4 (P = 0·010) and week-8 (P = 0·001) as compared to the placebo group, indicating the potential to reduce risks of pregnancy-induced constipation. CONCLUSIONS: Lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrated the preventive and modulatory roles of lactobacilli strains against VC in pregnant women. Taken altogether, our present data illustrated that lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC, thus could be a potential strategy for the maintenance of vaginal health during pregnancy.

The prevalence and correlates of bulimia nervosa, binge-eating disorder, and anorexia nervosa: The Saudi National Mental Health Survey.

OBJECTIVE: Limited studies have been conducted in the Kingdom of Saudi Arabia on eating disorders (EDs). This study presents national epidemiological survey data on the prevalence and correlates of anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) and their association with other mental health disorders, impairment in role functioning, and individual help-seeking behaviors in the Saudi National Mental Health Survey (SNMHS). METHOD: A face-to-face survey was conducted in a nationally representative household sample of Saudi citizens aged 15-65 (n = 4004). The Composite International Diagnostic Interview (CIDI 3.0) was used to produce estimates of lifetime and 12-month prevalence and treatment of common DSM-IV mental disorders. RESULTS: Twelve-month prevalence of any of the three EDs was 3.2%; the overall lifetime prevalence was 6.1%. Education and marital status were significantly associated with both 12-month and lifetime EDs prevalence. Significant mental health comorbidities associated with 12-month EDs were anxiety, mood, and impulse-control disorders, while lifetime EDs were significantly related to all disorders. A similar percentage of respondents that reported having ED-related treatment at some point in their lifetime utilized healthcare and nonhealthcare sector. There was a significant relationship between body mass index category, and lifetime BED and BN. DISCUSSION: The 12-month prevalence of EDs in the Saudi population was higher than the EDs rates reported worldwide. These findings can help healthcare experts, and policymakers in the implementation of initiatives for raising awareness of EDs among the Saudi population, and the development of a country-wide plan for the prevention of EDs. PUBLIC SIGNIFICANCE STATEMENT: The study presents data on the prevalence, correlates, and help-seeking behaviors of AN, BN, and BED, in the Saudi National Mental Health Survey (SNMHS). Obtaining information on this underrepresented region is essential due to the large differences in cross-national data in addition to cultural beliefs about mental illness and treatment seeking to exert an important influence on eating disorders. Such knowledge could provide a better understand of mechanisms underlying the development of eating disorders and thereby improve prediction, prevention, and treatment.

Human brucellosis: Six years retrospective study on seropositivity in Malaysia.

INTRODUCTION: Human brucellosis is a zoonotic disease in Malaysia. This study analysed six-year retrospective seropositivity trends of human brucellosis cases from 2014 to 2019. METHODS AND MATERIALS: A total of 1,281 serum samples were obtained from suspected brucellosis patients were included. The sera were tested using an enzyme-linked immunosorbent assay for IgM and IgG antibodies for Brucella spp. Samples with equivocal or positive antibody index were confirmed with an immunocapture agglutination. RESULTS: During the study period, 5.8% (n=74) of suspected cases showed seropositivity for human brucellosis. The central region has the highest seropositivity cases of human brucellosis. Consumption of unpasteurised milk was significantly associated with human brucellosis in this study with adjusted odds ratio ((AOR) = 4.56, 95% CI = 2.6, 8.02, p-value < 0.001). The age group of less than 15 years old was more likely to contract brucellosis ((AOR) = 2.81, 95% CI = 1.01, 7.84 p-value < 0.048). CONCLUSION: Serological tests have been widely used for the diagnosis of human brucellosis. However, diagnosis using serology is often challenging without the presence of a convalescent sample. In conclusion, even though human brucellosis has a low prevalence rate, the disease has serious public health implications. The usage of effective diagnostic tools as well as implementation of 'One Health' approach are the way forward to prevent and control of brucellosis in the country.

Dual Antiplatelet Therapy After Percutaneous Coronary Intervention and Drug-Eluting Stents: A Systematic Review and Network Meta-Analysis.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents remains uncertain. We compared short-term (<6-month) DAPT followed by aspirin or P2Y12 inhibitor monotherapy; midterm (6-month) DAPT; 12-month DAPT; and extended-term (>12-month) DAPT after percutaneous coronary intervention with drug-eluting stents. METHODS: Twenty-four randomized, controlled trials were selected using Medline, Embase, Cochrane library, and online databases through September 2019. The coprimary end points were myocardial infarction and major bleeding, which constituted the net clinical benefit. A frequentist network meta-analysis was conducted with a random-effects model. RESULTS: In 79 073 patients, at a median follow-up of 18 months, extended-term DAPT was associated with a reduced risk of myocardial infarction in comparison with 12-month DAPT (absolute risk difference, -3.8 incident cases per 1000 person-years; relative risk, 0.68 [95% CI, 0.54-0.87]), midterm DAPT (absolute risk difference, -4.6 incident cases per 1000 person-years; relative risk, 0.61 [0.45-0.83]), and short-term DAPT followed by aspirin monotherapy (absolute risk difference, -6.1 incident cases per 1000 person-years; relative risk, 0.55 [0.37-0.83]), or P2Y12 inhibitor monotherapy (absolute risk difference, -3.7 incident cases per 1000 person-years; relative risk, 0.69 [0.51-0.95]). Conversely, extended-term DAPT was associated with a higher risk of major bleeding than all other DAPT groups. In comparison with 12-month DAPT, no significant differences in the risks of ischemic end points or major bleeding were observed with midterm or short-term DAPT followed by aspirin monotherapy, with the exception that short-term DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduced risk of major bleeding. There were no significant differences with respect to mortality between the different DAPT strategies. In acute coronary syndrome, extended-term in comparison with 12-month DAPT was associated with a reduced risk of myocardial infarction without a significant increase in the risk of major bleeding. CONCLUSIONS: The present network meta-analysis suggests that, in comparison with 12-month DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy reduces major bleeding after percutaneous coronary intervention with drug-eluting stents, whereas extended-term DAPT reduces myocardial infarction at the expense of more bleeding events.