Exploring the Antimicrobial Efficacy of Low-Cost Commercial Disinfectants Utilized in the Agro-Food Industry Wash Tanks: Towards Enhanced Hygiene Practices.

The increase in vegetable consumption has underlined the importance of minimizing the risks associated with microbiological contamination of fresh produce. The critical stage of the vegetable washing process has proven to be a key point for cross-contamination and the persistence of pathogens. In this context, the agri-food industry has widely adopted the use of disinfectants to reduce the bacterial load in the wash water. Therefore, we conducted laboratory-scale experiments in order to demonstrate the antimicrobial activity of disinfectants used in the wash tank of agro-food industries. Different wash water matrices of shredded lettuce, shredded cabbage, diced onion, and baby spinach were treated with sodium hypochlorite (NaClO), chlorine dioxide (ClO2), and per-oxyacetic acid (PAA) at recommended concentrations. To simulate the presence of pathogenic bacteria, a cocktail of E. coli O157:H7 was inoculated into the process water samples (PWW) to determine whether concentrations of disinfectants inhibit the pathogen or bring it to a viable non-culturable state (VBNC). Hereby, we used quantitative qPCR combined with different photo-reactive dyes such as ethidium monoazide (EMA) and propidium monoazide (PMA). The results indicated that concentrations superior to 20 ppm NaClO inhibit the pathogen E. coli O157:H7 artificially inoculated in the process water. Concentrations between 10-20 ppm ClO2 fail to induce the pathogen to the VBNC state. At concentrations of 80 ppm PAA, levels of culturable bacteria and VBNC of E. coli O157:H7 were detected in all PWWs regardless of the matrix. Subsequently, this indicates that the recommended concentrations of ClO2 and PAA for use in the fresh produce industry wash tank do not inhibit the levels of E. coli O157:H7 present in the wash water.

Translating global evidence into local implementation through technical assistance: a realist evaluation of the Bloomberg philanthropies initiative for global Road safety.

BACKGROUND: Traffic-related crashes are a leading cause of premature death and disability. The safe systems approach is an evidence-informed set of innovations to reduce traffic-related injuries and deaths. First developed in Sweden, global health actors are adapting the model to improve road safety in low- and middle-income countries via technical assistance (TA) programs; however, there is little evidence on road safety TA across contexts. This study investigated how, why, and under what conditions technical assistance influenced evidence-informed road safety in Accra (Ghana), Bogotá (Colombia), and Mumbai (India), using a case study of the Bloomberg Philanthropies Initiative for Global Road Safety (BIGRS). METHODS: We conducted a realist evaluation with a multiple case study design to construct a program theory. Key informant interviews were conducted with 68 government officials, program staff, and other stakeholders. Documents were utilized to trace the evolution of the program. We used a retroductive analysis approach, drawing on the diffusion of innovation theory and guided by the context-mechanism-outcome approach to realist evaluation. RESULTS: TA can improve road safety capabilities and increase the uptake of evidence-informed interventions. Hands-on capacity building tailored to specific implementation needs improved implementers' understanding of new approaches. BIGRS generated novel, city-specific analytics that shifted the focus toward vulnerable road users. BIGRS and city officials launched pilots that brought evidence-informed approaches. This built confidence by demonstrating successful implementation and allowing government officials to gauge public perception. But pilots had to scale within existing city and national contexts. City champions, governance structures, existing political prioritization, and socio-cultural norms influenced scale-up. CONCLUSION: The program theory emphasizes the interaction of trust, credibility, champions and their authority, governance structures, political prioritization, and the implement-ability of international evidence in creating the conditions for road safety change. BIGRS continues to be a vehicle for improving road safety at scale and developing coalitions that assist governments in fulfilling their role as stewards of population well-being. Our findings improve understanding of the complex role of TA in translating evidence-informed interventions to country-level implementation and emphasize the importance of context-sensitive TA to increase impact.

CFTR pathogenic variants spectrum in a cohort of Mexican patients with cystic fibrosis.

Background: Molecular diagnosis of cystic fibrosis (CF) is challenging in Mexico due to the population's high genetic heterogeneity. To date, 46 pathogenic variants (PVs) have been reported, yielding a detection rate of 77%. We updated the spectrum and frequency of PVs responsible for this disease in mexican patients. Methods: We extracted genomic DNA from peripheral blood lymphocytes obtained from 297 CF patients and their parents. First, we analyzed the five most frequent PVs in the Mexican population using PCR-mediated site-directed mutagenesis. In patients with at least one identified allele, CFTR sequencing was performed using next-generation sequencing tools and multiplex ligation-dependent probe amplification. For variants not previously classified as pathogenic, we used a combination of in silico prediction, CFTR modeling, and clinical characteristics to determine a genotype-phenotype correlation. Results: We identified 95 PVs, increasing the detection rate to 87.04%. The most frequent variants were p.(PheF508del) (42.7%), followed by p.(Gly542*) (5.6%), p.(Ser945Leu) (2.9%), p.(Trp1204*) and p.(Ser549Asn) (2.5%), and CFTRdel25-26 and p.(Asn386Ilefs*3) (2.3%). The remaining variants had frequencies of <2.0%, and some were exclusive to one family. We identified 10 novel PVs localized in different exons (frequency range: 0.1-0.8%), all of which produced structural changes, deletions, or duplications in different domains of the protein, resulting in dysfunctional ion flow. The use of different in silico software and American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) criteria allowed us to assume that all of these PVs were pathogenic, causing a severe phenotype. Conclusions: In a highly heterogeneous population, combinations of different tools are needed to identify the variants responsible for CF and enable the establishment of appropriate strategies for CF diagnosis, prevention, and treatment.

Characterization of sperm motility and testosterone secretion in the taiep myelin mutant, a model of demyelination.

Presently, demyelinating diseases have been reported to affect the reproductive life of patients who suffer from them, but the progression of the alterations is unknown, especially in men. To better understand these effects, it is necessary to perform studies in animal models, such as the male taiep rat, which exhibits progressive demyelination of the central nervous system, altered kisspeptin expression at the hypothalamic level, and decreased luteinizing hormone, which could alter sperm quality and testicular diameter. Thus, the objective of the present study was to analyze the diameter of the seminiferous tubules, the sperm motility, and the testosterone levels of 90-day-old male taiep rats. The obtained results indicate that male taiep rats show an increase in testicular size accompanied by an increase in the diameter of the seminiferous tubules of the left testicle. There was also a decrease in progressive motility in sperm samples from the left epididymis of male taiep rats compared to the control group, with no changes in serum testosterone concentration. Therefore, we conclude that male taiep rats with central demyelination show altered testicular diameter and decreased motility in sperm from the left side. This type of studies serves as a basis for proposing possible reproductive strategies to improve the fertility and testicular function of men with demyelinating diseases of the central nervous system.

Use of a digital job-aid in improving antenatal clinical protocols and quality of care in rural primary-level health facilities in Burkina Faso: a quasi-experimental evaluation.

OBJECTIVE: We assessed the impact of a digital clinical decision support (CDS) tool in improving health providers adherence to recommended antenatal protocols and service quality in rural primary-level health facilities in Burkina Faso. DESIGN: A quasi-experimental evaluation based on a cross-sectional post-intervention assessment comparing the intervention district to a comparison group. SETTING AND PARTICIPANTS: The study included 331 direct observations and exit interviews of pregnant women seeking antenatal care (ANC) across 48 rural primary-level health facilities in Burkina Faso in 2021. INTERVENTION: Digital CDS tool to improve health providers adherence to recommended antenatal protocols. OUTCOME MEASURES: We analysed the quality of care on both the supply and demand sides. Quality-of-care service scores were based on actual care provided and expected care according to standards. Pregnant women's knowledge of counselling and satisfaction score after receiving care were also calculated. Other outcomes included time of clinical encounter. RESULTS: The overall quality of health service provision was comparable across intervention and comparison health facilities (52% vs 51%) despite there being a significantly higher proportion of lower skilled providers in the intervention arm (42.5% vs 17.8%). On average, ANC visits were longer in the intervention area (median 24 min, IQR 18) versus comparison area (median 12 min, IQR: 8). The intervention arm had a significantly higher score difference in women's knowledge of received counselling (16.4 points, 95% CI 10.37 to 22.49), and women's satisfaction (16.18 points, 95% CI: 9.95 to 22.40). CONCLUSION: Digital CDS tools provide a valuable opportunity to achieve substantial improvements of the quality of ANC and broadly maternal and newborn health in settings with high burden mortality and less trained health cadres when adequately implemented.

Total Antioxidant Capacity in Obese and Non-Obese Subjects and Its Association with Anthropo-Metabolic Markers: Systematic Review and Meta-Analysis.

The total antioxidant capacity (TAC) has been related to the development of and complications associated with chronic diseases, but its importance during obesity is not entirely clear. We conducted a systematic review and meta-analysis to clarify whether there are differences or similarities in the TAC between subjects with obesity (SO) and subjects with normal weight (NW). Following the recommendations of PRISMA and Cochrane, we performed a systematic search in the PubMed, Scopus, Web of Science, Cochrane, and PROSPERO databases, identifying 1607 studies. Among these, 22 studies were included in the final analysis, comprising 3937 subjects (1665 SO and 2272 NW) in whom serum TAC was measured, and from these 19,201 subjects, the correlation of serum TAC with anthropo-metabolic parameters was also estimated. The Newcastle-Ottawa method was used for the evaluation of the risk of bias. Using a random-effect model (REM), TAC was reduced in SO independently of age (SMD, -0.86; 95% CI -1.38 to -0.34; p = 0.0012), whereas malondialdehyde (SMD, 1.50; 95% CI 0.60 to 2.41), oxidative stress index (SMD, 1.0; 95% CI 0.16 to 1.84), and total oxidant status (SMD, 0.80; 0.22 to 1.37) were increased. There were seven significant pooled correlations of TAC with anthropometric and metabolic parameters: weight (r = -0.17), hip circumference (r= -0.11), visceral adipose index (r = 0.29), triglycerides (r = 0.25), aspartate aminotransferase (r = 0.41), alanine aminotransferase (r = 0.38), and uric acid (r = 0.53). Our results confirm a decrease in TAC and an increase in markers of oxidative stress in SO and underpin the importance of these serum biomarkers in obesity.

DNA Methylation Remodeling after Bariatric Surgery Correlates with Clinical Parameters.

The altered functions of adipose tissue are one of the main issues in obesity. Bariatric surgery is associated with improvement of obesity associated comorbidities. Here DNA methylation remodeling in adipose tissue after bariatric surgery is examined. After six months postoperative, DNA methylation shows changes in 1155 CpG sites, 66 of these sites correlate with body mass index. Some sites also show correlation with LDL-C, HDL-C, total cholesterol, and triglycerides. CpG sites are located in genes that have not previously been linked to obesity or metabolic diseases. GNAS complex locus is one of those that presented CpG site with the greatest changes after surgery, and the most significant correlation with BMI and lipid profiles. These results show that epigenetic regulation may be involved in the alteration of adipose tissue functions in obesity.

Single nucleotide variants in microRNA biosynthesis genes in Mexican individuals.

Background: MicroRNAs (miRNAs) are important regulators in a variety of biological processes, and their dysregulation is associated with multiple human diseases. Single nucleotide variants (SNVs) in genes involved in the processing of microRNAs may alter miRNA regulation and could present high allele heterogeneity in populations from different ethnic groups. Thus, the aim of this study was to genotype 15 SNVs in eight genes involved in the miRNA processing pathway in Mexican individuals and compare their frequencies across 21 populations from five continental groups. Methods: Genomic DNA was obtained from 399 healthy Mexican individuals. SNVs in AGO2 (rs2293939 and rs4961280), DGCR8 (rs720012), DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), GEMIN3 (rs197388 and rs197414), GEMIN4 (rs7813, rs2740349, and rs4968104), TNRC6B (rs9611280), and XP05 (rs11077 and rs34324334) were genotyped using TaqMan probes. The minor allele frequency of each SNV was compared to those reported in the 1,000 Genomes database using chi-squared. Sankey plot was created in the SankeyMATIC package to visualize the frequency range of each variant in the different countries analyzed. Results: In Mexican individuals, all 15 SNVs were found in Hardy-Weinberg equilibrium, with frequencies ranging from 0.04 to 0.45. The SNVs rs4961280, rs2740349, rs34324334, and rs720012 in Mexican individuals had the highest minor allele frequencies worldwide, whereas the minor allele frequencies of rs197388, rs10719, rs197414, and rs1107 were among the lowest in Mexican individuals. The variants had high allele heterogeneity among the sub-continental populations, ranging from monomorphic, as was the case for rs9611280 and rs34324334 in African groups, to >0.50, which was the case for variants rs11077 and rs10719 in most of the populations. Importantly, the variants rs197388, rs720012, and rs197414 had FST values > 0.18, indicating a directional selective process. Finally, the SNVs rs13078 and rs10719 significantly correlated with both latitude and longitude. Conclusion: These data indicate the presence of high allelic heterogeneity in the worldwide distribution of the frequency of SNVs located in components of the miRNA processing pathway, which could modify the genetic susceptibility associated with human diseases in populations with different ancestry.

Frequent copy number variants in a cohort of Mexican-Mestizo individuals.

BACKGROUND: The human genome presents variation at distinct levels, copy number variants (CNVs) are DNA segments of variable lengths that range from several base pairs to megabases and are present at a variable number of copies in human genomes. Common CNVs have no apparent influence on the phenotype; however, some rare CNVs have been associated with phenotypic traits, depending on their size and gene content. CNVs are detected by microarrays of different densities and are generally visualized, and their frequencies analysed using the HapMap as default reference population. Nevertheless, this default reference is inadequate when the samples analysed are from people from Mexico, since population with a Hispanic genetic background are minimally represented. In this work, we describe the variation in the frequencies of four common CNVs in Mexican-Mestizo individuals. RESULTS: In a cohort of 147 unrelated Mexican-Mestizo individuals, we found that the common CNVs 2p11.2 (99.6%), 8p11.22 (54.5%), 14q32.33 (100%), and 15q11.2 (71.1%) appeared with unexpectedly high frequencies when contrasted with the HapMap reference (ChAS). Yet, while when comparing to an ethnically related reference population, these differences were significantly reduced or even disappeared. CONCLUSION: The findings in this work contribute to (1) a better description of the CNVs characteristics of the Mexican Mestizo population and enhance the knowledge of genome variation in different ethnic groups. (2) emphasize the importance of contrasting CNVs identified in studied individuals against a reference group that-as best as possible-share the same ethnicity while keeping this relevant information in mind when conducting CNV studies at the population or clinical level.

Brain radiotoxicity-related 15CAcBRT gene expression signature predicts survival prognosis of glioblastoma patients.

BACKGROUND: Glioblastoma is the most common and devastating primary brain cancer. Radiotherapy is standard of care; however, it is associated with brain radiation toxicity (BRT). This study used a multi-omics approach to determine whether BRT-related genes (RGs) harbor survival prognostic value and whether their encoded proteins represent novel therapeutic targets for glioblastoma. METHODS: RGs were identified through analysis of single-nucleotide variants associated with BRT (R-SNVs). Functional relationships between RGs were established using Protein-Protein Interaction networks. The influence of RGs and their functional groups on glioblastoma prognosis was evaluated using clinical samples from the Glioblastoma Bio-Discovery Portal database and validated using the Chinese Glioma Genome Atlas dataset. The identification of clusters of radiotoxic and putative pathogenic variants in proteins encoded by RGs was achieved by computational 3D structural analysis. RESULTS: We identified the BRT-related 15CAcBRT molecular signature with prognostic value in glioblastoma, by analysis of the COMT and APOE protein functional groups. Its external validation confirmed clinical relevance independent of age, MGMT promoter methylation status, and IDH mutation status. Interestingly, the genes IL6, APOE, and MAOB documented significant gene expression levels alteration, useful for drug repositioning. Biological networks associated with 15CAcBRT signature involved pathways relevant to cancer and neurodegenerative diseases. Analysis of 3D clusters of radiotoxic and putative pathogenic variants in proteins coded by RGs unveiled potential novel therapeutic targets in neuro-oncology. CONCLUSIONS: 15CAcBRT is a BRT-related molecular signature with prognostic significance for glioblastoma patients and represents a hub for drug repositioning and development of novel therapies.

Minimally Invasive Management of Post-treatment Rectovesical Fistulae.

Objective: The aim of this study is to report our experience in minimally invasive management of rectovesical fistulae (RVFs). Materials and Methods: Between 2004 and 2021, 24 patients who underwent minimally invasive RVF repair by a single surgeon at 3 international institutions were retrospectively reviewed. Baseline demographic characteristics and perioperative and postoperative variables were collected. Complications were reported using the modified Clavien-Dindo Classification System and the European Association of Urology Complication Guidelines Panel Assessment and Recommendations. Fistula repair was defined as confirmation of fistula closure by imaging and complete resolution of fistula-related symptoms at the 12-month follow-up. Continuous variables are reported as medians and quartiles, whereas categorical variables are reported as frequencies and percentages. Results: Twenty-four patients with RVFs were treated: 22 males (91.7%) and 2 females with a median age of 66 (64.2-68) years. Twenty cases (83.3%) occurred postsurgery, three cases (12.5%) after surgery with combined radiotherapy, and one case (4.1%) after a combination of energy treatments. A robotic approach was performed in 19 patients (79%) and laparoscopic approach in 5 patients (21%). Ninety-six percent of patients had previous fecal diversions. No intraoperative complications were recorded. The median operative time was 180 (140-282) minutes, estimated blood loss was 50 (40-125) mL, and length of hospital stay was 2 (2-3) days. There were two Grade II complications and one Grade IIIb complication. All patients met criteria for repair. Conclusions: Minimally invasive management of RVFs is feasible. More studies are needed to assess the role of this approach among all RVF management options.

Unraveling Signatures of Local Adaptation among Indigenous Groups from Mexico.

Few studies have addressed how selective pressures have shaped the genetic structure of the current Native American populations, and they have mostly limited their inferences to admixed Latin American populations. Here, we searched for local adaptation signals, based on integrated haplotype scores and population branch statistics, in 325 Mexican Indigenous individuals with at least 99% Native American ancestry from five previously defined geographical regions. Although each region exhibited its own local adaptation profile, only PPARG and AJAP1, both negative regulators of the Wnt/ß catenin signaling pathway, showed significant adaptation signals in all the tested regions. Several signals were found, mainly in the genes related to the metabolic processes and immune response. A pathway enrichment analysis revealed the overrepresentation of selected genes related to several biological phenotypes/conditions, such as the immune response and metabolic pathways, in agreement with previous studies, suggesting that immunological and metabolic pressures are major drivers of human adaptation. Genes related to the gut microbiome measurements were overrepresented in all the regions, highlighting the importance of studying how humans have coevolved with the microbial communities that colonize them. Our results provide a further explanation of the human evolutionary history in response to environmental pressures in this region.

DNA methylation and gene expression analysis in adipose tissue to identify new loci associated with T2D development in obesity.

BACKGROUND: Obesity is accompanied by excess adipose fat storage, which may lead to adipose dysfunction, insulin resistance, and type 2 diabetes (T2D). Currently, the tendency to develop T2D in obesity cannot be explained by genetic variation alone-epigenetic mechanisms, such as DNA methylation, might be involved. Here, we aimed to identify changes in DNA methylation and gene expression in visceral adipose tissue (VAT) that might underlie T2D susceptibility in patients with obesity. METHODS: We investigated DNA methylation and gene expression in VAT biopsies from 19 women with obesity, without (OND = 9) or with T2D (OD = 10). Differences in genome-scale methylation (differentially methylated CpGs [DMCs], false discovery rate < 0.05; and differentially methylated regions [DMRs], p value < 0.05) and gene expression (DEGs, p value <0.05) between groups were assessed. We searched for overlap between altered methylation and expression and the impact of altered DNA methylation on gene expression, using bootstrap Pearson correlation. The relationship of altered DNA methylation to T2D-related traits was also tested. RESULTS: We identified 11 120 DMCs and 96 DMRs distributed across all chromosomes, with the greatest density of epigenomic alterations at the MHC locus. These alterations were found in newly and previously T2D-related genes. Several of these findings were supported by validation and extended multi-ethnic analyses. Of 252 DEGs in the OD group, 68 genes contained DMCs (n = 88), of which 24 demonstrated a significant relationship between gene expression and methylation (p values <0.05). Of these, 16, including ATP11A, LPL and EHD2 also showed a significant correlation with fasting glucose and HbA1c levels. CONCLUSIONS: Our results revealed novel candidate genes related to T2D pathogenesis in obesity. These genes show perturbations in DNA methylation and expression profiles in patients with obesity and diabetes. Methylation profiles were able to discriminate OND from OD individuals; DNA methylation is thus a potential biomarker.

Kazak mitochondrial genomes provide insights into the human population history of Central Eurasia.

As a historical nomadic group in Central Asia, Kazaks have mainly inhabited the steppe zone from the Altay Mountains in the East to the Caspian Sea in the West. Fine scale characterization of the genetic profile and population structure of Kazaks would be invaluable for understanding their population history and modeling prehistoric human expansions across the Eurasian steppes. With this mind, we characterized the maternal lineages of 200 Kazaks from Jetisuu at mitochondrial genome level. Our results reveal that Jetisuu Kazaks have unique mtDNA haplotypes including those belonging to the basal branches of both West Eurasian (R0, H, HV) and East Eurasian (A, B, C, D) lineages. The great diversity observed in their maternal lineages may reflect pivotal geographic location of Kazaks in Eurasia and implies a complex history for this population. Comparative analyses of mitochondrial genomes of human populations in Central Eurasia reveal a common maternal genetic ancestry for Turko-Mongolian speakers and their expansion being responsible for the presence of East Eurasian maternal lineages in Central Eurasia. Our analyses further indicate maternal genetic affinity between the Sherpas from the Tibetan Plateau with the Turko-Mongolian speakers.

Connectedness Is Critical: A Social Network Analysis to Support Emerging Women Leaders in Global Health.

Background: Global health networks serve to bring members together towards a specific objective. However, for myriad reasons, women often lack access to networks that facilitate leadership and career development. In 2020, the Johns Hopkins Center for Global Health launched Emerging Women Leaders in Global Health (EDGE) with a virtual seminar series featuring diverse women leaders followed by an online networking space. Objectives: The purpose of this paper is to use social network analysis (SNA) to describe the network, the connections within it, and the values placed on those connections to inform future programming. Methods: We asked EDGE participants to fill out a survey to collect network-specific data. Then, we developed a sociogram and calculated social network metrics based on region, type of organization, and professional career stage. Findings: The EDGE network had 103 unique connections, and each node, on average, was connected to two other nodes. Early professionals that work in Global North academic institutions were the most prevalent members and most efficiently connected with other members of the network. However, senior professionals from the Global South are key to bridging gaps between regions and across sectors. Conclusions: Early career professionals from the Global North and senior professionals from the Global South need to work in synergy to improve the connectedness of emerging women leaders around the world.

What the American Journal of Critical Care Junior Peer Reviewers Were Reading During Year 2 of the Program.

The American Journal of Critical Care's Junior Peer Reviewer program aims to mentor novice reviewers in the peer review process. To grow their critical appraisal skills, the participants take part in discussion sessions in which they review articles published in other journals. Here we summarize the articles reviewed during the second year of the program, which again focused on the care of critically ill patients with COVID-19. This article aims to share these reviews and the reviewers' thoughts regarding the relevance, design, and applicability of the findings from the selected studies. High rates of delirium associated with COVID-19 may be impacted by optimizing sedation strategies and allowing safe family visitation. Current methodology in crisis standards of care may result in inequity and further research is needed. The use of extracorporeal carbon dioxide removal to facilitate super low tidal volume ventilation does not improve 90-day mortality outcomes. Continued research to better understand the natural history of COVID-19 and interventions useful for improving outcomes is imperative.

Minimally Invasive Management of Rectourethral Fistulae.

OBJECTIVE: To report our experience and outcomes in minimally invasive management of rectourethral fistula (RUF). METHODS: From 2004 to 2021, 15 patients who underwent minimally invasive RUF repair by a single surgeon at 2 international institutions were retrospectively reviewed. Baseline demographic characteristics, perioperative, and postoperative data were collected. Complications were reported using the modified Clavien-Dindo Classification System and the European Association of Urology Complication Panel Assesment and Recommendations. Success was defined as complete resolution of fistula-related symptoms at 12-month follow-up along with confirmation of fistula closure by imaging or cystoscopy. Categorical variables were presented as frequencies and percentages whereas continuous variables were reported as median and quartiles. RESULTS: Fifteen male patients with a median age of 71 (64-79.2) years were treated. Four cases (26.6%) occurred postsurgery, 8 cases (53.3%) occurred after energy treatments, and 3 cases (20%) after surgery combined with an energy treatment modality. A robotic and laparoscopic approach was performed in 9 (60%) and 6 (40%) patients, respectively. No intraoperative complications were reported. Median operative time was 264 (217.5-341) minutes, estimated blood loss was 175 (137.5-200) mL, and the length of hospital stay was 4 days. Nine postoperative complications were reported. All patients were followed-up for 12 months with no recurrence reported. All patients reached our criteria for successful RUF repair. CONCLUSIONS: Minimally invasive surgery could represent an efficient way to manage RUF in selected patients. More studies and treatment standardization are needed to assess the role of minimally invasive surgery in the management of RUF.

Exome Sequencing Data Analysis and a Case-Control Study in Mexican Population Reveals Lipid Trait Associations of New and Known Genetic Variants in Dyslipidemia-Associated Loci.

Background: Plasma lipid levels are a major risk factor for cardiovascular diseases. Although international efforts have identified a group of loci associated with the risk of dyslipidemia, Latin American populations have been underrepresented in these studies. Objective: To know the genetic variation occurring in lipid-related loci in the Mexican population and its association with dyslipidemia. Methods: We searched for single-nucleotide variants in 177 lipid candidate genes using previously published exome sequencing data from 2838 Mexican individuals belonging to three different cohorts. With the extracted variants, we performed a case-control study. Logistic regression and quantitative trait analyses were implemented in PLINK software. We used an LD pruning using a 50-kb sliding window size, a 5-kb window step size and a r2 threshold of 0.1. Results: Among the 34251 biallelic variants identified in our sample population, 33% showed low frequency. For case-control study, we selected 2521 variants based on a minor allele frequency ≥1% in all datasets. We found 19 variants in 9 genes significantly associated with at least one lipid trait, with the most significant associations found in the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster on chromosome 11. Notably, all 11 variants associated with hypertriglyceridemia were within this cluster; whereas variants associated with hypercholesterolemia were located at chromosome 2 and 19, and for low high density lipoprotein cholesterol were in chromosomes 9, 11, and 19. No significant associated variants were found for low density lipoprotein. We found several novel variants associated with different lipemic traits: rs3825041 in BUD13 with hypertriglyceridemia, rs7252453 in CILP2 with decreased risk to hypercholesterolemia and rs11076176 in CETP with increased risk to low high density lipoprotein cholesterol. Conclusions: We identified novel variants in lipid-regulation candidate genes in the Mexican population, an underrepresented population in genomic studies, demonstrating the necessity of more genomic studies on multi-ethnic populations to gain a deeper understanding of the genetic structure of the lipemic traits.

Sex-specific hypothalamic expression of kisspeptin, gonadotropin releasing hormone, and kisspeptin receptor in progressive demyelination model.

Demyelinating diseases, such as multiple sclerosis, decrease the quality of life of patients and can affect reproduction. Assisted reproductive therapies are available, which although effective, aggravate motor symptoms. For this reason, it is important to determine how the control of the hypothalamus-pituitary-gonadal axis is affected in order to develop better strategies for these patients. One way to determine this is using animal models such as the taiep rat, which shows progressive demyelination of the central nervous system, and was used in the present study to characterize the expression of gonadotrophin-releasing hormone (GnRH), Kisspeptin, and kisspeptin receptor (Kiss1R) and luteinizing hormone (LH) secretion. The expression of kisspeptin, GnRH, and Kiss1R was determined at the hypothalamic level by immunofluorescence and serum LH levels were determined by ELISA. The expression of kisspeptin at the hypothalamic level showed sexual dimorphism, where there was an increase in males and a decrease in females during oestrus. There was no change in the expression of GnRH or kisspeptin receptor, regardless of sex. However, a decrease in serum LH concentration was observed in both sexes. The taiep rat showed changes in the expression of kisspeptin at the hypothalamic level. These changes are different from those reported in the literature with the use of animals with experimental allergic encephalomyelitis, this is because both animal models represent different degrees of progression of multiple sclerosis. Our results suggest that the effects on the hypothalamus-pituitary-gonadal axis depend on the differences between the demyelinating processes, their progression, and even individual factors, and it is thus important that fertility treatments are individualized to maximize therapeutic effects.

What the American Journal of Critical Care Junior Peer Reviewers Were Reading During the First Year of the Program: Caring for Patients With COVID-19.

The Junior Peer Reviewer program of the American Journal of Critical Care provides mentorship in the peer review process to novice reviewers. The program includes discussion sessions in which participants review articles published in other journals to practice and improve their critical appraisal skills. The articles reviewed during the first year of the program focused on caring for patients with COVID-19. The global pandemic has placed a heavy burden on nursing practice. Prone positioning of patients with acute respiratory failure is likely to improve their outcomes. Hospitals caring for patients needing prolonged ventilation should use evidence-based, standardized care practices to reduce mortality. The burden on uncompensated caregivers of COVID-19 survivors is also high, and such caregivers are likely to require assistance with their efforts. Reviewing these articles was helpful for building the peer review skills of program participants and identifying actionable research to improve the lives of critically ill patients.