Brain Cell-based Genetic Subtyping and Drug Repositioning for Alzheimer Disease.

Alzheimer's Disease (AD) is characterized by its complex and heterogeneous etiology and gradual progression, leading to high drug failure rates in late-stage clinical trials. In order to better stratify individuals at risk for AD and discern potential therapeutic targets we employed a novel procedure utilizing cell-based co-regulated gene networks and polygenic risk scores (cbPRSs). After defining genetic subtypes using extremes of cbPRS distributions, we evaluated correlations of the genetic subtypes with previously defined AD subtypes defined on the basis of domain-specific cognitive functioning and neuroimaging biomarkers. Employing a PageRank algorithm, we identified priority gene targets for the genetic subtypes. Pathway analysis of priority genes demonstrated associations with neurodegeneration and suggested candidate drugs currently utilized in diabetes, hypertension, and epilepsy for repositioning in AD. Experimental validation utilizing human induced pluripotent stem cell (hiPSC)-derived astrocytes demonstrated the modifying effects of estradiol, levetiracetam, and pioglitazone on expression of APOE and complement C4 genes, suggesting potential repositioning for AD.

Body mass index, diet, and outdoor activity linked with meibomian gland abnormalities in children.

SIGNIFICANCE: Dry eye disease is frequently underdiagnosed in pediatric patients. Meibomian gland morphology abnormalities (atrophy and tortuosity) may be associated with dry eye. This study examined risk factors for gland morphology abnormalities in children. PURPOSE: This study aimed to characterize meibomian gland morphological abnormalities (atrophy and tortuosity) and identify risk factors for the same in children. METHODS: A total of 160 children, primarily African American and Hispanic, aged 5 to <18 years underwent a comprehensive eye exam including slit-lamp examination to evaluate the meibomian glands, conjunctival papillae, and tear film. Infrared photography was performed including assessment of noninvasive tear film breakup time and tear meniscus height. Meibomian gland atrophy and tortuosity were assessed. A modified Ocular Surface Disease Index survey was administered along with surveys on screen time, diet, and outdoor activity. Linear multiple regression was performed to determine risk factors for meibomian gland abnormalities. RESULTS: The average age of participants (76 male, 84 female) was 10.9 ± 3.0 years. Severe meibomian gland atrophy (score ≥2) was found in 31.0% of participants in at least one eyelid. Severe meibomian gland tortuosity (score ≥2) was found in 84.0% of participants in at least one eyelid. The median symptom score was 9.8 (range, 0 to 71), with 16.9, 8.8, and 12.5% of the children having mild, moderate, and severe dry eye symptoms, respectively. Elevated body mass index (p<0.001), reduced outdoor activity (p=0.02), and unhealthy diet (p=0.01) were found to be risk factors for meibomian gland abnormalities. Screen time, symptom score, age, gender, and race/ethnicity were not associated with gland abnormalities (all p values >0.05). CONCLUSIONS: This study determined that meibomian gland morphological abnormalities were commonly found in children aged 5 to <18 years. Risk factors for these abnormalities include elevated body mass index, an unhealthy diet, and reduced outdoor activity.

Endoscopic-Assisted Presigmoid Approach to the Internal Auditory Canal. A Feasibility Study.

HYPOTHESIS: The retrolabyrinthine (presigmoid) approach has been utilized in various skull base surgeries but has not been fully utilized in the management of internal auditory canal (IAC) lesions, such as vestibular schwannoma (VS). Microsurgical retrolabyrinthine approach provides limited visualization of the IAC, while endoscopic-assisted techniques allow for further lateral exposure with labyrinthine preservation. BACKGROUND: Traditional approaches to the IAC have the disadvantage of hearing sacrifice or retraction of brain tissue. With the introduction of endoscopic techniques and enhanced visualization, access to this region of complex anatomy is possible. METHODS: Radiomorphometric and anatomical dissection was performed on two cadaveric temporal bones. High-resolution computed tomography was used to segment and delineate the volume of the IAC. Projected accessible IAC was compared to actual postdissection data with preservation of the posterior semicircular canal (PSCC) via the retrolabyrinthine corridor. RESULTS: While preserving the PSCC, the 0° and 30° endoscopes visualized 57.1% and 78.6% of the IAC for cadaver 1, and 64.0% and 76.0% of the IAC for cadaver 2, respectively. Sacrificing the PSCC, the 0° and 30° endoscopes provided visualization of 78.6% 85.7% of the IAC for cadaver 1, and 88.0% and 95.1% of the IAC for cadaver 2, respectively. CONCLUSIONS: Retrolabyrinthine approach to resection of VS is a potentially viable hearing-preserving alternative to traditional approaches. This approach provides access to the majority of the IAC, while angled endoscopes or sacrifice of the PSCC can provide additional access toward the fundus. Further studies are needed to determine the clinical feasibility of this approach.

Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry.

INTRODUCTION: Despite a two-fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts. METHODS: Genome-wide association studies (GWAS) of 2,903 AD cases and 6,265 controls of African ancestry. Within-dataset results were meta-analyzed, followed by functional genomics analyses. RESULTS: A novel AD-risk locus was identified in MPDZ on chromosome (chr) 9p23 (rs141610415, MAF = 0.002, P = 3.68×10-9). Two additional novel common and nine rare loci were identified with suggestive associations (P < 9×10-7). Comparison of association and linkage disequilibrium (LD) patterns between datasets with higher and lower degrees of African ancestry showed differential association patterns at chr12q23.2 (ASCL1), suggesting that this association is modulated by regional origin of local African ancestry. DISCUSSION: These analyses identified novel AD-associated loci in individuals of African ancestry and suggest that degree of African ancestry modulates some associations. Increased sample sets covering as much African genetic diversity as possible will be critical to identify additional loci and deconvolute local genetic ancestry effects. HIGHLIGHTS: Genetic ancestry significantly impacts risk of Alzheimer's Disease (AD). Although individuals of African ancestry are twice as likely to develop AD, they are vastly underrepresented in AD genomics studies. The Alzheimer's Disease Genetics Consortium has previously identified 16 common and rare genetic loci associated with AD in African American individuals. The current analyses significantly expand this effort by increasing the sample size and extending ancestral diversity by including populations from continental Africa. Single variant meta-analysis identified a novel genome-wide significant AD-risk locus in individuals of African ancestry at the MPDZ gene, and 11 additional novel loci with suggestive genome-wide significance at P < 9×10-7. Comparison of African American datasets with samples of higher degree of African ancestry demonstrated differing patterns of association and linkage disequilibrium at one of these loci, suggesting that degree and/or geographic origin of African ancestry modulates the effect at this locus. These findings illustrate the importance of increasing number and ancestral diversity of African ancestry samples in AD genomics studies to fully disentangle the genetic architecture underlying AD, and yield more effective ancestry-informed genetic screening tools and therapeutic interventions.

Subjective Cognitive Decline Plus and Longitudinal Assessment and Risk for Cognitive Impairment.

Importance: Subjective cognitive decline (SCD) is recognized to be in the Alzheimer disease (AD) cognitive continuum. The SCD Initiative International Working Group recently proposed SCD-plus (SCD+) features that increase risk for future objective cognitive decline but that have not been assessed in a large community-based setting. Objective: To assess SCD risk for mild cognitive impairment (MCI), AD, and all-cause dementia, using SCD+ criteria among cognitively normal adults. Design, Setting, and Participants: The Framingham Heart Study, a community-based prospective cohort study, assessed SCD between 2005 and 2019, with up to 12 years of follow-up. Participants 60 years and older with normal cognition at analytic baseline were included. Cox proportional hazards (CPH) models were adjusted for baseline age, sex, education, APOE ε4 status, and tertiles of AD polygenic risk score (PRS), excluding the APOE region. Data were analyzed from May 2021 to November 2023. Exposure: SCD was assessed longitudinally using a single question and considered present if endorsed at the last cognitively normal visit. It was treated as a time-varying variable, beginning at the first of consecutive, cognitively normal visits, including the last, at which it was endorsed. Main Outcomes and Measures: Consensus-diagnosed MCI, AD, and all-cause dementia. Results: This study included 3585 participants (mean [SD] baseline age, 68.0 [7.7] years; 1975 female [55.1%]). A total of 1596 participants (44.5%) had SCD, and 770 (21.5%) were carriers of APOE ε4. APOE ε4 and tertiles of AD PRS status did not significantly differ between the SCD and non-SCD groups. MCI, AD, and all-cause dementia were diagnosed in 236 participants (6.6%), 73 participants (2.0%), and 89 participants (2.5%), respectively, during follow-up. On average, SCD preceded MCI by 4.4 years, AD by 6.8 years, and all-cause dementia by 6.9 years. SCD was significantly associated with survival time to MCI (hazard ratio [HR], 1.57; 95% CI, 1.22-2.03; P <.001), AD (HR, 2.98; 95% CI, 1.89-4.70; P <.001), and all-cause dementia (HR, 2.14; 95% CI, 1.44-3.18; P <.001). After adjustment for APOE and AD PRS, the hazards of SCD were largely unchanged. Conclusions and Relevance: Results of this cohort study suggest that in a community setting, SCD reflecting SCD+ features was associated with an increased risk of future MCI, AD, and all-cause dementia with similar hazards estimated in clinic-based settings. SCD may be an independent risk factor for AD and other dementias beyond the risk incurred by APOE ε4 and AD PRS.

Teaching an Infant to Request Help.

Teaching an infant manual signs is beneficial as it promotes early communication, improves socialization, and can functionally replace behaviors such as crying and whining. Improving early communication also may reduce the probability of an infant engaging in dangerous behavior, like unsafe climbing. The purpose of this study was to extend Thompson et al. (Journal of Applied Behavior Analysis 40:15-23, 2007) by teaching an 8-month-old infant, who was noted to display developmental delays, to sign for "help" when preferred items were inaccessible. Similar to Thompson et al., delayed prompting and differential reinforcement was efficacious in teaching the infant to sign for "help," and the skill generalized to situations that were previously associated with unsafe climbing. However, undesirable generalization of signs for "help" when the infant could independently access the items was observed. Additional teaching was necessary to ensure signing for "help" occurred under appropriate antecedent control. Supplementary Information: The online version contains supplementary material available at 10.1007/s40616-023-00198-9.

The Impact of Training on Nurses' Attitudes Toward Reporting Child Sexual Abuse: a Pilot Study.

The purpose of this project is to assess, for practicing pediatric nurses in the U.S., what is the impact of the Stewards of Children Child Sexual Abuse (CSA) program on their attitudes about reporting suspected CSA. A sample size of 32 nurses completed an online 2-hour continuing education course by Stewards of Children, with a pre/post-test survey. A modified 14-item version of the Teachers Reporting Attitudes Scale for Child Sexual Abuse (TRAS-CSA) was used to measure the nurses' attitudes before and after educational training. The surveys were analyzed to assess changes in attitudes using two-tailed sign tests. Nurses' commitment to reporting CSA is high, even before training. Nurses' confidence in the system of reporting and in the response of authorities related to CSA increased after taking the Stewards of Children online course. While these results are limited in strength by low sample sizes and some null changes, they indicate that trainings like the Stewards of Children course can positively impact nurses' attitudes towards reporting CSA, particularly with regards to confidence in reporting, and therefore warrant further investigation into CSA training for nurses and its effects. Supplementary Information: The online version contains supplementary material available at 10.1007/s40653-023-00581-7.

Patients With Spina Bifida Have Longer Length of Hospital Stay: Statewide Health Care Utilization in California From 1995 to 2017.

INTRODUCTION: Our goal was to better understand the health care utilization of patients with spina bifida (SB) by evaluating length of hospital stay (LOS) as well as identifying what characteristics within the SB population are contributing to shorter or longer LOS. METHODS: By querying the Department of Health Care Access and Information database of all encounters at California-licensed hospitals from January 1995 through December 2017, this study analyzed LOS as a measure of health care utilization. Patients with SB were identified using the International Classification of Diseases-9 and -10 coding system, and the data collected for both SB and control cohorts were compared using linear and logistic regression models. RESULTS: Patients with SB spent a mean LOS of 7.3 days compared to 4.7 days among the control cohort (P < .001). In multivariable analysis, SB was found to be an independent predictor of longer LOS. Within the SB encounters, increasing comorbidities and nonprivate insurance were associated with longer LOS, while being female and Hispanic were associated with a shorter LOS. CONCLUSIONS: SB is an independent predictor of longer LOS when compared to the control cohort. These findings highlight the importance of understanding the preventive health care access and needs of the vulnerable SB population to decrease hospital utilization rates.

Transcriptional response of Arabidopsis thaliana's root-tip to spaceflight.

Plants are expected to play a critical role in the biological life support systems of crewed spaceflight missions, including in the context of upcoming missions targeting the Moon and Mars. Therefore, understanding the response of plants to spaceflight is essential for improving the selection and engineering of plants and spaceflight conditions. In particular, understanding the root-tip's response to spaceflight is of importance as it is the center of orchestrating the development of the root, the primary organ for the absorption of nutrients and anchorage. GLDS-120 is a pioneering study by Paul et al. that used transcriptomics to evaluate the spaceflight response of the root-tip of the model plant Arabidopsis thaliana in dark and light through separate analyses of three genotype groups (Wassilewskija, Columbia-0, and Columbia-0 PhyD) and comparison of genotype responses. Here, we provide a complementary analysis of this dataset through a combined analysis of all samples while controlling for the genotypes in a paired analysis. We identified a robust transcriptional response to spaceflight with 622 DEGs in light and 200 DEGs in dark conditions. Gene enrichment analysis identified 37 and 13 significantly enriched terms from biological processes in light and dark conditions, respectively. Prominent enrichment for hypoxia-related terms in both conditions suggests hypoxia is a key stressor for root development during spaceflight. Additional enriched terms in light conditions include the circadian cycle, light response, and terms for the metabolism of flavonoid and indole-containing compounds. These results further our understanding of plants' responses to the spaceflight environment.

Computerized Suicide Prevention Clinical Training Simulations: A Pilot Study.

Purpose: Mental health providers are well-positioned to engage in suicide prevention efforts, yet implementation depends on skill acquisition and providers often report feeling underprepared. This pilot study explored the acceptability, feasibility, and preliminary effectiveness of three suicide prevention-focused simulations with virtual clients. Method: Students (n=22) were recruited from a MSW program, completed pre- and post-test surveys, and engaged with three simulated trainings: 1) suicide risk assessment, 2) safety planning, and 3) motivating a client to treatment. Results: Simulations were reported to be acceptable and feasible, with strong student desire and need for greater suicide prevention training. We observed significant improvements over time in clinical skills via simulated training scores and perceptions of clinical preparedness. Discussion: Preliminary findings indicate simulated training with virtual clients is promising and suggest the three suicide prevention simulations may be useful, scalable, and effective in social work training programs and beyond.

micronuclAI: Automated quantification of micronuclei for assessment of chromosomal instability.

Chromosomal instability (CIN) is a hallmark of cancer that drives metastasis, immune evasion and treatment resistance. CIN results from chromosome mis-segregation events during anaphase, as excessive chromatin is packaged in micronuclei (MN), that can be enumerated to quantify CIN. Despite recent advancements in automation through computer vision and machine learning, the assessment of CIN remains a predominantly manual and time-consuming task, thus hampering important work in the field. Here, we present micronuclAI , a novel pipeline for automated and reliable quantification of MN of varying size, morphology and location from DNA-only stained images. In micronucleAI , single-cell crops are extracted from high-resolution microscopy images with the help of segmentation masks, which are then used to train a convolutional neural network (CNN) to output the number of MN associated with each cell. The pipeline was evaluated against manual single-cell level counts by experts and against routinely used MN ratio within the complete image. The classifier was able to achieve a weighted F1 score of 0.937 on the test dataset and the complete pipeline can achieve close to human-level performance on various datasets derived from multiple human and murine cancer cell lines. The pipeline achieved a root-mean-square deviation (RMSE) value of 0.0041, an R 2 of 0.87 and a Pearson's correlation of 0.938 on images obtained at 10X magnification. We tested the approach in otherwise isogenic cell lines in which we genetically dialed up or down CIN rates, and also on a publicly available image data set (obtained at 100X) and achieved an RMSE value of 0.0159, an R 2 of 0.90, and a Pearson's correlation of 0.951. Given the increasing interest in developing therapies for CIN-driven cancers, this method provides an important, scalable, and rapid approach to quantifying CIN on routinely obtained images. We release a GUI-implementation for easy access and utilization of the pipeline.

Trajectories of suicidal risk among individuals with first-episode psychosis: Relationship to recovery and symptoms.

This study examined trajectories of suicide-risk and their relationship to symptoms, recovery, and quality of life over time. Data was obtained from the Recovery after an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) study. 404 individuals with first-episode psychosis (FEP) completed measures of suicide-risk, depression, positive symptoms, recovery, and quality of life at baseline, 6mo, 12mo, 18mo, and 24mo. Latent class analysis was used to identify temporal trajectories of suicide-risk. General linear mixed models for repeated measures were used to examine the relationship between the latent trajectories of suicide-risk and clinical variables. Results identified three latent trajectories of suicide-risk (low-risk, worsening, and improving). The low-risk and improving classes experienced improvements in depression, positive symptoms, quality of life, and recovery over time. The worsening class experienced improvements in positive symptoms and quality of life, but no change in depression or recovery. These results suggest that some individuals with FEP are at risk for persistent depression and worsening suicide-risk during treatment despite experiencing improvements in positive symptoms and quality of life. These findings have important clinical implications, as persistent depression and worsening suicide-risk might be masked by the primary focus on positive symptoms and quality of life in most FEP clinics.

Astronaut omics and the impact of space on the human body at scale.

Future multi-year crewed planetary missions will motivate advances in aerospace nutrition and telehealth. On Earth, the Human Cell Atlas project aims to spatially map all cell types in the human body. Here, we propose that a parallel Human Cell Space Atlas could serve as an openly available, global resource for space life science research. As humanity becomes increasingly spacefaring, high-resolution omics on orbit could permit an advent of precision spaceflight healthcare. Alongside the scientific potential, we consider the complex ethical, cultural, and legal challenges intrinsic to the human space omics discipline, and how philosophical frameworks may benefit from international perspectives.

The association between circulating CD34+CD133+ endothelial progenitor cells and reduced risk of Alzheimer's disease in the Framingham Heart Study.

Aim: Endothelial dysfunction has been associated with both cerebrovascular pathology and Alzheimer's disease (AD). However, the connection between circulating endothelial cells and the risk of AD remains uncertain. The objective was to leverage data from the Framingham Heart Study to investigate various circulating endothelial subtypes and their potential correlations with the risk of AD. Methods: The study conducted data analyses using Cox proportional hazard regression and linear regression methods. Additionally, genome-wide association study (GWAS) was carried out to further explore the data. Results: Among the eleven distinct circulating endothelial subtypes, only circulating endothelial progenitor cells (EPCs) expressing CD34+CD133+ were found to be negatively and dose-dependently associated with reduced AD risk. This association persisted even after adjusting for age, sex, years of education, apolipoprotein E (APOE) ε4 status, and various vascular diseases. Particularly noteworthy was the significant association observed in individuals with hypertension and cerebral microbleeds. Consistently, positive associations were identified between CD34+CD133+ EPCs and specific brain regions, such as higher proportions of circulating CD34+CD133+ cells correlating with increased volumes of white matter and the hippocampus. Additionally, a GWAS study unveiled that CD34+CD133+ cells influenced AD risk specifically in individuals with homozygous genotypes for variants in two stem cell-related genes: kirre like nephrin family adhesion molecule 3 (KIRREL3, rs580382 CC and rs4144611 TT) and exocyst complex component 6B (EXOC6B, rs61619102 CC). Conclusions: The findings suggest that circulating CD34+CD133+ EPCs possess a protective effect and may offer a new therapeutic avenue for AD, especially in individuals with vascular pathology and those carrying specific genotypes of KIRREL3 and EXOC6B genes.

DREAMER: a computational framework to evaluate readiness of datasets for machine learning.

BACKGROUND: Machine learning (ML) has emerged as the predominant computational paradigm for analyzing large-scale datasets across diverse domains. The assessment of dataset quality stands as a pivotal precursor to the successful deployment of ML models. In this study, we introduce DREAMER (Data REAdiness for MachinE learning Research), an algorithmic framework leveraging supervised and unsupervised machine learning techniques to autonomously evaluate the suitability of tabular datasets for ML model development. DREAMER is openly accessible as a tool on GitHub and Docker, facilitating its adoption and further refinement within the research community.. RESULTS: The proposed model in this study was applied to three distinct tabular datasets, resulting in notable enhancements in their quality with respect to readiness for ML tasks, as assessed through established data quality metrics. Our findings demonstrate the efficacy of the framework in substantially augmenting the original dataset quality, achieved through the elimination of extraneous features and rows. This refinement yielded improved accuracy across both supervised and unsupervised learning methodologies. CONCLUSION: Our software presents an automated framework for data readiness, aimed at enhancing the integrity of raw datasets to facilitate robust utilization within ML pipelines. Through our proposed framework, we streamline the original dataset, resulting in enhanced accuracy and efficiency within the associated ML algorithms.

Urinary and Oral Microbiota Among Men Undergoing Buccal Urethroplasty.

OBJECTIVE: To assess changes in the urinary microbiota after buccal urethroplasty. METHODS: At the University of California San Francisco, we enrolled 9 adult males with urethral strictures undergoing buccal urethroplasty where we collected urine and oral swabs intraoperatively and 3 months postoperatively. 16S rRNA sequencing was used to profile the microbiota. RESULTS: At baseline, the mouth contains twice the number of unique bacteria (alpha diversity) and the microbial community is significantly distinct compared to the urinary tract. Despite having a buccal mucosa in the urinary tract after urethroplasty, the number of unique bacteria in the urine remained stable. However, the bacterial community composition and structure significantly changed in the urinary tract with the enrichment of Corynebacterium genus at 3 months post-urethroplasty procedure. CONCLUSION: In this pilot study, we showed that the alpha diversity in the urinary microbiota did not significantly change despite having a buccal tissue with the capacity to support high bacterial diversity in the urinary tract. To our surprise, the post-urethroplasty urinary microbiota was not a hybrid of baseline oral and urine microbiotas; the changes detected, such as an enrichment of the Corynebacterium genus, were more nuanced yet could profoundly impact surgical outcomes like graft changes and stricture recurrence. Our study not only established the feasibility but also outlined a blueprint for conducting a large-scale study to assess alterations in the urinary microbiome in relation to surgical outcomes.

Emergence of the novel sixth Candida auris Clade VI in Bangladesh.

Candida auris, initially identified in 2009, has rapidly become a critical concern due to its antifungal resistance and significant mortality rates in healthcare-associated outbreaks. To date, whole-genome sequencing (WGS) has identified five unique clades of C. auris, with some strains displaying resistance to all primary antifungal drug classes. In this study, we presented the first WGS analysis of C. auris from Bangladesh, describing its origins, transmission dynamics, and antifungal susceptibility testing (AFST) profile. Ten C. auris isolates collected from hospital settings in Bangladesh were initially identified by CHROMagar Candida Plus, followed by VITEK2 system, and later sequenced using Illumina NextSeq 550 system. Reference-based phylogenetic analysis and variant calling pipelines were used to classify the isolates in different clades. All isolates aligned ~90% with the Clade I C. auris B11205 reference genome. Of the 10 isolates, 8 were clustered with Clade I isolates, highlighting a South Asian lineage prevalent in Bangladesh. Remarkably, the remaining two isolates formed a distinct cluster, exhibiting >42,447 single-nucleotide polymorphism differences compared to their closest Clade IV counterparts. This significant variation corroborates the emergence of a sixth clade (Clade VI) of C. auris in Bangladesh, with potential for international transmission. AFST results showed that 80% of the C. auris isolates were resistant to fluconazole and voriconazole, whereas Clade VI isolates were susceptible to azoles, echinocandins, and pyrimidine analogue. Genomic sequencing revealed ERG11_Y132F mutation conferring azole resistance while FCY1_S70R mutation found inconsequential in describing 5-flucytosine resistance. Our study underscores the pressing need for comprehensive genomic surveillance in Bangladesh to better understand the emergence, transmission dynamics, and resistance profiles of C. auris infections. Unveiling the discovery of a sixth clade (Clade VI) accentuates the indispensable role of advanced sequencing methodologies.IMPORTANCECandida auris is a nosocomial fungal pathogen that is commonly misidentified as other Candida species. Since its emergence in 2009, this multidrug-resistant fungus has become one of the five urgent antimicrobial threats by 2019. Whole-genome sequencing (WGS) has proven to be the most accurate identification technique of C. auris which also played a crucial role in the initial discovery of this pathogen. WGS analysis of C. auris has revealed five distinct clades where isolates of each clade differ among themselves based on pathogenicity, colonization, infection mechanism, as well as other phenotypic characteristics. In Bangladesh, C. auris was first reported in 2019 from clinical samples of a large hospital in Dhaka city. To understand the origin, transmission dynamics, and antifungal-resistance profile of C. auris isolates circulating in Bangladesh, we conducted a WGS-based surveillance study on two of the largest hospital settings in Dhaka, Bangladesh.

Lipid Testing among Youth in Medicaid: The Role of Social Determinants of Health and Providers.

OBJECTIVES: To assess recent temporal trends in guideline-compliant pediatric lipid testing, and to examine the influence of social determinants of health (SDoH) and provider characteristics on the likelihood of testing in youth. STUDY DESIGN: In this observational, multi-year cross-sectional study, we calculated lipid testing prevalence by year among 268,627 12-year-olds from 2015 through 2019 who were enrolled in Florida Medicaid and eligible for universal lipid screening during age 9 to 11, and 11,437 22-year-olds (2017-2019) who were eligible for screening during age 17-21. We compared trends in testing prevalence by SDoH and health risk factors at two recommended ages and modeled the associations between patient characteristics and provider type on lipid testing using generalized estimating equations. RESULTS: Testing among 12-year-olds remained low between 2015 through 2019 with the highest prevalence in 2015 (8.0%) and lowest in 2017 (6.7%). Screening compliance among 22-year-olds was highest in 2017 (21.1%) and fell to 17.8% in 2019. Hispanics and non-Hispanic Blacks in both age groups had about 2-3% lower testing prevalence than non-Hispanic Whites. Testing in 12-year-olds was 12.3% versus 7.7% with and without obesity, and 14.4% versus 7.6% with and without antipsychotic use. Participants who saw providers who were more likely to prescribe lipid testing were more likely to receive testing (odds ratio=2.3, 95% CI 2.0-2.8, P<.001). CONCLUSIONS: Although lipid testing prevalence was greatest among high-risk children, overall prevalence of lipid testing in youth remains very low. Provider specialty and choices by individual providers play important roles in improving guideline-compliant pediatric lipid testing.