Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology.

While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine trials. Each vaccine regimen induced a unique humoral "Fc fingerprint." Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive.

Evaluation of vaginal microbiome equilibrium states identifies microbial parameters linked to resilience after menses and antibiotic therapy.

The vaginal microbiome (VMB) is a complex microbial community that is closely tied to reproductive health. Optimal VMB communities have compositions that are commonly defined by the dominance of certain Lactobacillus spp. and can remain stable over time or transition to non-optimal states dominated by anaerobic bacteria and associated with bacterial vaginosis (BV). The ability to remain stable or undergo transitions suggests a system with either single (mono-stable) or multiple (multi-stable) equilibrium states, though factors that contribute to stability have been difficult to determine due to heterogeneity in microbial growth characteristics and inter-species interactions. Here, we use a computational model to determine whether differences in microbial growth and interaction parameters could alter equilibrium state accessibility and account for variability in community composition after menses and antibiotic therapies. Using a global uncertainty and sensitivity analysis that captures parameter sets sampled from a physiologically relevant range, model simulations predicted that 79.7% of microbial communities were mono-stable (gravitate to one composition type) and 20.3% were predicted to be multi-stable (can gravitate to more than one composition type, given external perturbations), which was not significantly different from observations in two clinical cohorts (HMP cohort, 75.2% and 24.8%; Gajer cohort, 78.1% and 21.9%, respectively). The model identified key microbial parameters that governed equilibrium state accessibility, such as the importance of non-optimal anaerobic bacteria interactions with Lactobacillus spp., which is largely understudied. Model predictions for composition changes after menses and antibiotics were not significantly different from those observed in clinical cohorts. Lastly, simulations were performed to illustrate how this quantitative framework can be used to gain insight into the development of new combinatorial therapies involving altered prebiotic and antibiotic dosing strategies. Altogether, dynamical models could guide development of more precise therapeutic strategies to manage BV.

Curated single cell multimodal landmark datasets for R/Bioconductor.

BACKGROUND: The majority of high-throughput single-cell molecular profiling methods quantify RNA expression; however, recent multimodal profiling methods add simultaneous measurement of genomic, proteomic, epigenetic, and/or spatial information on the same cells. The development of new statistical and computational methods in Bioconductor for such data will be facilitated by easy availability of landmark datasets using standard data classes. RESULTS: We collected, processed, and packaged publicly available landmark datasets from important single-cell multimodal protocols, including CITE-Seq, ECCITE-Seq, SCoPE2, scNMT, 10X Multiome, seqFISH, and G&T. We integrate data modalities via the MultiAssayExperiment Bioconductor class, document and re-distribute datasets as the SingleCellMultiModal package in Bioconductor's Cloud-based ExperimentHub. The result is single-command actualization of landmark datasets from seven single-cell multimodal data generation technologies, without need for further data processing or wrangling in order to analyze and develop methods within Bioconductor's ecosystem of hundreds of packages for single-cell and multimodal data. CONCLUSIONS: We provide two examples of integrative analyses that are greatly simplified by SingleCellMultiModal. The package will facilitate development of bioinformatic and statistical methods in Bioconductor to meet the challenges of integrating molecular layers and analyzing phenotypic outputs including cell differentiation, activity, and disease.

Evidence-based procedures to improve the reliability of circulating miRNA biomarker assays.

Circulating cell-free microRNAs (cfmiRNA) are an emerging class of biomarkers that have shown great promise in the clinical diagnosis, treatment, and monitoring of several pathological conditions, including cancer. However, validation and clinical implementation of cfmiRNA biomarkers has been hindered by the variability introduced during different or suboptimal specimen collection and handling practices. To address the need for standardization and evidence-based guidance, the National Cancer Institute (NCI) developed a new Biospecimen Evidenced-Based Practices (BEBP) document, entitled "Cell-free miRNA (cfmiRNA): Blood Collection and Processing". The BEBP, the fourth in the document series, contains step-by-step procedural guidelines on blood collection, processing, storage, extraction, and quality assessment that are tailored specifically for cfmiRNA analysis of plasma and serum. The workflow outlined in the BEBP is based on the available literature and recommendations of an expert panel. The BEBP contains the level of detail required for development of evidence-based standard operating procedures (SOPs) as well as the flexibility needed to accomodate (i) discovery- and inquiry-based studies and (ii) the different constraints faced by research labs, industry, clinical and academic institutions to foster widespread implementation. Guidance from the expert panel also included recommendations on study design, validating changes in workflow, and suggested quality thresholds to delineate meaningful changes in cfmiRNA levels. The NCI cfmiRNA: Blood Collection and Processing BEBP is available here as supplementary information as well as through the NCI Biorepositories and Biospecimen Research Branch (BBRB) (https://biospecimens.cancer.gov/resources/bebp.asp).

Epidermal nevi and epidermolytic hyperkeratosis: A review of cases, highlighting indications for biopsy and genetics referral.

Epidermal nevi are common benign cutaneous hamartomas that may rarely demonstrate histopathologic evidence of epidermolytic hyperkeratosis (EHK), representing cutaneous mosaicism for pathogenic keratin variants. Rarely, individuals with linear epidermal nevi transmit to their children the inherited form of EHK, also known as epidermolytic ichthyosis, characterized by generalized erythema, blistering, and scaling at birth evolving to widespread hyperkeratosis. We present an updated review of reported cases of linear epidermal nevi with EHK exhibiting transmission of epidermolytic ichthyosis to guide important considerations in the care of individuals with epidermal nevi. Clinical characteristics of linear epidermal nevi do not reliably predict the presence of EHK. All reported cases of transmission to offspring have occurred in individuals with linear epidermal nevi involving more than one anatomic area suggesting increased reproductive risk with involvement of two or more anatomic sites. Therefore, genetics consultation is recommended for these individuals with biopsy-confirmed EHK. For individuals with smaller areas of epidermal nevus involvement, the implications are less well known, though genetics consultation may still be considered for those interested in further discussion of general reproductive risk.

Screening, Brief Intervention, and Referral to Treatment Plus (SBIRT-Plus): A Novel Interprofessional Training for Rehabilitation Science Professional Students.

IMPORTANCE: With the increasing amount of substance use-related health conditions in the United States, it is important for rehabilitation science professionals to receive screening and prevention training. OBJECTIVE: To describe and examine the preliminary effectiveness of a novel educational program, Screening, Brief Intervention, and Referral to Treatment Plus (SBIRT-Plus), that combines traditional SBIRT training with new modules for cannabis, stimulant, and opioid use. DESIGN: Prospective, cohort design. SETTING: Academic institution. PARTICIPANTS: One hundred eighty-one rehabilitation science graduate students. INTERVENTION: SBIRT-Plus curriculum. OUTCOMES AND MEASURES: Outcomes included satisfaction with training, perception of interprofessional training, attitudes, knowledge, and stigma, as assessed with the Readiness for Interprofessional Learning Scale, Alcohol and Alcohol Problems Perception Questionnaire, Drug and Drug Problems Perception Questionnaire, Knowledge Screening Scale, and two stigma instruments. RESULTS: Most students (>80%) expressed satisfaction with their training, would recommend the training to a colleague, and believed that the training would influence and change the way they practiced with patients at risk for substance use disorders. Students' attitudes and knowledge increased from pre- to post-training, and stigma perceptions were significantly reduced. CONCLUSIONS AND RELEVANCE: SBIRT-Plus is an evidence-based interprofessional training that is feasible to implement in graduate-level education programs. Integrating SBIRT-Plus into professional graduate programs may be an optimal and low-cost model for training rehabilitation health care professionals. Plain-Language Summary: Screening, Brief Intervention, and Referral to Treatment Plus (SBIRT-Plus) is an evidence-based interprofessional training that can be easily adopted in curricula to train professional students about the importance of screening for substance use disorders.

Association of Kidney Function With Major Postoperative Events After Noncardiac Ambulatory Surgeries: A Population-Based Cohort Study.

OBJECTIVE: The aim of this study was to estimate the association between estimated glomerular filtration rate (eGFR) and acute myocardial infarction (AMI) or death after ambulatory noncardiac surgery. SUMMARY BACKGROUND DATA: People with chronic kidney disease (CKD) commonly undergo surgical procedures. Although most are performed in an ambulatory setting, the risk of major perioperative outcomes after ambulatory surgery for people with CKD is unknown. METHODS: In this retrospective population-based cohort study using administrative health data from Alberta, Canada, we included adults with measured preoperative kidney function undergoing ambulatory noncardiac surgery between April 1, 2005 and February 28, 2017. Participants were categorized into 6 eGFR categories (in mL/min/1.73m 2 )of ≥60 (G1-2), 45 to 59 (G3a), 30 to 44 (G3b), 15 to 29 (G4), <15 not receiving dialysis (G5ND), and those receiving chronic dialysis (G5D). The odds of AMI or death within 30 days of surgery were estimated using multivariable generalized estimating equation models. RESULTS: We identified 543,160 procedures in 323,521 people with a median age of 66 years (IQR 56-76); 52% were female. Overall, 2338 people (0.7%) died or had an AMI within 30 days of surgery. Compared with the G1-2 category, the adjusted odds ratio of death or AMI increased from 1.1 (95% confidence interval: 1.0-1.3) for G3a to 3.1 (2.6-3.6) for G5D. Emergency Department and Urgent Care Center visits within 30 days were frequent (17%), though similar across eGFR categories. CONCLUSIONS: Ambulatory surgery was associated with a low risk of major postoperative events. This risk was higher for people with CKD, which may inform their perioperative shared decision-making and management.

An interactive childbirth education platform to improve pregnancy-related anxiety: a randomized trial.

BACKGROUND: Perinatal anxiety is one of the most common conditions during pregnancy and is associated with adverse maternal and neonatal outcomes. Interventions that are focused on childbirth education and health literacy have been shown to help decrease pregnancy-related anxiety. These programs, however, have limitations. Transportation, childcare, and work conflicts pose barriers to patients. In addition, many of these programs have not been studied in high-risk patients, who are most at risk for pregnancy-related anxiety. Thus, it is uncertain whether an online childbirth education course can help to improve outcomes in a high-risk patient population. OBJECTIVE: This study aimed to compare an interactive online platform for childbirth education (Birthly) with usual prenatal education on anxiety, emergency healthcare utilization, and delivery outcomes for high-risk pregnancies. STUDY DESIGN: We performed a randomized trial comparing an interactive online childbirth education platform combined with usual prenatal education (intervention) with usual prenatal education alone (usual care). Nulliparous, English-speaking patients with internet access and a high-risk pregnancy (medical or mental health disorders) were included. Patients in 2 urban clinics that serve underresourced patients were enrolled at <20 weeks of gestation. The intervention included 3 interactive courses (prenatal bootcamp, breastfeeding, newborn care) and access to a clinician-moderated online community. Pregnancy-related Anxiety Scale questionnaires were administered at randomization and at 34 to 40 weeks. The primary outcome was third-trimester Pregnancy-related Anxiety Scale score. Secondary outcomes included change in Pregnancy-related Anxiety Scale score, unscheduled emergency visits, delivery, and postpartum outcomes. To demonstrate a 15% decrease in Pregnancy-related Anxiety Scale score, 37 patients would be needed per group. Accounting for a 20% loss to follow-up rate, we planned to recruit 90 total patients or 45 per group. RESULTS: A total of 90 patients were randomized with no differences in demographics or baseline Pregnancy-related Anxiety Scale scores. Most patients self-identified as Black and were publicly insured. More than 60% of patients (62.2%) in the intervention arm completed at least 1 Birthly course. Patients in the intervention arm had significantly lower third-trimester Pregnancy-related Anxiety Scale scores (indicating lower anxiety) compared with those receiving usual care (44.6±7.3 vs 53.9±13.8; P<.01), with a decrease in score of 8.3 points vs 0.7 for usual care (P<.01). Patients in the intervention arm also had fewer emergency visits (1 [0-2] vs 2 [1-3]; P=.003). There were no differences in delivery outcomes. Patients in the intervention arm were more likely to breastfeed at delivery, although this was not different by the postpartum visit. Finally, patients who received the intervention were more likely to be satisfied with their childbirth education (94.6% vs 64.9%; P<.01). CONCLUSION: An interactive online childbirth education platform can reduce pregnancy-related anxiety and emergency healthcare utilization while improving satisfaction in a high-risk patient population.

Standardizing Opioids Prescribed at Discharge in Trauma Surgery.

INTRODUCTION: Excessive opioid use after sustaining trauma has contributed to the opioid epidemic. Standardizing the quantity of opioids prescribed at discharge can improve prescribing behavior. We hypothesized that adopting new electronic medical record order sets would be associated with decreased morphine milligram equivalents (MME) prescribed at discharge for trauma patients. METHODS: This was a quasi-experimental study examining opioid prescribing practices at a Level 1 Trauma Center. All patients ages 18-89 admitted to the Trauma Service from January 2017 through March 2021 and hospitalized for at least 2 d were included. In November 2020, new trauma admission and discharge order sets were implemented with recommended discharge opioid quantity based on inpatient opioid usage the day prior to discharge multiplied by five. Postintervention prescribing practices were compared to historical controls. The primary outcome was MME at discharge. RESULTS: Baseline characteristics between preintervention and postintervention cohorts were comparable. There was a significant reduction in median MME prescribed at discharge postintervention (112.5 versus 75.0, P < 0.0001). Median inpatient MME usage also significantly reduced postintervention (184.1 versus 160.5; P < 0.0001). There were trends toward increased ideal prescribing per order set recommendation and a reduction in overprescribing. Patients receiving the recommended opioid quantity at discharge had the lowest opioid refill prescription rate (under: 29.6%, ideal: 7.3%, over: 19.7%, P < 0.0001). CONCLUSIONS: For trauma patients requiring inpatient opioid therapy, a pragmatic and individualized intervention was associated with a reduced quantity of discharge opioids without negative outcomes. Reduction in inpatient opioid use was also associated with standardizing prescribing practices of surgeons with electronic medical record order sets.

Perioperative management for people with kidney failure receiving dialysis: A scoping review.

BACKGROUND: People with kidney failure receiving dialysis (CKD-G5D) are more likely to undergo surgery and experience poorer postoperative outcomes than those without kidney failure. In this scoping review, we aimed to systematically identify and summarize perioperative strategies, protocols, pathways, and interventions that have been studied or implemented for people with CKD-G5D. METHODS: We searched MEDLINE, EMBASE, CINAHL Plus, Cochrane Database of Systematic Reviews, and Cochrane Controlled Trials registry (inception to February 2020), in addition to an extensive grey literature search, for sources that reported on a perioperative strategy to guide management for people with CKD-G5D. We summarized the overall study characteristics and perioperative management strategies and identified evidence gaps based on surgery type and perioperative domain. Publication trends over time were assessed, stratified by surgery type and study design. RESULTS: We included 183 studies; the most common study design was a randomized controlled trial (27%), with 67% of publications focused on either kidney transplantation or dialysis vascular access. Transplant-related studies often focused on fluid and volume management strategies and risk stratification, whereas dialysis vascular access studies focused most often on imaging. The number of publications increased over time, across all surgery types, though driven by non-randomized study designs. CONCLUSIONS: Despite many current gaps in perioperative research for patients with CKD-G5D, evidence generation supporting perioperative management is increasing, with recent growth driven primarily by non-randomized studies. Our review may inform organization of evidence-based strategies into perioperative care pathways where evidence is available while also highlighting gaps that future perioperative research can address.

Prediction of major postoperative events after non-cardiac surgery for people with kidney failure: derivation and internal validation of risk models.

BACKGROUND: People with kidney failure often require surgery and experience worse postoperative outcomes compared to the general population, but existing risk prediction tools have excluded those with kidney failure during development or exhibit poor performance. Our objective was to derive, internally validate, and estimate the clinical utility of risk prediction models for people with kidney failure undergoing non-cardiac surgery. DESIGN, SETTING, PARTICIPANTS, AND MEASURES: This study involved derivation and internal validation of prognostic risk prediction models using a retrospective, population-based cohort. We identified adults from Alberta, Canada with pre-existing kidney failure (estimated glomerular filtration rate [eGFR] < 15 mL/min/1.73m2 or receipt of maintenance dialysis) undergoing non-cardiac surgery between 2005-2019. Three nested prognostic risk prediction models were assembled using clinical and logistical rationale. Model 1 included age, sex, dialysis modality, surgery type and setting. Model 2 added comorbidities, and Model 3 added preoperative hemoglobin and albumin. Death or major cardiac events (acute myocardial infarction or nonfatal ventricular arrhythmia) within 30 days after surgery were modelled using logistic regression models. RESULTS: The development cohort included 38,541 surgeries, with 1,204 outcomes (after 3.1% of surgeries); 61% were performed in males, the median age was 64 years (interquartile range [IQR]: 53, 73), and 61% were receiving hemodialysis at the time of surgery. All three internally validated models performed well, with c-statistics ranging from 0.783 (95% Confidence Interval [CI]: 0.770, 0.797) for Model 1 to 0.818 (95%CI: 0.803, 0.826) for Model 3. Calibration slopes and intercepts were excellent for all models, though Models 2 and 3 demonstrated improvement in net reclassification. Decision curve analysis estimated that use of any model to guide perioperative interventions such as cardiac monitoring would result in potential net benefit over default strategies. CONCLUSIONS: We developed and internally validated three novel models to predict major clinical events for people with kidney failure having surgery. Models including comorbidities and laboratory variables showed improved accuracy of risk stratification and provided the greatest potential net benefit for guiding perioperative decisions. Once externally validated, these models may inform perioperative shared decision making and risk-guided strategies for this population.

NK cells clear α-synuclein and the depletion of NK cells exacerbates synuclein pathology in a mouse model of α-synucleinopathy.

The pathological hallmark of synucleinopathies, including Lewy body dementia and Parkinson's disease (PD), is the presence of Lewy bodies, which are primarily composed of intracellular inclusions of misfolded α-synuclein (α-syn) among other proteins. α-Syn is found in extracellular biological fluids in PD patients and has been implicated in modulating immune responses in the central nervous system (CNS) and the periphery. Natural killer (NK) cells are innate effector lymphocytes that are present in the CNS in homeostatic and pathological conditions. NK cell numbers are increased in the blood of PD patients and their activity is associated with disease severity; however, the role of NK cells in the context of α-synucleinopathies has never been explored. Here, we show that human NK cells can efficiently internalize and degrade α-syn aggregates via the endosomal/lysosomal pathway. We demonstrate that α-syn aggregates attenuate NK cell cytotoxicity in a dose-dependent manner and decrease the release of the proinflammatory cytokine, IFN-γ. To address the role of NK cells in PD pathogenesis, NK cell function was investigated in a preformed fibril α-syn-induced mouse PD model. Our studies demonstrate that in vivo depletion of NK cells in a preclinical mouse PD model resulted in exacerbated motor deficits and increased phosphorylated α-syn deposits. Collectively, our data provide a role of NK cells in modulating synuclein pathology and motor symptoms in a preclinical mouse model of PD, which could be developed into a therapeutic for PD and other synucleinopathies.

Patient Perception of Plant Based Diets for Kidney Disease.

OBJECTIVE: Plant-based diets can delay the progression of chronic kidney disease (CKD) and help manage complications and comorbid conditions such as hypertension, acidosis, diabetes, and cardiovascular disease. The objective of this study was to understand nephrology patients' familiarity, perception, and use of plant-based diets. DESIGN & METHODS: A survey was shared via the National Kidney Foundation's social media channels. Analysis included 844 responses. Survey items were evaluated with descriptive statistics. Differences across items were determined using chi-square tests. RESULTS: Most respondents were 61-70 years of age (26.7%, n = 225), female (56.5%, n = 477) and achieved a Bachelor's or advanced degree (49.9%, n = 421). The majority of respondents suffered from nondialysis-dependent CKD (34%) or received a kidney transplant (34%). About half (45%) of respondents were familiar with plant-based diets and most (58%) were aware that plant-based diets can improve CKD. Twenty-two percent reported following some version of a vegetarian diet, and 29% reported "eating less meat". Respondents were not confident (Mdn = 2, IQR = 2, on a scale of 1-5) in their ability to plan a balanced plant-based meal, and were moderately confident that a plant-based diet could help blood pressure (Mdn = 3, IQR = 2) and slow progression of CKD (Mdn = 3, IGR = 2). Family eating preference, meal planning skills, preference for meat, figuring out what is healthy to eat, food cost, time constraints, and ease of cooking were rated as equal barriers to following a plant-based diet (Mdn = 3). A sample meal plan, individual counseling session with a Registered Dietitian Nutritionist (RDN), handouts, and cooking classes were resources rated most helpful to transition to a plant-based diet (Mdn = 4). CONCLUSION: Approximately half of respondents were aware that plant-based diets can be beneficial for CKD. Many patients are following a vegetarian or plant-based eating pattern. More research should be done to see how effective RDNs are in educating and moving patients toward a plant-based eating pattern, as they are an underutilized resource in the CKD population.

A vocational rehabilitation partnership to provide transition services to young adults with neurodevelopmental disabilities: The cognitive skills enhancement program.

BACKGROUND: There is an urgent need for services that support a successful transition to postsecondary education and employment for young adults with neurodevelopmental and cognitive disabilities (e.g. autism spectrum disorder, attention-deficit/hyperactivity disorder, traumatic brain injury). OBJECTIVE: The purpose of this expository article is to describe the Cognitive Skills Enhancement Program (CSEP), a comprehensive clinical program designed for young adults with neurodevelopmental and cognitive disabilities transitioning to postsecondary education. METHODS: CSEP was developed through a community-academic partnership between a university and a state vocational rehabilitation program. Young adult participants complete programming that addresses four primary clinical targets: (1) emotion regulation, (2) social skills, (3) work readiness, and (4) community participation with the overall goal to increase awareness and promote successful employment outcomes while they transition to post-secondary education. RESULTS: To date, CSEP has supported 18 years of sustained programming and clinical services to 621 young adults with neurodevelopmental and cognitive disabilities. CONCLUSION: This partnership model allows for flexible responses to participant needs, implementation barriers, and advances in evidence-based practices. CSEP meets the needs of diverse stakeholders (e.g. state vocational rehabilitation, postsecondary training facilities, participants, universities) while providing high-quality and sustainable programming. Future directions include examining the clinical efficacy of current CSEP programming.

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults, Canada, 2015-2019.

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015-2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015-2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.

Impact of vaginal microbiome communities on HIV antiretroviral-based pre-exposure prophylaxis (PrEP) drug metabolism.

Despite the efficacy of antiretroviral-based pre-exposure prophylactics (PrEP) in men who have sex with men, studies in women have produced widely varying outcomes. Recent evidence demonstrates that vaginal microbial communities are associated with increased HIV acquisition risk and may impact PrEP efficacy. Here, we investigate the mechanisms underlying how vaginal bacteria alter PrEP drug levels and impact HIV infection rates ex vivo. Using cervicovaginal lavages (CVLs) from women with or without bacterial vaginosis (BV), we identified microbial metabolism of PrEP drugs in BV samples through LC-MS/MS analysis of soluble drug levels and metabolite formation in dual T-cell cultures. CVL samples were assessed for microbiome analysis using sequencing of bacterial 16S rRNA genes. We also observed non-Lactobacillus bacteria that are associated with BV may potentially impact PrEP efficacy through increased HIV infection rates in co-cultures containing Lactobacillus or BV bacteria, PrEP drugs, CEM-GFP cells, and HIV-1LAI virus. Finally, we used these data to develop a novel predictive mathematical simulation modeling system to predict these drug interactions for future trials. These studies demonstrate how dysbiotic vaginal microbiota may impact PrEP drugs and provides evidence linking vaginal bacteria to PrEP efficacy in women.

Longitudinal CSF Iron Pathway Proteins in Posthemorrhagic Hydrocephalus: Associations with Ventricle Size and Neurodevelopmental Outcomes.

OBJECTIVE: Iron has been implicated in the pathogenesis of brain injury and hydrocephalus after preterm germinal matrix hemorrhage-intraventricular hemorrhage, however, it is unknown how external or endogenous intraventricular clearance of iron pathway proteins affect the outcome in this group. METHODS: This prospective multicenter cohort included patients with posthemorrhagic hydrocephalus (PHH) who underwent (1) temporary and permanent cerebrospinal fluid (CSF) diversion and (2) Bayley Scales of Infant Development-III testing around 2 years of age. CSF proteins in the iron handling pathway were analyzed longitudinally and compared to ventricle size and neurodevelopmental outcomes. RESULTS: Thirty-seven patients met inclusion criteria with a median estimated gestational age at birth of 25 weeks; 65% were boys. Ventricular CSF levels of hemoglobin, iron, total bilirubin, and ferritin decreased between temporary and permanent CSF diversion with no change in CSF levels of ceruloplasmin, transferrin, haptoglobin, and hepcidin. There was an increase in CSF hemopexin during this interval. Larger ventricle size at permanent CSF diversion was associated with elevated CSF ferritin (p = 0.015) and decreased CSF hemopexin (p = 0.007). CSF levels of proteins at temporary CSF diversion were not associated with outcome, however, higher CSF transferrin at permanent CSF diversion was associated with improved cognitive outcome (p = 0.015). Importantly, longitudinal change in CSF iron pathway proteins, ferritin (decrease), and transferrin (increase) were associated with improved cognitive (p = 0.04) and motor (p = 0.03) scores and improved cognitive (p = 0.04), language (p = 0.035), and motor (p = 0.008) scores, respectively. INTERPRETATION: Longitudinal changes in CSF transferrin (increase) and ferritin (decrease) are associated with improved neurodevelopmental outcomes in neonatal PHH, with implications for understanding the pathogenesis of poor outcomes in PHH. ANN NEUROL 2021;90:217-226.

Plant-based Diets in Kidney Disease: Nephrology Professionals' Perspective.

OBJECTIVE: Plant-based diets can delay the progression of chronic kidney disease (CKD) and help manage complications and co-morbid conditions such as hypertension, acidosis, diabetes, and cardiovascular disease. However, it is unclear how often plant-based diets are recommended to patients with kidney disease. The objective of this study was to understand nephrology professionals' familiarity, perception, and recommendation of plant-based diets to people with kidney disease. DESIGN AND METHODS: A survey to understand perception of recommendation of plant-based diets for patients with CKD was developed. Nephrology professionals from the National Kidney Foundation's member directory were e-mailed a link to complete the survey online. This directory includes professionals who work in a variety of nephrology settings, including both CKD and end-stage renal disease care. Survey items were evaluated with descriptive statistics. Differences across items were determined using chi-square tests and t-tests. RESULTS: A total of 3,901 professionals were sent the survey, and 644 completed the survey. A majority were dietitians (58%) and worked in dialysis clinics (54%). Most (88%) had heard of using plant-based diets for kidney disease treatment, and a majority (88%) believed it could improve CKD management, cardiovascular disease (90%), hypertension (90%), diabetes (84%), high cholesterol (90%), and obesity (84%). Dietitians were more likely to report plant-based diets as beneficial for each health condition (P < .05). Professionals were most confident that a plant-based diet could help control hypertension (3.75 ± 0.99 on a scale of 1-5), compared with delaying progression of CKD (3.68 ± 1.15) or treating acidosis (3.68 ± 1.13). Dietitians felt more confident in their ability to plan a balanced plant-based diet compared with other specialties (3.49 vs. 2.74, P < .001). CONCLUSION: Nephrology professionals who work in nondialysis-dependent CKD settings, and those who work with patients on dialysis, are aware of the benefits of plant-based diets in kidney disease. However, plant-based diets are not routinely being offered as a treatment option. Nephrology practices should work to increase dietitian referrals to offer patients support in transitioning to a plant-based diet.

Using the Biopsychosocial Approach to Identify Factors Associated with Major Depressive Disorder for Individuals with Hypothyroidism.

Previous research has found that major depressive disorder (MDD) commonly occurs in hypothyroid populations. The purpose of this study was to use the biopsychosocial model to investigate factors associated with MDD and hypothyroidism by comparing hypothyroid patients with MDD and without MDD. A sample of 386 participants with hypothyroidism completed both cognitive and psychosocial self-reported assessments along with a questionnaire rating the severity of common hypothyroid symptoms. Participants were divided into two groups (MDD and no MDD) using the diagnostic criteria of the Patient Health Questionnaire. Univariate comparisons were used to assess differences in the severity of physical, psychological, and social correlates in participants with and without MDD. Participants with MDD reported significantly worse symptom severity, increased stress, and disruptions of cognitive functioning. Compared to individuals without MDD, they also indicated poorer quality of life, doctor-patient relationships, and treatment adherence. Individuals with comorbid depression and hypothyroidism reported worse outcomes across physical symptoms, social factors, and psychological and cognitive states than individuals without MDD. Integrating depression screeners and independent treatment for MDD, in addition to the patient's hypothyroid treatment plan, may result in hypothyroid symptom relief and greater quality of life.

Predictors and Outcomes for COVID-19 Re-Admissions in the Anticipate Cohort.

Aims To describe readmissions of hospitalised patients with COVID-19, define predictors of readmission and explore the long term outcomes using the SF-12 score compared to patients who were not readmitted and those not hospitalised. Methods A single centre retrospective in North Inner-City Dublin. Recruitment was done through a COVID follow up clinic. Predictors of readmission and SF-12 scores at two timepoints post follow up at median 3 months and 12 months. Results Seventy (45%) participants were admitted, with a median age of 49.5 years (IQR 41.3-56.9), 36(51%) of whom were female. Unscheduled readmissions at ≤30 days in COVID-19 patients were 9(12.9%) and length of stay was four days (IQR 2-5). Readmissions were due to ongoing symptoms(n=9(64.3%)) or new complications(n=5(35.7%)). Mechanical ventilation and having symptoms of nausea and vomiting on index admission were predictive of readmission. (p=0.002). SF-12 scores at one year of readmitted patients were not different to patients who were never admitted at median one year follow up, p=.089. Conclusions Most readmissions were of short duration. Early follow up of patients post MV or who had nausea and vomiting on index admission should be prioritised. Wellbeing of readmitted patients was not different to those never hospitalised, at one year.