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Objective: To define the biochemical and molecular characteristics and diagnostic outcomes of a large US cohort of VLCAD deficiency positive cases as detected by newborn screening (NBS) with MS:MS. This relatively common disorder of fatty acid oxidation is screened for in every state in America and often results in extensive testing of multiple samples to arrive at a diagnostic conclusion., Materials and Methods: We compared NBS dried blood spot (DBS) acylcarnitine profile (ACP) C14, C14:1, C14:2, C14:1/C12:1 ratio and plasma C14, C14:1, C14:2, C14:1/C12:1, C14:1/C16 and C14:1/C2 ratios among true positive and false positive cases. Results of VLCAD enzyme analysis, molecular testing and fibroblast fatty acid oxidation probe assay were analyzed., Results: The presence of compound heterozygous or homozygous pathogenic variants, along with elevations of C14, C14:1 and C14:1/C12:1 ratio, identified 19 VLCAD deficiency cases. All were asymptomatic at most recent follow-up visits. The C14:1/C12:1 ratio in NBS-DBS ACP and plasma acylcarnitine profiles at follow-up (follow-up plasma ACP), is the most useful marker to differentiate between true and false positive cases. Among all cases with molecular analysis data available, approximately 56.7% had a single pathogenic mutation. Lymphocyte enzyme analysis ( n  = 61) was uninformative in 23% of cases studied., Conclusion: VLCAD deficiency NBS by MS:MS is highly effective at identifying asymptomatic affected infants. Our cohort showed that elevation of C14:1/C12:1, in both NBS DBS and plasma ACP, was informative in discriminating affected from unaffected individuals and contributes to improve the accuracy of confirmatory testing of infants with presumptive positive for VLCAD deficiency., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Background: Recovery from shoulder arthroscopy may vary between professional pitchers and position players in Major League Baseball (MLB). The time that it takes to return to play (RTP) and the level of skills to be regained after surgery are important factors for an athlete to consider when making career decisions., Purpose: To identify MLB players who had arthroscopic shoulder surgery and observe their rates of RTP to MLB and the minor league, as well as to compare pre- and postinjury performance statistics and career metrics., Study Design: Descriptive epidemiology study., Methods: Public records (press releases, http://www.prosportstransactions.com, http://www.baseball-reference.com) were searched and analyzed to determine the number of days from shoulder arthroscopy to RTP and pre- and postinjury statistics for pitchers and position players in the MLB and minor league from 1998 to 2018. To meet inclusion criteria, a player must have undergone shoulder arthroscopy after having played at least 1 game in the MLB and had no identifiable concomitant injuries., Results: Of 134 players, 89 (66.4%) returned to MLB. Fifty-four of 89 pitchers (60.7%) and 35 of 45 position players (77.8%) returned to MLB ( P = .048). Forty-nine of 54 pitchers (90.7%) and 23 of 35 position players (65.7%) who returned to MLB returned to the minor league first. The mean time to RTP was 469.6 days (range, 100-1079 days) for pitchers and 301.6 days (range, 94-1488) for position players ( P = .002). The WAR statistic (wins above replacement) for the pitchers decreased significantly ( P = .004) after shoulder arthroscopy., Conclusion: MLB position players returned to play at higher rates and more quickly than did pitchers. The WAR statistic declined in pitchers during the first season of RTP. Players undergoing arthroscopic shoulder surgery should be aware of these possible outcomes in time to RTP and postoperative performance., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.K.M. has received education payments from Alon Medical Technology, Arthrex, and Quest Medical and nonconsulting fees from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Study Objective: Non-Hispanic Black (NHB) adults have high hypertension (HTN) and cardiovascular disease (CVD) burden. Medication nonadherence limits control and self-measured blood pressure (SMBP) improves diagnosis and adherence. This predominantly NHB cohort pilot, via community-clinical linkages, with uncontrolled HTN and low adherence, utilized bidirectional electronic messaging (BEM) with team-care, to assess medication adherence, quality of life, and BP., Setting: Academic clinic and community sources., Design: Recruitment included: uncontrolled HTN (BP ≥130/80 mm Hg), low adherence (Krousel-Wood Medication Adherence Scale (K-Wood-MAS-4) ≥1 score), and smartphone access., Participants and Interventions: Participants (N = 36) received validated Bluetooth-enabled BP devices, synced to smartphones, via a secured cloud-based application., Main Outcome Measures: Demographics, adherence scores, Centers for Disease Control and Prevention (CDC) health-related quality of life (HRQOL-14), BP, body mass index (BMI), 8 weeks daily BEM, SMBP and text responses were obtained., Results: Age was 58.7 ± 12.8 years; BMI 34.8 ± 7.9; 63.9 % female; 88.9 % self-identified NHB adults; 72.2 % with obesity; 74.3 % with diabetes. K-Wood-MAS-4 adherence composite score improved: 2.19 to 1.58 (median -0.5, p = 0.0001). Systolic BP decreased by 10.5 ± 20.0 mm Hg (median -11.0, p = 0.0027). QOL did not significantly change. Mean 7-day average SBP/DBP differences were -4.94 ± 16.82 (median -3.5, p = 0.0285) and -0.17 ± 7.42 (median 0, p = 0.7001), respectively. Social support with taking BP medication was: "yes" (n = 19); 143.8 mm Hg to 131.5 mm Hg (median -12.5, p = 0.0198) and "no" (n = 14); 142.32 mm Hg to 130.25 mm Hg (median -4.0, p = 0.0771)., Conclusions: Community-clinical linkages and SMBP with BEM significantly improved medication adherence and SBP without modifying pharmacotherapy., Competing Interests: Conflicts of interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Keith C. Ferdinand is a consultant for Amgen, Novartis, Pfizer, Medtronic, Boehringer-Ingelheim, Janssen and principal investigator of HHCPP. Daphne P. Ferdinand is the executive director of HHCPP.

Objectives/hypothesis: To evaluate survival for nasopharyngeal carcinoma in relation to socioeconomic status., Study Design: Retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) Census Tract-level Socioeconomic Status Database (2000-2016)., Methods: Patients with nasopharyngeal carcinoma diagnosed between 2000 and 2016 were identified. Data were stratified based on socioeconomic status, divided into three groups: group 1 being the poorest and group 3 the wealthiest. Univariate analysis as well as multivariate Cox regression analysis adjusted for individual variables was performed., Results: A total of 5,527 patients were included in the study, with 33% in group 1, 34% in group 2, and 33% in group 3. There was a significant difference between groups in regard to age at diagnosis, race, histologic subtype, overall stage, tumor stage, nodal stage, and whether or not they received radiation. Patients in group 1, the poorest socioeconomic status, were more likely to be young (P = .003), black (P < .0001), present with higher overall stage (P = .009), tumor stage (P = .01), and nodal stage (P = .02), and less likely to receive radiation (P = .005). In multivariate analysis, there was a significant difference in survival between the groups, with group 1 patients less likely to survive compared to group 3 (hazard ratio = 1.28; 95% CI 1.07-1.57)., Conclusions: Patients in the poorest socioeconomic status presented with more advanced nasopharyngeal cancer and were less likely to receive radiation when compared with individuals of higher socioeconomic status. The poorest socioeconomic status groups were less likely to survive from their disease when controlling for other variables., Level of Evidence: NA Laryngoscope, 131:2719-2723, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc..)

Background: The soluble prorenin receptor (sPRR), a member of the renin-angiotensin system (RAS), is elevated in plasma of patients with preeclampsia, hypertension, chronic kidney disease (CKD), and type 2 diabetes. Our goal was to examine the relationship between sPRR and RAS activation to define whether sexual dimorphisms in sPRR might explain sex disparities in renal outcomes in patients with type 2 diabetes., Methods: Two hundred sixty-nine participants were included in the study (mean age, 48 ± 16 years; 42% men, 58% women), including 173 controls and 96 subjects with type 2 diabetes. In plasma and urine, we measured sPRR, plasma renin activity (PRA), and prorenin. In the urine, we also measured angiotensinogen along with other biomarkers of renal dysfunction., Results: Plasma sPRR and PRA were significantly higher in women with type 2 diabetes compared to men. In these women, plasma sPRR was positively correlated with PRA, age, and body mass index (BMI). In contrast, in men the sPRR in urine but not in plasma positively correlated with eGFR in urine, but negatively correlated with urine renin activity, plasma glucose, age, and BMI., Conclusions: In patients with type 2 diabetes, sPRR contributes to RAS stimulation in a sex-dependent fashion. In diabetic women, increased plasma sPRR parallels the activation of systemic RAS; while in diabetic men, decreased sPRR in urine matches intrarenal RAS stimulation. sPRR might be a potential indicator of intrarenal RAS activation and renal dysfunction in men and women with type 2 diabetes.

Objective: Coronavirus disease 2019 (COVID-19) has disproportionately impacted the African American community. This study aims to identify the risk factors for severe COVID-19 disease in African American patients., Methods: This was a retrospective cross-sectional analysis of African American patients with COVID-19 treated between March 12 and April 9, 2020, at a single tertiary center. The primary outcome of interest was severe disease defined as those requiring intensive care unit (ICU) admission., Results: The study included 158 consecutive patients. The mean age was 57 years, and 61% were women. The mean (SD) of BMI was 33.2 (8.6) kg/m 2 . Overall, patients admitted to the ICU were older (62 vs. 55 years, P = 0.003) and had higher BMI (36.5 kg/m 2 vs. 31.9 kg/m 2 , P = 0.002). In unadjusted and adjusted analysis, the factors most associated with ICU admission in this sample were age (adjusted odds ratio [aOR]: 1.073; 95% CI: 1.033-1.114), BMI (aOR: 1.115; 95% CI: 1.052-1.182), and lung disease (aOR: 3.097; 95% CI: 1.137-8.437)., Conclusions: This study identified risk factors for severe disease in COVID-19, specifically in an African American population. Further inclusive research aimed at optimizing clinical care relevant to the African American population is critical to ensure an equitable response to COVID-19., (© 2020 The Obesity Society.)

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive decline of lung function. Here, we tested the importance of differential proportions of blood immune cells to IPF clinical outcomes. We used Cibersort to deconvolute immune cell components based on PBMCs or whole blood IPF genomics datasets. We found that a higher proportion of resting memory (RM) T cells was associated with a better survival and a higher DLco (diffusing capacity for carbon monoxide) in IPF patients. The association was also found in opposite direction for monocytes. Additionally, in IPF patients as compared to healthy controls, proportions of monocytes were observed to be higher, yet RM T cells were observed to be lower. Taken together, our result suggests a beneficial effect of RM T cells and a detrimental effect of monocytes for IPF. Future genomics studies of IPF should be more focused on these two types of cells., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: More effective treatments are needed for patients with postinfectious, diarrhoea-predominant, irritable bowel syndrome (IBS-D). Accordingly, we conducted a randomised, double-blind, placebo-controlled, 8-week-long trial to assess the efficacy and safety of oral glutamine therapy in patients who developed IBS-D with increased intestinal permeability following an enteric infection., Methods: Eligible adults were randomised to glutamine (5 g/t.i.d.) or placebo for 8 weeks. The primary end point was a reduction of ≥50 points on the Irritable Bowel Syndrome Severity Scoring System (IBS-SS). Secondary endpoints included: raw IBS-SS scores, changes in daily bowel movement frequency, stool form (Bristol Stool Scale) and intestinal permeability., Results: Fifty-four glutamine and 52 placebo subjects completed the 8-week study. The primary endpoint occurred in 43 (79.6%) in the glutamine group and 3 (5.8%) in the placebo group (a 14-fold difference). Glutamine also reduced all secondary endpoint means: IBS-SS score at 8 weeks (301 vs 181, p<0.0001), daily bowel movement frequency (5.4 vs 2.9±1.0, p<0.0001), Bristol Stool Scale (6.5 vs 3.9, p<0.0001) and intestinal permeability (0.11 vs 0.05; p<0.0001). 'Intestinal hyperpermeability' (elevated urinary lactulose/mannitol ratios) was normalised in the glutamine but not the control group. Adverse events and rates of study-drug discontinuation were low and similar in the two groups. No serious adverse events were observed., Conclusions: In patients with IBS-D with intestinal hyperpermeability following an enteric infection, oral dietary glutamine supplements dramatically and safely reduced all major IBS-related endpoints. Large randomised clinical trials (RCTs) should now be done to validate these findings, assess quality of life benefits and explore pharmacological mechanisms., Trial Registration Number: NCT01414244; Results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Bioinformatics and data science research have boundless potential across Africa due to its high levels of genetic diversity and disproportionate burden of infectious diseases, including malaria, tuberculosis, HIV and AIDS, Ebola virus disease, and Lassa fever. This work lays out an incremental approach for reaching underserved countries in bioinformatics and data science research through a progression of capacity building, training, and research efforts. Two global health informatics training programs sponsored by the Fogarty International Center (FIC) were carried out at the University of Sciences, Techniques and Technologies of Bamako, Mali (USTTB) between 1999 and 2011. Together with capacity building efforts through the West Africa International Centers of Excellence in Malaria Research (ICEMR), this progress laid the groundwork for a bioinformatics and data science training program launched at USTTB as part of the Human Heredity and Health in Africa (H3Africa) initiative. Prior to the global health informatics training, its trainees published first or second authorship and third or higher authorship manuscripts at rates of 0.40 and 0.10 per year, respectively. Following the training, these rates increased to 0.70 and 1.23 per year, respectively, which was a statistically significant increase ( p < 0.001). The bioinformatics and data science training program at USTTB commenced in 2017 focusing on student, faculty, and curriculum tiers of enhancement. The program's sustainable measures included institutional support for core elements, university tuition and fees, resource sharing and coordination with local research projects and companion training programs, increased student and faculty publication rates, and increased research proposal submissions. Challenges reliance of high-speed bandwidth availability on short-term funding, lack of a discounted software portal for basic software applications, protracted application processes for United States visas, lack of industry job positions, and low publication rates in the areas of bioinformatics and data science. Long-term, incremental processes are necessary for engaging historically underserved countries in bioinformatics and data science research. The multi-tiered enhancement approach laid out here provides a platform for generating bioinformatics and data science technicians, teachers, researchers, and program managers. Increased literature on bioinformatics and data science training approaches and progress is needed to provide a framework for establishing benchmarks on the topics.

Sleep abnormalities are common among children with neurodevelopmental disorders. The human chr16p11.2 microdeletion is associated with a range of neurological and neurobehavioral abnormalities. Previous studies of a mouse model of human chr16p11.2 microdeletion (chr16p11.2df/+) have demonstrated pathophysiological changes at the synapses in the hippocampus and striatum; however, the impact of this genetic abnormality on system level brain functions, such as sleep and neural oscillation, has not been adequately investigated. Here, we show that chr16p11.2df/+ mice have altered sleep architecture, with increased wake time and reduced time in rapid eye movement (REM) and non-REM (NREM) sleep. Importantly, several measurements of REM sleep are significantly changed in deletion mice. The REM bout number and the bout number ratio of REM to NREM are decreased in mutant mice, suggesting a deficit in REM-NREM transition. The average REM bout duration is shorter in mutant mice, indicating a defect in REM maintenance. In addition, whole-cell patch clamp recording of the ventrolateral periaqueductal gray (vlPAG)-projecting gamma-aminobutyric acid (GABA)ergic neurons in the lateral paragigantocellular nucleus of ventral medulla of mutant mice reveal that these neurons, which are important for NREM-REM transition and REM maintenance, have hyperpolarized resting membrane potential and increased membrane resistance. These changes in intrinsic membrane properties suggest that these projection-specific neurons of mutant mice are less excitable, and thereby may play a role in deficient NREM-REM transition and REM maintenance. Furthermore, mutant mice exhibit changes in neural oscillation involving multiple frequency classes in several vigilance states. The most significant alterations occur in the theta frequency during wake and REM sleep., (© Sleep Research Society 2018. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Collaborative care models incorporating pharmacists have been shown to improve quality of care for patients with hypertension and/or diabetes. Little is known about how to integrate such services outside of clinical trials. The authors implemented a 22-month observational study to evaluate pharmacy collaborative care for hypertension and diabetes in a safety net medical home that incorporated population risk stratification, clinical decision support, and medication dose adjustment protocols. Patients in the pharmacy group saw their primary care provider (PCP) more often and had higher baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) and A1c levels compared to patients who only received care from their PCPs. There were no significant differences in the proportion of patients achieving treatment goals (SBP <140, DBP <90; A1c < 8) or the magnitude of change in BP or A1c among patients who underwent collaborative care versus those who did not. Age, race, and number of PCP encounters were associated with BP and A1c trends. The median time to achieve disease control was longer in the pharmacy group. Although 70% of all patients with poorly controlled hypertension achieved treatment goals within 7 months, less than 50% of patients with poorly controlled diabetes achieved A1c < 8 within 15 months, suggesting that diabetes was harder to manage overall. Contextual factors that facilitated or hindered practice redesign included organizational culture, health information technology and related workflows, and pharmacy caseload optimization. Future studies should further examine implementation strategies that work best in specific settings to optimize the benefits of team-based care with clinical pharmacists.

Little is known about how to integrate primary care with mental/behavioral services outside of clinical trials. The authors implemented a collaborative care model (CCM) for depression in a safety net patient-centered medical home. The model focused on universal screening for symptoms, risk stratification based on symptom severity, care management for intensive follow-up, and psychiatry consultation. CCM increased rates of primary care physician encounters, timely follow-up for monitoring symptoms of depression, and documentation of treatment response. Contextual factors that facilitated or hindered practice redesign included clinic leadership, quality improvement culture, staffing, technology infrastructure, and external incentives/disincentives for organizational change.