Overcoming barriers to single-cell RNA sequencing adoption in low- and middle-income countries

The advent of single-cell resolution sequencing and spatial transcriptomics has enabled the delivery of cellular and molecular atlases of tissues and organs, providing new insights into tissue health and disease. However, if the full potential of these technologies is to be equitably realised, ancestrally inclusivity is paramount. Such a goal requires greater inclusion of both researchers and donors in low- and middle-income countries (LMICs). In this perspective, we describe the current landscape of ancestral inclusivity in genomic and single-cell transcriptomic studies. We discuss the collaborative efforts needed to scale the barriers to establishing, expanding, and adopting single-cell sequencing research in LMICs and to enable globally impactful outcomes of these technologies

Is Emotion Recognition Impaired in Individuals with Autism Spectrum Disorders?

Researchers have argued that individuals with autism spectrum disorders (ASDs) use an effortful “systematizing” process to recognize emotion expressions, whereas typically developing (TD) individuals use a more holistic process. If this is the case, individuals with ASDs should show slower and less efficient emotion recognition, particularly for socially complex emotions. We tested this account by assessing the speed and accuracy of emotion recognition while limiting exposure time and response window. Children and adolescents with ASDs showed quick and accurate recognition for most emotions, including pride, a socially complex emotion, and no differences emerged between ASD and TD groups. Furthermore, both groups trended toward higher accuracy when responding quickly, even though systematizing should promote a speed-accuracy trade-off for individuals with ASDs

The stroke oxygen pilot study: a randomized control trial of the effects of routine oxygen supplementation early after acute stroke--effect on key outcomes at six months

Introduction: Post-stroke hypoxia is common, and may adversely affect outcome. We have recently shown that oxygen supplementation may improve early neurological recovery. Here, we report the six-month outcomes of this pilot study. Methods: Patients with a clinical diagnosis of acute stroke were randomized within 24 h of admission to oxygen supplementation at 2 or 3 L/min for 72 h or to control treatment (room air). Outcomes (see below) were assessed by postal questionnaire at 6 months. Analysis was by intention-to-treat, and statistical significance was set at p#0.05. Results: Out of 301 patients randomized two refused/withdrew consent and 289 (148 in the oxygen and 141 in the control group) were included in the analysis: males 44%, 51%; mean (SD) age 73 (12), 71 (12); median (IQR) National Institutes of Health Stroke Scale score 6 (3, 10), 5 (3, 10) for the two groups respectively. At six months 22 (15%) patients in the oxygen group and 20 (14%) in the control group had died; mean survival in both groups was 162 days (p= 0.99). Median (IQR) scores for the primary outcome, the modified Rankin Scale, were 3 (1, 5) and 3 (1, 4) for the oxygen and control groups respectively. The covariate-adjusted odds ratio was 1.04 (95% CI 0.67, 1.60), indicating that the odds of a lower (i.e. better) score were non-significantly higher in the oxygen group (p= 0.86). The mean differences in the ability to perform basic (Barthel Index) and extended activities of daily living (NEADL), and quality of life (EuroQol) were also non-significant. Conclusions: None of the key outcomes differed at 6 months between the groups. Although not statistically significant and generally of small magnitude, the effects were predominantly in favour of the oxygen group; a larger trial, powered to show differences in longer-term functional outcomes, is now on-going. Trial Registration: Controlled-Trials.com ISRCTN12362720; Eudract.ema.europa.eu 2004-001866-4

Evaluation of Xpert® MTB/RIF and ustar easyNAT™ TB IAD for diagnosis of tuberculous lymphadenitis of children in Tanzania : a prospective descriptive study

Fine needle aspiration biopsy has become a standard approach for diagnosis of peripheral tuberculous lymphadenitis. The aim of this study was to compare the performance of Xpert MTB/RIF and Ustar EasyNAT TB IAD nucleic acid amplification assays, against acid-fast bacilli microscopy, cytology and mycobacterial culture for the diagnosis of TB lymphadenitis in children from a TB-endemic setting in Tanzania.; Children of 8 weeks to 16 years of age, suspected of having TB lymphadenitis, were recruited at a district hospital in Tanzania. Fine needle aspirates of lymph nodes were analysed using acid-fast bacilli microscopy, liquid TB culture, cytology, Xpert MTB/RIF and EasyNAT. Latent class analysis and comparison against a composite reference standard comprising "culture and/or cytology" was done, to assess the performance of Xpert MTB/RIF and EasyNAT for the diagnosis of TB lymphadenitis.; Seventy-nine children were recruited; 4 were excluded from analysis. Against a composite reference standard of culture and/or cytology, Xpert MTB/RIF and EasyNAT had a sensitivity and specificity of 58 % and 93 %; and 19 % and 100 % respectively. Relative to latent class definitions, cytology had a sensitivity of 100 % and specificity of 94.7 %.; Combining clinical assessment, cytology and Xpert MTB/RIF may allow for a rapid and accurate diagnosis of childhood TB lymphadenitis. Larger diagnostic evaluation studies are recommended to validate these findings and on Xpert MTB/RIF to assess its use as a solitary initial test for TB lymphadenitis in children

Integrated care in mental health: next steps after the NHS Long Term Plan.

Health and social care face growing and conflicting pressures: mounting complex needs of an ageing population, restricted funding and a workforce recruitment and retention crisis. In response, in the UK the NHS Long Term Plan promises increased investment and an emphasis on better 'integrated' care. We describe key aspects of integration that need addressing.Declaration of interestD.K.T. and S.S.S. are on the editorial board of the British Journal of Psychiatry and executives of the Academic Faculty at the Royal College of Psychiatrists. A.J.B.J., H.P. and Z.M. have roles at the Royal College of Psychiatrists that include evaluation of integrated care systems. A.J.B.J. is married to Dr Sarah Wollaston, Member of Parliament for Totnes and Chair of the Health Select Committee

Exenatide once weekly treatment maintained improvements in glycemic control and weight loss over 2 years

<p>Abstract</p> <p>Background</p> <p>The once-weekly (QW) formulation of the glucagon-like peptide-1 receptor agonist exenatide has been demonstrated to improve A1C, fasting plasma glucose (FPG), body weight, serum lipid profiles, and blood pressure in patients with type 2 diabetes through 52 weeks of treatment. In this report, we describe the 2-year results of the open-label, open-ended extension to the DURATION-1 trial of exenatide QW for type 2 diabetes.</p> <p>Methods</p> <p>A 2-stage protocol was used: patients received either exenatide QW (2 mg) or exenatide twice daily for 30 weeks (5 μg for the first 4 weeks and 10 μg thereafter), followed by 1.5 years of treatment with exenatide QW (2 mg), for a total of 2 years (104 weeks) of exenatide treatment. Of the 295 (intent-to-treat [ITT]) patients who entered the trial, 73% (n = 216) completed 2 years of treatment (completer population). Baseline characteristics (mean ± SE) for these patients were: A1C, 8.2 ± 0.1%; FPG, 168.4 ± 43.0 mg/dL; body weight, 101.1 ± 18.7 kg; and diabetes duration, 7 ± 5 years.</p> <p>Results</p> <p>In the completer population, significant improvements (LS mean ± SE [95% CI]) were maintained after 2 years of treatment in A1C (-1.71 ± 0.08% [-1.86 to -1.55%]), FPG (-40.1 ± 2.9 mg/dL [-45.7 to -34.5 mg/dL]), and body weight (-2.61 ± 0.52 kg [-3.64 to -1.58 kg]) compared with baseline. The percentages of patients who achieved an A1C of <7.0% and ≤6.5% at 2 years were 60% and 39%, respectively. A significant reduction in systolic blood pressure (SBP; -3.0 ± 1.0 mmHg [-4.9 to -1.1 mmHg]) was maintained through 2 years of treatment. Serum lipid profiles were also significantly improved, including triglycerides (geometric LS mean change from baseline, -15 ± 2.7% [-21% to -10%]), total cholesterol (-8.6 ± 2.8 mg/dL [-14.0 to -3.1 mg/dL]), and low-density lipoproteins (-4.5 ± 2.2 mg/dL [-8.9 to -0.01 mg/dL]). Changes in A1C, body weight, FPG, SBP, and lipids in the ITT population were similar to those seen in the completer population. Nausea (predominantly mild in intensity) was the most common adverse event, although the frequency and intensity of nausea decreased over time. No severe hypoglycemia was observed.</p> <p>Conclusions</p> <p>Exenatide QW was well tolerated during the 2-year treatment period. This study demonstrated sustained glucose control and weight loss throughout 2 years of treatment with exenatide QW.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00308139">NCT00308139</a></p

A Cross-Sectional Characterization of Insulin Resistance by Phenotype and Insulin Clamp in East Asian Americans with Type 1 and Type 2 Diabetes

Classic features of type 1 and type 2 diabetes may not apply in Asian Americans, due to shared absence of common HLA DR-DQ genotype, low prevalence of positive anti-islet antibodies and low BMI in both types of diabetes. Our objective was to characterize diabetic phenotypes in Asian Americans by clamp and clinical features.This was a cross-sectional study conducted in a referral center. Thirty East young Asian American adult volunteers (27.6±5.5 years) with type 1, type 2 diabetes or controls underwent hyperinsulinemic euglycemic clamp to assess insulin resistance and DEXA to assess adiposity.Gender, BMI, waist/hip ratio, leptin, LDL, anti-GAD, anti-IA2 antibodies and C-reactive protein were similar among three groups. Serum C-peptide, adiponectin, free fatty acid, HDL concentrations and truncal fat by DEXA, were different between diabetic groups. Glucose disposal rate by clamp was lowest in type 2 diabetes, followed by type 1 diabetes and controls (5.43±2.70, 7.62±2.59, 8.61±2.37 mg/min/kg, respectively, p = 0.001). Free fatty acid concentration universally plummeted during steady state of the clamp procedure regardless of diabetes types in all three groups. Adipocyte fatty acid binding protein in the entire cohort (r = -0.625, p = 0.04) and controls (r = -0.869, p = 0.046) correlated best with insulin resistance, independent of BMI.Type 2 diabetes in Asian Americans was associated with insulin resistance despite having low BMI as type 1 diabetes, suggesting a potential role for targeting insulin resistance apart from weight loss. Adipocyte fatty acid binding protein, strongly associated with insulin resistance, independent of adiposity in the young Asian American population, may potentially serve as a biomarker to identify at-risk individuals. Larger studies are needed to confirm this finding