CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

Renal AAV2-Mediated Overexpression of Long Non-Coding RNA H19 Attenuates Ischemic Acute Kidney Injury Through Sponging of microRNA-30a-5p

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Ascertainment and Prevalence of Post-Traumatic Stress Disorder (PTSD) in People with Intellectual Disabilities

ABSTRACT

Introduction: Post-traumatic stress disorder (PTSD) may be under-recognized in people with intellectual disabilities (PWID) and reviews on appropriate screening tools and prevalence are lacking. This review aims to identify PTSD screening tools for PWID and estimate the prevalence of PTSD within this population. Method: Medline, PubMed, Embase, PsycINFO, Cochrane, Global Health, and Web of Science databases were searched (inception to October 2017) to identify eligible literature. Papers were also found via manual searches of the references of eligible studies. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines, subjected to exclusion criteria and quality appraised using STROBE criteria for observational studies and an adapted form of the Newcastle-Ottawa scale for cross-sectional studies. Seven studies were identified. Meta-analysis was carried out on the prevalence studies and heterogeneity quantified using I². Results: Three tools for screening PTSD in PWID were found: two for use in adults (the Lancaster and Northgate Trauma Scale and the Impact of Event Scale – Intellectual Disabilities) and the Adapted Anxiety Disorders Interview Schedule for Children with PTSD. Five studies reported PTSD prevalence in PWID. The weighted pooled prevalence of PTSD in PWID was found to be 10%, 95% CI [0.4%, 19.5%], toward the upper limit of estimated PTSD prevalence in the general population (5–10%). Conclusion: PTSD can be diagnosed in PWID but may go unrecognized by health-care professionals. The identified tools should be further compared and assessed for acceptability and efficacy to improve the identification of PTSD in PWID.     

Grappling with complexity: Medical students’ reflective writings about challenging patient encounters as a window into professional identity formation

Aim: Clerkship-specific interactive reflective writing (IRW)-enhanced reflection may enhance professional identity formation (PIF), a fundamental goal of medical education. PIF process as revealed in students? reflective writing (RW) has been understudied.

Methods: The authors developed an IRW curriculum within a Family Medicine Clerkship (FMC) and analyzed students? reflections about challenging/difficult patient encounters using immersion-crystallization qualitative analysis.

Results: The qualitative analysis identified 26 unique emergent themes and five distinct thematic categories (1. Role of emotions, 2. Role of cognition, 3. Behaviorally responding to situational context, 4. Patient factors, and 5. External factors) as well as an emergent PIF model from a directed content analysis. The model describes students? backgrounds, emotions and previous experiences in medicine merging with external factors and processed during student?patient interactions. The RWs also revealed that processing often involves polarities (e.g. empathy/lack of empathy or encouragement/disillusionment) as well as dissonance between idealized visions and lived reality.

Conclusions: IRW facilitates and ideally supports grappling with the lived reality of medicine; uncovering a “positive hidden curriculum” within medical education. The authors propose engaging learners in guided critical reflection about complex experiences for meaning-making within a safe learning climate as a valuable way to cultivate reflective, resilient professionals with “prepared” minds and hearts for inevitable challenges of healthcare practice.