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.

     

Body mass index is a predictor of discharge to a postacute care facility following total shoulder arthroplasty

BackgroundThe purpose of this study is to evaluate the effect of body mass index (BMI) on discharge to a postacute care (PAC) facility following elective total shoulder arthroplasty (TSA).MethodsThe National Surgical Quality Improvement Program database was queried to identify adult patients (>18 years old) who underwent inpatient TSA for primary osteoarthritis between 2005 and 2018. Hemiarthroplasty, revision TSA, trauma indications, and outpatient procedures were excluded. Patient and perioperative data were identified. Univariate analysis and multivariate logistic regression were used to assess the relationship between BMI and discharge to PAC facilities.ResultsA total of 10,198 patients with a primary TSA were identified. The majority (93%) of patients were discharged home vs. 7% to PAC facilities. Patients discharged to PAC had significantly higher mean BMI (P = .006). After controlling for demographic and comorbid factors, BMI was the only modifiable risk factor that was independently associated with an increased risk of discharge to a PAC. For every increase in BMI point, there was an increased risk of discharge to a PAC by 2.9% (odds ratio [OR] 1.029, confidence interval [CI] 1.016-1.041, P < .001). Additional covariates associated with PAC discharge were older age (OR 1.113, CI 1.099-1.127, P < .001), female gender (OR 3.037, CI 2.489-3.705, P < .001), and dependent functional status (OR 8.322, CI 5.544-12.492, P < .001).ConclusionMost patients undergoing TSA were discharged home following surgery. While age, sex, and functional status also affect disposition, elevated BMI is the only modifiable risk factor that independently predicts PAC discharge. Consideration of patient BMI prior to elective TSA may greatly improve discharge planning and management of patient expectations.     

Patterns of relapse after successful completion of initial therapy in primary central nervous system lymphoma: a case series

Journal of Neuro-Oncology - Primary central nervous system lymphoma (PCNSL) is a subtype of non-Hodgkin’s lymphoma that involves the brain, spinal cord, or leptomeninges, without evidence of...     

Gender equity: how do the forensic sciences fare?

ABSTRACT

Females are underrepresented in science, technology, engineering and mathematics (STEM) at all levels of society. Fewer females are completing STEM school subjects, graduating with STEM degrees, being employed as STEM professionals, and holding senior leadership and academic positions in STEM. However, unlike almost every other STEM discipline, the overall ratio of females is higher in many forensic science disciplines. For our sector, rather than having difficulty in attracting females, the bigger issue is how we retain and promote female talent. This complex issue is exacerbated by: gender pay gaps; family role expectations; lack of visible role models or mentors; discrimination and harassment; and bias during recruitment and promotion practices. We discuss barriers relevant for women in the forensic industry and offer potential solutions. These include flexible work arrangements, sponsorship programmes, and fostering and practising an inclusive workplace culture. Gender equity programmes and exemplar STEM organizations focused on a commitment to gender parity will be explored. Harnessing untapped female talent is as much a social justice issue as employing best practices for improving the quality, diversity and output of our forensic science workforce, and research and innovation strategies.     

Predictions of genotoxic potential,mode of action,molecular targets,and potency via a tiered multiflow® assay data analysis strategy

The in vitro MultiFlow® DNA Damage Assay multiplexes γH2AX, p53, phospho-histone H3, and polyploidization biomarkers into a single flow cytometric analysis. The current report describes a tiered sequential data analysis strategy based on data generated from exposure of human TK6 cells to a previously described 85 chemical training set and a new pharmaceutical-centric test set (n = 40). In each case, exposure was continuous over a range of closely spaced concentrations, and cell aliquots were removed for analysis following 4 and 24 hr of treatment. The first data analysis step focused on chemicals' genotoxic potential, and for this purpose, we evaluated the performance of a machine learning (ML) ensemble, a rubric that considered fold increases in biomarkers against global evaluation factors (GEFs), and a hybrid strategy that considered ML and GEFs. This first tier further used ML output and/or GEFs to classify genotoxic activity as clastogenic and/or aneugenic. Test set results demonstrated the generalizability of the first tier, with particularly good performance from the ML ensemble: 35/40 (88%) concordance with a priori genotoxicity expectations and 21/24 (88%) agreement with expected mode of action (MoA). A second tier applied unsupervised hierarchical clustering to the biomarker response data, and these analyses were found to group certain chemicals, especially aneugens, according to their molecular targets. Finally, a third tier utilized benchmark dose analyses and MultiFlow biomarker responses to rank genotoxic potency. The relevance of these rankings is supported by the strong agreement found between benchmark dose values derived from MultiFlow biomarkers compared to those generated from parallel in vitro micronucleus analyses. Collectively, the results suggest that a tiered MultiFlow data analysis pipeline is capable of rapidly and effectively identifying genotoxic hazards while providing additional information that is useful for modern risk assessments—MoA, molecular targets, and potency. Environ. Mol. Mutagen. 60:513–533, 2019. © 2019 Wiley Periodicals, Inc.     

The effects of locomotor training in children with spinal cord injury: a systematic review

Purpose: Discuss the effectiveness of locomotor training (LT) in children following spinal cord injury (SCI). This intervention was assessed following an exhaustive search of the literature using the Preferred Reporting Items for Systematic Reviews and Meta- Analyses: The PRISMA Statement as a guideline.

Method: Six databases were searched including PubMed, PEDro, CINAHL, Cochrane, PsycINFO, and Web of Knowledge in January 2016 and November 2016, without date restrictions. Inclusion criteria were: studies in English and peer-reviewed and journal articles with a primary intervention of LT in children following SCI.

Results: Twelve articles, reporting eleven studies, were included. A systematic review assessing locomotor training in children with SCI published in April 2016 was also included. Participants were ages 15 months to 18 years old. Forms of LT included body-weight supported treadmill or over ground training, functional electrical stimulation, robotics, and virtual reality. Protocols differed in set-up and delivery mode, with improvements seen in ambulation for all 41 participants following LT.

Conclusion: Children might benefit from LT to develop or restore ambulation following SCI. Age, completeness, and level of injury remain the most important prognostic factors to consider with this intervention. Additional benefits include improved bowel/ bladder management and control, bone density, cardiovascular endurance, and overall quality of life. Looking beyond the effects LT has just on ambulation is crucial because it can offer benefits to all children sustaining a SCI, even if restoration or development of walking is not the primary goal. Further rigorous research is required to determine the overall effectiveness of LT.