"Meet people where they are": a qualitative study of community barriers and facilitators to HIV testing and HIV self-testing among African Americans in urban and rural areas in North Carolina.

BACKGROUND: HIV testing programs in the United States aim to reach ethnic minority populations who experience high incidence of HIV, yet 40% of African Americans have never been tested for HIV. The objective of this study is to identify community-based strategies to increase testing among African Americans in both urban and rural areas. METHODS: This study conducted focus group discussions (FGDs) informed by community-based participatory research principles to examine African American's concerns and ideas around HIV testing and HIV self-testing. Participants included highly affected (i.e., PLWH, MSM, PWID, low-income, teens and young adults) populations from African American communities in North Carolina, aged 15 years and older. We digitally transcribed and analyzed qualitative data using MAXQDA and axial coding to identify emergent themes. RESULTS: Fifty-two men and women between 15 to 60 years old living in urban (n=41) and rural (n=11) areas of North Carolina participated in focus group discussions. HIV testing barriers differed by HIV testing setting: facility-based, community-based, and HIV self-testing. In community-based settings, barriers included confidentiality concerns. In facility-based settings (e.g., clinics), barriers included negative treatment by healthcare workers. With HIV self-testing, barriers included improper use of self-testing kits and lack of post-test support. HIV testing facilitators included partnering with community leaders, decentralizing testing beyond facility-based sites, and protecting confidentiality. CONCLUSIONS: Findings suggest that HIV testing concerns among African Americans vary by HIV testing setting. African Americans may be willing to test for HIV at community events in public locations if client confidentiality is preserved and use HIV self-testing kits in private if post-test social support and services are provided. These community-identified facilitators may improve African American testing rates and uptake of HIV self-testing kits

Isolated IgG2 deficiency is an independent risk factor for exacerbations in bronchiectasis

BACKGROUND: Immunoglobulin G (IgG) subclass 2 deficiency is the most frequent IgG subclass deficiency identified in patients with bronchiectasis, but its clinical significance is not known. AIM: To analyse if bronchiectasis patients with isolated IgG2 deficiency at risk of recurrent exacerbations and/or hospitalization? Do patients with IgG2 deficiency have worse disease progression? DESIGN AND METHODS: This is a retrospective study (2015–20) exploring independent risk factors for recurrent exacerbations (3 or more per year) and/or hospitalization with bronchiectasis exacerbations using multivariable models using binary logistic regression. There was no patient with IgG deficiency, IgG 1, 3 or 4 deficiency, or IgA or IgM deficiency included. In this model, the authors included: serum IgG2 level; lung function; body mass index; MRC breathlessness scale; age; sex; number of bronchiectatic lobes; bacterial colonization; comorbidities; and the use of long-term immunosuppressant drugs or antibiotics for more than 28 days. Analysing 2-year longitudinal data, one-way ANOVA and Mann–Whitney U-test were used to compare bronchiectasis severity between patients with different IgG2 levels. RESULTS: Serum IgG2 levels (4.45 g/l) (P = 0.003, 0.013). CONCLUSION: Reduced IgG2 levels were an independent predictor for bronchiectasis exacerbations and have increased disease progression

2D-infrared spectroscopy of proteins in water : using the solvent thermal response as an internal standard

Ultrafast two-dimensional infrared (2D-IR) spectra can now be obtained in a matter of seconds, opening up the possibility of high-throughput screening applications of relevance to the biomedical and pharmaceutical sectors. Determining quantitative information from 2D-IR spectra recorded on different samples and different instruments is however made difficult by variations in beam alignment, laser intensity, and sample conditions. Recently, we demonstrated that 2D-IR spectroscopy of the protein amide I band can be performed in aqueous (H2O) rather than deuterated (D2O) solvents, and we now report a method that uses the magnitude of the associated thermal response of H2O as an internal normalization standard for 2D-IR spectra. Using the water response, which is temporally separated from the protein signal, to normalize the spectra allows significant reduction of the impact of measurement-to-measurement fluctuations on the data. We demonstrate that this normalization method enables creation of calibration curves for measurement of absolute protein concentrations and facilitates reproducible difference spectroscopy methodologies. These advances make significant progress toward the robust data handling strategies that will be essential for the realization of automated spectral analysis tools for large scale 2D-IR screening studies of protein-containing solutions and biofluids

Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the licenseRATIONALE: Muscle atrophy confers a poor prognosis in patients with chronic obstructive pulmonary disease (COPD), yet the molecular pathways responsible are poorly characterised. Muscle-specific microRNAs and serum response factor (SRF) are important regulators of muscle phenotype that contribute to a feedback system to regulate muscle gene expression. The role of these factors in the skeletal muscle dysfunction that accompanies COPD is unknown. METHODS: 31 patients with COPD and 14 healthy age-matched controls underwent lung and quadriceps function assessments, measurement of daily activity and a percutaneous quadriceps muscle biopsy. The expression of muscle-specific microRNAs, myosin heavy chains and components of the serum response factor signalling pathway were determined by qPCR. RESULTS: A reduction in expression of miR-1 (2.5-fold, p=0.01) and the myocardin-related transcription factors (MRTFs) A and B was observed in patients compared with controls (MRTF-A mRNA: twofold, p=0.028; MRTF-B mRNA: fourfold, p=0.011). miR-1 expression was associated with smoking history, lung function, fat-free mass index, 6 min walk distance and percentage of type 1 fibres. miR-133 and miR-206 were negatively correlated with daily physical activity. Insulin-like growth factor 1 mRNA was increased in the patients and miR-1 was negatively correlated with phosphorylation of the kinase Akt. Furthermore, the protein levels of histone deacetylase 4, another miR-1 target, were increased in the patients. CONCLUSIONS: Downregulation of the activity of the MRTF-SRF axis and the expression of muscle-specific microRNAs, particularly miR-1, may contribute to COPD-associated skeletal muscle dysfunction.BBSRC, Wellcome Trust and the National Institute for Health Research (NIHR) Respiratory Biomedical Unit at the Royal Brompton Hospital and Imperial College. AL is a BBSRC PhD student, SAN received a Wellcome Trust Fellowship, AD received a NIHR Respiratory Biomedical Unit fellowship and WM is a NIHR Clinician Scientist. NSH is a HEFCE Clinical Senior Lecturer. MIP's salary is part funded by the NIHR Respiratory Biomedical Unit at the Royal Brompton Hospital and National Heart & Lung Institute

A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity

High-grade serous ovarian carcinoma is characterised by TP53 mutation and extensive chromosome instability (CIN). Because our understanding of CIN mechanisms is based largely on analysing established cell lines, we developed a workflow for generating ex vivo cultures from patient biopsies to provide models that support interrogation of CIN mechanisms in cells not extensively cultured in vitro. Here, we describe a “living biobank” of ovarian cancer models with extensive replicative capacity, derived from both ascites and solid biopsies. Fifteen models are characterised by p53 profiling, exome sequencing and transcriptomics, and karyotyped using single-cell whole-genome sequencing. Time-lapse microscopy reveals catastrophic and highly heterogeneous mitoses, suggesting that analysis of established cell lines probably underestimates mitotic dysfunction in advanced human cancers. Drug profiling reveals cisplatin sensitivities consistent with patient responses, demonstrating that this workflow has potential to generate personalized avatars with advantages over current pre-clinical models and the potential to guide clinical decision making