A combined microfinance and training intervention can reduce HIV risk behaviour in young female participants.

OBJECTIVE: To assess effects of a combined microfinance and training intervention on HIV risk behavior among young female participants in rural South Africa. DESIGN: : Secondary analysis of quantitative and qualitative data from a cluster randomized trial, the Intervention with Microfinance for AIDS and Gender Equity study. METHODS: Eight villages were pair-matched and randomly allocated to receive the intervention. At baseline and after 2 years, HIV risk behavior was assessed among female participants aged 14-35 years. Their responses were compared with women of the same age and poverty group from control villages. Intervention effects were calculated using adjusted risk ratios employing village level summaries. Qualitative data collected during the study explored participants' responses to the intervention including HIV risk behavior. RESULTS: After 2 years of follow-up, when compared with controls, young participants had higher levels of HIV-related communication (adjusted risk ratio 1.46, 95% confidence interval 1.01-2.12), were more likely to have accessed voluntary counseling and testing (adjusted risk ratio 1.64, 95% confidence interval 1.06-2.56), and less likely to have had unprotected sex at last intercourse with a nonspousal partner (adjusted risk ratio 0.76, 95% confidence interval 0.60-0.96). Qualitative data suggest a greater acceptance of intrahousehold communication about HIV and sexuality. Although women noted challenges associated with acceptance of condoms by men, increased confidence and skills associated with participation in the intervention supported their introduction in sexual relationships. CONCLUSIONS: In addition to impacts on economic well being, women's empowerment and intimate partner violence, interventions addressing the economic and social vulnerability of women may contribute to reductions in HIV risk behavior

Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis.

Pulmonary tuberculosis (TB) is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular matrix (ECM) modulates M. tuberculosis-driven matrix metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair. Medium from monocytes stimulated with M. tuberculosis induced collagenase activity in bronchial epithelial cells, which was reduced by ~87% when cells were cultured on a type I collagen matrix. Matrix metalloproteinase-1 had a focal localization, which is consistent with cell migration, and overall secretion decreased by 32% on type I collagen. There were no associated changes in the specific tissue inhibitors of metalloproteinases. Decreased matrix metalloproteinase-1 secretion was due to ligand-binding to the α2β1 integrin and was dependent on the actin cytoskeleton. In lung biopsies, samples from patients with pulmonary TB, integrin α2β1 is highly expressed on the bronchial epithelium. Areas of lung with disrupted collagen matrix showed an increase in matrix metalloproteinases-1 expression compared with areas where collagen was comparable to control lung. Type I collagen matrix increased respiratory epithelial cell migration in a wound-healing assay, and this too was matrix metalloproteinase-dependent, since it was blocked by the matrix metalloproteinase inhibitor GM6001. In summary, we report a novel mechanism by which α2β1-mediated signals from the ECM modulate matrix metalloproteinase-1 secretion by HBECs, regulating their migration and epithelial repair in TB

Interstitial lung disease:A review of classification, aetiology, epidemiology, clinical diagnosis, pharmacological and non-pharmacological treatment

IInterstitial lung diseases (ILDs) refer to a heterogeneous and complex group of conditions characterized by inflammation, fibrosis, or both, in the interstitium of the lungs. This results in impaired gas exchange, leading to a worsening of respiratory symptoms and a decline in lung function. While the etiology of some ILDs is unclear, most cases can be traced back to factors such as genetic predispositions, environmental exposures (including allergens, toxins, and air pollution), underlying autoimmune diseases, or the use of certain medications. There has been an increase in research and evidence aimed at identifying etiology, understanding epidemiology, improving clinical diagnosis, and developing both pharmacological and non-pharmacological treatments. This review provides a comprehensive overview of the current state of knowledge in the field of interstitial lung diseases

Home monitoring of physiology and symptoms to detect interstitial lung disease exacerbations and progression:a systematic review

Background: Acute exacerbations (AEs) and disease progression in interstitial lung disease (ILD) pose important challenges to clinicians and patients. AEs of ILD are variable in presentation but may result in rapid progression of ILD, respiratory failure and death. However, in many cases AEs of ILD may go unrecognised so that their true impact and response to therapy is unknown. The potential for home monitoring to facilitate early, and accurate, identification of AE and/or ILD progression has gained interest. With increasing evidence available, there is a need for a systematic review on home monitoring of patients with ILD to summarise the existing data. The aim of this review was to systematically evaluate the evidence for use of home monitoring for early detection of exacerbations and/or progression of ILD. Method: We searched Ovid-EMBASE, MEDLINE and CINAHL using Medical Subject Headings (MeSH) terms in accordance with the PRISMA guidelines (PROSPERO registration number CRD42020215166). Results: 13 studies involving 968 patients have demonstrated that home monitoring is feasible and of potential benefit in patients with ILD. Nine studies reported that mean adherence to home monitoring was &gt;75%, and where spirometry was performed there was a significant correlation (r=0.72–0.98, p&lt;0.001) between home and hospital-based readings. Two studies suggested that home monitoring of forced vital capacity might facilitate detection of progression in idiopathic pulmonary fibrosis. Conclusion: Despite the fact that individual studies in this systematic review provide supportive evidence suggesting the feasibility and utility of home monitoring in ILD, further studies are necessary to quantify the potential of home monitoring to detect disease progression and/or AEs.</p

Nalbuphine Tablets for Cough in Patients with Idiopathic Pulmonary Fibrosis

BACKGROUND There are no approved therapies for cough in patients with idiopathic pulmonary fibrosis (IPF). In this small crossover trial we administered nalbuphine extended-release tablets (NAL ER) as a potential cough therapy for such patients. METHODS This randomized, double-blind, placebo-controlled, crossover trial involved two 22-day treatment periods (NAL ER!placebo and placebo!NAL ER) separated by a 2-week washout period. NAL ER was started at a dose of 27 mg once daily and was titrated up to 162 mg twice daily at day 16. The primary end point was percent change from baseline in hourly daytime objective cough frequency as measured by an electronic cough monitor. The daytime period was defined as the patient-reported time of awakening and bedtime. Secondary end points included change in objective 24-hour cough frequency, changes in cough frequency, cough severity, and breathlessness, per patient-reported outcomes. RESULTS A total of 41 patients were randomly assigned and received one or more doses of study medication. There was a 75.1% reduction in daytime objective cough frequency during the NAL ER treatment period versus the placebo treatment period of 22.6%, a 52.5 percentage point placebo-adjusted decrease from baseline (P<0.001) at day 21. There was a 76.1% (95% confidence interval, 83.1 to 69.1) decrease in the 24-hour objective cough frequency with NAL ER, versus a 25.3% (43.9 to 6.7) decrease with placebo, a 50.8 percentage point placebo-adjusted change. Nausea, fatigue, constipation, and dizziness were more common with NAL ER than with placebo. CONCLUSIONS In this short-term crossover trial, NAL ER reduced cough in individuals with IPF. Larger and longer trials are needed to assess the impact on cough versus drug adverse effects. (Funded by Trevi Therapeutics; ClinicalTrials.gov number, NCT04030026.

Voice and Agency: Empowering women and girls for shared prosperity

This document presents Voice and Agency: Empowering women and girls for shared prosperity is a major new report by the World Bank that shines a spotlight on the value of voice and agency, the patterns of constraints that limit their realization, and the associated costs, not only to individual women but to their families, communities, and societies. It highlights promising policies and interventions, and it identifies priority areas where further research and more and better data and evidence are needed. Underlining that agency has both intrinsic and instrumental, concrete value, this report puts advancing women's voice and agency squarely on the international development agenda

Home Monitoring to Detect Progression of Interstitial Lung Disease:A Prospective Cohort Study

In this prospective observational cohort study, 20 IPF and non-IPF patients, as diagnosed by a multidisciplinary team were recruited from the University College London Hospital (UCLH) between August 2021 and January 2022 using 2018 ATS criteria. Patients who met the criteria for ILD other than IPF, including those with sarcoidosis, and hypersensitivity pneumonitis, were grouped together as non-IPF. They were monitored over 26 weeks using the RADAR-Base mHealth platform. Data collection tools included: questionnaires, a Garmin wearable device, finger pulse oximeter and a NuvoAir smart-spirometer.7 In addition, participants underwent lung function testing in a hospital setting as part of their usual hospital visits. Patients were divided into two groups: progressed and stable. Progression was defined as a ≥5% decline in forced vital capacity (FVC) at6 months by hospital-based spirometry and/or death

An acidic microenvironment in Tuberculosis increases extracellular matrix degradation by regulating macrophage inflammatory responses

Mycobacterium tuberculosis (M.tb) infection causes marked tissue inflammation leading to lung destruction and morbidity. The inflammatory extracellular microenvironment is acidic, however the effect of this acidosis on the immune response to M.tb is unknown. Using RNA-seq we show that acidosis produces system level transcriptional change in M.tb infected human macrophages regulating almost 4000 genes. Acidosis specifically upregulated extracellular matrix (ECM) degradation pathways with increased expression of Matrix metalloproteinases (MMPs) which mediate lung destruction in Tuberculosis. Macrophage MMP-1 and -3 secretion was increased by acidosis in a cellular model. Acidosis markedly suppresses several cytokines central to control of M.tb infection including TNF-α and IFN-γ. Murine studies demonstrated expression of known acidosis signaling G-protein coupled receptors OGR-1 and TDAG-8 in Tuberculosis which are shown to mediate the immune effects of decreased pH. Receptors were then demonstrated to be expressed in patients with TB lymphadenitis. Collectively, our findings show that an acidic microenvironment modulates immune function to reduce protective inflammatory responses and increase extracellular matrix degradation in Tuberculosis. Acidosis receptors are therefore potential targets for host directed therapy in patients

Supporting self-management for patients with Interstitial Lung Diseases:Utility and acceptability of digital devices

INTRODUCTION: Patients diagnosed with Interstitial Lung Diseases (ILD) use devices to self-monitor their health and well-being. Little is known about the range of devices, selection, frequency and terms of use and overall utility. We sought to quantify patients' usage and experiences with home digital devices, and further evaluate their perceived utility and barriers to adaptation.METHODS: A team of expert clinicians and patient partners interested in self-management approaches designed a 48-question cross-sectional electronic survey; specifically targeted at individuals diagnosed with ILD. The survey was critically appraised by the interdisciplinary self-management group at Royal Devon University Hospitals NHS Foundation Trust during a 6-month validation process. The survey was open for participation between September 2021 and December 2022, and responses were collected anonymously. Data were analysed descriptively for quantitative aspects and through thematic analysis for qualitative input.RESULTS: 104 patients accessed the survey and 89/104 (86%) reported a diagnosis of lung fibrosis, including 46/89 (52%) idiopathic pulmonary fibrosis (IPF) with 57/89 (64%) of participants diagnosed &gt;3 years and 59/89 (66%) female. 52/65(80%) were in the UK; 33/65 (51%) reported severe breathlessness medical research council MRC grade 3-4 and 32/65 (49%) disclosed co-morbid arthritis or joint problems. Of these, 18/83 (22%) used a hand- held spirometer, with only 6/17 (35%) advised on how to interpret the readings. Pulse oximetry devices were the most frequently used device by 35/71 (49%) and 20/64 (31%) measured their saturations more than once daily. 29/63 (46%) of respondents reported home-monitoring brought reassurance; of these, for 25/63 (40%) a feeling of control. 10/57 (18%) felt it had a negative effect, citing fluctuating readings as causing stress and 'paranoia'. The most likely help-seeking triggers were worsening breathlessness 53/65 (82%) and low oxygen saturation 43/65 (66%). Nurse specialists were the most frequent source of help 24/63 (38%). Conclusion: Patients can learn appropriate technical skills, yet perceptions of home-monitoring are variable; targeted assessment and tailored support is likely to be beneficial.</p

Platelets Regulate Pulmonary Inflammation and Tissue Destruction in Tuberculosis.

RATIONALE: Platelets may interact with the immune system in tuberculosis (TB) to regulate human inflammatory responses that lead to morbidity and spread of infection. OBJECTIVES: To identify a functional role of platelets in the innate inflammatory and matrix-degrading response in TB. METHODS: Markers of platelet activation were examined in plasma from 50 patients with TB before treatment and 50 control subjects. Twenty-five patients were followed longitudinally. Platelet-monocyte interactions were studied in a coculture model infected with live, virulent Mycobacterium tuberculosis (M.tb) and dissected using qRT-PCR, Luminex multiplex arrays, matrix degradation assays, and colony counts. Immunohistochemistry detected CD41 (cluster of differentiation 41) expression in a pulmonary TB murine model, and secreted platelet factors were measured in BAL fluid from 15 patients with TB and matched control subjects. MEASUREMENTS AND MAIN RESULTS: Five of six platelet-associated mediators were upregulated in plasma of patients with TB compared with control subjects, with concentrations returning to baseline by Day 60 of treatment. Gene expression of the monocyte collagenase MMP-1 (matrix metalloproteinase-1) was upregulated by platelets in M.tb infection. Platelets also enhanced M.tb-induced MMP-1 and -10 secretion, which drove type I collagen degradation. Platelets increased monocyte IL-1 and IL-10 and decreased IL-12 and MDC (monocyte-derived chemokine; also known as CCL-22) secretion, as consistent with an M2 monocyte phenotype. Monocyte killing of intracellular M.tb was decreased. In the lung, platelets were detected in a TB mouse model, and secreted platelet mediators were upregulated in human BAL fluid and correlated with MMP and IL-1β concentrations. CONCLUSIONS: Platelets drive a proinflammatory, tissue-degrading phenotype in TB