Recommendations for Implementing Hepatitis C Virus Care in Homeless Shelters: The Stakeholder Perspective.

Compared with the general population, homeless individuals are at higher risk of hepatitis C infection (HCV) and may face unique barriers in receipt of HCV care. This study sought the perspectives of key stakeholders toward establishing a universal HCV screening, testing, and treatment protocol for individuals accessing homeless shelters. Four focus groups were conducted with homeless shelter staff, practice providers, and social service outreach workers (n = 27) in San Francisco, California, and Minneapolis, Minnesota. Focus groups evaluated key societal, system, and individual-level facilitators and barriers to HCV testing and management. Interviews were transcribed and analyzed thematically. The societal-level barriers identified were lack of insurance, high-out-of-pocket expenses, restriction of access to HCV treatment due to active drug and/or alcohol use, and excessive paperwork required for HCV treatment authorization from payers. System-level barriers included workforce constraints and limited health care infrastructure, HCV stigma, low knowledge of HCV treatment, and existing shelter policies. At the individual level, client barriers included competing priorities, behavioral health concerns, and health attitudes. Facilitators at the system level for HCV care service integration in the shelter setting included high acceptability and buy in, and linkage with social service providers. Conclusion: Despite societal, system, and individual-level barriers identified with respect to the scale-up of HCV services in homeless shelters, there was broad support from key stakeholders for increasing capacity for the provision of HCV services in shelter settings. Recommendations for the scale-up of HCV services in homeless shelter settings are discussed

Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy

Metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and mitochondrial biogenesis in subpopulations of CD4+ and CD8+ T cells from 18 virologically-suppressed HIV-positive individuals on combination antiretroviral therapy (cART; median CD4+ cell count: 728 cells/μl) and 13 HIV seronegative controls. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production were also analysed in total CD4+ and CD8+ T cells. Among HIV+/cART individuals, expression of glucose transporter (Glut1) and mitochondrial density were highest within central memory and naïve CD4+ T cells, and lowest among effector memory and transitional memory T cells, with similar trends in HIV-negative controls. Compared to HIV-negative controls, there was a trend towards higher percentage of circulating CD4+Glut1+ T cells in HIV+/cART participants. There were no significant differences in mitochondrial dynamics between subject groups. Glut1 expression was positively correlated with mitochondrial density and MMP in total CD4+ T cells, while MMP was also positively correlated with ROS production in both CD4+ and CD8+ T cells. Our study characterizes specific metabolic features of CD4+ and CD8+ T cells in HIV-negative and HIV+/cART individuals and will invite future studies to explore the immunometabolic consequences of HIV infection

Relative performance and predictive values of plasma and dried blood spots with filter paper sampling techniques and dilutions of the lymphatic filariasis Og4C3 antigen ELISA for samples from Myanmar

Diagnostic testing of blood samples for parasite antigen Og4C3 is used to assess Wuchereria bancrofti in endemic populations. However, the Tropbio ELISA recommends that plasma and dried blood spots (DBS) prepared using filter paper be used at different dilutions, making it uncertain whether these two methods and dilutions give similar results, especially at low levels of residual infection or resurgence during the post-program phase. We compared results obtained using samples of plasma and DBS taken simultaneously from 104 young adults in Myanmar in 2014, of whom 50 (48.1%) were positive for filariasis antigen by rapid antigen test. Results from DBS tests at recommended dilution were significantly lower than results from plasma tested at recommended dilution, with comparisons between plasma and DBS at unmatched dilutions yielding low sensitivity and negative predictive values of 60.0% and 70.6% respectively. While collection of capillary blood on DBS is cheaper and easier to perform than collecting plasma or serum, and does not need to be stored frozen, dilutions between different versions of the test must be reconciled or an adjustment factor applied

Concordance between plasma and filter paper sampling techniques for the lymphatic filariasis Bm14 antibody ELISA

Diagnostic testing for the antibody Bm14 is used to assess the prevalence of bancroftian and brugian filariasis in endemic populations. Using dried blood spots (DBS) collected on filter paper is ideal in resource-poor settings, but concerns have been raised about the performance of DBS samples compared to plasma or serum. In addition, two versions of the test have been used: the Bm14 CELISA (Cellabs Pty Ltd., Manly, Australia) or an in-house CDC version. Due to recent improvements in the CELISA, it is timely to validate the latest versions of the Bm14 ELISA for both plasma and DBS, especially in settings of residual infection with low antibody levels. We tested plasma and DBS samples taken simultaneously from 92 people in Myanmar, of whom 37 (40.2%) were positive in a rapid antigen test. Comparison of results from plasma and DBS samples demonstrated no significant difference in positive proportions using both the CELISA (46.7% and 44.6%) and CDC ELISA (50.0% and 47.8%). Quantitative antibody unit results from each sample type were also highly correlated, with coefficients >0.87. The results of this study demonstrate that DBS samples are a valid collection strategy and give equivalent results to plasma for Bm14 antibody ELISA testing by either test type

Lymphatic filariasis increases tissue compressibility and extracellular fluid in lower limbs of asymptomatic young people in Central Myanmar

When normal lymphatic function is hampered, imperceptible subcutaneous edema can develop and progress to overt lymphedema. Low-cost reliable devices for objective assessment of lymphedema are well accepted in clinical practice and research on breast-cancer related lymphedema but are untested in populations with lymphatic filariasis (LF). This is a cross-sectional analysis of baseline data in a longitudinal study on asymptomatic, LF antigen-positive and -negative young people in Myanmar. Rapid field screening was used to identify antigen-positive cases and a group of antigen-negative controls of similar age and gender were invited to continue in the study. Tissue compressibility was assessed with three tissue tonometers, and free fluids were assessed using bio-impedance spectroscopy (BIS). Infection status was confirmed by Og4C3 antigen assay. At baseline (n= 98), antigen-positive cases had clinically relevant increases in tissue compressibilityat the calf using a digital Indurometer (11.1%, p = 0.021), and in whole-leg free fluid using BIS (9.2%, p = 0.053). Regression analysis for moderating factors (age, gender, hydration) reinforced the between-infection group differences. Results demonstrate that sub-clinical changes associated with infection can be detected in asymptomatic cases. Further exploration of these low-cost devices in clinical and research settings on filariasis-related lymphedema are warranted

Analysis of the Listeria monocytogenes Population Structure among Isolates from 1931 to 2015 in Australia

Listeriosis remains among the most important bacterial illnesses, with a high associated mortality rate. Efforts to control listeriosis require detailed knowledge of the epidemiology of the disease itself, and its etiological bacterium, Listeria monocytogenes. In this study we provide an in-depth analysis of the epidemiology of 224 L. monocytogenes isolates from Australian clinical and non-clinical sources. Non-human sources included meat, dairy, seafood, fruit, and vegetables, along with animal and environmental isolates. Serotyping, Multi-Locus Sequence Typing, and analysis of inlA gene sequence were performed. Serogroups IIA, IIB, and IVB comprised 94% of all isolates, with IVB over-represented among clinical isolates. Serogroup IIA was the most common among dairy and meat isolates. Lineage I isolates were most common among clinical isolates, and 52% of clinical isolates belonged to ST1. Overall 39 STs were identified in this study, with ST1 and ST3 containing the largest numbers of L. monocytogenes isolates. These STs comprised 40% of the total isolates (n = 90), and both harbored isolates from clinical and non-clinical sources. ST204 was the third most common ST. The high prevalence of this group among L. monocytogenes populations has not been reported outside Australia. Twenty-seven percent of the STs in this study contained exclusively clinical isolates. Analysis of the virulence protein InlA among isolates in this study identified a truncated form of the protein among isolates from ST121 and ST325. The ST325 group contained a previously unreported novel mutation leading to production of a 93 amino acid protein. This study provides insights in the population structure of L. monocytogenes isolated in Australia, which will contribute to public health knowledge relating to this important human pathogen

Report on the 2022 excavations at Wogan Cavern (Pembroke, Pembrokeshire, UK)

In a previous article in this journal (Dinnis et al., 2022), we described the first season of archaeological excavations at Wogan Cavern (Pembroke, southwest Wales). Although based on excavation of a very small volume of deposits, we suggested that the sediments in Wogan Cavern may have very good potential for preserving archaeological remains. Specifically, an intact early Holocene archaeological layer and underlying, bone-bearing Pleistocene deposits encouraged us to believe that the cave might be an important early prehistoric site. Here, we provide an update on our previous work, detailing the findings of the 2022 excavation season. The 2022 work identified several phases of historic and prehistoric activity. The early Holocene archaeological layer containing diagnostic Mesolithic artefacts, found previously in the eastern part of the cave, was shown to extend towards the centre of the cave. Stratigraphically lower deposits dating to the Pleistocene, previously demonstrated close to the cave's eastern wall, were also shown to extend towards the cave's centre. Excavation of the Pleistocene deposits close to the cave's eastern wall revealed evidence for human occupation, with one and possibly two Upper Palaeolithic layers present. The archaeological assemblage(s) from these lower deposits bear similarities to the Palaeolithic stone tool assemblage from the famous Paviland Cave, located c.30 miles (c.50km) to the east. Overall, our 2022 work confirms that Wogan Cavern is an early prehistoric site of national, and potentially international, significance

The archaeological potential of Wogan Cavern (Pembroke, UK):Results of the first fieldwork season

Funding Information: Acknowledgements Many thanks are due to numerous people for their help with our work on Wogan Cavern, including (but not limited to) Jon Williams and the staff at Pembroke Castle, Sian Williams, several colleagues at Dyfed Archaeological Trust, Mark Lewis and Eloise Chapman at Tenby Museum, and Louise Mees at Cadw. We are also grateful to the reviewers for a careful reading of this article and for providing some insightful comments, and to David Lowe, whose comments and advice benefitted the final version of the Paper. The work described here and that planned for the future is funded by the Natural History Museum’s Human Origins Research Fund, the BCRA’s CSTRF scheme, and the Prehistoric Society. ELJ acknowledges the Belspo-ICHIE project for funding her contribution to this research.Peer reviewedPublisher PD

Report on the 2022 excavations at Wogan Cavern (Pembroke, Pembrokeshire, UK)

Publisher Copyright: © 2023 British Cave Research Association. All rights reserved.Peer reviewe

Cardiac troponins: from myocardial infarction to chronic disease.

Elucidation of the physiologically distinct subunits of troponin in 1973 greatly facilitated our understanding of cardiac contraction. Although troponins are expressed in both skeletal and cardiac muscle, there are isoforms of troponin I/T expressed selectively in the heart. By exploiting cardiac-restricted epitopes within these proteins, one of the most successful diagnostic tests to-date has been developed: cardiac troponin (cTn) assays. For the past decade, cTn has been regarded as the gold-standard marker for acute myocardial necrosis: the pathological hallmark of acute myocardial infarction (AMI). Whilst cTn is the cornerstone for ruling-out AMI in patients presenting with a suspected acute coronary syndrome (ACS), elevated cTn is frequently observed in those without clinical signs indicative of AMI, often reflecting myocardial injury of 'unknown origin'. cTn is commonly elevated in acute non-ACS conditions, as well as in chronic diseases. It is unclear why these elevations occur; yet they cannot be ignored as cTn levels in chronically unwell patients are directly correlated to prognosis. Paradoxically, improvements in assay sensitivity have meant more differential diagnoses have to be considered due to decreased specificity, since cTn is now more easily detected in these non-ACS conditions. It is important to be aware cTn is highly specific for myocardial injury, which could be attributable to a myriad of underlying causes, emphasising the notion that cTn is an organ-specific, not disease-specific biomarker. Furthermore, the ability to detect increased cTn using high-sensitivity assays following extreme exercise is disconcerting. It has been suggested troponin release can occur without cardiomyocyte necrosis, contradicting conventional dogma, emphasising a need to understand the mechanisms of such release. This review discusses basic troponin biology, the physiology behind its detection in serum, its use in the diagnosis of AMI, and some key concepts and experimental evidence as to why cTn can be elevated in chronic diseases