Sources of Social Capital for Malawi People Living With HIV.

With one of the highest rates of poverty and HIV in the world, Malawi faith-based organizations (FBOs), non-governmental organizations (NGOs), and community-based organizations (CBOs) are expected to provide tangible and emotional support to people living with HIV (PLWH). Using Lin's social capital theoretical approach, we examine the perspective of PLWH regarding the adequacy of support responses. Forty-six rural Malawi HIV+ adults provided interviews that were recorded digitally, translated, and transcribed by Malawi research assistants. Atlas.ti was used to organize the data and to aid in the analytic process. Participants expressed disappointment in the lack of resources that could be accessed through the FBOs although their expectations may have been unrealistic. Outcomes from accessing and mobilizing the FBO network were negative in terms of stigmatization by FBO leaders and members, whereas outcomes related to CBOs and NGOs were generally positive in terms of empowerment through HIV information and attendance at support groups

Building Collaborative Research to Drive Improvement of West Virginia Health Outcomes

Mortality rates in Appalachia have not declined in recent years as they have for the remainder of the US. Appalachian mortality rates have actually increased. Most counties of southern West Virginia have mortality rates well in excess of the US average. West Virginia ranks at or near the bottom in most U.S. chronic disease categories, with the highest rate of drug overdose deaths and near the highest rates of cancer and cardiovascular mortality. And yet, West Virginia has many dedicated heath care providers, committed to the care of their patients. The West Virginia Clinical and Translational Science Institute (WVCTSI) seeks to facilitate finding solutions for vexing health problems in West Virginia, working with the many committed healthcare providers to collaboratively improve health outcomes in our state

P-glycoprotein-mediated chemoresistance is reversed by carbonic anhydrase XII inhibitors

Carbonic anhydrase XII (CAXII) is a membrane enzyme that maintains pH homeostasis and sustains optimum P-glycoprotein (Pgp) efflux activity in cancer cells. Here, we investigated a panel of eight CAXII inhibitors (compounds 1-8), for their potential to reverse Pgp mediated tumor cell chemoresistance. Inhibitors (5 nM) were screened in human and murine cancer cells (colon, lung, breast, bone) with different expression levels of CAXII and Pgp. We identified three CAXII inhibitors (compounds 1, 2 and 4) that significantly (≥ 2 fold) increased the intracellular retention of the Pgp-substrate and chemotherapeutic doxorubicin, and restored its cytotoxic activity. The inhibitors lowered intracellular pH to indirectly impair Pgp activity. Ca12-knockout assays confirmed that the chemosensitizing property of the compounds was dependent on active CAXII. Furthermore, in a preclinical model of drug-resistant breast tumors compound 1 (1900 ng/kg) restored the efficacy of doxorubicin to the same extent as the direct Pgp inhibitor tariquidar. The expression of carbonic anhydrase IX had no effect on the intracellular doxorubicin accumulation. Our work provides strong evidence that CAXII inhibitors are effective chemosensitizer agents in CAXII-positive and Pgp-positive cancer cells. The use of CAXII inhibitors may represent a turning point in combinatorial chemotherapeutic schemes to treat multidrug-resistant tumors.Full Tex

Draamaohjelman vaikutus oppilaiden sosiaalisiin suhteisiin ja kiusaamiskokemuksiin alakoulussa

Draamamenetelmiä käytetään yleisesti lasten terveyden edistämisen ohjelmissa. Kuitenkin näytöt menetelmien vaikuttavuudesta ovat vähäiset. Tässä artikkelissa kuvataan koulussa toteutetun draamaohjelman vaikutuksia 4.–5.-luokkien (keski-ikä 10,4 vuotta) oppilaiden sosiaalisiin suhteisiin ja koulukiusaamiskokemuksiin. Oppilaat (N=190) rekrytoitiin kahdesta yhtenäiskoulusta ja jaettiin kahteen ryhmään: ohjelma- tai kontrollikouluun. Draamaohjelma sisälsi luokkahuonedraamatilanteita, kotiharjoituksia ja vanhempainiltoja lukuvuonna 2007–2008. Aineisto kerättiin ennen draamaohjelmaa ja ohjelman jälkeen kyselylomakkeilla (n=134). Vastausprosentti oli 71. Ohjelmakoulun oppilaiden arviot luokan sosiaalisista suhteista paranivat, kun taas kontrollikoulussa ne pysyivät samalla tasolla; ajan ja ryhmän yhteisvaikutus lähestyi tilastollista merkitsevyyttä (p=0.065). Myönteinen vaikutus sosiaalisiin suhteisiin oli tilastollisesti merkitsevä luokissa, joissa ohjelma toteutettiin intensiivisesti (p=0.011). Kiusaamiskokemukset vähenivät alku- ja loppumittauksen välillä ohjelmaryhmässä (

Mapping Selective Inhibition of the Cancer-Related Carbonic Anhydrase IX Using Structure-Activity Relationships of Glucosyl-Based Sulfamates

Inhibition of human carbonic anhydrase IX (hCA IX) has shown to be therapeutically advantageous for treating many types of highly aggressive cancers. However, designing selective inhibitors for hCA IX has been difficult due to its high structural homology and sequence similarity with off-target hCAs. Recently, the use of glucosyl sulfamate inhibitors has shown promise as selective inhibitors for hCA IX. In this study, we present five X-ray crystal structures, determined to a resolution of 1.7 Å or better, of both hCA II (a ubiquitous CA) and an engineered hCA IX-mimic in complex with selected glucosyl sulfamates and structurally rationalize mechanisms for hCA IX selectivity. Results from this study have allowed us, for the first time, to empirically “map” key interactions of the hCA IX active site in order to establish parameters needed to design novel hCA IX selective inhibitors.No Full Tex

Impact of Scottish smoke-free legislation on smoking quit attempts and prevalence

<p><b>Objectives:</b> In Scotland, legislation was implemented in March 2006 prohibiting smoking in all wholly or partially enclosed public spaces. We investigated the impact on attempts to quit smoking and smoking prevalence.</p> <p><b>Methods:</b> We performed time series models using Box-Jenkins autoregressive integrated moving averages (ARIMA) on monthly data on the gross ingredient cost of all nicotine replacement therapy (NRT) prescribed in Scotland in 2003–2009, and quarterly data on self-reported smoking prevalence between January 1999 and September 2010 from the Scottish Household Survey.</p> <p><b>Results:</b> NRT prescription costs were significantly higher than expected over the three months prior to implementation of the legislation. Prescription costs peaked at £1.3 million in March 2006; £292,005.9 (95% CI £260,402.3, £323,609, p<0.001) higher than the monthly norm. Following implementation of the legislation, costs fell exponentially by around 26% per month (95% CI 17%, 35%, p<0.001). Twelve months following implementation, the costs were not significantly different to monthly norms. Smoking prevalence fell by 8.0% overall, from 31.3% in January 1999 to 23.7% in July–September 2010. In the quarter prior to implementation of the legislation, smoking prevalence fell by 1.7% (95% CI 2.4%, 1.0%, p<0.001) more than expected from the underlying trend.</p> <p><b>Conclusions:</b> Quit attempts increased in the three months leading up to Scotland's smoke-free legislation, resulting in a fall in smoking prevalence. However, neither has been sustained suggesting the need for additional tobacco control measures and ongoing support.</p&gt

Evaluating Social and Spatial Inequalities of Large Scale Rapid Lateral Flow SARS-CoV-2 Antigen Testing in COVID-19 Management: An Observational Study of Liverpool, UK (November 2020 to January 2021)

Background: The aim of the study is to explore social and spatial inequalities in uptake and case-detection of rapid lateral flow SARS-CoV-2 antigen tests (LFTs) offered to people without symptoms of COVID-19.Methods: Linked pseudonymised records for asymptomatic residents in Liverpool (UK) who received a LFT for COVID-19 between 6th November 2020 to 31st January 2021 were accessed using the Combined Intelligence for Population Health Action (CIPHA) data resource. Bayesian Hierarchical Poisson Besag, York, and Mollié models were used to estimate ecological associations for uptake and positivity of testing.Findings: 214 525 residents (43%) received a LFT identifying 5557 individuals as positive cases of COVID-19 (1.3%). Uptake was highest in November when there was military assistance. High uptake was observed again in the week preceding Christmas and was sustained into a national lockdown. Overall uptake and repeat testing were lower among males (e.g. 40% uptake over the whole period), Black Asian and other Minority Ethnic groups (e.g. 27% uptake for ‘Mixed’ ethnicity) and in the most deprived areas (e.g. 32% uptake in most deprived areas). These population groups were also more likely to have received positive tests for COVID-19. Models demonstrated that uptake and repeat testing were lower in areas of higher deprivation, areas located further from test sites and areas containing populations less confident in the using Internet technologies. Positive tests were spatially clustered in deprived areas.Interpretation: Large-scale voluntary asymptomatic community testing saw social, ethnic, and spatial inequalities in an ‘inverse care’ pattern, but with an added digital exclusion factor. COVID-19 testing and support to isolate need to be more accessible to the vulnerable communities most impacted by the pandemic, including non-digital means of access.Funding: Department of Health and Social Care (UK), National Institute for Health Research and Economic and Social Research Council).Conflict of Interest: None declared.Ethical Approval: The University of Liverpool has provided secondary data analysis as part of a national service evaluation with data collected by Department of Health and Social Care (Sponsor) for quality assurance of Innova lateral flow tests in a public health service intervention. There was no research commissioned by Department of Health and Social Care on this aspect of the Liverpool pilot of asymptomatic, community testing. As such, research ethics approval was not sought by the Department of Health and Social Care. Some aspects of the evaluation requiring fieldwork and primary data collection by the University of Liverpool were subject to ethical approval, which was confirmed prior to the commencement of activities by the University of Liverpool’s Research Ethics Committee. The provision of secondary data analysis and interpretation did not require further ethical approval. Cheshire & Merseyside Health & Care Partnership Combined Intelligence for Population HealthAction (CIPHA) Data Access Committee approved access to the data and analysis contained in the study. MAST/SMART was defined as ‘an emergency public health intervention during an extraordinary event’ which were subject to the legal and ethical provisions of a health protection activity and COVID-19 specifically. The secondary analysis of data provided in a health protection activity is not classified as research, and so does not require research ethics committee review (see http://www.hradecisiontools.org.uk/research/docs/DefiningResearchTable_Oct2017-1.pdf)