PrEP Use, Sexual Behaviour, and PrEP Adherence Among Men who have Sex with Men Living in Wales Prior to and During the COVID-19 Pandemic.

We examined PrEP use, condomless anal sex (CAS), and PrEP adherence among men who have sex with men (MSM) attending sexual health clinics in Wales, UK. In addition, we explored the association between the introduction of measures to control transmission of SARS-CoV-2 on these outcomes. We conducted an ecological momentary assessment study of individuals in receipt of PrEP in Wales. Participants used an electronic medication cap to record PrEP use and completed weekly sexual behaviour surveys. We defined adherence to daily PrEP as the percentage of CAS episodes covered by daily PrEP (preceded by ≥ 3 days of PrEP and followed by ≥ 2 days). Sixty participants were recruited between September 2019 and January 2020. PrEP use data prior to the introduction of control measures were available over 5785 person-days (88%) and following their introduction 7537 person-days (80%). Data on CAS episodes were available for 5559 (85%) and 7354 (78%) person-days prior to and following control measures respectively. Prior to the introduction of control measures, PrEP was taken on 3791/5785 (66%) days, there were CAS episodes on 506/5559 (9%) days, and 207/406 (51%) of CAS episodes were covered by an adequate amount of daily PrEP. The introduction of pandemic-related control measures was associated with a reduction in PrEP use (OR 0.44, 95%CI 0.20-0.95), CAS (OR 0.35, 95%CI 0.17-0.69), and PrEP adherence (RR = 0.55, 95%CI 0.34-0.89) and this may have implications for the health and wellbeing of PrEP users and, in addition to disruption across sexual health services, may contribute to wider threats across the HIV prevention cascade.

An evaluation of urinary microRNA reveals a high sensitivity for bladder cancer.

BACKGROUND: Urinary biomarkers are needed to improve the care and reduce the cost of managing bladder cancer. Current biomarkers struggle to identify both high and low-grade cancers due to differing molecular pathways. Changes in microRNA (miR) expression are seen in urothelial carcinogenesis in a phenotype-specific manner. We hypothesised that urinary miRs reflecting low- and high-grade pathways could detect bladder cancers and overcome differences in genetic events seen within the disease. METHODS: We investigated urinary samples (n=121) from patients with bladder cancer (n=68) and age-matched controls (n=53). Fifteen miRs were quantified using real-time PCR. RESULTS: We found that miR is stable within urinary cells despite adverse handling and detected differential expression of 10 miRs from patients with cancer and controls (miRs-15a/15b/24-1/27b/100/135b/203/212/328/1224, ANOVA P<0.05). Individually, miR-1224-3p had the best individual performance with specificity, positive and negative predictive values and concordance of 83%, 83%, 75% and 77%, respectively. The combination of miRs-135b/15b/1224-3p detected bladder cancer with a high sensitivity (94.1%), sufficient specificity (51%) and was correct in 86% of patients (concordance). CONCLUSION: The use of this panel in patients with haematuria would have found 94% of urothelial cell carcinoma, while reducing cystoscopy rates by 26%. However, two invasive cancers (3%) would have been missed.

Hepatitis E virus coinfection in patients with HIV infection.

OBJECTIVES: Hepatitis E virus (HEV) infection is an emerging infection in developed countries and is thought to be a porcine zoonosis. HEV can cause chronic infection and cirrhosis in the immunosuppressed, including patients with HIV infection. Little is known about HEV and HIV coinfection. The aim of the study was to document the incidence of chronic HEV coinfection in patients with HIV infection and to determine the anti-HEV seroprevalence and compare it with that of a control population. METHODS: A cohort/case-control study was carried out in two teaching hospitals in southwest England. A total of 138 patients with HIV infection were tested for HEV using an immunoassay for anti-HEV immunoglobulin M (IgM) and IgG and reverse transcriptase-polymerase chain reaction (RT-PCR), and 464 control subjects were tested for anti-HEV IgG. Demographic, lifestyle and laboratory data were prospectively collected on each patient with HIV infection. The anti-HEV IgG seroprevalence in patients with HIV infection was compared with that in controls and demographic risk factors for HEV exposure were explored using logistic regression models. RESULTS: There was no difference in anti-HEV IgG seroprevalence between the HIV-infected patients and controls. The only risk factor predictive of anti-HEV seropositivity was the consumption of raw/undercooked pork; sexual risk factors were unrelated. No patient with HIV infection had evidence of chronic coinfection with HEV CONCLUSIONS: Anti-HEV seroprevalence is similar in controls and patients with HIV infection. Risk factor analysis suggests that HEV is unlikely to be transmitted sexually. Chronic coinfection with HEV was absent, indicating that chronic HEV/HIV coinfection is not a common problem in this cohort.

Construct Validation of the Dietary Inflammatory Index among African Americans.

OBJECTIVE: Chronic inflammation is linked to many chronic conditions. One of the strongest modulators of chronic inflammation is diet. The Dietary Inflammatory Index (DII) measures dietary inflammatory potential and has been validated previously, but not among African Americans (AAs). DESIGN: Cross-sectional analysis using baseline data from the Healthy Eating and Active Living in the Spirit (HEALS) intervention study. SETTING: Baseline data collection occurred between 2009 and 2012 in or near Columbia, SC. PARTICIPANTS: African-American churchgoers. MEASUREMENTS: Baseline data collection included c-reactive protein (CRP) and interleukin-6 from blood draws, anthropometric measures, and numerous questionnaires. The questionnaires included a food frequency questionnaire which was used for DII calculation. The main analyses were performed using quantile regression. RESULTS: Subjects in the highest DII quartile (i.e., more pro-inflammatory) were younger, more likely to be married, and had less education and greater BMI. Individuals in DII quartile 4 had statistically significantly greater CRP at the 75th and 90th percentiles of CRP versus those in quartile 1 (i.e., more anti-inflammatory). CONCLUSION: Construct validation provides support for using the DII in research among AA populations. Future research should explore avenues to promote more anti-inflammatory diets, with use of the DII, among AA populations to reduce risk of chronic disease.

Polypropylenimine dendrimer-induced gene expression changes: the effect of complexation with DNA, dendrimer generation and cell type.

Polypropylenimine (PPI) dendrimers appear attractive non-viral vectors for the delivery of genes, antisense oligonucleotides, and small interfering RNA (siRNA). However, the effects of these synthetic gene delivery vectors on global gene expression are poorly understood. Here we have examined the toxicogenomics of generation 2 (DAB-8) and generation 3 (DAB-16) PPI dendrimers in two human cell lines. At concentrations and treatment protocols routinely used for gene and oligonucleotide transfection, PPI dendrimers alone elicited marked changes in endogenous gene expression in A431 epithelial cells. The extent of PPI-induced gene changes appeared to be dependent on the dendrimer generation as the number of genes affected was greater with G3 compared to G2 PPI dendrimers in A431 cells. The signature of DAB16-induced gene changes in A549 cells was different to those elicited in A431 cells implying a strong dependence on cell type. The DAB-16 polymer complexed with DNA (dendriplexes) also elicited marked gene expression changes in A549 cells but with a signature that was different from the polymer alone implying that dendriplexes are "recognised" by cells as chemical entities that are distinct from the polymer alone. Alterations in expression of a variety of gene ontologies were observed including those involved in defence responses, cell proliferation and apoptosis. Although there was a tendency for increased DNA damage in cells treated with DAB16 alone or its DNA dendriplexes as detected by the COMET assay, these differences were not statistically significant. These data show for the first time that PPI-dendrimers, separate from their capability as transfection reagents, can intrinsically alter the expression of many endogenous genes that could potentially lead to them exerting multiple biological effects in cells. The impact and consequences of polymer-induced gene changes should guide their rational use as delivery systems for gene-based therapeutics.

Patients' attitudes towards increasing the offer of HIV testing in primary and secondary care.

The UK National Guidelines on HIV testing (2008) recommend routinely offering an HIV test to patients in certain clinical settings. We wished to investigate the acceptability of implementing these guidelines in a population with a low HIV prevalence. Patients accessing primary and secondary care were asked to circle one of the five responses to a series of statements regarding HIV testing. Of the 616 respondents, 579 (94%) stated they would be willing to be tested if presenting with a condition known to be associated with HIV. Four hundred and forty out of 616 (71%) stated they would be willing to be tested as part of their routine care, while 445/616 (72%) stated they would be willing to have the result in their main medical notes. Although the patients' responses were largely receptive to increased testing, we encountered notable negative attitudes to the project from professional and administrative staff. Resistance to increased HIV testing may be related to health-care workers rather than patients.