Secretion of Type IV Collagen by Keratinocytes of Human Adult

Secretion of type IV collagen by keratinocytes was studied by anti-type IV collagen immunoglobulin in pure keratinocyte culture of the human adult. The cultivated keratinocytes secreted type IV collagen into the space between skin collagen type I. The secreted collagen was accumulated on the cell surface to form junction structures

MAST CELLS OF THE OMENTUM IN RELATION TO STATES OF ADRENOCORTICAL DEFICIENCY AND EXCESS

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72967/1/j.1749-6632.1953.tb27390.x.pd

Development, Validation, and Field-Testing of an Instrument for Clinical Assessment of HIV-Associated Neuropathy and Neuropathic Pain in Resource-Restricted and Large Population Study Settings

HIV-associated sensory peripheral neuropathy (HIV-SN) afflicts approximately 50% of patients on antiretroviral therapy, and is associated with significant neuropathic pain. Simple accurate diagnostic instruments are required for clinical research and daily practice in both high- and low-resource setting. A 4-item clinical tool (CHANT: Clinical HIV-associated Neuropathy Tool) assessing symptoms (pain and numbness) and signs (ankle reflexes and vibration sense) was developed by selecting and combining the most accurate measurands from a deep phenotyping study of HIV positive people (Pain In Neuropathy Study–HIV-PINS). CHANT was alpha-tested in silico against the HIV-PINS dataset and then clinically validated and field-tested in HIV-positive cohorts in London, UK and Johannesburg, South Africa. The Utah Early Neuropathy Score (UENS) was used as the reference standard in both settings. In a second step, neuropathic pain in the presence of HIV-SN was assessed using the Douleur Neuropathique en 4 Questions (DN4)-interview and a body map. CHANT achieved high accuracy on alpha-testing with sensitivity and specificity of 82% and 90%, respectively. In 30 patients in London, CHANT diagnosed 43.3% (13/30) HIV-SN (66.7% with neuropathic pain); sensitivity = 100%, specificity = 85%, and likelihood ratio = 6.7 versus UENS, internal consistency = 0.88 (Cronbach alpha), average item-total correlation = 0.73 (Spearman’s Rho), and inter-tester concordance > 0.93 (Spearman’s Rho). In 50 patients in Johannesburg, CHANT diagnosed 66% (33/50) HIV-SN (78.8% neuropathic pain); sensitivity = 74.4%, specificity = 85.7%, and likelihood ratio = 5.29 versus UENS. A positive CHANT score markedly increased of pre- to post-test clinical certainty of HIV-SN from 43% to 83% in London, and from 66% to 92% in Johannesburg. In conclusion, a combination of four easily and quickly assessed clinical items can be used to accurately diagnose HIV-SN. DN4-interview used in the context of bilateral feet pain can be used to identify those with neuropathic pain

Interzone I

Puk Ewdokia: Aarhus rum Isa Paludan Asboe: Der gik en engel gennem stuen Jeppe Krogsgaard Christensen: gæsteværelse. Uddrag af fra hus og hje

Changes in chemsex and sexual behaviour over time, among a cohort of MSM in London and Brighton: Findings from the AURAH2 study.

BACKGROUND: Recent evidence has suggested that chemsex (the use of mephedrone, crystal methamphetamine and γ -hydroxybutyrate/ γ -butryolactone (GHB/GBL) to enable, enhance and prolong sexual interactions) has increased among men having sex with men (MSM) attending sexual health clinics in large UK cities. To date there has been no data from the UK or Europe that describes changes in chemsex over time within a cohort of MSM. METHODS: The prospective cohort study, Attitudes to and Understanding Risk of Acquisition of HIV over Time (AURAH2), collected online questionnaire data from HIV negative or undiagnosed MSM (at enrolment) from 2015 to 2018, recruited from sexual health clinics. We aim to investigate changes in chemsex, three individual drugs associated with chemsex, frequency of chemsex sessions and measures of sexual behaviour, among the cohort of MSM over the study's 3 year follow-up period. RESULTS: In total 622 MSM completed at least one online questionnaire for the AURAH2 study, of which 400 (64.3%) were still engaged with the study within the last six months of follow-up. Prevalence of chemsex significantly declined during the follow-up from 31.8% (198/622) at the first online questionnaire, to 11.1% (8/72; p < 0.001) at the 9th. This decline was reflected in the proportion of MSM reporting use of two of the three individual chemsex drugs: mephedrone use had significantly declined from 25.2% at the first online questionnaire to 9.7% (p < 0.001) at the 9th, GHB/GBL use had also declined from 19.9% to 8.3% (p = 0.001). While crystal methamphetamine use declined, but not significantly (11.1%-6.9% [p = 0.289]). Most measures of sexual behaviour (any anal sex, group sex, recent HIV test and bacterial STI) also tended to decline over the follow-up period, with the exception of CLAI with more than one and more than two partners. CONCLUSIONS: Chemsex and use of two individual chemsex drugs (mephedrone and GHB/GBL) significantly declined over time among individuals in the study, alongside most measures of sexual behaviour with the exception of those related to CLAI. Focusing health promotion and HIV prevention, such as awareness of post-exposure prophylaxis (PEP) and access to pre-exposure prophylaxis (PrEP), on MSM that report chemsex, and in particular problematic chemsex, would be highly beneficial, potentially only necessary for a relatively short period of time for individuals, and could have long term benefits for HIV and STI prevention

Changes in recreational drug use, drug use associated with chemsex, and HIV-related behaviours, among HIV-negative men who have sex with men in London and Brighton, 2013-2016.

OBJECTIVES: The objective of this study was to compare the prevalence of polydrug use, use of drugs associated with chemsex, specific drug use, and HIV-related behaviours, between two time periods , using two groups of HIV-negative men who have sex with men (MSM) attending the same sexual health clinics in London and Brighton, in two consecutive periods of time from 2013 to 2016. METHODS: Data from MSM in the cross-sectional Attitudes to and Understanding Risk of Acquisition of HIV (AURAH) study (June 2013 to September 2014) were compared with baseline data from different MSM in the prospective cohort study Attitudes to and Understanding Risk of Acquisition of HIV over Time (AURAH2) (November 2014 to April 2016). Prevalence of polydrug use, drug use associated with chemsex and specific drug use, and 10 measures of HIV-related behaviours including condomless sex, post-exposure prophylaxis (PEP) use, pre-exposure prophylaxis (PrEP) use, and HIV testing, were compared. Prevalence ratios (PRs) for the association of the study (time period) with drug use and HIV-related behaviour measures were estimated using modified Poisson regression analysis, unadjusted and adjusted for sociodemographic factors. RESULTS: In total, 991 MSM were included from AURAH and 1031 MSM from AURAH2. After adjustment for sociodemographic factors, use of drugs associated with chemsex had increased (adjusted PR (aPR) 1.30, 95% CI 1.11 to 1.53) and there were prominent increases in specific drug use; in particular, mephedrone (aPR 1.32, 95% CI 1.10 to 1.57), γ-hydroxybutyric/γ-butryolactone (aPR 1.47, 95% CI 1.15 to 1.87) and methamphetamine (aPR 1.42, 95% CI 1.01 to 2.01). Use of ketamine had decreased (aPR 0.54, 95% CI 0.38 to 0.78). Certain measures of HIV-related behaviours had also increased, most notably PEP use (aPR 1.50, 95% CI 1.21 to 1.88) and number of self-reported bacterial STI diagnoses (aPR 1.24, 95% CI 1.08 to 1.43). CONCLUSIONS: There have been significant increases in drug use associated with chemsex and some measures of HIV-related behaviours among HIV-negative MSM in the last few years. Changing patterns of drug use and associated behaviours should be monitored to enable sexual health services to plan for the increasingly complex needs of some clients

HLA Immunogenotype Determines Persistent Human Papillomavirus Virus Infection in HIV-Infected Patients Receiving Antiretroviral Treatment

A proportion of human immunodeficiency virus (HIV)–infected patients develop persistent, stigmatizing human papillomavirus (HPV)–related cutaneous and genital warts and anogenital (pre)cancer. This is the first study to investigate immunogenetic variations that might account for HPV susceptibility and the largest to date to categorize the HPV types associated with cutaneous warts in HIV-positive patients. The HLA class I and II allele distribution was analyzed in 49 antiretroviral (ART)–treated HIV-positive patients with persistent warts, 42 noninfected controls, and 46 HIV-positive controls. The allele HLA-B*44 was more frequently identified in HIV-positive patients with warts (P = .004); a susceptible haplotype (HLA-B*44, HLA-C*05; P = .001) and protective genes (HLA-DQB1*06; P = .03) may also contribute. Cutaneous wart biopsy specimens from HIV-positive patients harbored common wart types HPV27/57, the unusual wart type HPV7, and an excess of Betapapillomavirus types (P = .002), compared with wart specimens from noninfected controls. These findings suggest that HLA testing might assist in stratifying those patients in whom vaccination should be recommended

Risk factors and outcomes for the Q151M and T69 insertion HIV-1 resistance mutations in historic UK data

BACKGROUND: The prevalence of HIV-1 resistance to antiretroviral therapies (ART) has declined in high-income countries over recent years, but drug resistance remains a substantial concern in many low and middle-income countries. The Q151M and T69 insertion (T69i) resistance mutations in the viral reverse transcriptase gene can reduce susceptibility to all nucleoside/tide analogue reverse transcriptase inhibitors, motivating the present study to investigate the risk factors and outcomes associated with these mutations. METHODS: We considered all data in the UK HIV Drug Resistance Database for blood samples obtained in the period 1997-2014. Where available, treatment history and patient outcomes were obtained through linkage to the UK Collaborative HIV Cohort study. A matched case-control approach was used to assess risk factors associated with the appearance of each of the mutations in ART-experienced patients, and survival analysis was used to investigate factors associated with viral suppression. A further analysis using matched controls was performed to investigate the impact of each mutation on survival. RESULTS: A total of 180 patients with Q151M mutation and 85 with T69i mutation were identified, almost entirely from before 2006. Occurrence of both the Q151M and T69i mutations was strongly associated with cumulative period of virological failure while on ART, and for Q151M there was a particular positive association with use of stavudine and negative association with use of boosted-protease inhibitors. Subsequent viral suppression was negatively associated with viral load at sequencing for both mutations, and for Q151M we found a negative association with didanosine use but a positive association with boosted-protease inhibitor use. The results obtained in these analyses were also consistent with potentially large associations with other drugs. Analyses were inconclusive regarding associations between the mutations and mortality, but mortality was high for patients with low CD4 at detection. CONCLUSIONS: The Q151M and T69i resistance mutations are now very rare in the UK. Our results suggest that good outcomes are possible for people with these mutations. However, in this historic sample, viral load and CD4 at detection were important factors in determining prognosis

Clinically significant depressive symptoms and sexual behaviour among men who have sex with men.

BACKGROUND: The relationship between depression and sexual behaviour among men who have sex with men (MSM) is poorly understood. AIMS: To investigate prevalence and correlates of depressive symptoms (Patient Health Questionnaire-9 score ≥10) and the relationship between depressive symptoms and sexual behaviour among MSM reporting recent sex. METHOD: The Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) is a cross-sectional study of UK genitourinary medicine clinic attendees without diagnosed HIV (2013-2014). RESULTS: Among 1340 MSM, depressive symptoms (12.4%) were strongly associated with socioeconomic disadvantage and lower supportive network. Adjusted for key sociodemographic factors, depressive symptoms were associated with measures of condomless sex partners in the past 3 months (≥2 (prevalence ratio (PR) 1.42, 95% CI 1.17-1.74; P=0.001), unknown or HIV-positive status (PR 1.43, 95% CI 1.20-1.71; P<0.001)), sexually transmitted infection (STI) diagnosis (PR 1.46, 95% CI 1.19-1.79; P<0.001) and post-exposure prophylaxis use in the past year (PR 1.83, 95% CI 1.33-2.50; P<0.001). CONCLUSIONS: Management of mental health may play a role in HIV and STI prevention. DECLARATION OF INTEREST: A.N.P. has received payments for presentations made at meetings sponsored by Gilead in spring 2015. N.C.N. has received support for attendance at conferences, speaker fees and payments for attendance at advisory boards from Gilead Sciences, Viiv Healthcare, Janssen Pharmaceuticals and Bristol-Myers Squibb and a research grant from Gilead Sciences. D.A. served on the advisory board for Gilead in January 2016. M.M.G. has had sponsorship to attend conferences by Bristol-Myers Squibb, been on the BioCryst advisory board and run trials for Merck, Gilead, SSAT, BioCryst and Novartis. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license