Prevalence of HIV and sexually transmitted and blood-borne infections,and related preventive and risk behaviours,among gay,bisexual and other men who have sex with men in Montreal,Toronto and Vancouver: results from the Engage Study

ObjectivesThe last Canadian biobehavioural surveillance study of HIV and other sexually transmitted and blood-borne infections (STBBI) among gay, bisexual and other men who have sex with men (GBM) was conducted in 2010. We designed a study to measure STBBI prevalence among GBM in metropolitan Montreal, Toronto and Vancouver and to document related preventive and risk behaviours.MethodsThe Engage Cohort Study used respondent-driven sampling (RDS) to recruit GBM who reported sex with another man in the past 6 months. At baseline, we examined recruitment characteristics of the samples, and the RDS-II-adjusted distributions of socio-demographics, laboratory-confirmed HIV and other STBBI prevalence, and related behaviours, with a focus on univariate differences among cities.ResultsA total of 2449 GBM were recruited from February 2017 to August 2019. HIV prevalence was lower in Montreal (14.2%) than in Toronto (22.2%) or Vancouver (20.4%). History of syphilis infection was similar across cities (14–16%). Vancouver had more HIV-negative/unknown participants who reported never being HIV tested (18.6%) than Toronto (12.9%) or Montreal (11.5%). Both Montreal (74.9%) and Vancouver (78.8%) had higher proportions of men who tested for another STBBI in the past 6 months than Toronto (67.4%). Vancouver had a higher proportion of men who used pre-exposure prophylaxis (PrEP) in the past 6 months (18.9%) than Toronto (11.1%) or Montreal (9.6%).ConclusionThe three largest cities of Canada differed in HIV prevalence, STBBI testing and PrEP use among GBM. Our findings also suggest the need for scale-up of both PrEP and STI testing among GBM in Canada.     

New quantitative aPTT waveform analysis and its application in laboratory management of haemophilia A patients

Diagnosis of haemophilia A is usually made by the measurement of factor VIII (FVIII) activity that allows categorization of the disease severity. However, tests that assess global haemostasis may better reflect clinical features and give additional clinically relevant information. The aim of this study was to develop a new quantitative activated partial thromboplastin time (aPTT) waveform analysis and compare it with FVIII activities to find out whether waveform parameters are superior determinants of clinical phenotype. A total of 81 haemophilia A patients divided into two groups (37 severe, 44 non‐severe) were included in the study. The control group comprised 101 healthy male volunteers. Quantitative aPTT waveform analysis was performed with Actin FS on BCS (Siemens Healthcare Diagnostics, Marburg, Germany) using three parameters (DELTA, RATIO‐1, RATIO‐2) obtained from a single aPTT measurement with two evaluation modes. FVIII activities were measured by one‐stage clotting and two‐stage chromogenic assay. Statistically significant difference (P < 0.001) between control group and all haemophilia A patients, as well as between severe and non‐severe haemophilia A patients was obtained for all quantitative waveform parameters. Our study revealed parameter DELTA as the best waveform parameter, showing significant correlation with FVIII activities and clinical parameters, and excellent performance for distinguishing between severe and non‐severe haemophilia A patients (ROC analysis: sensitivity 97.3%, specificity 93.2%). The results obtained by new quantitative aPTT waveform analysis were superior to those obtained by standard laboratory methods. The simplicity and cost‐benefit of the method make this approach a reasonable and promising tool for assessing coagulation in haemophilia A patients.     

Safety,tolerability and immunogenicity of GS-4774, a hepatitis B virus-specific therapeutic vaccine,in healthy subjects: A randomized study

Background

GS-4774 is a recombinant, heat-killed, yeast-based immunotherapy engineered to express hepatitis B virus (HBV)-specific antigens. GS-4774 is being developed as a therapeutic vaccine for chronic HBV infection. The aim of this study was to assess the safety, tolerability and immunogenicity of GS-4774 in healthy subjects.

Design

This was a randomized, open-label, dose-ascending study. Subjects were allocated to one of three dose groups (n = 20 per group) to receive 10, 40 or 80 yeast units (YU; 1 YU = 10⁷ yeast) of GS-4774 in two immunization regimens (five subcutaneous injections at weekly intervals with one monthly booster or three subcutaneous injections at monthly intervals). T-cell-mediated responses were determined by interferon (IFN)-γ enzyme-linked immunospot (ELISpot) assay and lymphocyte-proliferation assay (LPA).

Results

Adverse events were reported by 39 of 60 (65%) subjects; all were mild or moderate and none was serious. Adverse events occurred most frequently in the highest dose group, 80 YU, and the number of individual events was higher after weekly immunization than monthly. The most common adverse events were injection-site reactions. Most (88%) subjects responded to GS-4774 by at least one of the T-cell assays. Following immunization with GS-4774, IFN-γ-producing T-cells specific for HBV antigens were detectable in 30 (51%) subjects. The ELISpot response was observed at all doses, with the highest frequency of responders occurring at the highest dose (10 YU: 45%; 40 YU: 35%; 80 YU: 74%). Proliferative responses to HBV recombinant antigens were observed in 90% subjects; responses were mainly independent of GS-4774 dose and immunization regimen.

Conclusions

GS-4774 was safe and well-tolerated in healthy subjects with injection-site reactions being the most frequently reported adverse events. With both weekly and monthly regimens, GS-4774 provided HBV-specific immune responses at all doses evaluated. Further evaluation of GS-4774 is ongoing in patients with chronic HBV infection.Clinical trial registry: Clinicaltrials.gov (NCT01779505)     

Development-specific sigma-factor essential for late-stage differentiation of Myxococcus xanthus

The gene for a developmentally expressed sigma-factor, sigB, has been isolated from Myxococcus xanthus by use of the sigA gene (formerly rpoD) of the vegetative sigma-factor as a probe. The sequence of sigB has been determined, and an open reading frame of 193 amino acid residues (Mr = 21,551) was identified. The amino-terminal region of SigB contains 69 residues, of which 35 are identical (50% identity) to the region of SigA required for core RNA polymerase binding and initiation of RNA polymerization. SigB also possesses many features commonly found in other prokaryotic sigma-factors. Analysis of an M. xanthus strain carrying a sigB-lacZ fusion gene revealed that sigB is expressed from a middle to late stage of differentiation corresponding to the period from the onset of sporulation to late development. A sigB deletion mutant displayed normal mound formation and sporulation; however, production of the ops gene product in myxospores of the delta sigB strain was shown to be blocked. Myxospores from the sigB deletion strain also exhibited severe defects in stability and viability during late development. Our data indicate that sigB encodes a sigma-factor essential for the maturation of myxospores at a late stage of M. xanthus differentiation. Our results also suggest that differentiation of M. xanthus is regulated by development-specific sigma-factors.     

Exercise in therapy and prevention of type II diabetes. Implications for blacks

The rationale for the use of exercise in the treatment of type II (non-insulin-dependent) diabetes and its special implications for Blacks are reviewed herein. When performed on a regular basis, exercise may improve glycemic control and improve several risk factors for coronary heart disease including hypertriglyceridemia, hypertension, and hyperinsulinemia. In addition, it may be a useful adjunct to diet in producing weight loss. The metabolic benefits of exercise in part appear to be related to its ability to enhance insulin sensitivity. Benefits are short lived after discontinuing exercise. Because of problems with compliance and concurrent medical problems, many patients with type II diabetes are not good candidates for an exercise-diet program. For this reason, the optimum target population may be people at risk for type II diabetes and premature atherosclerosis. Such a population might include the offspring of patients with these disorders and individuals with impaired glucose tolerance, hyperinsulinemia, gestational diabetes, and/or an android pattern of fat distribution. Type II diabetes is more common in Blacks than in the general population. In most instances, it is associated with cardiovascular risk factors benefited by exercise. Despite this, there are no available studies regarding the effects of regular exercise in Blacks with type II diabetes or those at risk for it.     

Prediction of Drug Release from Hydroxypropyl Methylcellulose (HPMC) Matrices: Effect of Polymer Concentration

Pharmaceutical Research -     

Gene expression profiling of Nm23-H2 overexpressing CAL 27 cells using DNA microarray

Nm23-H1/NDPKA and Nm23-H2/NDPKB belong to a large family of NDP kinases, group of structurally and functionally closely related enzymes. The Nm23/NDPs are known to catalyse the transfer of terminal phosphates from ATP to other NTPs and dNTPs. Besides their role in the maintenance of the cells NTP pool the nm23 genes/proteins are known to have additional different biological functions, the most important being its metastasis suppressor activity. The complete picture of roles, actions and targets of nm23 genes/proteins is yet to be discovered. Our goal was to identify the downstream targets of Nm23-H2 by subjecting Nm23-H2 overexpressing CAL 27 cells (oral squamous cell carcinoma of the tongue) to microarray analysis. Using this powerful technology we identified genes, groups of genes and signalling pathways that could be clustered into several groups: apoptosis related genes, cell cycle and DNA damage, TGFbeta (transforming growth factor beta) signalling pathway and related molecules, WNT signalling pathway, differentiation and epithelial structural and related molecules, cell adhesion, metalloproteinases and their inhibitors, vesicular transport related molecules, proteasome associated, ubiquitin mediated proteolysis and several metabolic pathways. Based on these results we suggest that nm23-H2 might have an important role in oral squamous cell carcinoma which is to be confirmed by future studies. Key words: nm23-H2, DNA microarray, oral squamous cell carcinoma.