The impact of the COVID-19 pandemic on social determinants of health, mental health, and substance use among key populations affected by sexually transmitted and blood-borne infections in Canada.

OBJECTIVES: We assessed the impact of the COVID-19 pandemic on social determinants of health, mental health, substance use, and access to mental health and harm reduction services among key populations disproportionately impacted by sexually transmitted and blood-borne infections (STBBI). METHODS: Online surveys (2021‒2022) were conducted in Canada among people who use drugs or alcohol (PWUD); African, Caribbean, and Black people (ACB); and First Nations, Inuit, and Métis peoples (FNIM). Descriptive analyses were conducted on social determinants of health, substance use, and access to services, stratified by changes in mental health status since the start of the pandemic. RESULTS: A total of 3773 participants (1034 PWUD, 1556 ACB, and 1183 FNIM) completed the surveys, with 45.6% reporting a major/moderate impact of the pandemic on their ability to pay bills and 53% experiencing food insecurity since the start of the pandemic. Half (49.4%) of participants reported deteriorating mental health. A higher increase in substance use and related behaviours was seen in those with worsening mental health. Among those using substances, two thirds (69.4%) of those with worsening mental health reported increasing their use of substances alone, compared to 46.9% of those with better/similar mental health. Access to mental health and harm reduction services was low. CONCLUSION: These intersecting health issues are among the risk factors for STBBI acquisition and act as barriers to care. Equitable interventions and policies addressing downstream and upstream determinants of health, with meaningful and sustainable leadership from key populations, may improve their health and well-being, to lower STBBI impact and improve future pandemic responses.

RéSUMé: OBJECTIFS: Nous avons évalué l'impact de la pandémie de COVID-19 sur les déterminants sociaux de la santé, la santé mentale, la consommation de substances et l'accès aux services de santé mentale et de réduction des méfaits des populations clés qui sont affectées de manière disproportionnée par les infections transmissibles sexuellement et par le sang (ITSS). MéTHODES: Des enquêtes en ligne (2021‒2022) ont été menées au Canada auprès de personnes utilisatrices de drogues ou d'alcool (PUD), de personnes africaines, caribéennes et noires (ACN) et des peuples des Premières Nations, des Inuits et des Métis (PNIM). Des analyses descriptives ont été effectuées sur les déterminants sociaux de la santé, la consommation de substances et l'accès aux services, stratifiés selon les changements dans l'état de santé mentale depuis le début de la pandémie. RéSULTATS: Un total de 3 773 participants (1 034 PUD, 1 556 ACN et 1 183 PNIM) ont complété les enquêtes, dont 45,6 % ont rapporté un impact majeur/modéré de la pandémie sur leur capacité à payer leurs factures et 53 % ont vécu de l'insécurité alimentaire depuis le début de la pandémie. La moitié (49,4 %) des participants ont signalé une détérioration de leur santé mentale. Une augmentation plus élevée de la consommation de substances et des comportements liés a été observée chez ceux dont la santé mentale s'est détériorée. Parmi ceux qui consommaient des substances, deux tiers (69,4 %) de ceux dont la santé mentale s'était détériorée ont signalé une augmentation de leur consommation solitaire de substances, comparativement à 46,9 % de ceux dont la santé mentale était meilleure ou similaire. L'accès aux services de santé mentale et de réduction des méfaits était faible. CONCLUSION: Ces problèmes de santé croisés font partie des facteurs de risque d'acquisition des ITSS et constituent des obstacles aux soins. Des interventions et des politiques équitables, tenant compte des déterminants de la santé en amont et en aval, avec un leadership significatif et durable des populations clés, peuvent améliorer leur santé et leur bien-être, réduire l'impact des ITSS et améliorer les réponses aux futures pandémies.

A role for cyclic-GMP dependent protein kinase in anoikis.

Anoikis is an essential process in which a loss of adhesion to the substratum alters intracellular signaling pathways that lead to apoptosis. Using phosphorylation of vasodilator stimulated phosphoprotein (VASP) as an indicator of cGMP-dependent protein kinase (PKG) activity in vivo, it was found that suspension of the colon epithelial cell line (CCD841) leads to rapid and transient activation of PKG that lasted several hours. The colon carcinoma lines SW480 and SW620 do not express endogenous PKG, but exogenously expressed PKG was similarly activated upon cell suspension. To determine whether PKG has a role in apoptosis following cell suspension, poly-ADP ribose polymerase (PARP) cleavage and propidium iodide staining were measured. After 24 h in suspension it was found that approximately 50% of CCD841 cells exhibited apoptosis, whereas apoptosis was not detected in either of the colon carcinoma cell lines. Inhibition of type 1 PKG by expression of a dominant negative PKG construct (G1alphaR-GFP), or by incubation with the PKG inhibitor peptide DT-2, blocked apoptosis in suspended CCD841 cells by approximately 50%. Furthermore, expression of exogenous PKG in SW620 and SW480 cells conferred partial sensitivity anoikis. Taken together these findings indicate that PKG has an important role in the induction of apoptosis following suspension of normal colon epithelial cells, and loss of PKG expression in colon tumor cells may contribute to resistance to anoikis.

Role of electron microscopy in Nipah virus outbreak investigation and control.

In 1998, a novel paramyxovirus (order Mononegavirales, family Paramyxoviridae, subfamily Paramyxovirinae, genus Henipavirus) emerged in peninsular Malaysia causing fatal encephalitis in humans and severe respiratory illness with encephalitis in pigs. The virus was successfully isolated in cultured mammalian cells. Transmission electron microscopy of infected tissue culture cells played a crucial role in the early preliminary identification of the causative agent of the outbreak. This in turn was pivotal to determine the correct direction of control measures that subsequently brought the epidemic under control. In light of this investigation, and indeed identification of infectious agents associated with other disease episodes, electron microscopy will remain an important frontline method for rapid diagnostic virology and investigation of any future outbreak of new and unusual cases of illness suspected of an infectious aetiology.

An anti-tumor role for cGMP-dependent protein kinase.

This study compared Type-1 cGMP-dependent protein kinase (PKG) expression in normal and tumor tissues and examined PKG function in tumor growth. Studies with a cDNA array revealed that PKG expression was reduced in many tumors compared to respective normal tissue. This decrease in PKG expression was confirmed using quantitative RT-PCR and western blotting of matched colon specimens from normal epithelium and tumor tissue, and also in colon derived cell lines where luciferase reporter analysis revealed that the decreased expression occurred at the transcriptional level. Using SW620 colon carcinoma cells engineered for inducible expression of PKG1beta, it was found that exogenous PKG1beta lead to decreased tumor growth and invasiveness in nude mouse xenografts.

The impact of syphilis mass treatment one year later: self-reported behaviour change among participants.

In 2000, syphilis mass treatment using oral azithromycin was delivered to at-risk British Columbians during a sex trade-related outbreak. The initiative included education, counselling and referral. This cross-sectional, observational study examines knowledge, attitudes and self-reported behaviour after one year among mass treatment participants compared with eligible non-participants. Participants self-reported positive changes: reduction in sexual partners overall (P=0.001) and for sex workers (P<0.01), decrease in unprotected oral sex (P=0.03), knowledge of asymptomatic syphilis (P=0.02), positive attitudes to mass treatment (P=0.02) and to the street nurses (P=0.01). Increased awareness was associated with increased condom use for vaginal sex overall (P=0.02) and for sex workers (P=0.03) and increased condom use for oral sex (P=0.05). There was no difference in syphilis incidence. Syphilis outbreak interventions that include education, support and referral can result in long-term positive behaviour changes.

Towards targeted screening for acute HIV infections in British Columbia.

BACKGROUND: Our objective was to describe the characteristics of acute and established HIV infections diagnosed in the Canadian province of British Columbia. Province-wide HIV testing and surveillance data were analyzed to inform recommendations for targeted use of screening algorithms to detect acute HIV infections. METHODS: Acute HIV infection was defined as a confirmed reactive HIV p24 antigen test (or HIV nucleic acid test), a non-reactive or reactive HIV EIA screening test and a non-reactive or indeterminate Western Blot. Characteristics of unique individuals were identified from the British Columbia HIV/AIDS Surveillance System. Primary drug resistance and HIV subtypes were identified by analyzing HIV pol sequences from residual sera from newly infected individuals. RESULTS: From February 2006 to October 2008, 61 individuals met the acute HIV infection case definition, representing 6.2% of the 987 newly diagnosed HIV infections during the analysis period. Acute HIV infection cases were more likely to be men who have sex with men (crude OR 1.71; 95% CI 1.01-2.89], to have had a documented previous negative HIV test result (crude OR 2.89; 95% CI 1.52-5.51), and to have reported a reason for testing due to suspected seroconversion symptoms (crude OR 5.16; 95% CI 2.88-9.23). HIV subtypes and rates of transmitted drug resistance across all classes of drugs were similar in persons with both acute and established HIV infections. CONCLUSIONS: Targeted screening to detect acute HIV infection is a logical public health response to the HIV epidemic. Our findings suggest that acute HIV infection screening strategies, in our setting, are helpful for early diagnosis in men who have sex with men, in persons with seroconversion symptoms and in previously negative repeat testers.

Eye position compensation improves estimates of response magnitude and receptive field geometry in alert monkeys.

Studies of visual function in behaving subjects require that stimuli be positioned reliably on the retina in the presence of eye movements. Fixational eye movements scatter stimuli about the retina, inflating estimates of receptive field dimensions, reducing estimates of peak responses, and blurring maps of receptive field subregions. Scleral search coils are frequently used to measure eye position, but their utility for correcting the effects of fixational eye movements on receptive field maps has been questioned. Using eye coils sutured to the sclera and preamplifiers configured to minimize cable artifacts, we reexamined this issue in two rhesus monkeys. During repeated fixation trials, the eye position signal was used to adjust the stimulus position, compensating for eye movements and correcting the stimulus position to place it at the desired location on the retina. Estimates of response magnitudes and receptive field characteristics in V1 and in LGN were obtained in both compensated and uncompensated conditions. Receptive fields were narrower, with steeper borders, and response amplitudes were higher when eye movement compensation was used. In sum, compensating for eye movements facilitated more precise definition of the receptive field. We also monitored horizontal vergence over long sequences of fixation trials and found the variability to be low, as expected for this precise behavior. Our results imply that eye coil signals can be highly accurate and useful for optimizing visual physiology when rigorous precautions are observed.