Non-alcoholic fatty liver disease in HIV infection associated with altered hepatic fatty acid composition

Hepatic fatty acid (FA) composition, especially a reduction in n-3 polyunsaturated FA (PUFA) may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is common in HIV-infection.. In a cross-sectional study we compared hepatic FA composition between 20 HIV-infected men with NAFLD (HIV/NAFLD), 21 HIV-negative men with NAFLD (NAFLD), and 7 healthy controls. Within HIV/NAFLD we compared simple steatosis (HIV/SS) to steatohepatitis (HIV/NASH). FA composition in liver and erythrocytes, oxidative stress, diet, and exercise were assessed. Major findings (P<0.05) were: 1) higher hepatic n-6/n-3 ratio in HIV/NAFLD [median (range)] [8.08 (1.08-21.52)] compared to controls [5.83 (3.58-6.93)] and NAFLD [5.97 (1.46-10.40)], with higher n-6 PUFA in HIV/NAFLD compared to NAFLD; 2) lower n-3 PUFA in erythrocytes (mol%), a marker for dietary intake, in HIV/NAFLD [5.26 (1.04-11.75)] compared to controls [8.92 (4.79-12.67)]; 3) the ratios of long-chain PUFA products to essential FA precursors of the n-6 and n-3 series were lower in HIV/NAFLD and NAFLD compared to controls. In contrast, the ratio of oleic/stearic acid was higher in HIV/NAFLD compared to the other groups. These ratios are indirect markers of enzymatic FA desaturation and elongation. Hepatic PUFA, especially biologically active long-chain PUFA, were also lower in HIV/NASH compared to HIV/SS. Oxidative stress was not different among the groups. We conclude that HIV/NAFLD is associated with altered hepatic FA composition. Changes may be due to impaired FA metabolism or suboptimal n-3 PUFA intake. The potential role of n-3 PUFA (e.g. fish oil) to treat or prevent HIV/NAFLD warrants further investigation.     

Regulation of activation-induced deaminase stability and antibody gene diversification by Hsp90

Activation-induced deaminase (AID) is the mutator enzyme that initiates somatic hypermutation and isotype switching of the antibody genes in B lymphocytes. Undesired byproducts of AID function are oncogenic mutations. AID expression levels seem to correlate with the extent of its physiological and pathological functions. In this study, we identify AID as a novel Hsp90 (heat shock protein 90 kD) client. We find that cytoplasmic AID is in a dynamic equilibrium regulated by Hsp90. Hsp90 stabilizes cytoplasmic AID, as specific Hsp90 inhibition leads to cytoplasmic polyubiquitination and proteasomal degradation of AID. Consequently, Hsp90 inhibition results in a proportional reduction in antibody gene diversification and off-target mutation. This evolutionarily conserved regulatory mechanism determines the functional steady-state levels of AID in normal B cells and B cell lymphoma lines. Thus, Hsp90 assists AID-mediated antibody diversification by stabilizing AID. Hsp90 inhibition provides the first pharmacological means to down-regulate AID expression and activity, which could be relevant for therapy of some lymphomas and leukemias.     

A paradigm to assess postural responses triggered by anteroposterior translations in healthy seated individuals

Postural adjustments following mechanical perturbations have been studied in healthy seated humans. However, little is known on the minimal intensity that should be used to provoke a reaction. This knowledge could be essential to assess seated postural deficits in some pathological populations. The goal of the present study was to identify a low-intensity perturbation that could elicit postural reactions in healthy seated individuals. Six healthy participants sat on an adapted ergonomic chair fixed on a moveable support surface that was submitted to forward and backward translations. The head and trunk kinematics as well as the activity of sixteen neck and trunk muscles were recorded. The head, arm and trunk center of mass was computed using kinematics and standard anthropometric tables. We found that ramp displacements with an acceleration profile reaching a maximal value of 1.17 m/s² elicited reliable kinematic and electromyographic reactions across participants. Head and trunk segments initially responded opposite to the direction of translation, then reversed direction. Median peak-to-peak angular displacements in the neck, head and trunk, respectively, reached 3.6°, 7.0° and 7.1° for forward translations, and 4.0°, 8.2° and 7.0° for backward translations. For forward translations, neck and trunk flexor muscles were activated first, followed by the extensor muscles, whereas for backward translations, extensor muscles were activated first, followed by flexors. Although this perturbation is of low-intensity compared to those typically used previously to evoke postural reactions, this stimulus is sufficient to elicit a reliable response. We suggest that such a perturbation could be used to assess the physical condition of individuals with neck injuries.     

COVAX and equitable access to COVID-19 vaccines

ObjectiveTo evaluate equity in the allocation and distribution of vaccines for coronavirus disease 2019 (COVID-19) to countries and territories participating in the COVID-19 Vaccines Global Access (COVAX) Facility.MethodsWe used publicly available data on the numbers of COVAX vaccine doses allocated and distributed to 88 countries and territories qualifying for COVAX-sponsored vaccine doses and 60 countries self-financing their vaccine doses facilitated by COVAX. We conducted a benefit–incident analysis to examine the allocation and distribution of vaccines based on countries’ gross domestic product (GDP) per capita. We plotted cumulative country-level per capita allocation and distribution of COVID-19 vaccines from COVAX against the ranked per capita GDP of the countries and territories to generate a measure of the equity of COVAX benefits.FindingsBy 23 January 2022 the COVAX Facility had allocated a total of 1 678 517 990 COVID-19 vaccine doses, of which 1 028 291 430 (61%) doses were distributed to 148 countries and territories. Taking account of COVAX subsidies, we found that countries and territories with low per capita GDP benefited more than higher-income countries in the numbers of vaccines. The benefits increased further when the analysis was adjusted by population age group (aged 65 years and older).ConclusionThe COVAX Facility is helping to balance global inequities in the allocation and distribution of COVID-19 vaccines. However, COVAX alone has not been enough to reverse the inequality of total COVID-19 vaccine distribution. Future studies could examine the equity of all COVID-19 vaccine allocation and distribution beyond the COVAX-facilitated vaccines.     

Formal and Informal Control of Cannabis: Regular Users' Experience

Background: The debate on recreational use of cannabis, recently relaunched by the election of the Liberal Party of Canada that intends to legalize and regulate its use and access, implies a better understanding of social control mechanisms that are in place, and their influence on users' behaviors. Objective: This study addresses the issue of formal and informal controls by providing, first, a theoretical perspective of this concept, and, second, by illustrating its operation from the users' perspective. Methods: Semi-structured interviews were conducted with 164 regular, adult cannabis users recruited in four large Canadian cities (Vancouver, Toronto, Montreal, and Halifax). An initial qualitative analysis based on the principles of grounded theory was conducted. The main categories identified were then used to find and re-code relevant material on the respondents' experience with formal and informal control (secondary analysis). Results: The users' perspective shows that mechanisms of informal control play an important role in defining the social context of their use (when, where, and with whom cannabis is consumed). In contrast, formal control had no deterrent impact on the cessation or reduction of use, but affected their behavior by influencing them to change the context of their practices to avoid criminal legal consequences and stigmatization. Conclusions/Importance: The regulatory controls based in public health that the Canadian government plans to implement (replacing criminal ones), should be based on a better understanding of current practices and patterns of cannabis users, and in accordance with informal controls already in place. Legislative formal controls, in a regulatory model, that are better defined and consistent with social practices, will be more accepted and respected by the user population and thus likely to be more effective in reducing harm.     

Psychological costs of bone marrow transplantation in children.

The emotional strain of bone marrow transplantation procedures on child patients, family members and hospital personnel is described, and an illustrative case history is offered. Reasons for the unusually close relationship between family and staff are considered, and the necessity of appropriate psychological support for patients, siblings, parents, and members of the medical team is delineated.