Impact of highly active antiretroviral therapy on anemia and relationship between anemia and survival in a large cohort of HIV-infected women: Women's Interagency HIV Study

BACKGROUND: Anemia is common in HIV-infected individuals and may be associated with decreased survival. OBJECTIVE: To ascertain the impact of highly active antiretroviral therapy (HAART) on anemia and the relationship between anemia and overall survival in HIV-infected women. METHODS: A prospective multicenter study of HIV-1 infection in women. Visits occurred every 6 months, including a standardized history, physical examination, and comprehensive laboratory evaluation. The setting was a university-affiliated clinic at 6 sites in the United States. Participants were 2056 HIV-infected women from the Women's Interagency HIV Study (WIHS). The outcome measure was anemia, defined as hemoglobin (Hb) <12 g/dL. Survival analysis was based on overall mortality during the follow-up period. RESULTS: Among HIV-infected women who were not anemic at baseline, 47% became anemic by 3.5 years of follow-up. On multivariate analysis, the use of HAART was associated with resolution of anemia even when used for only 6 months (odds ratio [OR] = 1.45; P < 0.05). In the multivariate model, a CD4 cell count <200 cells/microL (OR = 0.56; P < 0.001); HIV-1 RNA level > or =50,000 copies/mL (OR = 0.65; P < 0.001), and mean corpuscular volume (MCV) value <80 fL (OR = 0.40; P < 0.001) were also associated with an inability to correct anemia. Similarly, use of HAART for 12 months or more was associated with a protective effect against development of anemia (OR = 0.71; P < 0.001). Among HIV-infected women, anemia was independently associated with decreased survival (hazard ratio [HR] = 2.58; P < 0.001). Other factors associated with decreased survival included a CD4 cell count <200 cells/microL (HR = 5.83; P < 0.001), HIV-1 RNA level > or = 50,000 copies/mL (HR = 2.12; P < 0.001), and clinical diagnosis of AIDS (HR = 2.83; P < 0.001). CONCLUSIONS: Anemia is an independent risk factor for decreased survival among HIV-infected women. HAART therapy for as little as 6 months is associated with resolution of anemia.     

cC1q-R (calreticulin) and gC1q-R/p33: ubiquitously expressed multi-ligand binding cellular proteins involved in inflammation and infection

The first component of complement, C1, is a multi-molecular complex comprising of C1q and the Ca(2+)-dependent tetramer C1r(2)-C1s(2). The traditional role of C1q within the complex is that of recognition signal-a signal, which is instantly converted into a highly specific intramolecular proteolytic activation of the C1r(2)-C1s(2) tetramer thereby triggering activation of the classical pathway. Another important function of C1q is its ability to bind to a wide range of cell types resulting in the induction of cell-specific biological responses. These cells include polymorphonuclear leukocytes, monocytes, lymphocytes, dendritic cells, endothelial cells and platelets. Interaction of C1q with endothelial cells and platelets, for example, leads to cellular activation followed by release of biological mediators and/or expression of adhesion molecules, all of which contribute, directly or indirectly to the inflammatory process. These specific responses are mediated by the interaction of C1q with C1q binding proteins or receptors on the cell surface. To date, four types of putative C1q binding cell surface expressed proteins/receptors have been described. These include cC1q-R/CR, or calreticulin (CR), a 60 kDa protein, which is also known as collectin receptor; gC1q-R/p33, a 33 kDa homotrimeric protein; C1q-Rp (CD93), a 120 kDa, O-sialoglycoprotein; and CR1 (CD35), the receptor for C3b. Although the specific role of each of these molecules in a given C1q-mediated cellular response is yet to be worked out, all of them may, in one form or another, participate in the inflammatory processes associated with vascular or atherosclerotic lesions, autoimmune diseases, or infections. The main focus of our laboratory for the past 20 years has been to elucidate the structure and function of cC1q-R/CR and gC1q-R/p33, both of which have been isolated and characterized on the basis of their ability to bind C1q. The purpose of this article is therefore to provide an up to date overview of these two proteins with particular emphasis on their unique structural and functional features, their multi-faceted nature and most importantly their role in infection and inflammation.     

Outbreak of Rabbit Hemorrhagic Disease Virus 2 Infections,Ghana

In September 2019, high mortality in commercial rabbits was reported in the Greater Accra Region of Ghana. Rabbit hemorrhagic disease virus 2 phylogenetically related to isolates from 2015–2017 outbreaks in the Netherlands was confirmed as the causative agent. The virus has not yet been detected in native rabbits in Ghana.     

Australia's notifiable diseases status, 2002: Annual report of the National Notifiable Diseases Surveillance System.

There were 57 infectious diseases notifiable at the national level in Australia in 2002. States and territories reported 100,278 cases of infectious diseases to the National Notifiable Diseases Surveillance System (NNDSS), a fall of 4 per cent compared to the number of notifications in 2001. In 2002, the most frequently notified diseases were, sexually transmitted infections (31,929 reports, 32% of total notifications), gastrointestinal infections (26,708 reports, 27% of total notifications) and bloodborne infections (23,741, 24%). There were 11,711 (12% of total) cases of vaccine preventable diseases, 3,052 (3% of total) cases of vectorborne diseases, 1,155 (1% of total) cases of zoonotic infections, two cases of quarantinable diseases (Vibrio cholerae O1) and 1,980 cases of other bacterial diseases, notified to NNDSS. Compared to 2001, notifications of sexually transmitted infections increased by 16 per cent and gastrointestinal infections by 2 per cent while bloodborne infections fell by 18 per cent. The number of notifications of chlamydial infection and Q fever were the highest since 1991 and 1995 respectively. By contrast, the number of notification for hepatitis A and measles were the lowest since 1991. For other notifiable diseases, the number of notifications was within the range of the five years between 1997 and 2002 (range = five-year mean plus or minus two standard deviations). This report also includes 2002 summary data on communicable diseases from other surveillance systems including the Laboratory Virology and Serology Reporting Scheme and sentinel general practitioner schemes.     

Metabolic activation of fluoropyrrolidine dipeptidyl peptidase-IV inhibitors by rat liver microsomes.

The current study evaluated the potential for two dipeptidyl peptidase-IV (DPP-IV) inhibitor analogs (1S)-1-(trans-4-([(4-trifluoromethoxyphenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethanaminium chloride and (1S)-1-(trans-4-([(2,4-difluorophenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethanaminium chloride (MRL-A and MRL-B), containing a fluoropyrrolidine moiety in the structure, to undergo metabolic activation. The irreversible binding of these tritium-labeled compounds to rat liver microsomal protein was time- and NADPH-dependent and was attenuated by the addition of reduced glutathione (GSH) or N-acetylcysteine (NAC) to the incubation, indicating that chemically reactive intermediates were formed and trapped by these nucleophiles. Mass spectrometric analyses and further trapping experiments with semicarbazide indicated that the fluoropyrrolidine ring had undergone sequential oxidation and defluorination events resulting in the formation of GSH or NAC conjugates of the pyrrolidine moiety. The bioactivation of MRL-A was catalyzed primarily by rat recombinant CYP3A1 and CYP3A2. Pretreatment of rats with prototypic CYP3A1 and 3A2 inducers (pregnenolone-16alpha-carbonitrile and dexamethasone) enhanced the extent of bioactivation which, in turn, led to a higher degree of in vitro irreversible binding to microsomal proteins (5- and 9-fold increase, respectively). Herein, we describe studies that demonstrate that the fluoropyrrolidine ring is prone to metabolic activation and that GSH or NAC can trap the reactive intermediates to form adducts that provide insight into the mechanisms of bioactivation.     

A Systematic Review and Meta-Analysis of the Prevalence of Post-Traumatic Stress Disorder among Homeless People

Post-traumatic stress disorder (PTSD) is common among homeless people and is associated with an increased risk of mortality from suicide, medical causes, and drug-related problems. However, there are no previous systematic review and meta-analysis studies that reported the consolidated magnitude of PTSD among homeless people. A literature search was conducted on PubMed, Embase, and Scopus to discover pertinent studies that determined the prevalence of PTSD among the homeless. Articles were evaluated by titles, abstracts, and full-text. Comprehensive meta-analysis software was used to conduct the meta-analysis. Subgroup and sensitivity analysis were performed and Cochran’s Q- and the I² test were used to assess heterogeneity. The evidence of publication bias was evaluated by using Egger’s test and visual inspection of the symmetry in funnel plots. From the total, 19 studies with 20,364 participants across seven countries were included in the final analysis. Our meta-analysis revealed that the pooled prevalence of PTSD among homeless people was 27.38% (95% CI; 21.95–33.57). In our subgroup analysis, we found that the prevalence of PTSD was considerably high as measured by the screening instrument (35.93%) than the diagnostic instrument (23.57% %). The prevalence of PTSD among homeless showed a significant variation by the location of the studies, the instruments used to measure PTSD as well as the quality of the included studies. This review showed that the pooled prevalence estimate of PTSD among homeless peoples was remarkably high (27.38%). Early screening and treatment of PTSD among homeless peoples are warranted to alleviate suffering.