Racial Discrimination, Social Support, and Sexual HIV Risk among Black Heterosexual Men

Numerous studies document the adverse impact of racial discrimination on African Americans’ health outcomes, but few have focused on HIV risk. We examined the relationship between racial discrimination and sexual risk in a sample of 526 Black heterosexual men and tested the hypothesis that social support would moderate this relationship. Participants in the predominantly low-income urban sample ranged in age from 18 to 45. High social support had a buffering impact on the relationship between racial discrimination and sexual risk. Among men reporting high racial discrimination, those with more social support reported less sexual risk than men with low social support. Men who reported high racial discrimination and low social support reported more sexual risk than men in any of the other groups. The study highlights social support as an important but understudied protective factor that may reduce sexual risk for Black heterosexual men who report high levels of racial discrimination.     

Long‐term alterations in monocyte function after elective cardiac surgery

Optimal immunological homoeostasis determines the long‐term recovery of patients in the postoperative period. The functional adaptability of monocytes plays a pivotal role in adjusting the host's response to an insult, immunostasis and long‐term health, and may help to determine successful recovery. We undertook a longitudinal analysis of the functional adaptability of monocytes in 20 patients undergoing heart surgery with cardiopulmonary bypass, as a model of severe stress. Using each patient's pre‐cardiopulmonary bypass data as a baseline, we investigated the characteristics of peripheral blood monocytes’ functional plasticity in‐vitro before elective bypass, and three months afterwards. Approximately 30% of subjects showed diminished monocyte plasticity, as demonstrated by decreased monocyte differentiation into dendritic cells three months after bypass. Diminished monocyte functional plasticity was related to over‐production of macrophage colony‐stimulating factor. Adding a neutralising antibody to macrophage colony‐stimulating factor corrected the monocytes’ differentiation defect. Finally, patients with reduced monocyte plasticity had significantly elevated serum C‐reactive protein, with a concomitant increase in cytomegalovirus IgG antibody titres, suggestive of the acquisition of immuno‐suppressive traits. Our study shows that severe surgical stress resulted in a lasting immunological defect in individuals who had seemingly recovered.     

An Empiric Risk Score to Guide PrEP Targeting Among MSM in Coastal Kenya

Men who have sex with men (MSM), who have heterogeneous HIV-acquisition risks are not specifically targeted in Kenyan pre-exposure prophylaxis (PrEP) guidelines. We used data from an open cohort, which followed 753 initially HIV-negative MSM participants for more than 1378.5 person-years, to develop an empiric risk score for targeting PrEP delivery. Independent predictors of incident HIV-1 infection in this cohort were an age of 18–24 years, having only male sex partners, having receptive anal intercourse, having any unprotected sex, and having group sex. Poisson model coefficients were used to assign a numeric score to each statistically significant predictor. A risk score of ≥?1 corresponded to an HIV-1 incidence of ≥?2.2 [95% confidence interval (CI) 1.2–4.1] and identified 81.3% of the cohort participants as being at high risk for HIV-1 acquisition. The area under the receiver operating characteristic curve was 0.76 (95% CI 0.71–0.80). This empiric risk score may help Kenyan health care providers to assess HIV-1 acquisition risk and encourage PrEP uptake by high-risk MSM.     

Comparative examination of two Zanthoxylum benzophenanthridine alkaloids for effects in rabbits

Cardiovascular activities of nitidine chloride from Zanthoxylum chalybeum have been compared with those of 9-methoxychelerythrine. Whereas nitidine chloride was found to show significant hypotensive activity in rabbits, 9-methoxychelerythrine chloride showed no hypotensive activity. The effect of nitidine chloride on isolated rabbit heart was also compared with those of adrenaline and acetyicholine. 9-Methoxychelerythrine, which has hitherto been regarded as an artefact formed by recrystallization of chelerythrine base from methanol, has been shown in this work to be a true natural constituent of Zanthoxylum chalybeum.     

Acceptability of a Pilot Intervention of Voluntary Medical Male Circumcision and HIV Education for Street-Connected Youth in Western Kenya

Purpose

Street-connected youth (SCY) in Kenya and elsewhere in sub–Saharan Africa are at high risk of HIV. Voluntary Male Medical Circumcision (VMMC) reduces the risk of female-to-male HIV transmission. Circumcision is also a traditional coming-of-age process in many Kenyan ethnic groups. This paper describes the acceptability of VMMC delivered as part of a ten-day healing, educational, and ‘coming-of-age’ retreat implemented as a pilot with SCY.

Identification of small-molecule inhibitors of ricin and shiga toxin using a cell-based high-throughput screen

The Category B agents, ricin and shiga toxin (Stx), are RNA N-glycosidases that target a highly conserved adenine residue within the sarcin-ricin loop of eukaryotic 28S ribosomal RNA. In an effort to identify small-molecule inhibitors of these toxins that could serve as lead compounds for potential therapeutics, we have developed a simple Vero cell-based high-throughput cytotoxicity assay and have used it to screen ∼81,300 compounds in 17 commercially available chemical libraries. This initial screen identified ∼300 compounds with weak (≥30 to <50%), moderate (≥50 to <80%), or strong (≥80%) ricin inhibitory activity. Secondary analysis of 244 of these original “hits” was performed, and 20 compounds that were capable of reducing ricin cytotoxicity by >50% were chosen for further study. Four compounds demonstrated significant dose-dependent ricin inhibitory activity in the Vero cell-based assay, with 50% effective inhibitory concentration (EC₅₀) values ranging from 25 to 60 μM. The same 20 compounds were tested in parallel for the ability to inhibit ricin’s and Stx1’s enzymatic activities in an in vitro translation reaction. Three of the 20 compounds, including the most effective compound in the cell-based assay, had discernible anti-toxin activity. One compound in particular, 4-fluorophenyl methyl 2-(furan-2-yl)quinoline-4-carboxylate (“compound 8”), had 50% inhibitory concentration (IC₅₀) of 30 μM, a value indicating >10-fold higher potency than is the case for previously described ricin-Stx1 inhibitors. Computer modeling predicted that compound 8 is capable of docking within the ricin active site. In conclusion, we have used a simple high-throughput cell-based method to identify several new small-molecule inhibitors of ricin and Stx.     

Identification of new classes of ricin toxin inhibitors by virtual screening

We used two virtual screening programs, ICM and GOLD, to dock nearly 50,000 compounds into each of two conformations of the target protein ricin A chain (RTA). A limited control set suggests that candidates scored highly by two programs may have a higher probability of being ligands than those in a list from a single program. Based on the virtual screens, we purchased 306 compounds that were subjected to a kinetic assay. Six compounds were found to give modest, but significant, inhibition of RTA. They also tended to inhibit Shiga toxin A chain, with roughly the same IC₅₀. The compounds generally represent novel chemical platforms that do not resemble RTA substrates, as currently known inhibitors do. These six were also tested in a cell-based assay for their ability to protect cells from intact ricin. Two compounds were effective in this regard, showing modest to strong ricin inhibition, but also showing some cytotoxicity. RTA, with its large, polar active site is a difficult drug design target which is expected to bind small molecules only weakly. The ability of the method to find these novel platforms is encouraging and suggests virtual screening can contribute to the search for ricin and Shiga toxin inhibitors.     

We Asked the Experts: The Tropical Surgeon: Everywhere in Chains But Not Imprisoned

World Journal of Surgery -     

Depression Symptoms in Patients with Diabetic Peripheral Neuropathy

AIMThe study aimed to investigate the possible relationship between diabetic peripheral neuropathy (DPN) and the development of depressive symptoms in patients with type 2 diabetes mellitus (T2D).METHODSA comparative non-experimental study was conducted. Ninety-five T2D individuals aged 65 years and more were recruited. The sample was divided into two groups: 50 participants with T2D and without DPN and 45 participants with T2D and DPN. The Patient Health Questionnaire 9 (PHQ-9) was used to collect information about low mood and depression symptoms in the subjects recruited.RESULTSParticipants with DPN recorded higher scores on PHQ-9 than those with T2D only. The mean PHQ-9 score for the DPN group (6.09) was significantly higher than that for the T2D only group (2.24) (p < 0.001). Participants with DPN were more likely to have mild to moderate or moderately severe low mood and depression symptoms than T2D only participants who exhibited minimal to no low mood and depressive symptoms.CONCLUSIONSThe association between DPN and depression is confirmed by this study, with significant depressive symptoms found in patients with neuropathy when compared to diabetes patients with no neurological complications. It is therefore important that discomfort and emotional problems caused by DPN should be taken seriously and addressed closely in the management of DPN in order to prevent depression. Also, a change in screening practices to identify patients with diabetes and depressive symptoms is required.