The chemistry and pharmacology of synthetic cannabinoid SDB‐006 and its regioisomeric fluorinated and methoxylated analogs

Synthetic cannabinoids are the largest and most structurally diverse class of new psychoactive substances, with manufacturers often using isomerism to evade detection and circumvent legal restriction. The regioisomeric methoxy‐ and fluorine‐substituted analogs of SDB‐006 (N‐benzyl‐1‐pentyl‐1H‐indole‐3‐carboxamide) were synthesized and could not be differentiated by gas chromatography–mass spectrometry (GC–MS), but were distinguishable by liquid chromatography–quadrupole time‐of‐flight–MS (LC–QTOF–MS). In a fluorescence‐based plate reader membrane potential assay, SDB‐006 acted as a potent agonist at human cannabinoid receptors (CB₁ EC₅₀ = 19 nM). All methoxy‐ and fluorine‐substituted analogs showed reduced potency compared to SDB‐006, although the 2‐fluorinated analog (EC₅₀ = 166 nM) was comparable to known synthetic cannabinoid RCS‐4 (EC₅₀ = 146 nM). Using biotelemetry in rats, SDB‐006 and RCS‐4 evoked comparable reduction in body temperature (~0.7°C at a dose of 10 mg/kg), suggesting lower potency than the recent synthetic cannabinoid AB‐CHMINACA (>2°C, 3 mg/kg).     

Platelet-Derived MRP-14 Induces Monocyte Activation in Patients With Symptomatic Peripheral Artery Disease

Background

Peripheral artery disease (PAD), a diffuse manifestation of atherothrombosis, is a major cardiovascular threat. Although platelets are primary mediators of atherothrombosis, their role in the pathogenesis of PAD remains unclear.

Development of a symmetry index using discrete variables

The objective of this study was to introduce and evaluate a new methodology to quantify lower extremity movement symmetry using data from the stance phase in over-ground running. Seventeen subjects completed five heel–toe over-ground running trials per leg over a force platform at 3.33 ± 0.5 m s^?1 with retro-reflective markers on both legs and the pelvis. Thirty kinetic and kinematic variables were collected and 12 were chosen as important variables for calculating symmetry based on low variance of the data and their functional relevance with respect to symmetry. The developed formula uses the integral of the absolute value of the difference between the left and right leg during the stance phase. The results were divided into a sagittal, transverse, and frontal index, as well as a global index for all three planes of motion. This enabled analyses from both general and categorical perspectives, whereby individuals could be identified as symmetrical in one plane and asymmetrical in the other. The new methodology allows for the evaluation of symmetry over the entire stance phase and accounts for time lags between left and right legs. To learn more about symmetry during particular movements, future research should include larger cohorts, use consecutive force platforms, examine the flight phase of running and include subjects that are known to have asymmetrical gait.     

Microbial translocation, the innate cytokine response, and HIV-1 disease progression in Africa

Reports from the United States have demonstrated that elevated markers of microbial translocation from the gut may be found in chronic and advanced HIV-1 infection and are associated with an increase in immune activation. However, this phenomenon's role in HIV-1 disease in Africa is unknown. This study examined the longitudinal relationship between microbial translocation and circulating inflammatory cytokine responses in a cohort of people with varying rates of HIV-1 disease progression in Rakai, Uganda. Multiple markers for microbial translocation (lipopolysaccharide, endotoxin antibody, and sCD14) did not change significantly during HIV-1 disease progression. Moreover, circulating immunoreactive cytokine levels either decreased or remained virtually unchanged throughout disease progression. These data suggest that microbial translocation and its subsequent inflammatory immune response do not have a causal relationship with HIV-1 disease progression in Africa.     

Improved performance of enzyme-linked immunosorbent assays and the effect of human immunodeficiency virus coinfection on the serologic detection of herpes simplex virus type 2 in Rakai, Uganda

Ugandan subjects (820) were tested by Focus HerpeSelect enzyme-linked immunosorbent assay (ELISA), Kalon herpes simplex virus type 2 ELISA, and BioKit rapid test, and the results were compared to those of Western blotting. Higher-than-standard-index cutoff values gave optimal sensitivity and specificity. Kalon ELISA was the optimal assay when an index value of 1.5 was used (sensitivity, 91.7%; specificity, 92.4%).     

Paternal Pregnancy Intention and Breastfeeding Duration: Findings from the National Survey of Family Growth

Objectives Despite the benefits of breastfeeding, less than a fifth of American mothers breastfeed for the recommended duration. Paternal support plays a major role in maternal and child health outcomes; however, the influence of paternal pregnancy intention on breastfeeding duration is under investigated. This study examines the relationship between fathers’ pregnancy intention and breastfeeding duration. Methods Data from the 2011–2013 National Survey of Family Growth were analyzed using cross-sectional methodology. Women who were pregnant, never received medical help to become pregnant, whose partner was aged 18–49 years, and who responded to questions related to paternal pregnancy intention and breastfeeding were included in the analysis (N = 2089). Multinomial logistic regression, odds ratios and 95 % confidence intervals were calculated. There was a statistically significant interaction between father’s age and father’s pregnancy intention (P = 0.0385) and all models were stratified by paternal age. Results Fathers aged 18–24 years with a mistimed pregnancy were 2.3 times more likely to have a child who was never breastfed, (AOR 2.27, 95 % CI 1.39–3.70) and 1.7 times more likely to have a child who was breastfed 6 months or less (AOR 1.69, 95 % CI 1.28–2.23) compared to fathers with an intended pregnancy. No statistically significant association was observed among fathers aged 25–49 years. Conclusion Findings from this study show a relationship between mistimed pregnancies and breastfeeding duration among younger fathers. Healthcare professionals should develop breastfeeding interventions targeting fathers and young families.