Metabolic Profile of Individuals with and without Type 2 Diabetes from Sub-Saharan Africa.

Epidemiological data predicts that sub-Saharan Africa will have the largest increase in type 2 diabetes (T2D) prevalence over the next two decades. Metabolomics studies have identified biomarkers that could improve T2D diagnosis and follow-up. However, no studies have characterized the metabolome of people from sub-Saharan Africa. Plasma samples from Senegalese individuals with T2D (n = 31) or without T2D (n = 34) were compared using measures of oxidative stress damage and plasma antioxidant enzyme activity and mass-spectrometry-based metabolomics analyses. Results showed that glucose, lactate, and tricarboxylic acid metabolites (fumarate, malate, and succinate) were increased in the T2D group, suggesting alterations in glycolysis and mitochondrial dysfunction. Several amino acids (leucine, isoleucine, valine, and tryptophan) and long-to-very-long-chain fatty acids were higher in the T2D group. Finally, elevated levels of ketone bodies and acylcarnitines were observed along with increased levels of oxidative stress damage and antioxidant activity. In conclusion, the T2D group exhibited modifications in metabolites previously shown to be associated with T2D risk in populations from other areas of the world. Future studies should seek to test whether these metabolites could be used as predictors for T2D-related complications in people from sub-Saharan Africa.

Coaching for Surgeons: A Scoping Review of the Quantitative Evidence.

To characterize quantitative studies on coaching interventions for professional surgeons to understand how surgical coaching is defined; examine how different coaching programs are designed, implemented, and evaluated; and identify any relevant research gaps. Background: Surgical coaching is gaining attention as an approach that could help surgeons optimize performance and improve overall wellbeing. However, surgical coaching programs and definitions of coaching vary widely between studies. Methods: A systematic literature search of PubMed, Scopus, Web of Science, CENTRAL, clinicaltrials.gov, and WHO ICTRP was conducted according to the PRISMA-ScR framework to identify studies and registered clinical trials written in English. Original quantitative studies on coaching interventions for professional surgeons were included. Characteristics of the coachees, coaching programs, study designs, outcomes, and findings were charted and analyzed. Results: From 2589 references, 8 studies (6 published; 2 registered trials) met inclusion criteria. Published studies targeted technical or nontechnical skills, included 2-26 surgeons as coachees, and used coaches who were surgeons. Two studies demonstrated that surgeons react positively to coaching. Studies showed inconsistent effects on technical/nontechnical skills. Only two studies measured patient adverse events and reported no significant positive impacts. The registered randomized trials targeted surgeons' physiological parameters or wellbeing and used professional coaches. These trials measure surgeon and patient outcomes. Conclusions: There is an emerging interest in coaching programs to improve surgeons' performance by targeting their professional skills and personal factors. However, more randomized trials are needed to evaluate the impact of coaching interventions on patient outcomes and surgeon wellness.

Sex-related differences and effects of short and long trail running races on resting muscle-tendon mechanical properties.

The purpose of the study was to assess sex-related differences in resting mechanical properties and adaptations of skeletal muscles and tendons in response to trail running races of different distances using multi-site shear wave elastography assessments of the lower limb, force capacity and blood analyses. Sex differences in resting mechanical properties of knee extensor and plantar flexor muscles and tendons were characterized by shear wave velocity (SWV) measurements in healthy males (N = 42) and females (N = 25) trained in long-distance running. Effects of running distance on muscle and tendon properties were assessed in short (<60 km, N = 23) vs. long (>100 km, N = 26) distance races. Changes in isometric maximal voluntary contraction torque, serum C-reactive protein and creatine kinase activity were also quantified after running races. Higher SWV of relaxed triceps surae muscle was detected in females as compared to males before running races (+4.8%, p = 0.006), but the significant increases in triceps surae muscle group (+7.0%, p = 0.001) and patellar tendon SWV (+15.4%, p = 0.001) after short-distance races were independent of sex. A significant decrease in triceps surae muscle SWV was found after long-distance races in the whole experimental population (-3.1%, p = 0.049). Post-races increase in C-reactive protein and creatine kinase activity were significantly correlated to the relative decreases in triceps surae and quadriceps femoris skeletal muscle SWV (ρ = -0.56, p = 0.001 and ρ = -0.51, p = 0.001, respectively). Resting mechanical properties of muscles and tendons are affected by sex, and adaptations to trail races are related to running distance. Exercise-induced changes in resting skeletal muscle mechanical properties are associated with enhanced indirect markers of inflammation and muscle damage.

Hemodialysis-Related Complement and Contact Pathway Activation and Cardiovascular Risk: A Narrative Review.

Individuals receiving long-term hemodialysis are at increased risk of developing cardiovascular disease (CVD). Traditional cardiovascular risk factors do not fully explain the high CVD risk in this population. During hemodialysis, blood interacts with the biomaterials of the hemodialysis circuit. This interaction can activate the complement system and the factor XII-driven contact system. FXII activation triggers both the intrinsic pathway of coagulation and the kallikrein-kinin pathway, resulting in thrombin and bradykinin production, respectively. The complement system plays a key role in the innate immune response, but also contributes to the pathogenesis of numerous disease states. Components of the complement pathway, including mannose binding lectin and C3, are associated with CVD risk in people with end-stage kidney disease (ESKD). Both the complement system and the factor XII-driven contact coagulation system mediate proinflammatory and procoagulant responses that could contribute to or accelerate CVD in hemodialysis recipents. This review summarizes what is already known about hemodialysis-mediated activation of the complement system and in particular the coagulation contact system, emphasizing the potential role these systems play in the identification of new biomarkers for CVD risk stratification and the development of potential therapeutic targets or innovative therapies that decrease CVD risk in ESKD patients.

Acute Cycling Exercise Induces Changes in Red Blood Cell Deformability and Membrane Lipid Remodeling.

Here we describe the effects of a controlled, 30 min, high-intensity cycling test on blood rheology and the metabolic profiles of red blood cells (RBCs) and plasma from well-trained males. RBCs demonstrated decreased deformability and trended toward increased generation of microparticles after the test. Meanwhile, metabolomics and lipidomics highlighted oxidative stress and activation of membrane lipid remodeling mechanisms in order to cope with altered properties of circulation resulting from physical exertion during the cycling test. Of note, intermediates from coenzyme A (CoA) synthesis for conjugation to fatty acyl chains, in parallel with reversible conversion of carnitine and acylcarnitines, emerged as metabolites that significantly correlate with RBC deformability and the generation of microparticles during exercise. Taken together, we propose that RBC membrane remodeling and repair plays an active role in the physiologic response to exercise by altering RBC properties.

Red blood cell microvesicles activate the contact system, leading to factor IX activation via 2 independent pathways.

Storage lesion-induced, red cell-derived microvesicles (RBC-MVs) propagate coagulation by supporting the assembly of the prothrombinase complex. It has also been reported that RBC-MVs initiate coagulation via the intrinsic pathway. To elucidate the mechanism(s) of RBC-MV-induced coagulation activation, the ability of storage lesion-induced RBC-MVs to activate each zymogen of the intrinsic pathway was assessed in a buffer system. Simultaneously, the thrombin generation (TG) assay was used to assess their ability to initiate coagulation in plasma. RBC-MVs directly activated factor XII (FXII) or prekallikrein, but not FXI or FIX. RBC-MVs initiated TG in normal pooled plasma and in FXII- or FXI-deficient plasma, but not in FIX-deficient plasma, suggesting an alternate pathway that bypasses both FXII and FXI. Interestingly, RBC-MVs generated FIXa in a prekallikrein-dependent manner. Similarly, purified kallikrein activated FIX in buffer and initiated TG in normal pooled plasma, as well as FXII- or FXI-deficient plasma, but not FIX-deficient plasma. Dual inhibition of FXIIa by corn trypsin inhibitor and kallikrein by soybean trypsin inhibitor was necessary for abolishing RBC-MV-induced TG in normal pooled plasma, whereas kallikrein inhibition alone was sufficient to abolish TG in FXII- or FXI-deficient plasma. Heating RBC-MVs at 60°C for 15 minutes or pretreatment with trypsin abolished TG, suggesting the presence of MV-associated proteins that are essential for contact activation. In summary, RBC-MVs activate both FXII and prekallikrein, leading to FIX activation by 2 independent pathways: the classic FXIIa-FXI-FIX pathway and direct kallikrein activation of FIX. These data suggest novel mechanisms by which RBC transfusion mediates inflammatory and/or thrombotic outcomes.

Increased Prevalence of Type 2 Diabetes-Related Complications in Combined Type 2 Diabetes and Sickle Cell Trait.

OBJECTIVE: The prevalence of type 2 diabetes (T2D) is rapidly increasing in sub-Saharan Africa, where sickle cell trait (SCT) is also frequent. Although SCT is generally considered a benign condition, evidence suggests that SCT could exaggerate vascular dysfunction in T2D. However, it remains unclear whether SCT could increase the risk of the development of T2D complications. Therefore, this study was conducted to determine whether T2D complications were more prevalent among Senegalese individuals with SCT and T2D than among those with T2D only. RESEARCH DESIGN AND METHODS: Rates of hypertension, retinopathy, peripheral neuropathy, peripheral artery disease, and impaired renal function as well as arterial stiffness, blood rheology, and concentrations of plasma advanced glycation end products (AGEs) and cytokines were compared between groups of Senegalese individuals with combined SCT and T2D (T2D-SCT) (n = 60), T2D (n = 52), SCT (n = 53), and neither T2D nor SCT (control) (n = 56). Human aortic endothelial cell (HAEC) expression of inflammatory and adhesion factors was measured after treatment with tumor necrosis factor-α and subjects' plasma. Effects of AGE inhibition or tiron on HAEC expression of E-selectin were measured. RESULTS: Retinopathy, hypertension, and reduced renal function were more prevalent, and arterial stiffness, blood viscosity at high shear rates, and thixotropic index were higher, in the SCT group compared with the other groups. Multivariable analysis showed that plasma AGE concentration was significantly associated with arterial stiffness. E-selectin expression was elevated in HAECs treated with T2D-SCT plasma compared with the other groups, but AGE inhibition reversed this. CONCLUSIONS: SCT could potentially augment the risk of the development of T2D-related complications, including retinopathy, nephropathy, and hypertension.

A comparison of the clinical and cost-effectiveness of 3 intervention strategies for AIDS wasting.

OBJECTIVE: To compare oxandrolone (OX) or strength training with nutrition alone (NA) for AIDS wasting. SUBJECTS: Fifty patients with AIDS; 47 completing the study. INTERVENTIONS: Randomization to (1) NA with placebo pills, (2) nutrition with 10 mg of OX administered orally twice a day, or (3) nutrition with progressive resistance training (PRT) for 12 weeks. MAIN OUTCOME MEASURES: Midthigh cross-sectional muscle area (CSMA), physical functioning (PF), costs, and cost-effectiveness in dollars/quality-adjusted life-years (dollars/QALYs). RESULTS: The OX and PRT subjects had increases in CSMA (7.0% +/- 2.5%, P = 0.01; 5.0% +/- 2.0%, P = 0.04, respectively), although these increases did not differ significantly from the NA arm (NA: 1.0% +/- 1.0%; OX vs. NA: P = 0.09; PRT vs. NA: P = 0.26). Only PRT caused significant improvements in PF (mean +/- SE: 10.4 +/- 3.8 points on a 100-point scale) and 7 measures of strength (P values: 0.04 to <0.001). There were no overall differences between groups in PF change. Among patients with impaired baseline PF, however, OX was significantly less effective than NA and PRT was significantly better than NA. All treatments led to increases in protein intake and performance; NA and PRT also increased caloric intake. The institutional costs per subject in this trial were 983 dollars for NA, 3772 dollars for OX, and 3189 dollars for PRT. At a community-based level of intensity, the institutional costs per QALY were 45,000 dollars (range: 42,000 dollars-64,000 dollars) for NA, 147,000 dollars (range: 147,000 dollars-163,000 dollars) for OX, and 31,000 dollars (range: 21,000 dollars-44,000 dollars) for PRT. CONCLUSIONS: OX and PRT induce similar improvements in body composition, but PRT improves quality of life more than nutrition or OX, particularly among patients with impaired PF. PRT was the most cost-effective intervention, and OX was the least cost-effective intervention.

Nutrient intake and body weight in a large HIV cohort that includes women and minorities.

OBJECTIVE: Evaluate the baseline nutrient intake of an HIV positive population that includes significant representation from women and minorities, and determine the relationship between state of disease and nutritional intake. DESIGN: Baseline data from a prospective study (Nutrition for Healthy Living). SUBJECTS: Individuals with HIV in the Boston and Rhode Island area (n = 516); 25% were women and 30% were minorities. METHODS: Nutrient intakes from 3-day food records, which included vitamin/mineral supplements, were estimated by gender and nonwhite vs white categories, after grouping by CD4 lymphocyte counts. STATISTICAL ANALYSES: Spearman correlation coefficients, Wilcoxon signed rank test, Wilcoxon rank sum test, chi2 test, and restricted cubic spline model were used for data analyses as indicated. RESULTS: Macronutrient but not micronutrient intake was statistically and inversely associated with decreasing CD4 cell counts. The median intake of micronutrients was higher in the study sample compared with the same age and gender group in NHANES III data; however, 25% to 35% of the women in our study sample had dietary intakes of less than 75% of the DRIs for vitamins A, C, E and B-6, and iron and zinc. White men had statistically higher values of all micronutrients compared with nonwhite men. Body mass index for men and women ranged from 23 to 25. CONCLUSIONS/APPLICATIONS: Median values for micronutrient intake from food plus vitamin/mineral supplements were adequate in the overall population studied, but a large percent of women and minorities had inadequate nutrient intakes and would benefit from dietary assessment and counseling.