Cytokine Response to Traditional and Cluster Sets in Resistance-trained Women

Resistance exercise that incorporates intra-set rest between repetition blocks (i.e., cluster sets [CS]) can produce a smaller metabolic stress and endocrine response than traditional sets (TS). PURPOSE: To examine the effect of CS on the acute cytokine response in resistance trained women. METHODS: 12 resistance-trained women (mean ± SE; 23.7 ± 1.1 years; 160.1 ± 1.5 cm; 62.5 ± 1.7 kg; 5 ± 1 years training) completed 3 sessions in the follicular phase. One-repetition maximum (1RM) back squat (BS) (98.7 ± 4.1 kg), and BS:body mass (1.6 ± 0.1) were determined in Session 1. For Session 2 (3 days post Session 1) and Session 3 (7 days post Session 2), subjects were randomly assigned to either 4 sets of 10 reps with 120 seconds (s) inter-set rest (TS) or 4 x (2 x 5 reps) with 30s intra-set rest and 90s inter-set rest (CS). All performed both protocols at 70% 1RM BS. Instructions were to perform every rep “as explosively as possible”. Blood was collected pre-exercise (PRE), immediately after sets 1, 2, 3, 4 (IP), and at 5 (+5), 15 (+15), 30 (+30), and 60 (+60) min post-exercise and analyzed for interleukin (IL)-1β, IL-2, IL-6, IL-8, IL 10, and IL-15. Data were analyzed using repeated measures ANOVAs (2 × 9). RESULTS: A significant main effect of time (p\u3c0.05) was found for IL-1β, IL-2, IL-8, IL-10, and IL-15. Concentration of IL-1β was smaller at +5 (3.9 ± 0.4 ng/mL), +15 (3.6 ± 0.4) +30 (3.5 ± 0.3), and +60 (3.7 ± 0.4) compared to IP (4.1 ± 0.4). IL-2 was greater after set 1 (10.8 ± 1.0 ng/mL), and set 2 (11.0 ± 1.2) compared to PRE (10.2 ± 1.0), and smaller at +30 (9.9 ± 1.0) compared to IP (11.0 ± 1.0). IL-8 was greater after set 1 (8.4 ± 0.6 ng/mL), set 2 (8.6 ± 0.7), and set 3 (8.5 ± 0.7) compared to PRE (8.0 ± 0.6). IL-10 was smaller at +30 (31.3 ± 7.4 ng/mL) compared to PRE (34.0 ± 7.4), and also smaller at +15 (32.6 ± 7.9) +30 (31.3 ± 7.4), and +60 (33.4 ± 8.6) compared to IP (38.0 ± 8.6). IL-15 was greater at IP (15.5 ± 4.0 ng/mL) compared to PRE (13.4 ± 3.5), and smaller at PRE (13.4 ± 3.5), +30 (11.9 ± 3.3), and +60 (11.6 ± 3.2) compared to IP (15.5 ± 4.0). No condition × time point effects were observed. CONCLUSION: Both TS and CS induced an acute cytokine response in resistance-trained women; incorporating intra-set rest (CS) did not appear to affect this cytokine response

In-Plane Vibration of Hammerhead Resonators for Chemical Sensing Applications

Thermally excited and piezoresistively detected in-plane cantilever resonators have been previously demonstrated for gas- and liquid-phase chemical and biosensing applications. In this work, the hammerhead resonator geometry, consisting of a cantilever beam supporting a wider semicircular “head”, vibrating in an in-plane vibration mode, is shown to be particularly effective for gas-phase sensing with estimated limits of detection in the sub-ppm range for volatile organic compounds. This paper discusses the hammerhead resonator design and the particular advantages of the hammerhead geometry, while also presenting mechanical characterization, optical characterization, and chemical sensing results. These data highlight the distinct advantages of the hammerhead geometry over other cantilever designs

Existing and potential infection risk zones of yellow fever worldwide: a modelling analysis

Summary: Background: Yellow fever cases are under-reported and the exact distribution of the disease is unknown. An effective vaccine is available but more information is needed about which populations within risk zones should be targeted to implement interventions. Substantial outbreaks of yellow fever in Angola, Democratic Republic of the Congo, and Brazil, coupled with the global expansion of the range of its main urban vector, Aedes aegypti, suggest that yellow fever has the propensity to spread further internationally. The aim of this study was to estimate the disease's contemporary distribution and potential for spread into new areas to help inform optimal control and prevention strategies. Methods: We assembled 1155 geographical records of yellow fever virus infection in people from 1970 to 2016. We used a Poisson point process boosted regression tree model that explicitly incorporated environmental and biological explanatory covariates, vaccination coverage, and spatial variability in disease reporting rates to predict the relative risk of apparent yellow fever virus infection at a 5 × 5 km resolution across all risk zones (47 countries across the Americas and Africa). We also used the fitted model to predict the receptivity of areas outside at-risk zones to the introduction or reintroduction of yellow fever transmission. By use of previously published estimates of annual national case numbers, we used the model to map subnational variation in incidence of yellow fever across at-risk countries and to estimate the number of cases averted by vaccination worldwide. Findings: Substantial international and subnational spatial variation exists in relative risk and incidence of yellow fever as well as varied success of vaccination in reducing incidence in several high-risk regions, including Brazil, Cameroon, and Togo. Areas with the highest predicted average annual case numbers include large parts of Nigeria, the Democratic Republic of the Congo, and South Sudan, where vaccination coverage in 2016 was estimated to be substantially less than the recommended threshold to prevent outbreaks. Overall, we estimated that vaccination coverage levels achieved by 2016 avert between 94 336 and 118 500 cases of yellow fever annually within risk zones, on the basis of conservative and optimistic vaccination scenarios. The areas outside at-risk regions with predicted high receptivity to yellow fever transmission (eg, parts of Malaysia, Indonesia, and Thailand) were less extensive than the distribution of the main urban vector, A aegypti, with low receptivity to yellow fever transmission in southern China, where A aegypti is known to occur. Interpretation: Our results provide the evidence base for targeting vaccination campaigns within risk zones, as well as emphasising their high effectiveness. Our study highlights areas where public health authorities should be most vigilant for potential spread or importation events. Funding: Bill & Melinda Gates Foundation

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics