Reducing prolonged sedentary time using a treadmill desk acutely improves cardiometabolic risk markers in male and female adults

The objectives of this study were to evaluate the acute effects of interrupting prolonged sitting with an accumulated 2 h of light-intensity walking on postprandial cardiometabolic risk markers. In this randomised crossover trial, 24 participants (twelve males) aged 18-55 years took part in two, 6.5 h conditions: 1) prolonged sitting (SIT) and 2) sitting interrupted hourly with 20 min light-intensity treadmill desk walking at between 1.2-3.5 km/h-1 (INT-SIT). Standardized meals were provided at 0 h and 3 h. Blood samples and blood pressure measures were taken hourly. Statistical analyses were completed using linear mixed models. Postprandial incremental area under the curve responses (mmol/L∙6.5 h) for glucose (4.52 [3.47, 5.56] and 6.66 [5.62, 7.71] for INT-SIT and SIT, respectively) and triglycerides (1.96 [0.96, 2.96] and 2.71 [1.70, 3.71] mmol/L∙6.5 h, for INT-SIT and SIT, respectively) were significantly lower in INT-SIT than SIT. Mean systolic and diastolic blood pressure responses were lower by 3% and 4%, respectively, in INT-SIT than SIT (P0.05). These findings suggest that interrupting sitting with an accumulated 2 h of light-intensity walking acutely improves cardiometabolic risk levels in males and females compared with prolonged sitting

Modelling geomagnetically induced currents in midlatitude Central Europe using a thin-sheet approach

Geomagnetically induced currents (GICs) in power systems, which can lead to transformer damage over the short and the long term, are a result of space weather events and geomagnetic variations. For a long time, only high-latitude areas were considered to be at risk from these currents, but recent studies show that considerable GICs also appear in midlatitude and equatorial countries. In this paper, we present initial results from a GIC model using a thin-sheet approach with detailed surface and subsurface conductivity models to compute the induced geoelectric field. The results are compared to measurements of direct currents in a transformer neutral and show very good agreement for short-period variations such as geomagnetic storms. Long-period signals such as quiet-day diurnal variations are not represented accurately, and we examine the cause of this misfit. The modelling of GICs from regionally varying geoelectric fields is discussed and shown to be an important factor contributing to overall model accuracy. We demonstrate that the Austrian power grid is susceptible to large GICs in the range of tens of amperes, particularly from strong geomagnetic variations in the east–west direction

Bone geometry according to menstrual function in female endurance athletes

Athletes have higher bone mineral density (BMD) relative to nonathletes. In amenorrheic athletes BMD may be compromised by estrogen deficiency, but it is unknown whether this is accompanied by structural differences. We compared femoral neck bone geometry and density of a-/oligomenorrheic athletes (AAs), eumenorrheic athletes (EAs), and eumenorrheic controls (ECs). We recruited 156 women: (68 endurance athletes and 88 controls). Femoral neck BMD, section modulus (Z), and width were measured using dual-energy X-ray absorptiometry. Menstrual function was assessed by questionnaire and classified as EA(C10 periods/year) or AA(B9periods/year): 24 athletes were AA and 44 EA. Femoral neck BMD was significantly higher in EA than AA (8 %, difference) and EC (11 % difference): mean [SE] 1.118 [0.015], 1.023 [0.020] and 0.999 [0.014] g cm-2, respectively; p\0.001. Z was significantly higher in EA than EC (11 % difference): EA 667 [19], AA 625 [21], and EC 592 [10] cm3; p\0.001. Femoral neck width did not differ between groups. All differences persisted after adjustment for height, age, and body mass. The higher femoral neck Z and BMD in athletes, despite similar width, may indicate that exercise-related bone gains are endosteal rather than periosteal. Athletes with amenorrhea had smaller increments in bone mass rather than structural adaptation. The maintained femoral neck width in controls may be an adaptive mechanism to conserve bone strength in bending despite inactivity-related bone decrement

Higher whole-blood selenium is associated with improved immune responses in footrot-affected sheep

We reported previously that sheep affected with footrot (FR) have lower whole-blood selenium (WB-Se) concentrations and that parenteral Se-supplementation in conjunction with routine control practices accelerates recovery from FR. The purpose of this follow-up study was to investigate the mechanisms by which Se facilitates recovery from FR. Sheep affected with FR (n = 38) were injected monthly for 15 months with either 5 mg Se (FR-Se) or saline (FR-Sal), whereas 19 healthy sheep received no treatment. Adaptive immune function was evaluated after 3 months of Se supplementation by immunizing all sheep with a novel protein, keyhole limpet hemocyanin (KLH). The antibody titer and delayed-type hypersensitivity (DTH) skin test to KLH were used to assess humoral immunity and cell-mediated immunity, respectively. Innate immunity was evaluated after 3 months of Se supplementation by measuring intradermal responses to histamine 30 min after injection compared to KLH and saline, and after 15 months of Se supplementation by isolating neutrophils and measuring their bacterial killing ability and relative abundance of mRNA for genes associated with neutrophil migration. Compared to healthy sheep, immune responses to a novel protein were suppressed in FR-affected sheep with smaller decreases in FR-affected sheep that received Se or had WB-Se concentrations above 250 ng/mL at the time of the immune assays. Neutrophil function was suppressed in FR-affected sheep, but was not changed by Se supplementation or WB-Se status. Sheep FR is associated with depressed immune responses to a novel protein, which may be partly restored by improving WB-Se status (> 250 ng/mL)

Measuring the efficacy of anti-malarial drugs in vivo: quantitative PCR measurement of parasite clearance

BACKGROUND: Artemisinin-based combination therapy, currently considered the therapy of choice for uncomplicated Plasmodium falciparum malaria in endemic countries, may be under threat from newly emerging parasite resistance to the artemisinin family of drugs. Studies in Southeast Asia suggest some patients exhibit an extended parasite clearance time in the three days immediately following treatment with artesunate monotherapy. This phenotype is likely to become a more important trial endpoint in studies of anti-malarial drug efficacy, but currently requires frequent, closely spaced blood sampling in hospitalized study participants, followed by quantitation of parasite density by microscopy. METHODS: A simple duplex quantitative PCR method was developed in which distinct fluorescent signals are generated from the human and parasite DNA components in each blood sample. The human amplification target in this assay is the β tubulin gene, and the parasite target is the unique methionine tRNA gene (pgmet), which exhibits perfect sequence identity in all six Plasmodium species that naturally infect humans. In a small series of malaria cases treated as hospital in-patients, the abundance of pgmet DNA was estimated relative to the human DNA target in daily peripheral blood samples, and parasite clearance times calculated. RESULTS: The qPCR assay was reproducibly able to replicate parasite density estimates derived from microscopy, but provided additional data by quantification of parasite density 24 hours after the last positive blood film. Robust estimates of parasite clearance times were produced for a series of patients with clinical malaria. CONCLUSIONS: Large studies, particularly in Africa where children represent a major proportion of treated cases, will require a simpler blood sample collection regime, and a method capable of high throughput. The duplex qPCR method tested may fulfil these criteria, and should now be evaluated in such field studies

The influence of membrane physical properties on microvesicle release in human erythrocytes

Exposure of human erythrocytes to elevated intracellular calcium causes fragments of the cell membrane to be shed as microvesicles. This study tested the hypothesis that microvesicle release depends on microscopic membrane physical properties such as lipid order, fluidity, and composition. Membrane properties were manipulated by varying the experimental temperature, membrane cholesterol content, and the activity of the trans-membrane phospholipid transporter, scramblase. Microvesicle release was enhanced by increasing the experimental temperature. Reduction in membrane cholesterol content by treatment with methyl-β-cyclodextrin also facilitated vesicle shedding. Inhibition of scramblase with R5421 impaired vesicle release. These data were interpreted in the context of membrane characteristics assessed previously by fluorescence spectroscopy with environment-sensitive probes such as laurdan, diphenylhexatriene, and merocyanine 540. The observations supported the following conclusions: 1) calcium-induced microvesicle shedding in erythrocytes relates more to membrane properties detected by diphenylhexatriene than by the other probes; 2) loss of trans-membrane phospholipid asymmetry is required for microvesicle release

Improving Translational Relevance in Preclinical Psychopharmacology (iTRIPP)

Animal models are important in preclinical psychopharmacology to study mechanisms and potential treatments for psychiatric disorders. A working group of 14 volunteers, comprising an international team of researchers from academia and industry, convened in 2021 to discuss how to improve the translational relevance and interpretation of findings from animal models that are used in preclinical psychopharmacology. The following paper distils the outcomes of the working group’s discussions into 10 key considerations for the planning and reporting of behavioural studies in animal models relevant to psychiatric disorders. These form the iTRIPP guidelines (Improving Translational Relevance In Preclinical Psychopharmacology). These guidelines reflect the key considerations that the group thinks will likely have substantial impact in terms of improving the translational relevance of behavioural studies in animal models that are used to study psychiatric disorders and their treatment. They are relevant to the research community when drafting and reviewing manuscripts, presentations and grant applications. The iTRIPP guidelines are intended to complement general recommendations for planning and reporting animal studies that have been published elsewhere, by enabling researchers to fully consider the most appropriate animal model for the research purpose and to interpret their findings appropriately. This in turn will increase the clinical benefit of such research and is therefore important not only for the scientific community but also for patients and the lay public

Dietary iron intakes based on food composition data may underestimate the contribution of potentially exchangeable contaminant iron from soil

Iron intakes calculated from one-day weighed records were compared with those from same day analyzed duplicate diet composites collected from 120 Malawian women living in two rural districts with contrasting soil mineralogy and where threshing may contaminate cereals with soil iron. Soils and diet composites from the two districts were then subjected to a simulated gastrointestinal digestion and iron availability in the digests measured using a Caco-2 cell model. Median analyzed iron intakes (mg/d) were higher (p < 0.001) than calculated intakes in both Zombwe (16.6 vs. 10.1 mg/d) and Mikalango (29.6 vs. 19.1 mg/d), attributed to some soil contaminant iron based on high Al and Ti concentrations in diet composites. A small portion of iron in acidic soil from Zombwe, but not Mikalango calcareous soil, was bioavailable, as it induced ferritin expression in the cells, and may have contributed to higher plasma ferritin and total body iron for the Zombwe women reported earlier, despite lower iron intakes. In conclusion, iron intakes calculated from food composition data were underestimated, highlighting the importance of analyzing duplicate diet composites where extraneous contaminant iron from soil is likely. Acidic contaminant soil may make a small but useful contribution to iron nutrition

Effects of Dietary Nitrate Supplementation on Performance and Muscle Oxygenation during Resistance Exercise in Men

The purpose of the current study was to assess the effects of acute and short-term nitrate (NO3−)-rich beetroot juice (BR) supplementation on performance outcomes and muscle oxygenation during bench press and back squat exercise. Fourteen recreationally active males were assigned in a randomized, double-blind, crossover design to supplement for 4 days in two conditions: (1) NO3−-depleted beetroot juice (PL; 0.10 mmol NO3− per day) and (2) BR (11.8 mmol NO3− per day). On days 1 and 4 of the supplementation periods, participants completed 2 sets of 2 × 70%1RM interspersed by 2 min of recovery, followed by one set of repetitions-to-failure (RTF) at 60%1RM for the determination of muscular power, velocity, and endurance. Quadriceps and pectoralis major tissue saturation index (TSI) were measured throughout exercise. Plasma [NO3−] and nitrite ([NO2−]) were higher after 1 and 4 days of supplementation with BR compared to PL (p \u3c 0.05). Quadriceps and pectoralis major TSI were not different between conditions (p \u3e 0.05). The number of RTF in bench press was 5% greater after acute BR ingestion compared to PL (PL: 23 ± 4 vs. BR: 24 ± 5, p \u3c 0.05). There were no differences between BR and PL for RTF for back squat or power and velocity for back squat or bench press (p \u3e 0.05). These data improve understanding on the ergogenic potential of BR supplementation during resistance exercise

An ACAT inhibitor suppresses SARS-CoV-2 replication and boosts antiviral T cell activity

The severity of disease following infection with SARS-CoV-2 is determined by viral replication kinetics and host immunity, with early T cell responses and/or suppression of viraemia driving a favourable outcome. Recent studies uncovered a role for cholesterol metabolism in the SARS-CoV-2 life cycle and in T cell function. Here we show that blockade of the enzyme Acyl-CoA:cholesterol acyltransferase (ACAT) with Avasimibe inhibits SARS-CoV-2 pseudoparticle infection and disrupts the association of ACE2 and GM1 lipid rafts on the cell membrane, perturbing viral attachment. Imaging SARS-CoV-2 RNAs at the single cell level using a viral replicon model identifies the capacity of Avasimibe to limit the establishment of replication complexes required for RNA replication. Genetic studies to transiently silence or overexpress ACAT isoforms confirmed a role for ACAT in SARS-CoV-2 infection. Furthermore, Avasimibe boosts the expansion of functional SARS-CoV-2-specific T cells from the blood of patients sampled during the acute phase of infection. Thus, re-purposing of ACAT inhibitors provides a compelling therapeutic strategy for the treatment of COVID-19 to achieve both antiviral and immunomodulatory effects. Trial registration: NCT04318314