Sportomics analysis of a high-intensity functional training method, the CrossFit

To identify the acute hematological and biochemical changes induced by a Crossfit™ class, ten men were divided into CF group (N = 5) and control group (N = 5). Blood and urine were collected: pre-exercise (T1), after exercise (T2), and 12 post-exercise (T3). Blood cells, urea, cortisol, lactate, creatine Kinase (CK), and microalbuminuria (MAU) had measured. There was a record of handgrip strength (HGS), heart rate (HR), and systolic blood pressure (SBP), with the calculation of the double product (DP). MAU showed an increase in the order of 14,000%, with a return to normal (T3). The DP increased 83% in response to exercise, and this increase seems to be due to HR, which increased 76%. Cortisol and lactate showed an acute increase induced by the method, 47% for cortisol and 874% for lactate, respectively, with recovery less than 12 hours. The correlations between the study variables represent a future perspective for studies in sports medicine. The acute excretion of proteins by the kidneys in an acute way, already in the first exercise session, can in the long-term cause damage to this organ. MAU presented itself as more indicated than urea, the most usual renal marker. Para identificar as alterações hematológicas e bioquímicas agudas induzidas por uma aula Crossfit™, dez homens foram divididos em grupo CF (N = 5) e grupo controle (N = 5). Foram coletados sangue e urina: pré-exercício (T1), pós-exercício (T2) e 12 pós-exercício (T3). Células sanguíneas, uréia, cortisol, lactato, creatina quinase (CK) e microalbuminúria (MAU) foram medidos. Houve registro da força de preensão manual (FPM), frequência cardíaca (FC) e pressão arterial sistólica (PAS), com o cálculo do duplo produto (DP). A MAU apresentou aumento da ordem de 14.000%, com retorno ao normal (T3). O DP aumentou 83% em resposta ao exercício, e esse aumento parece ser devido à FC, que aumentou 76%. O cortisol e o lactato apresentaram aumento agudo induzido pelo método, 47% para o cortisol e 874% para o lactato, respectivamente, com recuperação inferior a 12 horas. As correlações entre as variáveis ​​de estudo representam uma perspectiva futura para os estudos em medicina do esporte. A excreção aguda de proteínas pelos rins de forma aguda, já na primeira sessão de exercícios, pode, a longo prazo, causar danos a esse órgão. O MAU apresentou-se mais indicado que a ureia, o marcador renal mais usual.

Effects of Different Types of Carbohydrates on Arterial Stiffness: A Comparison of Isomaltulose and Sucrose

Increased arterial stiffness during acute hyperglycemia is a risk factor for cardiovascular disease, but the type of carbohydrate that inhibits it is unknown. The purpose of this study was to determine the efficacy of low-glycemic-index isomaltulose on arterial stiffness during hyperglycemia in middle-aged and older adults. Ten healthy middle-aged and older adult subjects orally ingested a solution containing 25 g of isomaltulose (ISI trial) and sucrose (SSI trial) in a crossover study. In the SSI trial, the brachial–ankle (ba) pulse wave velocity (PWV) increased 30, 60, and 90 min after ingestion compared with that before ingestion (p < 0.01); however, in the ISI trial, the baPWV did not change after ingestion compared with that before ingestion. Blood glucose levels 30 min after intake were lower in the ISI trial than in the SSI trial (p < 0.01). The baPWV and systolic blood pressure were positively correlated 90 min after isomaltulose and sucrose ingestion (r = 0.640, p < 0.05). These results indicate that isomaltulose intake inhibits an acute increase in arterial stiffness. The results of the present study may have significant clinical implications on the implementation of dietary programs for middle-aged and elderly patients.

536 Intraoperative predictors of long-term pacing threshold improvement in leadless pacemakers

Aims Micra-VR transcatheter pacing system (TPS) has shown strong stability of electrical parameters over time. Nevertheless, a small percentage of patients develops high pacing threshold (PT) (&gt;1 [email protected] ms) which can decrease the longevity of battery. Our study sought to investigate the intraoperative electrical parameters able to predict device electrical performances during the time. Methods and results Patients (pts) implanted with Micra-VR TPS from March 2018 to January 2021 were prospectively considered at the Cardiology Department of Spedali Civili Hospital (Brescia) and Luigi Sacco Hospital (Milan). R-wave sensing amplitude (mV), pacing impedance (Ohm), and PT ([email protected] ms) were recorded twice: upon Micra final positioning, and after removal of the delivery system. All pts received a follow-up visit at 1- and 12-month after discharge. Electrical parameters were recorded at each visit. A total of 93 pts underwent Micra-VR implantation were enrolled. When compared to the first assessment, R-wave amplitude increased of 19.1% at second control performed after 13 ± 4 min (+1.71 ± 0.2 mV, 95% CI: 1.4–2.02; P &lt; 0.001). Conversely, PT significantly decreased of 22.1% at 12-month follow-up respect to baseline (−0.22 ± 0.03 V, 95% CI: −0.13 to − 0.31; P &lt; 0.001) (Figure 1). Among patients with high PT, acute increase of R-wave sensing of 1.5 mV after 14 ± 4 min significantly predicted PT normalization (≤1 [email protected] ms) 12 months post-implant (R = 0.72, 95% CI: 0.13–0.33, P &lt; 0.001) (Figure 2), with a sensitivity of 87.5% (95% CI: 0.61–0.98) and a specificity of 88.8% (95% CI: 0.51–0.99) (Figure 3). Conclusions A 1.5 mV increase in R-wave amplitude at implant time is predictive of PT normalization (&lt;1.0 V/0.24 ms) at 12-month FU. This finding may have practical implications for device repositioning in case of HPT at implant. This parameter could be considered for acute device repositioning, particularly in HPT patients. 536 Figure

Time for Universal Public Distribution System: Food Mountains and Pandemic Hunger in India

The latest National Family Health Survey (NFHS 5) indicates that child stunting in India was severe and has been deteriorating since 2015. This trend could have worsened since the pandemic and the stringent lockdowns meant to contain it. There has been an acute increase in impoverishment as governmental food policies have further exacerbated rather than mitigated inequalities. Families eligible under the National Food Security Act (NFSA), 2013, have been provided with double food grain rations during two waves of the pandemic. However, nearly 45% of India’s population without these ration cards have been largely excluded from additional food relief from the central government. Simultaneously, India’s food grain stocks in government granaries have accumulated to their all-time peak with 2 years of bumper harvests. Therefore, in light of the acute distress faced by marginalised communities due to the pandemic, this article analyses the availability of adequate food grain stocks and contends that the time is opportune for the universal expansion of the public distribution system.

Glucose controls co-translation of structurally related mRNAs via the mTOR and eIF2 pathways in human pancreatic beta cells

ABSTRACTPancreatic beta cell response to glucose is critical for the maintenance of normoglycemia. A strong transcriptional response was classically described in rodent models but, interestingly, not in human cells. In this study, we exposed human pancreatic beta cells to an increased concentration of glucose and analysed at a global level the mRNAs steady state levels and their translationalability. Polysome profiling analysis showed an early acute increase in protein synthesis and a specific translation regulation of more than 400 mRNAs, independently of their transcriptional regulation. We clustered the co-regulated mRNAs according to their behaviour in translation in response to glucose and discovered common structural and sequence mRNA features. Among them mTOR- and eIF2-sensitive elements have a predominant role to increase mostly the translation of mRNAs encoding for proteins of the translational machinery. Furthermore, we show that mTOR and eIF2α pathways are independently regulated in response to glucose, participating to a translational reshaping to adapt beta cell metabolism. The early acute increase in the translation machinery components prepare the beta cell for further protein demand due to glucose-mediated metabolism changes.AUTHOR SUMMARYAdaptation and response to glucose of pancreatic beta cells is critical for the maintenance of normoglycemia. Its deregulation is associated to Diabetic Mellitus (DM), a significant public health concern worldwide with an increased incidence of morbidity and mortality. Despite extensive research in rodent models, gene expression regulation in response to glucose remains largely unexplored in human cells. In our work, we have tackled this question by exposing human EndoC-BH1 cells to high glucose concentration. Using polysome profiling, the gold standard technique to analyse cellular translation activity, we observed a global protein synthesis increase, independent from transcription activity. Among the specific differentially translated mRNAs, we found transcripts coding for ribosomal proteins, allowing the cell machinery to be engaged in a metabolic response to glucose. Therefore, the regulation in response to glucose occurs mainly at the translational level in human cells, and not at the transcriptional level as described in the classically used rodent models.Furthermore, by comparing the features of the differentially translated mRNAs, and classifying them according to their translational response, we show that the early response to glucose occurs through the coupling of mRNA structure and sequence features impacting translation and regulation of specific signalling pathways. Collectively, our results support a new paradigm of gene expression regulation on the translation level in human beta cells.

Ampakine pretreatment enables a single hypoxic episode to produce phrenic motor facilitation with no added benefit of additional episodes

Repeated short episodes of hypoxia produces a sustained increase in phrenic nerve output lasting well beyond AIH exposure (i.e., phrenic long term facilitation, pLTF). Pretreatment with ampakines, drugs which allosterically modulate AMPA receptors, enables a single brief episode of hypoxia to produce pLTF, lasting up to 90 min after hypoxia. Here we tested the hypothesis that ampakine pretreatment would enhance the magnitude of pLTF evoked by repeated bouts of hypoxia. Phrenic nerve output was recorded in urethane-anesthetized, mechanically ventilated and vagotomized adult male Sprague-Dawley rats. Initial experiments demonstrated that ampakine CX717 (15 mg/kg, intravenous) caused an acute increase in phrenic nerve inspiratory burst amplitude reaching 70±48% baseline (BL) after 2 min (P=0.01. This increased bursting was not sustained (2±32%BL at 60 min, P=0.9). When CX717 was delivered 2 min prior to a single episode of isocapnic hypoxia (5-min, PaO2 = 44±9 mmHg) facilitation of phrenic nerve burst amplitude occurred (96±62%BL at 60 min, P<0.001). However, when CX717 was given 2 min prior to three, 5-min hypoxic episodes (PaO2 = 45±6 mmHg) pLTF was attenuated and did not reach statistical significance (24±29%BL, P=0.08). In the absence of CX717 pretreatment, pLTF was observed after three (74±33%BL at 60 min, P<0.001) but not one episode of hypoxia (1±8%BL at 60 min, P=0.9). We conclude that pLTF is not enhanced when ampakine pretreatment is followed by repeated bouts of hypoxia. Rather, the combination of ampakine and a single hypoxic episode appears to be ideal for producing sustained increase in phrenic motor output.

Activation of the hypothalamic–pituitary–adrenal axis by exogenous and endogenous GDF15

An acute increase in the circulating concentration of glucocorticoid hormones is essential for the survival of severe somatic stresses. Circulating concentrations of GDF15, a hormone that acts in the brain to reduce food intake, are frequently elevated in stressful states. We now report that GDF15 potently activates the hypothalamic–pituitary–adrenal (HPA) axis in mice and rats. A blocking antibody to the GDNF-family receptor α-like receptor completely prevented the corticosterone response to GDF15 administration. In wild-type mice exposed to a range of stressful stimuli, circulating levels of both corticosterone and GDF15 rose acutely. In the case of Escherichia coli or lipopolysaccharide injections, the vigorous proinflammatory cytokine response elicited was sufficient to produce a near-maximal HPA response, regardless of the presence or absence of GDF15. In contrast, the activation of the HPA axis seen in wild-type mice in response to the administration of genotoxic or endoplasmic reticulum toxins, which do not provoke a marked rise in cytokines, was absent in Gdf15−/− mice. In conclusion, consistent with its proposed role as a sentinel hormone, endogenous GDF15 is required for the activation of the protective HPA response to toxins that do not induce a substantial cytokine response. In the context of efforts to develop GDF15 as an antiobesity therapeutic, these findings identify a biomarker of target engagement and a previously unrecognized pharmacodynamic effect, which will require monitoring in human studies.

Repetitive head impacts in a collegiate football season: Exposure and effects

This study describes exposure to repetitive head impacts (RHI) by player position and activity during a collegiate football season, and investigates the relationship between RHI and acute (i.e., daily and weekly) and short-term (i.e., pre- to post-season) changes in balance, reaction time, symptoms, and cognition. We recorded RHI exposure in twenty Division I collegiate American football players during a single season using the Riddell InSite system. Participants sustained 4,586 impacts (4.20% high impact, i.e., >63 g; 95.79% low impact, i.e., 20–63 g). Greatest exposure to RHI was observed in running backs and defensive ends during games, and tight ends and defensive ends during practices. Running plays and team drills placed players at greatest risk for exposure during practice. Cumulative RHI exposure across the season was associated with short-term declines in reaction time (p = 0.045), but not balance or cognition. Acute decline in balance was associated with the number of impacts sustained in the past week (p < 0.05), but not the past 24 hours (p > 0.05). Acute increase in total symptom score was also associated with the number of impacts sustained in the past week (p < 0.01), but not the past 24 hours (p > 0.05). Reaction time did not decline based on impact exposure in the past 24 hours or week. This study identifies activities and positions that may put players at risk for RHI exposure, and demonstrates that RHI sustained during the course of typical American football play by non-concussed individuals may result in small changes in balance, reaction time, and symptoms, but not cognition.

Universal Public Distribution System: Food Mountains and Pandemic Hunger in India

The latest National Family Health Survey (NFHS 5), indicates that even before the pandemic, child stunting in India was severe and has been deteriorating since 2015. But after the stringent lockdown, there has been an acute increase in impoverishment as governmental food policies have further exacerbated rather than mitigated inequalities. Families eligible under the National Food Security Act (NFSA, 2013) have been provided with double food grain rations during two waves of the pandemic. But nearly 45 percent of India’s population without these ration cards have been excluded from any additional food relief from the central government. Simultaneously, India’s food grain stocks in government granaries have accumulated manifold with two years of bumper harvests. Therefore, in light of the acute distress faced by marginalised communities due to the pandemic and unprecedented economic recession, this paper analyses the availability of adequate foodgrain stocks and contends that the time is ripe for the universal expansion of the public distribution system.

Unexpected localization of AQP3 and AQP4 induced by migration of primary cultured IMCD cells

Aquaporin-2–4 (AQP) are expressed in the principal cells of the renal collecting duct (CD). Beside their role in water transport across membranes, several studies showed that AQPs can influence the migration of cells. It is unknown whether this also applies for renal CD cells. Another fact is that the expression of these AQPs is highly modulated by the external osmolality. Here we analyzed the localization of AQP2–4 in primary cultured renal inner medullary CD (IMCD) cells and how osmolality influences the migration behavior of these cells. The primary IMCD cells showed a collective migration behavior and there were no differences in the migration speed between cells cultivated either at 300 or 600 mosmol/kg. Acute increase from 300 to 600 mosmol/kg led to a marked reduction and vice versa an acute decrease from 600 to 300 mosmol/kg to a marked increase in migration speed. Interestingly, none of the analyzed AQPs were localized at the leading edge. While AQP3 disappeared within the first 2–3 rows of cells, AQP4 was enriched at the rear end. Further analysis indicated that migration induced lysosomal degradation of AQP3. This could be prevented by activation of the protein kinase A, inducing localization of AQP3 and AQP2 at the leading edge and increasing the migration speed.