Persisting exercise ventilatory inefficiency in subjects recovering from COVID-19. Longitudinal data analysis 34 months post-discharge.

BACKGROUND: SARS-CoV-2 infection has raised concerns about long-term health repercussions. Exercise ventilatory inefficiency (EVin) has emerged as a notable long-term sequela, potentially impacting respiratory and cardiovascular health. This study aims to assess the long-term presence of EVin after 34 months and its association with cardiorespiratory health in post-COVID patients. METHODS: In a longitudinal study on 32 selected post-COVID subjects, we performed two cardiopulmonary exercise tests (CPETs) at 6 months (T0) and 34 months (T1) after hospital discharge. The study sought to explore the long-term persistence of EVin and its correlation with respiratory and cardiovascular responses during exercise. Measurements included also V̇O2peak, end-tidal pressure of CO2 (PETCO2) levels, oxygen uptake efficiency slope (OUES) and other cardiorespiratory parameters, with statistical significance set at p < 0.05. The presence of EVin at both T0 and T1 defines a persisting EVin (pEVin). RESULTS: Out of the cohort, five subjects (16%) have pEVin at 34 months. Subjects with pEVin, compared to those with ventilatory efficiency (Evef) have lower values of PETCO2 throughout exercise, showing hyperventilation. Evef subjects demonstrated selective improvements in DLCO and oxygen pulse, suggesting a recovery in cardiorespiratory function over time. In contrast, those with pEvin did not exhibit these improvements. Notably, significant correlations were found between hyperventilation (measured by PETCO2), oxygen pulse and OUES, indicating the potential prognostic value of OUES and Evin in post-COVID follow-ups. CONCLUSIONS: The study highlights the clinical importance of long-term follow-up for post-COVID patients, as a significant group exhibit persistent EVin, which correlates with altered and potentially unfavorable cardiovascular responses to exercise. These findings advocate for the continued investigation into the long-term health impacts of COVID-19, especially regarding persistent ventilatory inefficiencies and their implications on patient health outcomes.

New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review.

This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation of visceral adipose tissue, and increased pericardial/epicardial adipose tissue (contributing to an increase in myocardial fat content and interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the enteroendocrine L-cells in the gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, and promoting the proliferation and differentiation of ß-cells. GLP-1 regulates gastric emptying and appetite, and GLP-1 RA is currently indicated for treating type 2 diabetes (T2D), obesity, and metabolic syndrome (MS). Recent evidence indicates that GLP-1 RA may play a significant role in preventing HFpEF in patients with obesity, MS, or obese T2D. This effect may be due to activating cardioprotective mechanisms (the endogenous counter-regulatory renin angiotensin system and the AMPK/mTOR pathway) and by inhibiting deleterious remodeling mechanisms (the PKA/RhoA/ROCK pathway, aldosterone levels, and microinflammation). However, there is still a need for further research to validate the impact of these mechanisms on humans.

Real-world performance of the MiniMed 780G advanced hybrid closed loop system in Latin America: Substantial improvement in glycaemic control with each technology iteration of the MiniMed automated insulin delivery system.

AIM: We studied real-world performance of MiniMed (MM) 780G system users from Argentina, Brazil, Colombia and Chile (geographical analysis), and the effect of each technology iteration of the MM system on glycaemic control (technology iteration analysis). MATERIALS AND METHODS: CareLink data from August 2020 to September 2022 were extracted. Endpoints included continuous glucose monitoring metrics. For the geographical analysis, aggregated endpoints for MM780G system users were calculated. For the technology iteration analysis, MM780G system user outcomes were compared with outcomes when the same individuals were still using the MM640G or MM670G system. RESULTS: On average, 1025 MM780G system users from the geographical analysis were followed for 136 (SD 135) days, spent 91.5 (14.3)% in advanced hybrid closed loop, showed a glucose management indicator (GMI) of 6.7 (0.3)%, a time in range between 70 and 180 mg/dl (TIR) of 76.5 (9.0)%, and a time below range 70 mg/dl (TBR) of 2.7 (2.1)%. The percentage of users reaching targets of GMI <7%, TIR >70% and TBR <4% was 80.8%, 78.1% and 80.1%, respectively. The technology iteration analysis on users transitioning from MM640G to MM780G system (N = 381) showed 0.4% decrease in GMI (7.1% to 6.7%, p < .0001), 10.7% increase in TIR (65.9% to 76.6%, p < .0001), while TBR remained. The percentage of insulin delivered automatically increased as well (47.5%-57.7%, p < .0001). Users transitioning from MM670G system (N = 78) showed a similar but less pronounced pattern. CONCLUSIONS: Real-world Latin American MM780G users on average showed good glucose control, achieving international targets. Glycaemic control increased with every technology iteration of the MM system, providing more automation each time.

Sarcopenia parameters in active older adults - an eight-year longitudinal study.

BACKGROUD: Sarcopenia is a common skeletal muscle syndrome that is common in older adults but can be mitigated by adequate and regular physical activity. The development and severity of sarcopenia is favored by several factors, the most influential of which are a sedentary lifestyle and physical inactivity. The aim of this observational longitudinal cohort study was to evaluate changes in sarcopenia parameters, based on the EWGSOP2 definition in a population of active older adults after eight years. It was hypothesized that selected active older adults would perform better on sarcopenia tests than the average population. METHODS: The 52 active older adults (22 men and 30 women, mean age: 68.4 ± 5.6 years at the time of their first evaluation) participated in the study at two time points eight-years apart. Three sarcopenia parameters were assessed at both time points: Muscle strength (handgrip test), skeletal muscle mass index, and physical performance (gait speed), these parameters were used to diagnose sarcop0enia according to the EWGSOP2 definition. Additional motor tests were also performed at follow-up measurements to assess participants' overall fitness. Participants self-reported physical activity and sedentary behavior using General Physical Activity Questionnaire at baseline and at follow-up measurements. RESULTS: In the first measurements we did not detect signs of sarcopenia in any individual, but after 8 years, we detected signs of sarcopenia in 7 participants. After eight years, we detected decline in ; muscle strength (-10.2%; p < .001), muscle mass index (-5.4%; p < .001), and physical performance measured with gait speed (-28.6%; p < .001). Similarly, self-reported physical activity and sedentary behavior declined, too (-25.0%; p = .030 and - 48.5%; p < .001, respectively). CONCLUSIONS: Despite expected lower scores on tests of sarcopenia parameters due to age-related decline, participants performed better on motor tests than reported in similar studies. Nevertheless, the prevalence of sarcopenia was consistent with most of the published literature. TRIAL REGISTRATION: The clinical trial protocol was registered on ClinicalTrials.gov, identifier: NCT04899531.

Near-infrared spectroscopy estimation of combined skeletal muscle oxidative capacity and O2 diffusion capacity in humans.

The final steps of the O2 cascade during exercise depend on the product of the microvascular-to-intramyocyte P O 2 ${P}_{{{\rm{O}}}_{\rm{2}}}$ difference and muscle O2 diffusing capacity ( D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ ). Non-invasive methods to determine D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ in humans are currently unavailable. Muscle oxygen uptake (m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) recovery rate constant (k), measured by near-infrared spectroscopy (NIRS) using intermittent arterial occlusions, is associated with muscle oxidative capacity in vivo. We reasoned that k would be limited by D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ when muscle oxygenation is low (kLOW ), and hypothesized that: (i) k in well oxygenated muscle (kHIGH ) is associated with maximal O2 flux in fibre bundles; and (ii) ∆k (kHIGH  - kLOW ) is associated with capillary density (CD). Vastus lateralis k was measured in 12 participants using NIRS after moderate exercise. The timing and duration of arterial occlusions were manipulated to maintain tissue saturation index within a 10% range either below (LOW) or above (HIGH) half-maximal desaturation, assessed during sustained arterial occlusion. Maximal O2 flux in phosphorylating state was 37.7 ± 10.6 pmol s-1  mg-1 (∼5.8 ml min-1  100 g-1 ). CD ranged 348 to 586 mm-2 . kHIGH was greater than kLOW (3.15 ± 0.45 vs. 1.56 ± 0.79 min-1 , P < 0.001). Maximal O2 flux was correlated with kHIGH (r = 0.80, P = 0.002) but not kLOW (r = -0.10, P = 0.755). Δk ranged -0.26 to -2.55 min-1 , and correlated with CD (r = -0.68, P = 0.015). m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ k reflects muscle oxidative capacity only in well oxygenated muscle. ∆k, the difference in k between well and poorly oxygenated muscle, was associated with CD, a mediator of D m O 2 $D{{\rm{m}}}_{{{\rm{O}}}_2}$ . Assessment of muscle k and ∆k using NIRS provides a non-invasive window on muscle oxidative and O2 diffusing capacity. KEY POINTS: We determined post-exercise recovery kinetics of quadriceps muscle oxygen uptake (m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) measured by near-infrared spectroscopy (NIRS) in humans under conditions of both non-limiting (HIGH) and limiting (LOW) O2 availability, for comparison with biopsy variables. The m V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ recovery rate constant in HIGH O2 availability was hypothesized to reflect muscle oxidative capacity (kHIGH ) and the difference in k between HIGH and LOW O2 availability (∆k) was hypothesized to reflect muscle O2 diffusing capacity. kHIGH was correlated with phosphorylating oxidative capacity of permeabilized muscle fibre bundles (r = 0.80). ∆k was negatively correlated with capillary density (r = -0.68) of biopsy samples. NIRS provides non-invasive means of assessing both muscle oxidative and oxygen diffusing capacity in vivo.

[Profile of glucose lowering drug use in outpatients with type 2 diabetes mellitus]. / Perfiles de hipoglicemiantes e insulinas en pacientes con diabetes mellitus tipo 2 y su efecto en control metabólico, hipoglicemia y otros efectos adversos.

BACKGROUND: The use of glucose lowering agents with favorable weight profile is a growing practice in Diabetology. AIM: To characterize medication combinations in patients with type 2 Diabetes (T2D) and their effect on metabolic control. MATERIAL AND METHODS: Review of medical records of 249 outpatients with T2D with a median age of 66 years, cared for at a medical network. Clinical characteristics, glycated hemoglobin (HbA1c), details of Diabetes treatment (types of drugs or insulin), renal function, lipids and B12 vitamin levels were registered. RESULTS: The median disease duration was 16 years. The most recent HbA1c was 7.4%. No patient was using sulfonylureas, 45 were using Dipeptidyl peptidase 4 inhibitors, 113 were using Sodium-glucose Cotransporter-2 (SGLT2i) Inhibitors, 21 used Glucagon-like Peptide-1 Receptor Agonists (GLP1ra), 158 used basal insulin and 61 on basal plus bolus insulin. The use of SGLT2i or GLP1ra was associated with a metabolic control similar to those patients not using them, while patients on rapid insulin had a significantly worse metabolic control and a tendency to greater body mass index. The use of basal insulin and rapid insulin was significantly associated with more hypoglycemia events. CONCLUSIONS: The use of SGLT2i and GLP1ra in patients with T2D is associated with better metabolic control than rapid insulin with less risk of hypoglycemia. The use of these therapies should be prioritized in the future.

Peripheral impairments of oxidative metabolism after a 10-day bed rest are upstream of mitochondrial respiration.

In order to identify peripheral biomarkers of impaired oxidative metabolism during exercise following a 10-day bed rest, 10 males performed an incremental exercise (to determine peak pulmonary V̇O2 (V̇O2 p)) and moderate-intensity exercises, before (PRE) and after (POST) bed rest. Blood flow response was evaluated in the common femoral artery by Eco-Doppler during 1 min of passive leg movements (PLM). The intramuscular matching between O2 delivery and O2 utilization was evaluated by near-infrared spectroscopy (NIRS). Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in isolated muscle fibres, and in vivo by NIRS by the evaluation of skeletal muscle V̇O2 (V̇O2 m) recovery kinetics. Resting V̇O2 m was estimated by NIRS. Peak V̇O2 p was lower in POST vs. PRE. The area under the blood flow vs. time curve during PLM was smaller (P = 0.03) in POST (274 ± 233 mL) vs. PRE (427 ± 291). An increased (P = 0.03) overshoot of muscle deoxygenation during a metabolic transition was identified in POST. Skeletal muscle citrate synthase activity was not different (P = 0.11) in POST (131 ± 16 nmol min-1  mg-1 ) vs. PRE (138 ± 19). Maximal ADP-stimulated mitochondrial respiration (66 ± 18 pmol s-1  mg-1 (POST) vs. 72 ± 14 (PRE), P = 0.41) was not affected by bed rest. Apparent Km for ADP sensitivity of mitochondrial respiration was reduced in POST vs. PRE (P = 0.04). The V̇O2 m recovery time constant was not different (P = 0.79) in POST (22 ± 6 s) vs. PRE (22 ± 6). Resting V̇O2 m was reduced by 25% in POST vs. PRE (P = 0.006). Microvascular-endothelial function was impaired following a 10-day bed rest, whereas mitochondrial mass and function (both in vivo and ex vivo) were unaffected or slightly enhanced. KEY POINTS: Ten days of horizontal bed rest impaired in vivo oxidative function during exercise. Microvascular impairments were identified by different methods. Mitochondrial mass and mitochondrial function (evaluated both in vivo and ex vivo) were unchanged or even improved (i.e. enhanced mitochondrial sensitivity to submaximal [ADP]). Resting muscle oxygen uptake was significantly lower following bed rest, suggesting that muscle catabolic processes induced by bed rest/inactivity are less energy-consuming than anabolic ones.

Heterogeneity of human adaptations to bed rest and hypoxia: a retrospective analysis within the skeletal muscle oxidative function.

This retrospective study was designed to analyze the interindividual variability in the responses of different variables characterizing the skeletal muscle oxidative function to normoxic (N-BR) and hypoxic (H-BR) bed rests and to a hypoxic ambulatory confinement (H-AMB) of 10 and 21 days. We also assessed whether and how the addition of hypoxia to bed rest might influence the heterogeneity of the responses. In vivo measurements of O2 uptake and muscle fractional O2 extraction were carried out during an incremental one-leg knee-extension exercise. Mitochondrial respiration was assessed in permeabilized muscle fibers. A total of 17 subjects were included in this analysis. This analysis revealed a similar variability among subjects in the alterations induced by N-BR and H-BR both in peak O2 uptake (SD: 4.1% and 3.3% after 10 days; 4.5% and 8.1% after 21 days, respectively) and peak muscle fractional O2 extraction (SD: 5.9% and 7.3% after 10 days; 6.5% and 7.3% after 21 days), independently from the duration of the exposure. The individual changes measured in these variables were significantly related (r = 0.66, P = 0.004 after N-BR; r = 0.61, P = 0.009 after H-BR). Mitochondrial respiration showed a large variability of response after both N-BR (SD: 25.0% and 15.7% after 10 and 21 days) and H-BR (SD: 13.0% and 19.8% after 10 and 21 days); no correlation was found between N-BR and H-BR changes. When added to bed rest, hypoxia altered the individual adaptations within the mitochondria but not those intrinsic to the muscle oxidative function in vivo, both after the short- and medium-term exposures.

Microvascular O2 delivery and O2 utilization during metabolic transitions in skeletal muscle. One-hundred years after the pioneering work by August Krogh.

Upon a sudden rise in work rate, ATP turnover increases immediately, whereas the adjustment of ATP resynthesis from oxidative phosphorylation is substantially slower. An "O2 deficit" (energy borrowed from substrate level phosphorylation) is therefore generated. A greater O2 deficit represents an epiphenomenon of a lower "metabolic stability" during the transition, a circumstance directly related to impaired exercise tolerance. In the search for factors responsible for the delayed adjustment of oxidative phosphorylation, we performed studies in the surgically isolated canine gastrocnemius muscle in situ. Enhancement of convective and diffusive microvascular O2 delivery, with respect to a "normal" condition, did not affect skeletal muscle V̇O2 kinetics during transitions to submaximal metabolic rates. V̇O2 kinetics, however, was slowed after experimentally impairing convective O2 delivery, a condition frequently encountered in pathological conditions. Among potential metabolic factors (pyruvate dehydrogenase activation, nitric oxide inhibition of cytochrome oxidase) a limiting role in V̇O2 kinetics was observed only for creatine kinase (CK) mediated phosphocreatine (PCr) breakdown. Following CK inhibition, faster muscle V̇O2 kinetics was observed. Thus, in skeletal muscle CK-catalysed PCr breakdown at contractions onset slows the increase of oxidative phosphorylation. By acting as a high-capacitance energy buffer, PCr breakdown delays or attenuates the increased concentrations of metabolites (such as ADP, Pi, Cr) mediating the V̇O2 increase. Upon sudden increases in ATP turnover, skeletal muscle fibers rely first on the bioenergetic pathway (PCr breakdown), which is fast to adjust to increased metabolic needs. Metabolites related to PCr breakdown regulate, but inevitably slow down, the adjustment of oxidative phosphorylation.

[Association of hyperglycemia with the length of stay in hospitalized patients]. / Prevalencia de hiperglicemia y su relación con el tiempo de estadía en un hospital terciario.

BACKGROUND: Hyperglycemia during hospital stay is associated with adverse outcomes. AIM: To characterize the frequency of hyperglycemia in a tertiary hospital and to correlate it with length of hospital stay (LOS). MATERIAL AND METHODS: Review of medical records of hospitalized patients. Demographic data and laboratory data, previous diabetes mellitus (DM) history, current main diagnosis, unit of hospitalization and the two highest capillary blood glucose values from the analyzed period were recorded for each patient. LOS was obtained from electronic clinical records. RESULTS: 210 subjects, aged 60 ± 19 years (104 women) were included. 113 patients (54%) developed hyperglycemia ≥ 140 mg/L. Thirty one percent of these had a previous history of diabetes and 29% had stress hyperglycemia (SHG). Patients with a history of DM had a higher average blood glucose than those with SHG (238.9 and 178.2 mg/dL, respectively, p < 0.01) and a greater percentage of cases with a blood glucose above 180 mg/dL (72 and 40.0%, respectively, p < 0.01). Hospital LOS was significantly longer in patients with hyperglycemia ≥ 140 mg/dL as compared with those with normoglycemia (29.3 and 12.8 days, respectively, p < 0.01). This association remained significant when introduced in a linear regression analysis including diagnosis, decreased glomerular filtration rate (GFR) and hospitalization unit (p < 0.01). CONCLUSIONS: Hyperglycemia during hospitalization affects more than half of hospitalized patients and is associated with a longer length of stay.

[Analysis of 4,164 type 1 diabetes antibody profiles in a Chilean health centre]. / Marcadores inmunológicos de diabetes tipo 1: análisis de 4.164 perfiles en un centro de salud de Chile.

BACKGROUND: Previous studies have assessed the role of Type 1 diabetes (DM1) antibodies as predictors of the natural history of disease. AIM: To determine the frequency and combinations of positivity for DM1 antibodies in patients with DM1 and the relationship between antibody positivity and the age of the patient. To explore the relationship between history of insulin therapy or diabetic ketoacidosis (DKA) at the onset of the disease with antibody positivity in a subsample. MATERIAL AND METHODS: Data was gathered from every sample processed for DM1 antibodies in our laboratory between January 2015 and September 2019. Medical records from 84 patients who tested positive for at least one antibody were revised to study the relationship between insulin therapy or DKA at the onset of the disease with antibody positivity. RESULTS: Forty percent of DM1 antibody tests were positive. Among positive tests, 1, 2, 3 or 4 DM1 antibodies were detected in 48%, 33%, 17% and 3% of cases, respectively. The likelihood of testing positive was inversely related with age for ICA, GAD, IA-2, ZnT8 and directlyproportionalforIAA (p= -0,012; -0,013; -0,014; -0,009; 0,005 respectively). An association between DKA at the onset of the disease and IA-2 positivity was observed (Odds ratio (OR) 5.38 95% confidence intervals (CI) 1.79 - 16.16, P < 0.01). No association was found between IAA positivity and history of insulin therapy (OR 2.25 95%CI 0.63 - 7.90, P = 0.2403). The results obtained from this study represent a novel local profile of DM1 antibody data, highlighting a relationship between antibody positivity and age.

Reduced burnout and higher mindfulness in medical students after a self-care program during the COVID-19 pandemic.

BACKGROUND: Medical students experience high levels of psychological stress during clinical training. However, most medical curricula do not teach self-care skills. The COVID-19 pandemic has disrupted medical education causing increased distress among students. AIM: To report the implementation and impact of an eight-week multifaceted mindfulness-based self-care program on medical students' distress and well-being during the COVID-19 pandemic. MATERIAL AND METHODS: One hundred twenty-three fourth-year medical students attended the program as part of a mandatory course from April to May 2020, during the rising phase of COVID-19 in Chile. They were evaluated using validated tests before and immediately after the program. The measures included burnout, dispositional mindfulness, perceived stress, traumatic stress reactions, general well-being, resilience, and stress coping strategies. RESULTS: Burnout prevalence decreased from 48% to 24%, whereas students with high dispositional mindfulness increased from 25% to 44%. Burnout reduction was mostly due to decreased emotional exhaustion. Additionally, students reported lower levels of stress, self-blaming, and traumatic stress reactions alongside an increased use of active coping strategies and resilience levels after the program. CONCLUSIONS: A formal educational intervention, teaching self-awareness and self-regulation skills can help reduce medical students' distress and promote their well-being even amidst a pandemic.

Effect of acute nitrite infusion on contractile economy and metabolism in isolated skeletal muscle in situ during hypoxia.

KEY POINTS: Increased plasma nitrite concentrations may have beneficial effects on skeletal muscle function. The physiological basis explaining these observations has not been clearly defined and it may involve positive effects on muscle contraction force, microvascular O2 delivery and skeletal muscle oxidative metabolism. In the isolated canine gastrocnemius model, we evaluated the effects of acute nitrite infusion on muscle force and skeletal muscle oxidative metabolism. Under hypoxic conditions, but in the presence of normal convective O2 delivery, an elevated plasma nitrite concentration affects neither muscle force, nor muscle contractile economy. In accordance with previous results suggesting limited or no effects of nitrate/nitrite administrations in highly oxidative and highly perfused muscle, our data suggest that neither mitochondrial respiration, nor muscle force generation are affected by acute increased concentrations of NO precursors in hypoxia. ABSTRACT: Contrasting findings have been reported concerning the effects of augmented nitric oxide (NO) on skeletal muscle force production and oxygen consumption ( V̇O2 ). The present study examined skeletal muscle mitochondrial respiration and contractile economy in an isolated muscle preparation during hypoxia (but normal convective O2 delivery) with nitrite infusion. Isolated canine gastrocnemius muscles in situ (n = 8) were studied during 3 min of electrically stimulated isometric tetanic contractions corresponding to ∼35% of V̇O2peak . During contractions, sodium nitrite (NITRITE) or sodium chloride (SALINE) was infused into the popliteal artery. V̇O2 was calculated from the Fick principle. Experiments were carried out in hypoxia ( FIO2  = 0.12), whereas convective O2 delivery was maintained at normal levels under both conditions by pump-driven blood flow ( Q̇ ). Muscle biopsies were taken and mitochondrial respiration was evaluated by respirometry. Nitrite infusion significantly increased both nitrite and nitrate concentrations in plasma. No differences in force were observed between conditions. V̇O2 was not significantly different between NITRITE (6.1 ± 1.8 mL 100 g-1  min-1 ) and SALINE (6.2 ± 1.8 mL 100 g-1  min-1 ), even after being 'normalized' per unit of developed force (muscle contractile economy). No differences between conditions were found for maximal ADP-stimulated mitochondrial respiration (both for complex I and complex II), leak respiration and oxidative phosphorylation coupling. In conclusion, in the absence of changes in convective O2 delivery, muscle force, muscle contractile economy and mitochondrial respiration were not affected by acute infusion of nitrite. The previously reported positive effects of elevated plasma nitrite concentrations are presumably mediated by the increased microvascular O2 availability.

Effects of 3-month high-intensity interval training vs. moderate endurance training and 4-month follow-up on fat metabolism, cardiorespiratory function and mitochondrial respiration in obese adults.

PURPOSE: The purpose of this study was to investigate, in obese adults, changes in body composition, physical capacities, fat oxidation and ex vivo mitochondrial respiration induced by a 3-month either moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT); afterwards, the patients were followed for four months. METHODS: Thirty-two patients (mean age 39 years; mean body mass index [BMI] 36 kg∙m-2) participated in this study attending ~ 34 sessions of training. At baseline (PRE), at the end of the program (POST) and after follow-up, body composition, peak O2 uptake (V'O2peak) and fat oxidation rate were measured. Vastus lateralis biopsies for the evaluation of mitochondrial respiration were performed only at PRE and POST. RESULTS: At POST, body mass (BM) and fat mass (FM) decreased (- 6 and - 14%, respectively, P < 0.05) in MICT and HIIT; V'O2peak increased in both groups (+ 6 and + 16%, respectively, P < 0.05). Maximal fat oxidation rate increased only after HIIT (P < 0.001). Maximal ADP-stimulated mitochondrial respiration normalized by citrate synthase increased (P < 0.05) by 67% and 36% in MICT and HIIT, respectively, without significant difference. After follow-up, BM and FM were still lower (- 4 and - 20%, respectively, P < 0.050) compared with baseline in both groups. Only after HIIT, V'O2peak (+ 8%) and maximal fat oxidation rate were still higher (P < 0.05). CONCLUSIONS: HIIT was more effective in improving and maintaining V'O2peak and fat oxidation. These results may be relevant for an appropriate prescription of training programs designed to optimize aerobic fitness in obese subjects.

[Management of chylous ascites and chylothorax. Report of one case]. / Tratamiento de quilotórax y quiloascitis refractaria en paciente cirrótico. Caso clínico.

Chylous Ascites (CA) and chylothorax (CTx) are associated with obstruction, disruption or insufficiency of the lymphatic system. We report a 68-year-old male, with a history of alcoholic cirrhosis, who had recurrent events of CTx and CA. After a complete study, no other etiologies other than portal hypertension were found. Therapy with diuretics, nothing per mouth, parenteral feeding plus octreotide did not relieve symptoms. A transjugular intrahepatic portosystemic shunt (TIPS) was successfully placed and pleural effusion subsided. This case shows that CA and CTx can be caused by portal hypertension and they may subside employing a multimodal management strategy.

[Use of sodium-glucose cotrasporter 2 inhibitors in type 2 diabetics. Experience in 77 patients]. / Experiencia de uso de inhibidores del cotransportador sodio-glucosa 2 en diabéticos tipo 2.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a new pharmacological alternative for the treatment of diabetes. AIM: To report our experience with the use of this type of drugs in type 2 diabetics treated in an outpatient clinic. MATERIAL AND METHODS: We selected 77 type 2 diabetic patients aged 59 ± 11 years (45 men) who started SGLT2i, based on the advice of their treating physician. We registered their demographic characteristics and changes in metabolic parameters, weight, blood pressure, albuminuria and adverse effects, during a follow-up of at least three months. RESULTS: We observed a decrease of glycosylated hemoglobin A1c of 0.8 ± 1.14% (p < 0.01) and a weight decrease of 2.5 ± 2.24 kg (p < 0.01). The proportion of patients with a glycosylated hemoglobin A1c of less than 7% increased from 7.2% to 30.9% (p = 0.002). In addition, a relative decrease in albuminuria of 39.9% was observed (p = 0.07). The treatment was well tolerated with a rate of adverse effects of 21%, all of them being categorized as mild. Of these, most of them corresponded to genital mycotic infections. CONCLUSIONS: The effects observed in this study are comparable and of similar magnitude to randomized studies of SGLT2i reported in the international literature.

[Clinical features and management of 205 adults with type 1 diabetes mellitus]. / Características clínicas, esquemas de tratamiento, grado de control y variables asociadas a este en una cohorte de adultos con diabetes mellitus tipo 1 en un centro terciario.

BACKGROUND: Few studies have evaluated the details of insulin therapy for type 1 diabetes mellitus (T1D) in Chile. AIM: To describe clinical features and treatment details of adults with T1D and its association with metabolic control. MATERIAL AND METHODS: Review of medical records of patients with T1D treated in a clinical network. Demographic and clinical features, types and doses of insulin and glycated hemoglobin levels were registered. The use flash glucose monitors (FGM) and insulin pumps (CSII) were also recorded. RESULTS: 205 records were reviewed, with T1d lasting 12 ± 10 years. Twenty six percent had hypothyroidism, 1% had celiac disease, 12% had hypertension, 20% had dyslipidemia; 13% had diabetic retinopathy, 2% had diabetic nephropathy, 8% had neuropathy and 2% cardiovascular diseases. Mean body mass index was 25 kg/ m2 and mean glycated hemoglobin was 8%. Eighty-two percent used multiple daily injections, 18% used CSII and 24% used FGM. As basal insulin, 35% used slow acting analogs and 65% used ultra-slow analogs. As rapid acting insulin, 69 patients used Lispro, 79 Aspart and 50 Glulisin. Bolus doses were calculated using only capillary glucose in 22%, while 78% also considered carbohydrate consumption. Variables significantly associated to better control were the use of carbohydrates for dosing rapid insulin (A1c 7,85% vs 8,59%, p = 0,008), use of CSII (A1c 7,36% vs 8,16%, p = 0,008), and basal dose < 0,4 U/kg (A1c 7,81% vs 8,58%, p = 0,003). There were no differences regarding insulin type or use of FGM. CONCLUSIONS: The use of formulas considering carbohydrates for dosing rapid insulin, use of infusion pumps and physiological doses of basal insulin are significantly associated with a better metabolic control in adults with T1d.

PlanHab* : hypoxia does not worsen the impairment of skeletal muscle oxidative function induced by bed rest alone.

KEY POINTS: Superposition of hypoxia on 21 day bed rest did not worsen the impairment of skeletal muscle oxidative function induced by bed rest alone. A significant impairment of maximal oxidative performance was identified downstream of cardiovascular O2 delivery, involving both the intramuscular matching between O2 supply and utilization and mitochondrial respiration. These chronic adaptations appear to be relevant in terms of exposure to spaceflights and reduced gravity habitats (Moon or Mars), as characterized by low gravity and hypoxia, in patients with chronic diseases characterized by hypomobility/immobility and hypoxia, as well as in ageing. ABSTRACT: Skeletal muscle oxidative function was evaluated in 11 healthy males (mean ± SD age 27 ± 5 years) prior to (baseline data collection, BDC) and following a 21 day horizontal bed rest (BR), carried out in normoxia ( PIO2  = 133 mmHg; N-BR) and hypoxia ( PIO2  = 90 mmHg; H-BR). H-BR was aimed at simulating reduced gravity habitats. The effects of a 21 day hypoxic ambulatory confinement ( PIO2  = 90 mmHg; H-AMB) were also assessed. Pulmonary O2 uptake ( V̇O2 ), vastus lateralis fractional O2 extraction (changes in deoxygenated haemoglobin + myoglobin concentration, Δ[deoxy(Hb + Mb)]; near-infrared spectroscopy) and femoral artery blood flow (ultrasound Doppler) were evaluated during incremental one-leg knee-extension exercise (reduced constraints to cardiovascular O2 delivery) carried out to voluntary exhaustion in a normoxic environment. Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibres. V̇O2peak decreased (P < 0.05) after N-BR (0.98 ± 0.13 L min-1 ) and H-BR (0.96 ± 0.17 L min-1 ) vs. BDC (1.05 ± 0.14 L min-1 ). In the presence of a decreased (by ∼6-8%) thigh muscle volume, V̇O2peak normalized per unit of muscle mass was not affected by both interventions. Δ[deoxy(Hb + Mb)]peak decreased (P < 0.05) after N-BR (65 ± 13% of limb ischaemia) and H-BR (62 ± 12%) vs. BDC (73 ± 13%). H-AMB did not alter V̇O2peak or Δ[deoxy(Hb + Mb)]peak . An overshoot of Δ[deoxy(Hb + Mb)] was evident during the first minute of unloaded exercise after N-BR and H-BR. Arterial blood flow to the lower limb during both unloaded and peak knee extension was not affected by any intervention. Maximal ADP-stimulated mitochondrial respiration decreased (P < 0.05) after all interventions vs. control. In 21 day N-BR, a significant impairment of oxidative metabolism occurred downstream of cardiovascular O2 delivery, affecting both mitochondrial respiration and presumably the intramuscular matching between O2 supply and utilization. Superposition of H on BR did not worsen the impairment induced by BR alone.

Ergogenic effects of beetroot juice supplementation during severe-intensity exercise in obese adolescents.

Previous studies showed a higher O2 cost of exercise, and therefore, a reduced exercise tolerance in patients with obesity during constant work rate (CWR) exercise compared with healthy subjects. Among the ergogenic effects of dietary nitrate ([Formula: see text]) supplementation in sedentary healthy subjects, a reduced O2 cost and enhanced exercise tolerance have often been demonstrated. The aim of this study was to evaluate the effects of beetroot juice (BR) supplementation, rich in [Formula: see text], on physiological variables associated with exercise tolerance in adolescents with obesity. In a double-blind, randomized crossover study, 10 adolescents with obesity (8 girls, 2 boys; age = 16 ± 1 yr; body mass index = 35.2 ± 5.0 kg/m2) were tested after 6 days of supplementation with BR (5 mmol [Formula: see text] per day) or placebo (PLA). Following each supplementation period, patients carried out two repetitions of 6-min moderate-intensity CWR exercise and one severe-intensity CWR exercise until exhaustion. Plasma [Formula: see text] concentration was significantly higher in BR versus PLA (108 ± 37 vs. 15 ± 5 µM, P < 0.0001). The O2 cost of moderate-intensity exercise was not different in BR versus PLA (13.3 ± 1.7 vs. 12.9 ± 1.1 ml·min-1·W-1, P = 0.517). During severe-intensity exercise, signs of a reduced amplitude of the O2 uptake slow component were observed in BR, in association with a significantly longer time to exhaustion (561 ± 198 s in BR vs. 457 ± 101 s in PLA, P = 0.0143). In obese adolescents, short-term dietary [Formula: see text] supplementation is effective in improving exercise tolerance during severe-intensity exercise. This may prove to be useful in counteracting early fatigue and reduced physical activity in this at-risk population.