Telma Maria Araújo Moura Lemos

Background: Hypomagnesemia, characterized by decreased levels of magnesium in the blood, is common among patients with cancer and may be related to the administration of proton pump inhibitors (PPIs) and/or platinum derivatives. Objective: To evaluate the safety and potential impact on serum magnesium levels of concomitant use of the PPI omeprazole in patients receiving a platinum derivative. Methods: This prospective, randomized, double-blind, single-dose, placebo-controlled study involved fixed doses of PPI administered on an outpatient basis. It spanned 4 cycles of platinum-based combination chemotherapy (21 days per cycle), and entailed a screening period (14 days before chemotherapy), 2 PPI treatment periods (total of 60 days), and a follow-up period (1 cycle). Patients recruited between May 2019 and March 2020 at 3 hospitals in Brazil were randomly assigned to receive placebo or PPI in a 1:1 ratio. Data analysis employed a linear mixed-effects model and Kaplan–Meier analysis. Results: A total of 164 patients were included in the study, 83 in the placebo group and 81 in the PPI group. Blood magnesium levels showed a modest decrease over time (by approximately 20%) across all patients. A correlation was observed between treatment duration and decrease in serum magnesium in the total sample (β = –0.035, 95% confidence interval [CI] –0.048 to –0.0021; p < 0.001). Compared with the placebo group, the PPI group showed a slightly greater decline (β = –0.121, 95% CI –0.231 to –0.011; p = 0.031). Additionally, no differences were noted between groups regarding the occurrence of neuropathy (p = 0.77), anorexia (p = 0.77), diarrhea (p = 0.34), or constipation (p = 0.39). Omeprazole use was associated with a lower incidence of nausea and vomiting (p = 0.005). Conclusion: These exploratory findings suggest that the concomitant use of omeprazole with platinum derivatives may be associated with a slightly faster rate of serum magnesium depletion than occurs with chemotherapy alone, but without clinical relevance or occurrence of frank hypomagnesemia. Keywords: magnesium, clinical oncology, platinum compounds, proton pump inhibitors, adverse effects Clinical trial registration: Brazilian Registry of Clinical Trials (ReBEC) RBR-8vsb7k2 RÉSUMÉ Contexte : L’hypomagnésémie se caractérise par une réduction des taux de magnésium dans le sang. Elle est répandue chez les patients atteints d’un cancer et peut être liée à l’administration d’inhibiteurs de la pompe à protons (IPP) et/ou de dérivés du platine. Objectif : Évaluer l’innocuité et l’incidence potentielle sur les taux sériques de magnésium de l’utilisation concomitante de l’IPP oméprazole chez des patients recevant un dérivé du platine. Méthodologie : Cette étude prospective, randomisée, à double insu, à dose unique et contrôlée par placebo portait sur des doses fixes d’IPP administrées en ambulatoire. Elle s’est déroulée pendant 4 cycles de chimiothérapie combinée à base de platine (21 jours par cycle) et comprenait une période de sélection (14 jours avant la chimiothérapie), deux périodes de traitement à l’IPP (comprenant 60 jours au total) et une période de suivi (1 cycle). Des patients recrutés dans 3 hôpitaux du Brésil entre mai 2019 et mars 2020 ont été répartis de manière aléatoire pour recevoir soit un placebo, soit un IPP, selon un ratio de 1:1. Un modèle linéaire à effets mixtes ainsi qu’une analyse de Kaplan-Meier ont été utilisés pour l’analyse des données. Résultats : Au total, 164 patients ont été inclus dans l’étude : 83 dans le groupe placebo et 81 dans le groupe IPP. Une diminution modeste avec le temps (environ 20 %) des taux sanguins de magnésium chez l’ensemble des patients a été constatée. Une corrélation a été observée entre la durée du traitement et la diminution du magnésium sérique chez l’ensemble des patients (β = –0,035; intervalle de confiance [IC] à 95 % : –0,048 à –0,002 1; p < 0,001). Cette diminution était légèrement plus marquée dans le groupe IPP que dans le groupe placebo (β = –0,121; IC à 95 % : –0,231 à –0,011; p = 0,031). De plus, aucune différence n’a été observée entre les groupes concernant la survenuede neuropathie (p = 0,77), d’anorexie (p = 0,77), de diarrhée (p = 0,34) ou de constipation p = 0,39). L’utilisation de l’oméprazole était associée à une incidence plus faible de nausées et de vomissements (p = 0,005). Conclusion : Ces résultats exploratoires indiquent que l’utilisation concomitante de l’oméprazole avec des dérivés du platine pourrait être associée à une diminution légèrement plus rapide des taux sériques de magnésiumque celle observée avec la chimiothérapie seule, sans toutefois présenter de pertinence clinique ni entraîner la survenue d’une hypomagnésémie franche. Mots-clés : magnésium, oncologie clinique, composés du platine, inhibiteurs de la pompe à protons, effets indésirables Inscription à l’essai clinique : Brazilian Registry of Clinical Trials (ReBEC) RBR-8vsb7k2

Introduction Approximately two-thirds of Brazilian older adults have hypertension. Aerobic training is the first-line non-pharmacological therapy for hypertension. However, the effects of different aerobic training approaches on ambulatory blood pressure in older adults are uncertain. Here, we present the study protocol for the HEXA Study, which aims to investigate the effects of high-intensity interval (HIIT) and moderate-intensity continuous training (MICT) on 24-hour ambulatory blood pressure and cardiovascular outcomes in older adults with hypertension. Methods and analysis This is a single-centre, randomised, three-arm, parallel superiority trial with a 1:1:1 ratio. The trial is conducted with blinded outcome assessors and statistical analysts. 66 inactive older adults with hypertension aged 60–80 years without a history of major adverse cardiovascular events will be randomly assigned to one of the following groups: (1) HIIT (3 months; 3× week); (2) MICT (3 months; 3× week); (3) health education programme (control; 3 months; 1× week). Exercise training sessions involve rating of perceived exertion-based outdoor moderate walking, brisk walking and/or jogging. The primary outcome is 24-hour ambulatory blood pressure. Secondary cardiovascular outcomes are resting blood pressure, cardiorespiratory fitness, pulse wave velocity, carotid intima-media thickness, heart rate variability and cardiac function/structure. All outcomes are measured at baseline and after a 3-month period. In addition, feelings of pleasure/displeasure, adherence and safety are reported. Ethics and dissemination All procedures were approved by the Research Ethics Committee of the Onofre Lopes University Hospital (protocol, CAAE 07191019.8.0000.5292) and are executed in compliance with the Declaration of Helsinki. Additionally, the procedures adhered to Resolution 466/2012 issued by the Brazilian National Health Council for research involving human subjects. Trial registration number Brazilian Registry of Clinical Trials (ID: RBR-4ntszb).

Purpose: To compare the effects of 12-week high-intensity interval (HIIT), moderate-intensity continuous (MICT), and self-selected intensity training (SSIT) on health outcomes and affective responses. Methods: Seventy-three overweight/obese inactive adults (62% woman; age, 31.4 ± 7.2 years; height, 1.66 ± 0.09 cm; Body mass index, 28.9 ± 2.7 kg.m⁻²) who were randomized into HIIT (n = 23), MICT (n = 24) and SSIT (n = 26) groups. The training was conducted three times per week in an outdoor environment, with 4 weeks under direct supervision and 8 weeks with semi-supervision. Cardiorespiratory fitness, body composition, and metabolic profile were evaluated at baseline and at the end of the 4^th and 12^th weeks. Core affect was measured during all training sessions. Results: Peak oxygen uptake improved in all groups after 4 and 12 weeks compared with baseline. Only the SSIT had reductions in body fat throughout the intervention. No improvements were observed in the metabolic profile across all groups. SSIT was perceived as more pleasurable than HIIT; however, there were no differences in affective responses between SSIT and MICT. Affective responses in-task (e.g. negative and positive peak, rate of change and affect at the end of the exercise session) predicted the HIIT and SSIT exercises attendance rate. Conclusion: Regardless of the exercise training protocol, overweight/obese inactive adults improved health outcomes, which suggests the prescribing HIIT, MICT, and SSIT in outdoor environments. SSIT should be considered in order to optimize the pleasure during training sessions. Affective response more positive in-task of the HIIT and SSIT is associated with greater attendance rate in these exercise protocols.

Purpose: This study aimed to assess skin temperature (Tsk) changes after different magnitudes of exercise-induced muscle damage (EIMD) of the elbow flexor muscles and investigate whether Tsk is related to indirect markers of EIMD. Methods: Thirty healthy active men were randomly allocated to the mild (MiDG) (n = 15) or moderate (MoDG) (n = 15) muscle damage group. Muscle damage in elbow flexor muscles was induced by 10 (for MiDG) or 30 (for MoDG) maximal eccentric isokinetic contractions at 60 degrees/s. Tsk, maximal voluntary isometric contraction (MVIC), delayed-onset muscle soreness (DOMS), plasma creatine kinase (CK) activity, range of motion (ROM), and pressure pain threshold (PPT) were measured before and up to 72 hr after EIMD. Results: Tsk increased only immediately after EIMD (p < .05; f = 1.44) in the MoDG (4.2%) and MiDG (4.6%), returning to near baseline values 30 min after EIMD and remaining so thereafter. In addition, there was no intergroup difference (p > .05) at any of the times analyzed, or correlation between Tsk and most indirect markers of EIMD. Conclusions: In conclusion, Tsk should not be considered an indirect marker of mild or moderate muscle damage in active men, since alterations in this variable last less than 30 min after damaging exercise and showed no correlation with most indirect markers of EIMD.

Reactive oxygen species (ROS) are aerobic products generated during cellular respiration, but in the case of oxidative stress, they become key factors in the development of inflammatory processes and chronic diseases such as diabetes and rheumatoid arthritis. In this work, Euterpe oleracea oil (EOO), as well as the complexes produced by slurry (S) and kneading (K), were analyzed for antioxidant capacity in vitro, while only the β-cyclodextrin complex obtained by kneading (EOO-βCD-K), which showed better complexation, was selected for anti-inflammatory assays in vivo. In the scavenging activity of OH·, the hydroxypropyl-β-cyclodextrin complex obtained by kneading (EOO-HPβCD-K) exhibited an activity 437% higher than the pure oil. In the paw edema assay, EOO-βCD-K reduced edema by 200% and myeloperoxidase (MPO) activity by 112%. In an air pouch model, this treatment showed a reduction in leukocyte, MPO, and Interleukin-1β (IL-1β) levels; meanwhile those of glutathione and IL-10 were increased, demonstrating its ability to potentiate the anti-inflammatory effect of EOO.

The effect of physical activity counseling (PAC) in hypertensive adults is unclear. This study investigated the effect of PAC on blood pressure (BP), physical activity level, sitting time, metabolic profile, and body composition in hypertensive adults. Twenty-two hypertensive adults (48.8 ± 7.3 years) participated in this pilot trial. The 12-week PAC was based on the 5 A’s model considering the FITT principle (Frequency, Intensity, Time, and Type) of physical activity. The control group received instructions about FITT in one face-to-face meeting at baseline. Pedometer-measured physical activity, sitting time, resting and ambulatory BP, metabolic profile (cholesterol, triglycerides, fasting glucose), and body composition (fat mass, abdominal fat, fat free mass) were assessed. The PAC group showed higher steps per day (5839 ± 992 vs. 5028 ± 902; p = 0.044) and a trend for lower sitting time (5.6 ± 1.3 vs. 8.0 ± 4.0 h/day; p = 0.059) than the control group. No changes were observed in BP, metabolic profile, and body composition (p > 0.05). In conclusion, 12 weeks of a PAC program based on the 5 A’s model resulted in a modest increase of ~800 steps per day and a trend to decrease ~2 h/day in sitting time, but there were no associated reduction in BP and improvements in metabolic and body composition.

Children with acute lymphoblastic leukemia are at risk of malnutrition, but few studies have described the changes in nutritional status during the different phases of chemotherapy. To evaluate changes in nutritional status, food intake and appetite-regulating hormones among children and adolescents with acute lymphoblastic leukemia in the first phase of chemotherapy. Cohort study developed in the pediatric oncology departments of two hospitals in the city of Natal, Rio Grande do Norte, Brazil. Fourteen children/adolescents (mean age of 7 years; 50% female) with acute lymphoblastic leukemia were monitored over the 28 days of an induction chemotherapy cycle. Anthropometric measurements, 24-hours food weight records and appetite-regulating hormone levels (ghrelin, leptin, insulin and cortisol) were obtained at three different times (before, in the middle and at the end of the induction phase). Most of the patients (85.7%) had normal weight at the beginning of the treatment, and this did not change significantly during the 28 days. Energy and nutrient intakes improved from the start of the treatment to the midpoint, according to the ghrelin levels (from 511.1 ± 8.3 to 519.3 ± 6.6 pg/ml; P = 0.027). Other appetite-regulating hormones did not present changes. Food consumption improves during the first phase of treatment, without alterations in anthropometric nutritional status.

Several isatin derivatives have shown important biological activities, which have attracted interest from researchers. For this reason, the present study aimed to evaluate the anti-inflammatory and antinociceptive effects of the isatin derivative (Z)-2-(5-chloro-2-oxoindolin-3-ylidene)-N-phenyl-hydrazinecarbothioamide (COPHCT) in mice. Three doses of this compound were tested: 1.0, 2.5, and 5.0 mg/kg. The anti-inflammatory activity was assessed using the carrageenan-induced paw edema model and the zymosan-induced air pouch model. The evaluation of the antinociceptive effect was performed through the formalin test and the acetic acid-induced abdominal writhing test. The paw edema assay demonstrated that all doses of the compound showed a significant reduction of the edema in the second hour evaluated, but a better response was observed in the fourth hour. The zymosan-induced air pouch model indicated that the compound, in all doses, significantly reduced leukocyte migration and total protein concentration levels. In the formalin test, the doses 1.0, 2.5, and 5.0 mg/kg of COPHCT showed activity only in the second phase, with reduction in paw pain time of 73.61, 79.46, and 73.85%, respectively. The number of abdominal writhings decreased with the increasing dose, but only 5.0 mg/kg COPHCT exhibited a significant response, with a reduction of 24.88%. These results demonstrated the ability of this compound to interfere in the anti-inflammatory activity of edema, vascular permeability, and cell migration. In addition, its possible antinociceptive effect may be related to the dose used.

The use of strategies to assure better post-effort recovery is frequent in sports settings. There are several interventions available for exercise induced muscle damage recovery, but cold-water immersion (CWI) stands out among them. The effects of CWI are unclear in the literature and, although the number of street runners has been growing, there is a gap in the scientific evidence regarding the use of CWI to recover runners’ performance after a 10-km street run. Purpose: The goal of our study was to analyze the effects of CWI on the recovery of muscle damage markers after a 10-km street run. Method: We randomly assigned thirty male recreational street runners, immediately after a 10-km street run, into three recovery groups: control (rest for 10 minutes), immersion (10 min immersed in water without ice at room temperature) and CWI (10 min immersed in water with ice at 10ºC). We assessed pain, triple hop distance, extensor peak torque and blood creatine kinase levels pre- and post-run, post-intervention and 24 hours after the run. Results: The 10-km run was enough to decrease triple hop distance and extensor peak torque, and increase levels of creatine kinase (p < 0.05); however, we found no time/group interactions in any of the assessed variables after we applied the appropriate interventions (p > 0.05). Conclusion: 10-min CWI at 10°C was no more effective than water immersion and rest in recovering muscle damage markers after 10-km runs.