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Sodium-glucose co-transporter-2 inhibitors (SGLT2i) added to optimal medical therapy have been shown to reduce the risk of cardiovascular death and recurrent heart failure (HF) hospitalization in HF patients. But whether SGLT2i reduce ventricular arrhythmias and sudden cardiac death (SCD) is controversial. Ventricular repolarization heterogeneity is associated with ventricular arrhythmias. We aimed to evaluate the effect of Dapagliflozin on the ventricular repolarization markers (VRM) in patients with HF with reduced ejection fraction (HFrEF). This retrospective study included patients referred to our cardiology department between February 2022 and June 2023 for assessment of HFrEF and who were on beta-blocker, angiotensin-converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB) and mineralocorticoid receptor antagonist. They underwent before introduction of dapagliflozin and 6 months later electrocardiograms (ECG) with measurement of QT interval, QTc (corrected by Bazett formula), QT dispersion (QTd), QTc dispersion (QTc-d), Tpeak to Tend (Tp-e) interval, Tp-e/QT, and Tp-e/QTc ratios. A total of 50 patients in sinus rhythm were included. The mean age was 60.88 ± 11.36 years old, and 11 (22%) were female patients. The mean ejection fraction was 30.86 ± 7.2%. Diabetes, hypertension, and chronic kidney disease were reported in 48%, 30%, and 20% of the patients, respectively. We compared VRM before and after introduction of dapagliflozin and we noticed a significant decrease in QTc intervals (430.74 ± 33.81 ms vs. 408.74 ± 32.45 ms; P < 0.001), QT-d (54 ± 19.24 ms vs. 36.2 ± 11.8 ms; P < 0.001) and Tp-e interval (95.8 ± 24.83 ms vs. 74.8 ± 22.87 ms; P < 0.001). Following the introduction of dapagliflozin, we observed a significant increase in left ventricular ejection fraction (LVEF) (30.86 ± 7.2% vs. 38.93 ± 7.07%; P < 0.001). Additionally, left ventricular end-diastolic diameter and left ventricular end-systolic diameter decreased significantly (58.68 ± 7.05 mm vs. 56.28 ± 6.3 mm; P < 0.001, 46.7 ± 8.1 mm vs. 40.7 ± 7.82 mm; P < 0.001). In addition, study participants experienced an improvement in functional capacity. The addition of dapagliflozin to optimal medical therapy in HFrEF patients positively changes VRM (QT, QTc, QTd, Tp-e, and Tp-e/QTc). [ABSTRACT FROM AUTHOR]

Heart failure (HF) continues to be a prevalent condition with high morbidity and mortality despite numerous therapeutic advances. Thus, we created a Heart Failure Therapeutic Unit (HFTU) to optimize medical treatment promptly. Primary objective: to study the impact of the HFTU on reducing cardiovascular mortality and heart failure rehospitalizations at 1 year. Secondary objectives: to study the impact of the HFTU on treatment dose optimization and patient therapeutic adherence. We conducted a prospective, longitudinal, and single-center study at our cardiology department, with a follow-up period of 1 year. We included 159 patients with chronic HF (108 were included in the HFTU group and 51 in the control group). Patients included in the HFTU group received more frequent follow-up, early initiation of medical treatment with rapid progression to optimal doses, and transition to second-line treatments if there was no improvement and if indicated. The control group received standard care. The average age was 62.5 ± 11.7 years, with a male predominance (80.5%), and a high prevalence of diabetes (44%); ischemic cardiomyopathy was the dominant etiology (57.9%), with a mean left ventricular ejection fraction (LVEF) of 31.6 ± 8%. The most common inclusion criterion in the HFTU group was the absence of optimal medical treatment (97.2%). We observed a significant reduction in cardiovascular mortality and HF rehospitalizations at 1 year, as well as a significant decrease in HF rehospitalizations at 1 year in the UTIC group compared to the control group (15.7% vs 41.2%; P < 0.001; 11.1% vs 35.3%; P < 0.001 respectively), regardless of age, gender, and comorbidities (P < 0.001). Acquisition of optimal medical treatment (P < 0.001) and therapeutic adherence (P = 0.015) were more frequent in the HFTU group. We noted an improvement in dyspnea (P = 0.003), in LVEF (from ≤ 40% to > 40%) (P < 0.001) and in heart rate control (HR < 70 bpm) (P < 0.001) in the HFTU group compared to the control group. HFTU was associated with a significant reduction in the combined endpoint of cardiovascular mortality and heart failure rehospitalizations, as well as a decrease in heart failure rehospitalizations. Additionally, it was associated with more therapeutic optimization and adherence, and an improvement in symptoms, LVEF, and heart rate control. [ABSTRACT FROM AUTHOR]

The effect of 40-min nap (NAP) opportunity on psycho-physiological outcomes and technical performance during small-sided basketball game (SSG) was examined in ten professional basketball players. Nocturnal sleep and naps were monitored by actigraphic recording and sleep diaries. Nocturnal total sleep time (TST), time in bed (TIB), sleep efficiency (SE), sleep onset latency (SOL) and wake after sleep onset (WASO) were analyzed. Subjective sleep quality was assessed with visual analogue scale (VAS). Profile of mood state (POMS) and simple reaction time (SRT) were measured before and after Nap and no-nap (CON) conditions. During both test sessions, participants played 10-min SSG. Technical and tactical performances were assessed using Team Sport Assessment Procedure. Volume of play (VP), attack with ball (AB), efficiency index (EI) and performance score (PS) were determined. Heart rate (HR) was measured during SSG, and rating of perceive excretion (RPE) after. Lower HR (p ≤ 0.03, d ≥ 0.78) and RPE (p = 0.007, d = 1.11) were obtained in NAP compared to CON. There was no significant difference in TIB, TST, SE, WASO and VAS between CON and NAP conditions. AB, EI and PS were higher in NAP compared to CON (0.0002 ≤ p ≤ 0.001, 1.3 ≤ d ≤ 1.8). A significant reduction was observed in POMS' fatigue (p = 0.005, d = -1.16, Δ = -53.6%), anxiety (p = 0.02, d = -0.9, Δ = -32.1%), anger (p = 0.01, d = -0.94, Δ = -30.3%), and an improvement in vigor (p = 0.01, d = 0.99, Δ = + 23.8%); which may reflect better readiness after nap and more concentration to start a game-situation. In summary, NAP reduced fatigue, anger, anxiety and enhanced vigor, allowing better technical and tactical performances during basketball SSG., (Copyright © Biology of Sport 2023.)

Background: Theory of mind (ToM) refers to the ability to understand others' states of mind, desires, emotions, beliefs, and intentions to predict the content of their mental representations. Two major dimensions within ToM have been studied. The first is the type of inferred mental state, which can be cognitive or affective. The second comprises the types of processes involved according to their degree of complexity (first- and second-order false belief and advanced ToM). ToM acquisition is fundamental-a key component in the development of everyday human social interactions. ToM deficits have been reported in various neurodevelopmental disorders through various tools assessing disparate facets of social cognition. Nevertheless, Tunisian practitioners and researchers lack a linguistically and culturally appropriate psychometric tool for ToM assessment among school-aged children., Objective: To assess the construct validity of a translated and adapted French ToM Battery for Arabic-speaking Tunisian school-aged children., Methods: The focal ToM Battery was designed with neuropsychological and neurodevelopmental theory and composed of 10 subtests distributed evenly in three parts: Pre-conceptual, cognitive, and affective ToM. Translated and adapted to the Tunisian sociocultural context, this ToM battery was individually administered to 179 neurotypical Tunisian children (90 girls and 89 boys) aged 7-12 years., Results: After controlling for the age effect, construct validity was empirically confirmed on two dimensions (cognitive and affective) via structural equation modeling (SEM) analysis, demonstrating that this solution has a good fit. The results confirmed that the age affected differentially the performance obtained on ToM tasks based on the two components of the battery., Conclusion: Our findings confirm that the Tunisian version of the ToM Battery has robust construct validity for the assessment of cognitive and affective ToM in Tunisian school-aged children; hence, it could be adopted in clinical and research settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Salhi, Lancelot, Marzouki, Souissi, Besbes, Le Gall and Bellaj.)

Passage experiments that sequentially infect hosts with parasites have long been used to manipulate virulence. However, for many invertebrate pathogens, passage has been applied naively without a full theoretical understanding of how best to select for increased virulence and this has led to very mixed results. Understanding the evolution of virulence is complex because selection on parasites occurs across multiple spatial scales with potentially different conflicts operating on parasites with different life histories. For example, in social microbes, strong selection on replication rate within hosts can lead to cheating and loss of virulence, because investment in public goods virulence reduces replication rate. In this study, we tested how varying mutation supply and selection for infectivity or pathogen yield (population size in hosts) affected the evolution of virulence against resistant hosts in the specialist insect pathogen Bacillus thuringiensis , aiming to optimize methods for strain improvement against a difficult to kill insect target. We show that selection for infectivity using competition between subpopulations in a metapopulation prevents social cheating, acts to retain key virulence plasmids, and facilitates increased virulence. Increased virulence was associated with reduced efficiency of sporulation, and possible loss of function in putative regulatory genes but not with altered expression of the primary virulence factors. Selection in a metapopulation provides a broadly applicable tool for improving the efficacy of biocontrol agents. Moreover, a structured host population can facilitate artificial selection on infectivity, while selection on life-history traits such as faster replication or larger population sizes can reduce virulence in social microbes., Competing Interests: This work formed part of international patent application number WO 2019/030529 A1 by BR & NC., (© 2023 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

The present study aimed to assess the effects of repeated administration of low-dose caffeine during a night of total sleep deprivation on physical and cognitive performance. Twelve recreational runners (being non-habitual caffeine users) performed four test sessions in a double-blind randomized order after (i) a placebo or 6 mg/kg of caffeine ingestion during a baseline night (BN) or (ii) a placebo or three doses of 2 mg/kg of caffeine during a night of total sleep deprivation (TSD). At each session, they completed an exhaustive run at 75% of the final velocity in a Vameval test (Vvameval) around a 400 m outdoor athletics track and performed the correct detection and reaction time tasks. In comparison with BN, the TSD condition significantly impaired running performance, reaction time, and correct detections. On the contrary, caffeine intake improved exhaustive running performance after BN by 5.2% (p < .001) and after TSD by 8.9% (p < .001), increased correct detections after BN (p < .05) and TSD (p < .05), and decreased reaction time after BN (p < .01) and TSD (p < .05) compared to placebo. Therefore, the repeated ingestion of low-dose caffeine is an effective strategy to counteract the detrimental effects of total sleep deprivation on physical and cognitive performance.

Cry41Aa, also called parasporin-3, belongs to a group of toxins from the entomopathogenic bacterium Bacillus thuringiensis that show activity against human cancer cells. Cry41Aa exhibits preferential cytocidal activity towards HL-60 (human promyelocytic leukaemia cells) and HepG2 (human liver cancer cells) cell lines after being proteolytically activated. To better understand the mechanism of action of Cry41Aa, we evolved resistance in HepG2 cells through repeated exposure to increasing doses of the toxin. Concentrations of Cry41Aa that killed over 50% of the parental HepG2 cells had no significant effect on the viability of the resistant cells and did not induce either pore formation or p38 phosphorylation (both characteristic features of pore-forming toxins). Preliminary RNA sequencing data identified AQP9 as a potential mediator of resistance, but extensive investigations failed to show a causal link and did not support an enhanced cell repair process as the resistance mechanism.

This study examined the effect of time of day (TOD) on physical performance, and physiological and perceptual responses to a 10-km cycling time trial (TT 10km ). Twelve physically trained subjects (20.3 ± 1.2 years, 74.3 ± 7.4 kg, 179.7 ± 5.5 cm) completed, in a randomized order, a TT 10km in the morning and in the evening. Intra-aural temperature (IAT) was measured at rest and following the TT 10km . Completion time, power output (PO), rating of perceived exertion (RPE), heart rate (HR), minute ventilation (V̇E), oxygen uptake (V̇O 2 ), carbon dioxide production (V̇CO 2 ) and respiratory exchange ratio (RER) were assessed every km during the TT 10km . Blood lactate concentration [La] and blood glucose concentration [Glu] were assessed before, during and immediately after the TT 10km . Faster completion time (Δ = 15.0s, p = 0.03) and higher IAT (Δ = 0.33°C, p = 0.02 for pre-TT 10km ) were obtained in the evening compared to the morning with a significant correlation between Δ completion time and Δ IAT at post-TT 10 km (r = -0.83, p = 0.04). V̇O 2 , [La] and [Glu] increased significantly during both test sessions (p < 0.001) with higher values in the evening compared to the morning (p = 0.015, p = 0.04, p = 0.01, respectively). However, the remaining parameters were found to be only affected by the TT 10km (p < 0.001). The TT 10km generates a higher V̇O 2 and higher [La] and [Glu] responses, contributing to a better cycling performance in the evening compared to the morning. The similar magnitude of the TOD effect on completion time and IAT at post-TT 10km confirms that core temperature is one of the underlying factors contributing to the diurnal variation in physical performance., Competing Interests: The authors declare that they have no competing interests. The authors alone are responsible for the content and writing of the article. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors., (Copyright © Biology of Sport 2021.)

The current study aimed to assess the effects of caffeine administration on performance time, cognition, psychomotor state, and blood levels of oxidative stress markers following a 3-km run competition. Thirteen recreational runners performed two test sessions in a double-blind randomized order after placebo or 3 mg/kg of body mass of caffeine. At each session, subjects completed a 3-km running competition around a 400 m outdoor athletics track. Cognitive tasks (attention and reaction time), psychological tests (Feeling scale and Hooper), and blood collection were carried out before and after the run. In comparison with placebo, caffeine ingestion enhanced the 3-km performance time by 1.1% (p < 0.001) (10.13 ± 0.69 min versus 10.25 ± 0.72 min), improved attention by 15.6% (p < 0.001) and reaction-time by 5.9% (p < 0.05), increased good-feeling by 15.7% (p < 0.01), and lowered stress-feeling by 17.6% (p < 0.01) and pain-sensation by 11.3% (p < 0.05). However, no significant effects of caffeine were observed on oxidative stress markers. Only exercise resulted in increased levels of glutathione peroxidase (GPX) (12.2%, 8.8%) (p < 0.05), reduced glutathione (GSH) (17.6%, 10.1%) (p < 0.05), superoxide dismutase (SOD) (7.6%, 6.5%) (p < 0.05) and malondialdehyde (MDA) (10.3%, 9.6%) (p < 0.05), for both the placebo and caffeine groups respectively. In conclusion, our study highlighted that the consumption of 3 mg/kg caffeine could be an improving agent for the physical, cognitive, and psychological states without affecting the oxidative stress state during such a running competition., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Cervical artery dissections are not exceptional in the pediatric population. Typically, it affects the internal carotid artery or the vertebral artery. To our knowledge, this is the first case of common carotid artery (CCA) dissection in a child., Case: We present a case of a 7-year-old-boy admitted to our neurology department complaining of cervical pain after a minor neck trauma. The neurological examination was normal. The ultrasound showed a mural hematoma with an intimal flap. The magnetic resonance angiography revealed an irregular segment of the left CCA just before its bifurcation. The diagnosis of an acute dissection on the left CCA was confirmed and antiplatelet therapy was started., Conclusion: The diagnosis of cervical artery dissections remains a challenge because of its variable clinical presentation. It should be suspected in the context of neck trauma and treatment should be initiated rapidly to reduce the risk of ischemic stroke., Competing Interests: None

Purpose: This study aimed to investigate the effects of partial sleep deprivation (PSD) on physical performance and psychophysiological responses during 12-minute self-paced running exercise., Methods: Twenty runners (20.8±1.1 years, 70.6±4.9 kg, 175.1±3.9 cm) performed, in a randomized order, two running self-paced field exercises after a normal sleep night (CONT, bedtime from 22:30 h to 06:30 h) and one night of PSD (bedtime from 00:30 h to 04:30 h). Core temperature and motivation were recorded before exercise. Speed, covered distance, heart rate (HR), rating of perceived exertion (RPE) and respiratory parameters (i.e., minute ventilation (VE), oxygen uptake (VO 2 ) and carbon dioxide production (VCO 2 )) were assessed during exercise. Blood lactate concentration [La] was assessed 2 min after exercise. Simple reaction time (SRT), mood and barrage test (BT) were assessed before and after exercise., Results: Higher RPE (p=0.01, d=0.90) and lower physical performance (i.e., p=0.001, d=0.59 for running speed and p=0.01, d=0.7 and Δ (%)=-6% for covered distance), following PSD, were obtained compared to CONT. Similarly, PSD attenuated core temperature (p=0.01, d=0.84), HR (p=0.006, ɳp 2 =0.45), VE (p=0.001, ɳp 2 =0.73), VO 2 (p=0.001, ɳp 2 =0.96), BT (p<0.0005, ɳp 2 =0.86), SRT (p=0.0009, ɳp 2 =0.44) and mood (p<0.0005). However, VCO 2 , [La] and motivation score were not affected by sleep conditions., Conclusion: The decrease of running performance and the increase of physical discomfort after PSD could be the origin of the lower cardio-respiratory responses to the 12-minute self-paced exercise. Effective strategies should be introduced to overcome the deterioration of physical performance and physiological responses after PSD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The aim of this study was to examine the effect of running exercise modality on oxidative stress. Thirteen endurance athletes (age: 21.46 ± 0.66 years) performed three different running exercise modalities (Continuous running exercise (CR): continuous running exercise at 75% of VO 2max for 25 min; intermittent running exercise #1 (15/15): intermittent running protocol, 15 s running at 75% of VO 2max , 15 s passive recovery, performed for 50 min; intermittent running exercise #2 (30/30): intermittent running protocol, 30 s running at 75% of VO 2max , 30 s passive recovery, performed for 50 min) in a randomized order. Blood samples were drawn at rest and immediately after each running exercise and assessed for malondialdehyde (MDA), advanced oxidation protein products (AOPP), superoxide dismutase(SOD), and glutathione peroxidase (GPX) activities. MDA increased by 55% following 30/30 exercise ( p < 0.01), while it remained unchanged with CR and15/15 exercise. SOD increased after CR (+13.9%, p < 0.05), and also remained unchanged after 15/15 ( p > 0.05) and decreased after 30/30 (-19.7% p < 0.05). GPX and AOPP did not change after exercise in all experimental sessions ( p > 0.05). In conclusion, 30/30 intermittent running induced higher lipid damages than the 15/15 and CR exercise. 15/15 intermittent exercise promoted a better balance between free radicals production and antioxidant defense compared to continuous exercise and intermittent 30/30 exercise.

Bacillus thuringiensis (Bt) is a gram positive spore forming bacterium which produces intracellular protein crystals toxic to a wide variety of insect larvae and is the most commonly used biological pesticide worldwide. More recently, Bt crystal proteins known as parasporins have been discovered, that have no known insecticidal activity but target some human cancer cells exhibiting strong cytocidal activities with different toxicity spectra and varied activity levels. Parasporin-3, also called Cry41Aa, has only been shown to exhibit cytocidal activity towards HL-60 (Human promyelocytic leukemia cells) and HepG2 (Human liver cancer cells) cell lines after being proteolytically cleaved. In order to understand this activation mechanism various mutations were made in the N-terminal region of the protein and the toxicity against both HepG2 and HL-60 cell lines was evaluated. Our results indicate that only N-terminal cleavage is required for activation and that N-terminally deleted mutants show some toxicity without the need for proteolytic activation. Furthermore, we have shown that the level of toxicity towards the two cell lines depends on the protease used to activate the toxin. Proteinase K-activated toxin was significantly more toxic towards HepG2 and HL-60 than trypsin-activated toxin. N-terminal sequencing of activated toxins showed that this difference in toxicity is associated with a difference of just two amino acids (serine and alanine at positions 59 and 60, respectively) which we hypothesize occlude a binding motif., (© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

A new series of cationic gold(i) pyrazole complexes were prepared in excellent yields as their perchlorate salts. Results of cell viability assays show that these novel complexes have good cytotoxic properties against the human HepG2 cancer cell line. These complexes showed promising anti-cancer activities and to our knowledge, pyrazoles have never been tested against this cell line. The regioselectivity of the complexation is also discussed in regards to the substitution pattern of the pyrazoles.

Background: To study the disturbances of biochemical parameters which make it possible to evaluate the nutritional state during the cystic fibrosis., Methods: Prospective study about 13 cases hospitalized over a 7 months period, whose age varies between 2 months and 12 years and addressed for a suspicion of cystic fibrosis. For all the patients we made a clinical collection of the data and a biochemical study., Results: Hypoprotidemia (protidemia < 60 g/l) was noted in 6 cases. Three cases presented a hypocalcaemia (calcemia < 2.20 mmol/l). A hypomagnesaemia (magnesemia < 0.70 mmol/L) was observed in 2 cases. The totality of the patients presented zinc concentrations lower than the normal value. Iron concentrations lower than the normal (11- 24 mmol/l) was noted in 5 cases. Four patients (4/13) presented a concentration of iron between 11.2 and 20 mmol/l, whereas a high concentration (32.3 mmol/l) was noted in only one case (7.7%)., Conclusion: The study of the biochemical parameters allowed to evaluate the variation of some trace elements in cystic fibrosis and their consequence on the nutritional state of the patients, which constitutes an essential element for the assessment of these patients.