An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis.

Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy's efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy.

Influence of Titanium Surface Residual Stresses on Osteoblastic Response and Bacteria Colonization.

Grit basting is the most common process applied to titanium dental implants to give them a roughness that favors bone colonization. There are numerous studies on the influence of roughness on osseointegration, but the influence of the compressive residual stress associated with this treatment on biological behavior has not been determined. For this purpose, four types of surfaces have been studied using 60 titanium discs: smooth, smooth with residual stress, rough without stress, and rough with residual stress. Roughness was studied by optic interferometry; wettability and surface energy (polar and dispersive components) by contact angle equipment using three solvents; and residual stresses by Bragg-Bentano X-ray diffraction. The adhesion and alkaline phosphatase (ALP) levels on the different surfaces were studied using Saos-2 osteoblastic cultures. The bacterial strains Streptococcus sanguinis and Lactobacillus salivarius were cultured on different surfaces, determining the adhesion. The results showed that residual stresses lead to increased hydrophilicity on the surfaces, as well as an increase in surface energy, especially on the polar component. From the culture results, higher adhesion and higher ALP levels were observed in the discs with residual stresses when compared between smooth and roughened discs. It was also found that roughness was the property that mostly influenced osteoblasts' response. Bacteria colonize rough surfaces better than smooth surfaces, but no changes are observed due to residual surface tension.

Effectiveness of a formulation based on Ocimum gratissimum essential oil and cashew gum as inhibitors of quality loss and melanosis in shrimp.

In this study, two nanoemulsions were formulated with essential oil (EO) of Ocimum gratissimum with (EON) or without (EOE) cashew gum (CG). Subsequently, inhibition of melanosis and preservation of the quality of shrimp stored for 16 days at 4 ± 0.5 °C were evaluated. A computational approach was performed to predict the system interactions. Dynamic light scattering (DLS) and atomic force microscopy (AFM) were used for nanoparticle analysis. Gas chromatography and flame ionization detector (GC-FID) determined the chemical composition of the EO constituents. Shrimps were evaluated according to melanosis's appearance, psychrotrophic bacteria's count, pH, total volatile basic nitrogen, and thiobarbituric acid reactive substances. EON exhibited a particle size three times smaller than EOE. The shrimp treated with EON showed a more pronounced sensory inhibition of melanosis, which was considered mild by the 16th day. Meanwhile, in the other groups, melanosis was moderate (EOE) or severe (untreated group). Both EON and EOE treatments exhibited inhibition of psychrotrophic bacteria and demonstrated the potential to prevent lipid oxidation, thus extending the shelf life compared to untreated fresh shrimp. EON with cashew gum, seems more promising due to its physicochemical characteristics and superior sensory performance in inhibiting melanosis during shrimp preservation.

Sleep duration is associated with appetitive traits in school-age years - results from the Generation XXI birth cohort.

Sleep may influence appetite regulation through physiological and neurocognitive pathways. However, the association between sleep and appetite in childhood has been scarcely reported, particularly using a prospective design. We aimed to test associations between sleep duration at 7 years of age (y) and appetitive traits at both 7 and 10 y. Participants are from the population-based birth cohort Generation XXI (Porto, Portugal), at 7 (n = 2437) and 10 y (n = 1938) follow-ups. Data on sleep was gathered at 7 y and, considering bedtime and get-up time, total mean sleep duration was calculated and further categorized according to the 10th and 90th percentiles. Appetitive traits were assessed at 7 and 10 y using the parent-reported Children's Eating Behaviour Questionnaire. Associations were tested through Generalized Linear Models (co-variates: child's sex; maternal age, education and pre-pregnancy body mass index at 7 y). At 10 y, associations were further adjusted for the respective appetitive trait at 7 y. Children slept a mean of 10.2 h/night, and 13% and 9% slept ≤9.5 and ≥ 11.0 h/night at 7 y, respectively. For each additional hour in sleep duration, children scored 0.078 (99%CI: -0.145; -0.011) lower on Food Responsiveness, 0.065 (99%CI: -0.129; -0.002) lower on Emotional Undereating and 0.096 (99%CI: -0.161; -0.032) lower on Food Fussiness. Lastly, children sleeping ≤9.5 h/night scored higher on Food Responsiveness (ß = 0.145 99%CI: 0.020; 0.271); while those sleeping ≥11.0 h/night scored lower on Food Fussiness (ß = -0.255 99%CI: -0.370; -0.079). No significant prospective associations were found. In conclusion, in 7 y children, sleep duration was cross-sectionally associated with lower scores on food approach (Food Responsiveness) and avoidant traits (Emotional Undereating and Food Fussiness). However, the magnitude of the associations was small and further studies are warranted.

Clinical phenotyping of children with nocturnal enuresis: A key classification to improve the approach.

INTRODUCTION: The literature shows that nocturnal enuresis is not an isolated phenomenon of urinary loss during sleep, but encompasses a set of systemic clinical manifestations that significantly influence children's quality of life and development. However, the understanding of the clinical and physiological relationship of these systemic manifestations remains a clinical challenge. The recognition of these manifestations and their subsequent categorisation, may provide better insights into integrated clinical manifestations, facilitating the understanding of pathophysiological mechanisms, and promote increased assertiveness in the assessment and the selection of appropriate therapies. OBJECTIVE: The aim of this study is to develop a phenotyping model for children with nocturnal enuresis based on evidence. METHODS: This study presents a clinical phenotyping model for children with nocturnal enuresis based on an analytical and methodological review of the literature, about nocturnal enuresis and its associated clinical manifestations. There was a bibliometric analysis carried out to better analyse outcomes. After reading and analysing the literature, the clinical manifestations were categorised into domains and submitted to the validation of an expert committee with extensive experience in their specific area of expertise. A visual representation of the categorised model was developed to make the phenotyping concept easily understandable to all professionals. RESULTS: The clinical manifestations related to nocturnal enuresis have been categorised according to frequency and relation found in the literature and validation by an expert committee and the development of the phenotyping model for children with nocturnal enuresis was completed. CONCLUSION: The present study developed an evidence-based phenotyping model for children with nocturnal enuresis.

Molecular Docking and GC/MS-Based Approach for Identification of Anxiolytic Alkaloids from Griffinia (Amaryllidaceae) Species in a Zebrafish Model.

Griffinia gardneriana Ravenna, Griffinia liboniana Morren and Griffinia nocturna Ravenna (Amarillydaceae) are bulbous plants found in tropical regions of Brazil. Our work aimed to determine the alkaloid profiles of Griffinia spp. and evaluate their anxiolytic potential through in vivo and in silico assays. The plants grown in greenhouses were dried and their ground bulbs were subjected to liquid-liquid partitions, resulting in alkaloid fractions that were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). Anxiolytic activity was evaluated in zebrafish (Danio rerio) through intraperitoneal injection at doses of 40, 100 and 200 mg/kg in light-dark box test. GC-MS analyses revealed 23 alkaloids belonging to different skeleton types: lycorine, homolychorine, galanthamine, crinine, haemanthamine, montanine and narcisclasine. The chemical profiles were relatively similar, presenting 8 alkaloids common to the three species. The major component for G. gardneriana and G. liboniana was lycorine, while G. nocturna consisted mainly of anhydrolycorine. All three alkaloid fractions demonstrated anxiolytic effect. Furthermore, pre-treatment with diazepam and pizotifen drugs was able to reverse the anxiolytic action, indicating involving the GABAergic and serotonergic receptors. Molecular docking showed that the compounds vittatine, lycorine and 11,12-dehydro-2-methoxyassoanine had high affinity with both receptors, suggesting them to be responsible for the anxiolytic effect.

Pulmonary Mucormycosis: Beyond Classic COVID-19-Associated Fungal Infections.

Coronavirus disease 2019 (COVID-19) is often linked to a broad range of opportunistic bacterial and fungal infections. The second wave of the COVID-19 pandemic has witnessed an unprecedented surge in mucormycosis cases, predominantly in India, while the disease remained relatively rare in Europe. The authors describe the case of a 62-year-old female patient admitted to the hospital for consolidation therapy with chemotherapy as a part of the treatment protocol for acute myeloid leukemia. During hospitalization, she was diagnosed with nosocomial COVID-19, which later progressed to respiratory deterioration. COVID-19 with bacterial superinfection was presumed, leading to the initiation of empirical antibiotic therapy. A bronchoscopy was performed several days later due to a lack of improvement, revealing an infection by the Rhizopus microsporus complex. Despite antifungal treatment, the patient experienced an unfavorable clinical course and ultimately died. Given the high index of suspicion required to diagnose pulmonary mucormycosis, which can lead to delays in appropriate treatment and increase the burden of disease, the authors are aiming to enhance its awareness.

Light transmittance through resin-matrix composite onlays adhered to resin-matrix cements or flowable composites.

OBJECTIVE: The aim of this study was to evaluate the influence of the thickness of resin-matrix composite blocks manufactured by CAD-CAM on the light transmittance towards different resin-matrix cements or flowable composites. METHODS: Sixty specimens of resin-matrix composite CAD-CAM blocks reinforced with 89 wt% inorganic fillers were cross-sectioned with 2 or 3 mm thicknesses. The specimens were conditioned with adhesive system and divided in groups according to the luting material, namely: two dual-cured resin-matrix cements, two traditional flowable resin-matrix composites, and one thermal-induced flowable resin-matrix composite. Specimens were light-cured at 900 mW/cm2 for 40s. Light transmittance assays were preformed using a spectrophotometer with an integrated monochromator before and after light-curing. Microstructural analysis was performed by optical and scanning electron microscopy (SEM). Nanoindentation tests were performed to evaluate mechanical properties for indirect evaluation of degree of monomers conversion. RESULTS: Optical and SEM images revealed low thickness values for the cementation interfaces for the traditional flowable resin-matrix composite. The cement thickness increased with the size and content of inorganic fillers. The highest light transmittance was recorded for the onlay blocks cemented with the traditional flowable resin-matrix composites while a group cemented with the dual-cured resin-matrix cement revealed the lowest light transmittance. The elastic modulus and hardness increased for specimens with high content of inorganic fillers as well as it increased in function of the light transmittance. CONCLUSIONS: The light transmittance of flowable resin-matrix composites was higher than that for resin-matrix cement after cementation to resin-matrix composites blocks. The type, size, and content of inorganic fillers of the luting material affected the thickness of the cement layer and light transmittance through the materials. CLINICAL RELEVANCE: On chair-side light curing, the transmission of visible light can be interfered by the chemical composition and viscosity of the luting materials. The increase in size and content of inorganic fillers of resin-matrix composites and luting materials can decrease the light transmittance leading to inefficient polymerization.

Appetitive traits from childhood to adolescence: Analysis of their stability, derivation of trajectory profiles, and associated characteristics.

This study aimed to assess the potential stability of appetitive traits from childhood to early adolescence, identify groups of individuals with distinct trajectories for these traits, and explore their association with other child and family characteristics. Participants were 5040 children from the Generation XXI cohort. Appetitive traits were assessed with the Children's Eating Behaviour Questionnaire (CEBQ) at ages seven, 10, and 13 (eight subscales). Mixed-effect models estimated individual trajectories of appetitive traits and Gaussian mixture models identified groups following different trajectories (appetitive trait trajectory profiles). Appetitive traits showed moderate-to-high stability across the three ages (intra-class correlation coefficients:0.66-0.83); most of the variance observed across time were due to persistent individual differences rather than age-related changes. Six appetitive trait trajectory profiles were identified: 'Moderate appetite' (scores close to the average) (29% of children), 'Small to moderate appetite' (lowest food approach and emotional eating) (26%), 'Increasing appetite' (increasing food approach) (15%), 'Avid appetite' (highest food approach and lowest food avoidance) (12%), 'Smallest appetite' (highest food avoidance and low food approach) (10%), and 'Small appetite but increasing' (decreasing high food avoidance and Desire to Drink) (8%). In multinomial logistic regression, these profiles were associated with different child and family characteristics. Compared to children with a 'Moderate appetite' profile, those with higher BMI, who desired a thinner body, whose mothers were younger, had lower education, higher pre-pregnancy BMI (OR = 1.07; 95%CI:1.04,1.09), smoked during pregnancy (OR = 1.51; 95%CI:1.21,1.90), and used more restrictive feeding practices (OR = 1.79; 95%CI:1.57,2.03) had increased odds of belonging to the 'Avid Appetite'. In conclusion, distinct appetitive trait trajectory profiles emerged, differentiating individuals with avid and small appetites. These findings have implications for identifying children at higher risk for obesogenic profiles.

Psoas Abscess and Pott's Disease Masked by Concomitant Invasive Staphylococcus aureus Disease: A Case of Misleading Diagnosis.

Psoas abscess is a rare infection classified as primary or secondary depending on the etiology of infection. Staphylococcus aureus is considered the most frequent causative agent. Nevertheless, psoas abscess persistent lack of improvement or any relapse after successful treatment should remind us to exclude other potential diagnoses. Although less frequently, Pott's disease is still one of the predisposing causes, especially in patients with immunocompromised status. This clinical condition has an indolent course and requires a high index of suspicion to avoid severe morbidity. Early recognition and targeted treatment are the principal means of ensuring tuberculosis control. Here we report a very interesting case of a psoas abscess and Pott's disease in a patient suffering from a misleading diagnosis of invasive staphylococcal disease.

Effect of inorganic fillers on the light transmission through traditional or flowable resin-matrix composites for restorative dentistry.

OBJECTIVES: The aim of this in vitro study was to evaluate the light transmission through five different resin-matrix composites regarding the inorganic filler content. METHODS: Resin-matrix composite disc-shaped specimens were prepared on glass molds. Three traditional resin-matrix composites contained inorganic fillers at 74, 80, and 89 wt. % while two flowable composites revealed 60 and 62.5 wt. % inorganic fillers. Light transmission through the resin-matrix composites was assessed using a spectrophotometer with an integrated monochromator before and after light curing for 10, 20, or 40s. Elastic modulus and nanohardness were evaluated through nanoindentation's tests, while Vicker's hardness was measured by micro-hardness assessment. Chemical analyses were performed by FTIR and EDS, while microstructural analysis was conducted by optical microscopy and scanning electron microscopy. Data were evaluated using two-way ANOVA and Tukey's test (p < 0.05). RESULTS: After polymerization, optical transmittance increased for all specimens above 650-nm wavelength irradiation since higher light exposure time leads to increased light transmittance. At 20- or 40-s irradiation, similar light transmittance was recorded for resin composites with 60, 62, 74, or 78-80 wt. % inorganic fillers. The lowest light transmittance was recorded for a resin-matrix composite reinforced with 89 wt. % inorganic fillers. Thus, the size of inorganic fillers ranged from nano- up to micro-scale dimensions and the high content of micro-scale inorganic particles can change the light pathway and decrease the light transmittance through the materials. At 850-nm wavelength, the average ratio between polymerized and non-polymerized specimens increased by 1.6 times for the resin composite with 89 wt. % fillers, while the composites with 60 wt. % fillers revealed an increased ratio by 3.5 times higher than that recorded at 600-nm wavelength. High mean values of elastic modulus, nano-hardness, and micro-hardness were recorded for the resin-matrix composites with the highest inorganic content. CONCLUSIONS: A high content of inorganic fillers at 89 wt.% decreased the light transmission through resin-matrix composites. However, certain types of fillers do not interfere on the light transmission, maintaining an optimal polymerization and the physical properties of the resin-matrix composites. CLINICAL SIGNIFICANCE: The type and content of inorganic fillers in the chemical composition of resin-matrix composites do affect their polymerization mode. As a consequence, the clinical performance of resin-matrix composites can be compromised, leading to variable physical properties and degradation.

Identifying Imaging Predictors of Intermediate Age-Related Macular Degeneration Progression.

Purpose: Intermediate age-related macular degeneration (iAMD) is a risk factor for progression to advanced stages, but rates of progression vary between individuals. Predicting individual risk is advantageous for programing timely and effective treatment and for patient stratification into future clinical trials. Methods: We conducted a prospective and noninterventional study following patients with iAMD for 24 months. Optical coherence tomography parameters related with drusen, hyper-reflective foci (HRF), presence of incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) and ellipsoid zone (EZ) status were explored at the baseline. Patients were reclassified at the end of the follow-up period and divided according to their progression. A risk prediction model for progression to late AMD was developed. Results: A total of 135 patients were enrolled in the study and 30.4% developed late disease. A multivariate logistic regression model was created using those optical coherence tomography parameters, further optimized by backward feature elimination. Parameters offering the best fit in prediction progression were presence of iRORA, EZ status, drusen area and presence of HRF. iRORA is the feature that provides a higher probability of developing late AMD (odds ratio, 12.91; P = 0.000), followed by EZ disruption status (odds ratio, 3.54; P = 0.0018). The area under the receiver operating characteristic curve calculated for the testing set was 0.77 (95% confidence interval, 0.56-0.98). Conclusions: The combination of iRORA and EZ disruption constitute a high risk of progression to complete RORA within 2 years. Translational Relevance: We propose a practical and useful model to help clinicians in their daily practice in predicting individual progression to advanced AMD.

Overcoming attenuation bias in regressions using polygenic indices.

Measurement error in polygenic indices (PGIs) attenuates the estimation of their effects in regression models. We analyze and compare two approaches addressing this attenuation bias: Obviously Related Instrumental Variables (ORIV) and the PGI Repository Correction (PGI-RC). Through simulations, we show that the PGI-RC performs slightly better than ORIV, unless the prediction sample is very small (N < 1000) or when there is considerable assortative mating. Within families, ORIV is the best choice since the PGI-RC correction factor is generally not available. We verify the empirical validity of the simulations by predicting educational attainment and height in a sample of siblings from the UK Biobank. We show that applying ORIV between families increases the standardized effect of the PGI by 12% (height) and by 22% (educational attainment) compared to a meta-analysis-based PGI, yet estimates remain slightly below the PGI-RC estimates. Furthermore, within-family ORIV regression provides the tightest lower bound for the direct genetic effect, increasing the lower bound for the standardized direct genetic effect on educational attainment from 0.14 to 0.18 (+29%), and for height from 0.54 to 0.61 (+13%) compared to a meta-analysis-based PGI.

Identifying Clinical Predictors of Proliferative Sickle Cell Retinopathy.

PURPOSE: To identify systemic and/or ophthalmologic predictors of proliferative sickle retinopathy. METHODS: Cross-sectional study comparing clinical, laboratory, and structural choriorretinal aspects between sickle cell disease patients with and without proliferative retinopathy. Patients underwent complete systemic and ophthalmologic evaluation. Enhanced depth spectral domain optical coherence tomography with choroidal binarization and optic coherence tomography angiography were performed and choriorretinal vascular components were compared. RESULTS: Forty-five eyes from 45 sickle cell patients were included. Ninety-one percent of patients were diagnosed with sickle cell retinopathy, 29% with proliferative retinopathy. Mean corpuscular volume, lactate dehydrogenase, and percentage of fetal hemoglobin were reduced in the subgroup of patients with proliferative retinopathy when compared with patients without proliferative retinopathy (p ≤ 0.001; p = 0.04; p ≤ 0.001, respectively). The best predictor of proliferative retinopathy was mean corpuscular volume (AUC = 0.842; p = 0.001), followed by the percentage of fetal hemoglobin (AUC = 0.763, p = 0.009) and lactate dehydrogenase (AUC curve = 0.706; p = 0.039). No differences were found between groups in the quantitative analysis of retinal vascularization using OCTA and choroidal vascularization using OCT (p ≥ 0.05). CONCLUSION: Fetal hemoglobin and mean corpuscular volume may be good predictors of proliferative sickle retinopathy. The association between proliferative retinopathy and reduced levels of lactate dehydrogenase and mean corpuscular volume points to hypoxia and not hemolysis as a possible driving force in its pathophysiology.

Bone health, body composition and physical fitness dose-response effects of 16 weeks of recreational team handball for inactive middle-to-older-aged males - A randomised controlled trial.

In this study we aimed at analysing the effects of different weekly exercise volumes (1, 2 or 3 times 60-min) on bone health, body composition and physical fitness of inactive middle-to-older-aged males, after 16 weeks of recreational team handball (RTH). Fifty-four men (68 ± 4 years, stature 169 ± 6 cm; body mass 78.4 ± 10.7 kg; fat mass 27.1 ± 5.3%; BMI 27.4 ± 2.9 kg/m2; VO2peak 27.3 ± 4.8 mL/min/kg) were randomised into three intervention groups (TH1, n = 13; TH2, n = 15; or TH3, n = 12, performing 1, 2 and 3 weekly 60-min training sessions, respectively), and a control group (CG, n = 14). The training sessions consisted mainly of RTH matches played as small-sided and formal game formats (4v4, 5v5, 6v6 or 7v7) with adapted rules. Matches' mean and peak heart rate (HR) ranged from 78-80% and 86-89%HRmax, respectively, and distance covered from 4676 to 5202 m. A time x group interaction was observed for procollagen type-1 amino-terminal propeptide (P1NP), osteocalcin (OC), carboxy-terminal type-1 collagen crosslinks (CTX), sclerostin, upper and lower body dynamic strength, right arm fat mass, left and right arm, right leg and android total mass (TM; p ≤ 0.047) with the greatest effects being shown for TH2 and TH3 groups. Post-intervention group differences were observed in CTX, left arm and right leg TM (TH3 > TH1), P1NP (TH2 > CG), OC, right arm TM (TH3 > CG), upper (CG < TH1, TH2 and TH3) and lower body dynamic strength (CG < TH1 and TH3) (p ≤ 0.047). RTH was effective in enhancing bone health, body composition and physical fitness in middle-to-older-aged males, especially for the intervention groups that performed 2-3 weekly training sessions.ClinicalTrials.gov ID: NCT05295511.Trial registration: ClinicalTrials.gov identifier: NCT05295511.HighlightsAfter 16 weeks of recreational team handball small-sided and formal matches, inactive middle-to-older-aged males improved bone health, body composition and physical fitness, by performing 1, 2 or 3 60-min weekly sessions, however, greater improvements were shown in the groups that performed 2 or 3 weekly training sessions.Training intensity was similar across the intervention groups that performed recreational team handball for 1, 2 or 3 60-min weekly sessions, which means that training volume is most likely to be the reason for the different health effects shown.The very high fun levels reported by all intervention groups shows that recreational team handball is a social and fun exercise modality for middle-to-older-aged males, with potential to intrinsically motivate the participants and assure long-term adherence to exercise.

Mixed-gender small-sided recreational team handball games in middle-aged and elderly are physiologically more demanding for women than men.

This study examined the physical and physiological demands and perceived experience of a multicomponent exercise mode, recreational team handball (TH), for middle-aged/elderly men and women, played as same- vs. mixed-gender 6v6 game formats. Matches' heart rate (HR), blood lactate (BL), perceived experience, activity profile, player load and accelerometer variables were assessed. Forty-one participants, with at least 12 weeks of experience with recreational TH (22 men; 69±4 years, 19 women; 66±6 years), performed 2 same- and 2 mixed-gender matches on an indoor 40x20 m TH court. A game format-by-gender interaction was observed for mean HR (%HRmax), time spent ˃80 and ˃90%HRmax, respiratory rating of perceived exertion and for several of the external load variables (p≤0.05). During mixed-gender matches, time spent ˃80 and ˃90%HRmax, was higher for women vs. men (p≤0.017). During same- and mixed-gender matches, BL was lower for women than men (p≤0.015). Time spent ˃90%HRmax was lower for women (p = 0.036), whereas time spent ˃80%HRmax was higher for men during same- vs. mixed-gender matches (p = 0.034). The frequency, %total match time and distance covered with high-demanding movements were higher for men during same-gender than during mixed-gender matches (p≤0.036), and higher for men vs. women in same- and mixed-gender matches (p≤0.046). The frequency of high-intensity actions, accelerations, time spent in the higher player load zones and total accumulated player load, were higher for men vs. women during same- and mixed-gender matches (p≤0.044). Fun levels were very high (9.1-9.3 AU, 0-10). Mixed-gender small-sided recreational TH games are physiologically more demanding for middle-aged/elderly women compared to men. Men showed higher cardiovascular and activity profile demands when playing same-gender matches, which was opposite to women. Nevertheless, TH is a high-intensity and motivating exercise mode for both genders, regardless the gender game format, meaning that exercise interventions may use same- and mixed-gender matches to promote participants' health.

Dose-response effect of a recreational team handball-based exercise programme on cardiometabolic health and physical fitness in inactive middle-aged-to-elderly males - a randomised controlled trial.

This study aimed at examining the dose-response of a recreational team handball (TH) exercise-based programme on cardiometabolic health and physical fitness in inactive middle-aged-to-elderly males without TH experience. Fifty-four inactive middle-aged-to-elderly men (67.5 ± 4.2 years; stature 168.8 ± 6.2 cm; body mass 78.4 ± 10.7 kg; fat mass 27.1 ± 5.3%; BMI 27.4 ± 2.9 kg/m2; VO2peak 27.3 ± 4.8 mL/min/kg) were randomised into three intervention groups performing 1 (TH1, n = 13), 2 (TH2, n = 15), or 3 (TH3, n = 12) 60-min weekly recreational TH-based training sessions, for 16 weeks, and a control group (CG, n = 14). A time x group interaction was observed for VO2peak, aerobic performance, fasting plasma insulin and body and fat mass (p ≤ 0.043) with TH3 showing the greatest overall effects. Post-intervention differences were observed in aerobic performance (TH3>CG, TH1 and TH2; TH2>CG), body mass (TH3>CG and TH1), fat mass (TH3>CG), VO2peak (TH3>CG) and plasma insulin (TH3>CG) (p ≤ 0.040). In conclusion, recreational TH performed for 60-min thrice and twice per week results in improved aerobic performance for middle-aged-to-elderly men. Moreover, it was observed that three weekly sessions were more effective in providing overall cardiometabolic benefits compared to training with a lower weekly frequency. ClinicalTrials.gov ID: NCT05295511.Trial registration: ClinicalTrials.gov identifier: NCT05295511.Highlights: We observed high intensities and fun levels during recreational TH, organised as formal and small-sided games, for middle-aged-to-elderly men during a 16-week period, independently of the number of weekly training sessions.Marked positive effects on aerobic performance and cardiometabolic health were observed in the intervention group that performed 3 weekly sessions.The study results indicate that recreational TH training with low frequency and volume results in some beneficial effects on cardiometabolic fitness and health for middle-aged-to-elderly men, but future studies with more participants or longer intervention periods are warranted to explore this possibility.

UPLC-QTOF-MS/MS-based metabolomic approach and gastroprotective effect of two chemotypes of Egletes viscosa (L.) less. against ethanol-induced gastric ulcer in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Egletes viscosa (L.) (macela) is a native wild herb that can be found in different states of northeastern Brazil. The infusions of its flower buds are traditionally used for the treatment of gastrointestinal disorders. E. viscosa possesses two chemotypes (named A and B), distinguishable by the composition of the essential oil from the flower buds. Although there are previous studies of the gastroprotective effect of the isolated constituents of E. viscosa, its infusions have not been investigated yet. AIM OF THE STUDY: The present study aimed to evaluate and compare the chemical composition and the gastroprotective effect of flower bud infusions of E. viscosa from chemotype A (EVCA) and chemotype B (EVCB). MATERIALS AND METHODS: Sixteen infusions were brewed with flower buds according to the traditional preparation mode and were analyzed through a UPLC-QTOF-MS/MS based metabolomic approach for determination of their metabolic fingerprints and quantification of bioactive compounds. Afterward, these data were analyzed by chemometric methods (OPLS-DA) for discrimination of the two chemotypes. Additionally, infusions of EVCA and EVCB (50, 100 and 200 mg/kg, p.o.) were evaluated on gastric ulcers induced by absolute ethanol (96%, 0.2 mL, p.o.) in mice. To elucidate the gastroprotective mechanisms, the effect of EVCA and EVCB on gastric acid secretion and gastric wall mucus was determined and the role of TRPV1 channels, prostaglandins, nitric oxide and KATP channels were assessed. Moreover, the oxidative stress-related parameters and the histological aspects of the stomach tissue were analyzed. RESULTS: The chemotypes can be discriminated from each other using UPLC-QTOF-MS/MS chemical fingerprints. Both chemotypes presented similar chemical compositions, consisting basically of caffeic acid derivatives, flavonoids and diterpenes. The quantification of bioactive compounds demonstrated that chemotype A possesses more ternatin, tanabalin and centipedic than chemotype B. EVCA and EVCB (50, 100 and 200 mg/kg, p.o.) significantly decreased the severity of ethanol-induced gastric lesions, as shown by a reduction in histological alterations and leucocyte infiltration in gastric tissue. The gastroprotective mechanism of both infusions involves an antioxidant effect, maintenance of gastric mucus and reduction gastric secretion. Stimulation of endogenous prostaglandins and nitric oxide release, activation of TRPV1 channels, and KATP channels are also involved in the gastroprotection of the infusions. CONCLUSION: The gastroprotective effect of EVCA and EVCB was equivalent and mediated through antioxidant and antisecretory actions, including the activation of TRPV1 receptors, stimulation of endogenous prostaglandins and nitric oxide, and opening of KATP channels. The presence of caffeic acid derivatives, flavonoids and diterpenes in both infusions is involved in mediating this protective effect. Our findings support the traditional use of infusions of E. viscosa for gastric disorders regardless of the chemotype.

Multicomponent recreational team handball training improves global health status in postmenopausal women at the long term - A randomised controlled trial.

We studied the long-term effects of a multicomponent exercise training protocol (recreational team handball training, RTH) on global health status in inactive postmenopausal women. Participants (n = 45; age 65 ± 6 years, stature 157 ± 6 cm, body mass 66.2 ± 9.4 kg, fat mass 41.4 ± 5.5%, VO2peak 25.7 ± 3.6 mL/min/kg) were randomised into a control group (CG; n = 14) and a multicomponent exercise training group (EXG; n = 31, performing two to three weekly 60-min RTH sessions). Attendance was 2.0 ± 0.4 sessions/week (first 16 weeks) and 1.4 ± 0.5 (following 20 weeks) and mean heart rate (HR) loading was 77 and 79% of maximal HR (p = .002) for the first 16 and the following 20 weeks, respectively. Cardiovascular, bone, metabolic health, body composition and physical fitness markers were evaluated at baseline, and after 16 and 36 weeks. An interaction (p ≤ .046) was shown for the 2-h oral glucose tolerance test, HDL, Yo-Yo intermittent endurance level 1 test (YYIE1) and knee strength, in favour of EXG. At 36 weeks, YYIE1 and knee strength were higher (p ≤ .038) for EXG vs CG. Also, within-group improvements (p ≤ .043) were observed after 36 weeks for EXG in VO2peak, lumbar spine bone mineral density, lumbar spine bone mineral content, P1NP, osteocalcin, total cholesterol, HDL, LDL, body mass, android fat mass, YYIE1, knee strength, handgrip strength and postural balance. At 36 comparatively to 16 weeks, EXG showed an increase (p ≤ .036) in fasting blood glucose, HDL, knee strength and handgrip strength, and a decrease (p ≤ .025) in LDL. Collectively, this multicomponent exercise training (RTH) induces beneficial changes in global health status in postmenopausal women.HighlightsWe evaluated the long-term effects of a recreational team handball-based multicomponent training on broad-spectrum health and physical fitness markers of inactive postmenopausal women.Improvements in VO2peak and aerobic performance achieved after 16 weeks of training were maintained at 36 weeks.The 20-week extension of the training intervention resulted in further improvements in lipid profile markers and physical fitness variables.Recreational team handball could be suggested as an effective and safe strategy to counteract postmenopausal health-related constrains.