Hydroxytyrosol Linoleoyl Ether Ameliorates Metabolic-Associated Fatty Liver Disease Symptoms in Obese Zucker Rats.

A main hepatic consequence of obesity is metabolic-associated fatty liver disease (MAFLD), currently treated by improving eating habits and administrating fibrates yet often yielding suboptimal outcomes. Searching for a new therapeutic approach, we aimed to evaluate the efficacy of hydroxytyrosol linoleoyl ether (HTLE), a dual Ppar-α agonist/Cb1 antagonist with inherent antioxidant properties, as an antisteatotic agent. Using lean and obese Zucker rats, they were administrated daily doses of HTLE (3 mg/kg) over a 15-day period, evaluating its safety profile, pharmacokinetics, impact on body weight, hepatic fat content, expression of key enzymes involved in lipogenesis/fatty acid oxidation, and antioxidant capacity. HTLE decreased the body weight and food intake in both rat genotypes. Biochemical analysis demonstrated a favorable safety profile for HTLE along with decreased concentrations of urea, total cholesterol, and aspartate aminotransferase AST transaminases in plasma. Notably, HTLE exhibited potent antisteatotic effects in obese rats, evidenced by a decrease in liver fat content and downregulation of lipogenesis-related enzymes, alongside increased expression of proteins controlling lipid oxidation. Moreover, HTLE successfully counteracted the redox imbalance associated with MAFLD in obese rats, attenuating lipid peroxidation and replenishing both glutathione levels and the overall antioxidant. Our findings highlight the effectiveness of triple-action strategies in managing MAFLD effectively. Based on our results in the Zucker rat model, HTLE emerges as a promising candidate with triple functionality as an anorexigenic, antisteatotic, and antioxidant agent, offering potential relief from MAFLD symptoms associated with obesity while exhibiting minimal side effects. In conclusion, our study positions HTLE as a highly promising compound for therapeutic intervention in MAFLD treatment, warranting further exploration in clinical trials.

Parameterization of Biomechanical Variables through Inertial Measurement Units (IMUs) in Occasional Healthy Runners.

Running is one of the most popular sports practiced today and biomechanical variables are fundamental to understanding it. The main objectives of this study are to describe kinetic, kinematic, and spatiotemporal variables measured using four inertial measurement units (IMUs) in runners during treadmill running, investigate the relationships between these variables, and describe differences associated with different data sampling and averaging strategies. A total of 22 healthy recreational runners (M age = 28 ± 5.57 yrs) participated in treadmill measurements, running at their preferred speed (M = 10.1 ± 1.9 km/h) with a set-up of four IMUs placed on tibias and the lumbar area. Raw data was processed and analysed over selections spanning 30 s, 30 steps and 1 step. Very strong positive associations were obtained between the same family variables in all selections. The temporal variables were inversely associated with the step rate variable in the selection of 30 s and 30 steps of data. There were moderate associations between kinetic (forces) and kinematic (displacement) variables. There were no significant differences between the biomechanics variables in any selection. Our results suggest that a 4-IMU set-up, as presented in this study, is a viable approach for parameterization of the biomechanical variables in running, and also that there are no significant differences in the biomechanical variables studied independently, if we select data from 30 s, 30 steps or 1 step for processing and analysis. These results can assist in the methodological aspects of protocol design in future running research.

Estrategia metodológica inclusiva para la enseñanza-aprendizaje del fútbol, en estudiantes con trastorno por déficit de atención con hiperactividad, en la clase de Cultura Física

Es bien sabido que la forma más común de reducir los efectos del trastorno por déficit de atención con hiperactividad ha sido históricamente a través de productos farmacológicos. Sin embargo, es irrefutable que la influencia del ejercicio físico ha evitado indeseables efectos secundarios y ha logrado cambios favorables significativos en los pacientes. Esta actividad física fue implementada básicamente de forma preventiva, principalmente bajo condiciones médicas, crónicas y discapacidades, también para contribuir a la esfera cognitiva y comportamental. El objetivo de este trabajo consistió en proponer un grupo de recomendaciones metodológicas en la clase de Educación Física para mejorar las condiciones de vida de niños con trastorno por déficit de atención con hiperactividad en la Unidad Educativa Fiscomisional Sagrado Corazón de Esmeraldas, Ecuador. Los métodos empíricos que se utilizaron fueron la observación científica, la encuesta aplicada a estudiantes y la entrevista dirigida a profesores; también se emplea, una vez implementadas estas recomendaciones, una encuesta a ambos componentes del proceso para obtener una valoración preliminar sobre el efecto de esta propuesta, debido a que resultó ser una ayuda metodológica de alto valor para preparar los profesores y estudiantes en sus influencias como orientador en el caso del profesor y como colectivo social académico en el caso del grupo de estudiantes.

É bem sabido que a forma mais comum de reduzir os efeitos do transtorno de déficit de atenção e hiperatividade tem sido historicamente por meio de produtos farmacológicos. Contudo, é irrefutável que a influência do exercício físico evitou efeitos colaterais indesejáveis e alcançou mudanças favoráveis significativas nos pacientes. Essa atividade física foi implementada basicamente de forma preventiva, principalmente em condições médicas, crônicas e deficiências, também para contribuir na esfera cognitiva e comportamental. O objetivo deste trabalho foi propor um conjunto de recomendações metodológicas nas aulas de Educação Física para melhorar as condições de vida de crianças com transtorno de déficit de atenção e hiperatividade na Unidade Educacional Fiscomisional Sagrado Corazón de Esmeraldas, Equador. Os métodos empíricos utilizados foram a observação científica, o inquérito aplicado aos alunos e a entrevista dirigida aos professores; Uma vez implementadas estas recomendações, recorre-se também a um levantamento de ambas as componentes do processo para obter uma avaliação preliminar do efeito desta proposta, porque se revelou uma ajuda metodológica de elevado valor para preparar professores e alunos nas suas influências. como conselheiro no caso do professor e como coletivo social acadêmico no caso do grupo de alunos.

It is well known that the most common way to reduce the effects of Inclusive methodological strategy for teaching - learning football in students with attention deficit hyperactivity disorder in the physical culture class (ADHD) has historically been through pharmacological products. However, it is irrefutable that the influence of physical exercise has avoided undesirable side effects and has achieved significant favorable changes in patients. This physical activity was basically implemented preventively, mainly under medical, chronic conditions and disabilities, also to contribute to the cognitive and behavioral sphere. The objective of this work consisted of proposing a group of methodological recommendations in the Physical Education class to improve the living conditions of children with ADHD in the Sagrado Corazón Fiscomisional Educational Unit of Esmeraldas, Ecuador. The empirical methods used were scientific observation, the survey applied to students and the interview directed to teachers. Once these recommendations were implemented, a survey of both components of the process was also used to obtain a preliminary assessment of the effect of this proposal, because it turned out to be a methodological aid of high value to prepare teachers and students in their influences as a counselor in the case of the teacher and as an academic social collective in the case of the group of students.

Relationship between quadriceps femoris echotexture biomarkers and muscle strength and physical function in older adults with heart failure with preserved ejection fraction.

BACKGROUND: Muscle wasting is pronounced in patients with heart failure with preserved ejection fraction (HFpEF). The quadriceps femoris echotexture biomarkers assessed by ultrasound (US) have not been studied in these patients. OBJECTIVE: To describe echotexture biomarkers assessed by the US and to assess their relationship with sex, age, body mass index (BMI), self-reported outcomes, muscle strength and physical function in older adults with HFpEF. METHODS: A cross-sectional study was conducted. Patients 70 years and older with HFpEF were included. The sex, age, BMI, and self-reported outcomes were collected. The US assessed muscle and subcutaneous fat tissue contrast, correlation, energy, homogeneity, and entropy at rest and maximal voluntary isometrical contraction (MVIC). The six-minute walk test (6MWT), the short physical performance battery (SPPB), the timed up and go test (TUG), the usual pace gait speed test (UGS), and the fast pace gait speed test (FGS) were used to assess physical function. The five-repetitions sit-to-stand test (5-STS) was performed to assess muscle strength. Bivariant Pearson correlations and subsequent multivariate linear regression analyses were conducted. RESULTS: Seventy-two older adults with HFpEF [81.06 years, 29.13 BMI, and 55.60% females] were recruited. In women, relaxed and MVIC muscle energy and entropy explained 35.40% of the TUG variance; relaxed muscle entropy and MVIC muscle energy shared 24.00% of the UGS variance; relaxed and MVIC muscle entropy, MVIC muscle contrast and MVIC muscle energy explained 32.60% of the FGS variance, adjusted all the models by age and BMI. CONCLUSIONS: Echotexture biomarkers are related to women's muscle strength and physical function, especially muscle energy, contrast, and entropy. Echotexture biomarkers assessed by the US could facilitate the management of older adults with HFpEF, monitor its progression and assess the effectiveness of treatments on the musculoskeletal structure. TRIAL REGISTRATION: NCT03909919. April 10, 2019. Retrospectively registered.

Three-arm clinical trial of improved flour targeting intestinal microbiota (MALINEA).

The main objective of this project was to compare in the field conditions two strategies of re-nutrition of children with moderate acute malnutrition (MAM) aged from 6 to 24 months, targeting the microbiota in comparison with a standard regimen. A three-arm, open-label, pragmatic randomised trial was conducted in four countries (Niger, CAR, Senegal and Madagascar). Children received for 12 weeks either fortified blended flour (FBF control) = arm 1, or FBF + azithromycin (oral suspension of 20 mg/kg/day daily given with a syringe) for the first 3 days at inclusion = arm 2 or mix FBF with inulin/fructo-oligosaccharides (6 g/day if age ≥12 months and 4 g if age <12 months) = arm 3. For each arm, children aged from 6 to 11 months received 100 g x 2 per day of flours and those aged from 12 to 24 months received 100 g × 3 per day of FBF. The primary endpoint was nutritional recovery, defined by reaching a weight-for-height z-score (WHZ) ≥ -1.5 within 12 weeks. Overall, 881 children were randomised (297, 290 and 294 in arm 1, arm 2 and arm 3, respectively). Three hundred and forty-four children were males (39%) and median/mean age were 14.6/14.4 months (SD = 4.9, IQR = 10.5-18.4). At inclusion, the three arms were comparable for all criteria, but differences were observed between countries. Overall, 44% (390/881) of the children recovered at week 12 from MAM, with no significant difference between the three arms (41.4%, 45.5% and 45.9%, in arm 1, arm 2 and arm 3, respectively, p = 0.47). This study did not support the true advantages of adding a prebiotic or antibiotic to flour. When using a threshold of WHZ ≥ -2 as an exploratory endpoint, significant differences were observed between the three arms, with higher success rates in arms with antibiotics or prebiotics compared to the control arm (66.9%, 66.0% and 55.2%, respectively, p = 0.005).

Effectiveness of decentralizing outpatient acute malnutrition treatment with community health workers and a simplified combined protocol: a cluster randomized controlled trial in emergency settings of Mali.

Background: Outpatient treatment of acute malnutrition is usually centralized in health centers and separated into different programs according to case severity. This complicates case detection, care delivery, and supply chain management, making it difficult for families to access treatment. This study assessed the impact of treating severe and moderate cases in the same program using a simplified protocol and decentralizing treatment outside health centers through community health workers (CHWs). Methods: A three-armed cluster randomized controlled trial under a non-inferiority hypothesis was conducted in the Gao region of Mali involving 2,038 children between 6 and 59 months of age with non-complicated acute malnutrition. The control arm consisted of 549 children receiving standard treatment in health centers from nursing staff. The first intervention arm consisted of 800 children treated using the standard protocol with CHWs added as treatment providers. The second intervention arm consisted of 689 children treated by nurses and CHWs under the ComPAS simplified protocol, considering mid-upper arm circumference as the sole anthropometric criterion for admission and discharge and providing a fixed dose of therapeutic food for severe and moderate cases. Coverage was assessed through cross-sectional surveys using the sampling evaluation of access and coverage (SLEAC) methodology for a wide area involving several service delivery units. Results: The recovery rates were 76.3% in the control group, 81.8% in the group that included CHWs with the standard protocol, and 92.9% in the group that applied the simplified protocol, confirming non-inferiority and revealing a significant risk difference among the groups. No significant differences were found in the time to recovery (6 weeks) or in anthropometric gain, whereas the therapeutic food expenditure was significantly lower with the simplified combined program in severe cases (43 sachets fewer than the control). In moderate cases, an average of 35 sachets of therapeutic food were used. With the simplified protocol, the CHWs had 6% discharge errors compared with 19% with the standard protocol. The treatment coverage increased significantly with the simplified combined program (SAM +42.5%, MAM +13.8%). Implications: Implementing a simplified combined treatment program and adding CHWs as treatment providers can improve coverage while maintaining non-inferior effectiveness, reducing the expenditure on nutritional intrants, and ensuring the continuum of care for the most vulnerable children.

Developing a shortened spine functional index (SFI-10) for patients with sub-acute/chronic spinal disorders: a cross-sectional study.

BACKGROUND: Brief whole-spine patient-reported outcome measures (PROMs) provide regional solutions and future directions for quantifying functional status, evidence, and effective interventions. The whole-spine regional Spine Functional Index (SFI-25) is used internationally in clinical and scientific contexts to assess general sub-acute/chronic spine populations. However, to improve structural validity and practicality a shortened version is recommended. This study developed a shortened-SFI from the determined optimal number of item questions that: correlated with criteria PROMs being highly with whole-spine, moderately with regional-spine, condition-specific and patient-specific, and moderately-low with general-health and pain; retained one-dimensional structural validity and high internal consistency; and improved practicality to reduce administrative burden. METHODS: A cross-sectional study (n = 505, age = 18-87 yrs., average = 40.3 ± 10.1 yrs) of sub-acute/chronic spine physiotherapy outpatients from an international sample of convenience. Three shortened versions of the original SFI-25 were developed using 1) qualitative 'content-retention' methodology, 2) quantitative 'factorial' methodology, and 3) quantitative 'Rasch' methodology, with a fourth 'random' version produced as a comparative control. The clinimetric properties were established for structural validity with exploratory (EFA) and confirmatory (CFA) factorial analysis, and Rasch analysis. Criterion validity used the: whole-spine SFI-25 and Functional Rating Index (FRI); regional-spine Neck Disability Index (NDI), Oswestry Disability Index (ODI), and Roland Morris Questionnaire (RMQ), condition-specific Whiplash Disability Questionnaire (WDQ); and patient-specific functional scale (PSFS); and determined floor/ceiling effect. A post-hoc pooled international sub-acute/chronic spine sample (n = 1433, age = 18-91 yrs., average = 42.0 ± 15.7 yrs) clarified the findings and employed the general-health EuroQuol-Index (EQ-5D), and 11-point Pain Numerical Rating Scale (P-NRS) criteria. RESULTS: A 10-item SFI retained structural validity with optimal practicality requiring no computational aid. The SFI-10 concept-retention-version demonstrated preferred criterion validity with whole-spine criteria (SFI-25 = 0.967, FRI = 0.810) and exceeded cut-off minimums with regional-spine, condition-specific, and patient-specific measures. An unequivocal one-dimensional structure was determined. Internal consistency was satisfactory (α = 0.80) with no floor/ceiling effect. Post-hoc analysis of the international sample confirmed these findings. CONCLUSION: The SFI-10 qualitative concept-retention version was preferred to quantitative factorial and Rasch versions, demonstrated structural and criterion validity, and preferred correlation with criteria measures. Further longitudinal research is required for reliability, error, and responsiveness, plus an examination of the practical characteristics of readability and administrative burden.

Inhibition of Adult Neurogenesis in Male Mice after Repeated Exposure to Paracetamol Overdose.

Paracetamol, or acetaminophen (N-acetyl-para-aminophenol, APAP), is an analgesic and antipyretic drug that is commonly used worldwide, implicated in numerous intoxications due to overdose, and causes serious liver damage. APAP can cross the blood-brain barrier and affects brain function in numerous ways, including pain signals, temperature regulation, neuroimmune response, and emotional behavior; however, its effect on adult neurogenesis has not been thoroughly investigated. We analyze, in a mouse model of hepatotoxicity, the effect of APAP overdose (750 mg/kg/day) for 3 and 4 consecutive days and after the cessation of APAP administration for 6 and 15 days on cell proliferation and survival in two relevant neurogenic zones: the subgranular zone of the dentate gyrus and the hypothalamus. The involvement of liver damage (plasma transaminases), neuronal activity (c-Fos), and astroglia (glial fibrillar acidic protein, GFAP) were also evaluated. Our results indicated that repeated APAP overdoses are associated with the inhibition of adult neurogenesis in the context of elevated liver transaminase levels, neuronal hyperactivity, and astrogliosis. These effects were partially reversed after the cessation of APAP administration for 6 and 15 days. In conclusion, these results suggest that APAP overdose impairs adult neurogenesis in the hippocampus and hypothalamus, a fact that may contribute to the effects of APAP on brain function.

Exercise-based cardio-oncology rehabilitation for cardiotoxicity prevention during breast cancer chemotherapy: The ONCORE randomized controlled trial.

BACKGROUND: Breast cancer (BC) treatment with anthracyclines and/or anti-human epidermal growth factor receptor-2 (HER2) antibodies is associated with an increased risk of cardiovascular disease complications, including cancer therapy-related cardiac dysfunction (CTRCD). While Cardio-Oncology Rehabilitation (CORe) programs including exercise have emerged to minimize these risks, its role in preventing CTRCD is unclear. OBJECTIVES: We investigated the effectiveness of an exercise-based CORe program in preventing CTRCD [left ventricular ejection fraction (LVEF) drop ≥10% to a value <53% or a decrease >15% in global longitudinal strain (GLS)]. Secondary outcomes examined changes in cardiac biomarkers, physical performance including peak oxygen consumption, psychometric and lifestyle outcomes. Safety, adherence, and patient satisfaction were also assessed. METHODS: This is a randomized controlled trial including 122 early-stage BC women receiving anthracyclines and/or anti-HER2 antibodies, randomized to CORe (n = 60) or usual care with exercise recommendation (n = 62). Comprehensive assessments were performed at baseline and after cardiotoxic treatment completion. The average duration of the intervention was 5.8 months. RESULTS: No cases of CTRCD were identified during the study. LVEF decreased in both groups, but was significantly attenuated in the CORe group [-1.5% (-2.9, -0.1); p = 0.006], with no changes detected in GLS or cardiac biomarkers. The CORe intervention led to significant body mass index (BMI) reduction (p = 0.037), especially in obese patients [3.1 kg/m2 (1.3, 4.8)]. Physical performance and quality-of-life remained stable, while physical activity level increased in both groups. No adverse events were detected. CONCLUSIONS: This study suggests that CORe programs are safe and may help attenuate LVEF decline in BC women receiving cardiotoxic therapy and reduce BMI in obese patients.

Kinematic parameters related to functional capacity, fatigue, and breathlessness during the 6-min walk test in older adults with heart failure with preserved ejection fraction.

AIMS: This paper aims to assess kinematic parameters related to functional capacity, fatigue, and breathlessness during the 6-min walk test (6MWT) in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: A cross-sectional study was conducted in which adults 70 years or older with HFpEF were voluntarily recruited between April 2019 and March 2020. An inertial sensor was placed at the L3-L4 level and another on the sternum to assess kinematic parameters. The 6MWT was divided into two 3-min phases. Leg fatigue and breathlessness, assessed by the Borg scale, the heart rate (HR), and the oxygen saturation (SpO2), were measured at the beginning and the end of the 6MWT. The difference in kinematic parameters between the 6MWT two 3-min phases was also calculated. Bivariate Pearson correlations and subsequent multivariate linear regression analysis were performed. Seventy older adults with HFpEF (mean = 80.74 years old) were included. Kinematic parameters explained 81.00% of the functional capacity, 45.50% of the leg fatigue and 66.10% of the breathlessness variance. Moreover, kinematic parameters could explain 30.90% of the SpO2 variance at the end of the 6MWT. Kinematic parameters also explained 33.10% of the SpO2 difference between the beginning and end of 6MWT. Kinematic parameters explained neither the HR variance at the end of 6MWT nor the HR difference between the beginning and end. CONCLUSION: Gait kinematics from L3-L4 and sternum explain a part of the variance in subjective outcomes, assessed by the Borg scale, and objective outcomes such as functional capacity and SpO2. The kinematic assessment allows clinicians to quantify fatigue and breathlessness through objective parameters related to the patient's functional capacity. REGISTRATION: ClinicalTrials.gov NCT03909919.

Preventing chronic malnutrition in children under 2 years in rural Angola (MuCCUA trial): protocol for the economic evaluation of a three-arm community cluster randomised controlled trial.

INTRODUCTION: Chronic malnutrition is a serious problem in southern Angola with a prevalence of 49.9% and 37.2% in the provinces of Huila and Cunene, respectively. The MuCCUA (Mother and Child Chronic Undernutrition in Angola) trial is a community-based randomised controlled trial (c-RCT) which aims to evaluate the effectiveness of a nutrition supplementation plus standard of care intervention and a cash transfer plus standard of care intervention in preventing stunting, and to compare them with a standard of care alone intervention in southern Angola. This protocol describes the planned economic evaluation associated with the c-RCT. METHODS AND ANALYSIS: We will conduct a cost-efficiency and cost-effectiveness analysis nested within the MuCCUA trial with a societal perspective, measuring programme, provider, participant and household costs. We will collect programme costs prospectively using a combined calculation method including quantitative and qualitative data. Financial costs will be estimated by applying activity-based costing methods to accounting records using time allocation sheets. We will estimate costs not included in accounting records by the ingredients approach, and indirect costs incurred by beneficiaries through interviews, household surveys and focus group discussions. Cost-efficiency will be estimated as cost per output achieved by combining activity-specific cost data with routine data on programme outputs. Cost-effectiveness will be assessed as cost per stunting case prevented. We will calculate incremental cost-effectiveness ratios comparing the additional cost per improved outcome of the different intervention arms and the standard of care. We will perform sensitivity analyses to assess robustness of results. ETHICS AND DISSEMINATION: This economic evaluation will provide useful information to the Angolan Government and other policymakers on the most cost-effective intervention to prevent stunting in this and other comparable contexts. The protocol was approved by the República de Angola Ministério da Saúde Comité de Ética (27C.E/MINSA.INIS/2022). The findings of this study will be disseminated within academia and the wider policy sphere. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05571280).

Impact of a simplified treatment protocol for moderate acute malnutrition with a decentralized treatment approach in emergency settings of Niger.

Introduction: Of the 45.4 million children under five affected by acute malnutrition in the world, the majority (31.8 million) are affected by moderate acute malnutrition (MAM). Its treatment is particularly complex in emergency settings such as the Diffa region in Niger. This study aims to evaluate the effectiveness and coverage of a simplified treatment protocol with Community Health Workers (CHWs) as treatment providers. Methods: This study is a non-randomized controlled trial. The control group (n = 181) received the standard protocol currently used in country, delivered by nursing staff only in health centres and health posts, while the intervention group (n = 483) received the simplified protocol which included nursing at health centres and CHWs at health post as treatment providers. Results: The recovery rate was higher in the simplified protocol group (99.6% vs. 79.56%, p < 0.001) recording lower time to recover and higher anthropometric gain. Treatment coverage in the intervention group increased from 28.8% to 84.9% and reduced in the control group (25.3% to 13.6%). No differences were found in the recovery rate of children treated by CHWs and nursing staff. Conclusion: The outcomes using the simplified protocol exceeded humanitarian requirements and demonstrated improvements compared to the standard protocol showing that the simplified protocol could be safely provided by CHWs in an emergency context. Further research in other contexts is needed to scale up this intervention.

Impact of integrated preventive and curative health package on nutritional status of children under 2 years of age in the health area of Tama, Tahoua region (Niger).

Background: Niger, relevant in light of current political coup, is one of the countries with the worst human development indicators, characterized by high fertility rates and extremely high infant mortality rates. Food insecurity in the region is alarming, leading to high malnutrition rates in children. This study aimed to evaluate an integral preventive-curative health program targeting children aged under 2 years in the health area of Tama, district of Bouza, Tahoua. Methodology: Anthropometric follow-up data of 6,962 children aged under 2 years were included in this study. These children received complete vaccination and malaria chemoprevention, and those older than 6 months received nutritional supplementation with a small quantity of lipid-based nutrient supplements. Fundamental growth indicators (height-for-age, weight-for-height, weight-for-age, and middle-upper arm circumference) and the Composite Index of Anthropometric Failure were calculated at the beginning and end of the program (mean time spent in the program: 14.5 ± 6.6 months) The evolution of these indicators was compared with those of a sample from a vertical vaccination program conducted in the neighboring region of Madarounfa on similar dates. Results: The proportion of children without anthropometric failure decreased from 59.5 to 40.2% (p < 0.001), with the categories that included stunting increasing the most. When analyzing the anthropometric indicators according to the months of compliance with the program, there was a slight improvement in the indicators of acute malnutrition, whereas those of chronic malnutrition worsened significantly. However, when compared with the Madarounfa sample, the children in the present study registered a significantly lower worsening in all three indicators: height-age (-0.46 vs. -2.44; p < 0.001), weight-height (+0.31 vs. -0.55; p < 0.001) and weight-age (-0.03 vs. -1.63; p < 0.001) difference. Conclusion: The comprehensive preventive-curative health program slightly slows the worsening of cumulative malnutrition in the early years of life in complex contexts, such as southern Niger.

Effectiveness of a cardiac rehabilitation program on biomechanical, imaging, and physiological biomarkers in elderly patients with heart failure with preserved ejection fraction (HFpEF): FUNNEL + study protocol.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) have a low functional status, which in turn is a risk factor for hospital admission and an important predictor of survival in HFpEF. HFpFE is a heterogeneous syndrome and recent studies have suggested an important role for careful, pathophysiological-based phenotyping to improve patient characterization. Cardiac rehabilitation has proven to be a useful tool in the framework of secondary prevention in patients with HFpEF. Facilitating decision-making and implementing cardiac rehabilitation programs is a challenge in public health systems for HFpEF management. The FUNNEL + study proposes to evaluate the efficacy of an exercise and education-based cardiac rehabilitation program on biomechanical, physiological, and imaging biomarkers in patients with HFpEF. METHODS: A randomised crossover clinical trial is presented among people older than 70 years with a diagnosis of HFpEF. The experimental group will receive a cardiac rehabilitation intervention for 12 weeks. Participants in the control group will receive one educational session per week for 12 weeks on HFpEF complications, functional decline, and healthy lifestyle habits. VO2peak is the primary outcome. Biomechanical, imaging and physiological biomarkers will be assessed as secondary outcomes. Outcomes will be assessed at baseline, 12 weeks, and 24 weeks. DISCUSSION: Identifying objective functional parameters indicative of HFpEF and the subsequent development of functional level stratification based on functional impairment ("biomechanical phenotypes") may help clinicians identify cardiac rehabilitation responders and non-responders and make future clinical decisions. In this way, future pharmacological and non-pharmacological interventions, such as exercise, could be improved and tailored to improve quality of life and prognosis and reducing patients' hospital readmissions, thereby reducing healthcare costs. TRIAL REGISTRATION: NCT05393362 (Clinicaltrials.gov).

Experimental and Theoretical Analysis of the Thiol-Promoted Fragmentation of 2-Halo-3-tosyl-oxanorbornadienes.

2-Halo-3-tosyl-oxanorbornadienes are able to accept two thiol molecules through an initial nucleophilic substitution, giving isolable oxabicyclic thiovinyl sulfones that, subsequently, can react with a second thiol molecule via thio-Michael addition. The resulting oxanorbornenic thioketals undergo retro-Diels-Alder (rDA) fragmentation to release a furan derivative and a ketene S,S-acetal. The substitution pattern of the oxanorbornadienic skeleton influences the rate of the rDA through electronic and steric factors examined by quantum mechanical calculations.

Sex-Dependent Altered Expression of Cannabinoid Signaling in Hippocampal Astrocytes of the Triple Transgenic Mouse Model of Alzheimer's Disease: Implications for Controlling Astroglial Activity.

Alzheimer's disease (AD) is a common neurodegenerative disease. In AD-associated neuroinflammation, astrocytes play a key role, finding glial activation both in patients and in animal models. The endocannabinoid system (ECS) is a neurolipid signaling system with anti-inflammatory and neuroprotective properties implicated in AD. Astrocytes respond to external cannabinoid signals and also have their own cannabinoid signaling. Our main objective is to describe the cannabinoid signaling machinery present in hippocampal astrocytes from 3×Tg-AD mice to determine if they are actively involved in the neurodegenerative process. Primary cultures of astrocytes from the hippocampus of 3×Tg-AD and non-Tg offspring were carried out. We analyzed the gene expression of astrogliosis markers, the main components of the ECS and Ca2+ signaling. 3×Tg-AD hippocampal astrocytes show low inflammatory activity (Il1b, Il6, and Gls) and Ca2+ flow (P2rx5 and Mcu), associated with low cannabinoid signaling (Cnr1 and Cnr2). These results were more evident in females. Our study corroborates glial involvement in AD pathology, in which cannabinoid signaling plays an important role. 3×Tg-AD mice born with hippocampal astrocytes with differential gene expression of the ECS associated with an innate attenuation of their activity. In addition, we show that there are sex differences from birth in this AD animal, which should be considered when investigating the pathogenesis of the disease.

Transferring Substituents from Alkynes to Furans and Pyrroles through Heteronorbornadienes as Intermediates: Synthesis of ß-Substituted Pyrroles/Furans.

The use of 7-oxa/azanorbornadienes as synthetic intermediates for the preparation of 3/4-substituted (ß-substituted) furans/pyrroles is presented. The method lies in the inverse electron demand Diels-Alder (iEDDA) cycloaddition between a substituted heteronorbornadiene and an electron-poor tetrazine followed by spontaneous fragmentation of the resulting cycloadduct via two retro-Diels-Alder (rDA) reactions affording a ß-substituted furan/pyrrole. The scope of this tandem iEDDA/rDA/rDA reaction was explored in the preparation of 29 heterocycles. A one-pot procedure starting directly from the alkyne precursors of the heteronorbornadiene intermediates is also described.

Pain neuroscience education in persistent painful tendinopathies: A scoping review from the Tendon PNE Network.

OBJECTIVE: to conduct and report a scoping review of the available evidence of the effects and content of pain neuroscience education for patients with persistent painful tendinopathies. METHODS: PubMed, Embase, Web of Science, CINAHL, SPORTDiscus, and grey literature databases were searched from database inception to May 2022. Randomised and non-randomised controlled trials, non-controlled clinical trials, cohort studies, case series, case studies including people with persistent painful tendinopathy aged ≥18 years, a pain education intervention, and in English were included. Studies were excluded if they were cross-sectional studies, reviews, editorials, abstracts, or full-text not available or if included heterogeneous study cohorts, patients with tendon rupture, or patients with systemic diseases. RESULTS: five studies (n = 164) were included. Pain neuroscience education entailed face-to-face discussion sessions or educational materials including videos, brochures, paper drawings, and review questions. All studies used pain neuroscience education in conjunction with other interventions, obtaining significant benefits in outcomes related to pain, physical performance, or self-reported function, among others. CONCLUSIONS: The application of pain neuroscience education in conjunction with other interventions seemed to improve several outcomes. However, considering the current knowledge about tendon pain and the scarcity of well-designed trials studying pain neuroscience education in tendinopathy, additional research is needed.

Effectiveness of a gamified digital intervention based on lifestyle modification (iGAME) in secondary prevention: a protocol for a randomised controlled trial.

INTRODUCTION: Combating physical inactivity and reducing sitting time are one of the principal challenges proposed by public health systems. Gamification has been seen as an innovative, functional and motivating strategy to encourage patients to increase their physical activity (PA) and reduce sedentary lifestyles through behaviour change techniques (BCT). However, the effectiveness of these interventions is not usually studied before their use. The main objective of this study will be to analyse the effectiveness of a gamified mobile application (iGAME) developed in the context of promoting PA and reducing sitting time with the BCT approach, as an intervention of secondary prevention in sedentary patients. METHODS AND ANALYSIS: A randomised clinical trial will be conducted among sedentary patients with one of these conditions: non-specific low back pain, cancer survivors and mild depression. The experimental group will receive a 12-week intervention based on a gamified mobile health application using BCT to promote PA and reduce sedentarism. Participants in the control group will be educated about the benefits of PA. The International Physical Activity Questionnaire will be considered the primary outcome. International Sedentary Assessment Tool, EuroQoL-5D, MEDRISK Instruments and consumption of Health System resources will be evaluated as secondary outcomes. Specific questionnaires will be administered depending on the clinical population. Outcomes will be assessed at baseline, at 6 weeks, at the end of the intervention (12 weeks), at 26 weeks and at 52 weeks. ETHICS AND DISSEMINATION: The study has been approved by the Portal de Ética de la Investigación Biomédica de Andalucía Ethics Committee (RCT-iGAME 24092020). All participants will be informed about the purpose and content of the study and written informed consent will be completed. The results of this study will be published in a peer-reviewed journal and disseminated electronically and in print. TRIAL REGISTRATION NUMBER: NCT04019119.

Effectiveness and Coverage of Severe Acute Malnutrition Treatment with a Simplified Protocol in a Humanitarian Context in Diffa, Niger.

BACKGROUND: the aim of this study is to evaluate the effectiveness and coverage of a simplified protocol that is implemented in health centers (HCs) and health posts (HPs) for children who are suffering from severe acute malnutrition (SAM) in the humanitarian context of Diffa. METHODS: We conducted a non-randomized community-controlled trial. The control group received outpatient treatment for SAM, without medical complications, at HCs and HPs with the standard protocol of community management of acute malnutrition (CMAM). Meanwhile, with respect to the intervention group, the children with SAM received treatment at the HCs and HPs through a simplified protocol wherein the mid-upper arm circumference (MUAC) and the presence of edema were used as the admission criteria, and the children with SAM were administered doses of fixed ready-to-use therapeutic food (RUTF). RESULTS: A total of 508 children, who were all under 5 years and had SAM, were admitted into the study. The cured proportion was 87.4% in the control group versus 96.6% in the intervention group (p value = 0.001). There was no difference between the groups in the length of stay, which was 35 days, but the intervention group used a lower quantity of RUTF-70 sachets versus 90 sachets, per child cured. Coverage increases were observed in both groups. DISCUSSION: the simplified protocol used at the HCs and HPs did not result in worse recovery and resulted in fewer discharge errors compared to the standard protocol.