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The aggregation of Amyloid-β (Aβ) peptides is associated with neurodegeneration in Alzheimer's disease (AD). We previously identified novel naphtalene derivatives, including the lead compound Amylovis-201, able to form thermodynamically stable complexes with Aβ species, peptides and fibrils. As the drug showed a chemical scaffold coherent for an effective interaction with the σ1 receptor chaperone and as σ1 agonists are currently developed as potent neuroprotectants in AD, we investigated the pharmacological action of Amylovis-201 on the σ1 receptor. We report that Amylovis-201 is a potent σ1 agonist by several in silico, in vitro and in vivo assays and that its anti-amnesic and neuroprotective effects involve a pharmacological action at σ1 receptors. Furthermore, we show for the first time that classical σ1 receptor agonist (PRE-084), and antagonist (NE-100) are able to interact and disaggregate Aβ25–35 fibrils. Interestingly, Amylovis-201 was the only compound inhibiting Aβ25–35 aggregates formation. Our results therefore highlight a dual action of Amylovis-201 as anti-aggregating agent and σ1 receptor agonist that could be highly effective in long-term treatment against neurodegeneration in AD.

Background: Measures that assess muscle strength and its development, either voluntarily or involuntarily, are important in the clinical and research context. The main aim of this study was to verify the interday reliability and the minimum detectable change (MDC) of the knee extensors muscles torque using evoked contractions and explosive voluntary contractions (EVC), across six different joint angles. Methods: 20 participants, 16 men and 4 women (26.5 ± 6.6 years; 174.5 ± 11.1 cm; 73.7 ± 11.3 kg), participated in this study. Evoked twitch contractions and voluntary explosive contractions of the knee extensors were performed in 2 days (test-retest) at 20, 40, 70, 90, 105 and 115 degrees. Results: The most reliable twitch parameters were peak torque (PT), contraction time (CT), half relaxation-time (½ time), total impulse and peak rate of torque development (RTD[subscript Peak]), with coefficient of variation (CV) ranging from [approximately] 8% at 20° to 5% at 115° angle. It was verified that CT and ½ time become more reliable as the knee angle changed from 20 to 115 degrees, from shorter to longer muscle lengths (7.3 to 2.7% and 8.8% to 4.0%, respectively). The more reliable parameters for voluntary contraction were PT, RTD[subscript 250 ms], RTD[subscript Peak] and impulse[subscript 250 ms] (CV from around [approximately] 8% at 20°/115° and 5% at 70°/90°). For voluntary contractions, all measures performed at 70° angle were more reliable compared to the other angles. Conclusion: It was concluded that for the knee extensor muscles, evoked twitch contractions presented greater reliability across knee angles, with lower CV values when compared to the voluntary measures for the same time windows. Specifically, for the evoked twitch contractions, angles from 70 to 115 degree proved to be highly reliable. On the other hand, for the voluntary contractions, the central angles (70 and 90 degree) were the most reliable.

The aim of this study was to verify the concurrent validity and the biological error-free reliability of a novel low-cost commercial encoder (Ergonauta I). Validity protocol involved comparisons with a custom system and other encoder commercially available (Vitruve). Reliability protocols involved interdevices and interunit comparisons. No participants were recruited, and reliability assessments were performed in a Smith Machine by bar free fall tests. Our results showed a significant bias for mean velocity (MV) estimated by both encoders only in one of the four conditions investigated (bias = 0.05 m/s). Regarding sensitivity, the smallest detectable change suggests only values higher than 0.03 m/s must to be considered as real changes in performance, when monitoring MV and mean propulsive velocity (MPV) through Ergonauta I and Vitruve. Between-days intra-device reliability showed Ergonauta I remains highly reliable after one week for most assessments, whereas slightly less sensitive for peak velocity and peak power output.

The host-microbiome associations occurring on the skin of vertebrates significantly influence hosts health. However, the factors mediating their interactions remain largely unknown. Herein, we used integrated technical and ecological frameworks to investigate the skin metabolites sustaining a beneficial symbiosis between tree frogs and bacteria. We characterize macrocyclic acylcarnitines as the major metabolites secreted by the frogs skin and trace their origin to an enzymatic unbalance of carnitine palmitoyltransferases. We found that these compounds colocalize with bacteria on the skin surface and are mostly represented by members of the Pseudomonas community. We showed that Pseudomonas sp. MPFS isolated from frogs skin can exploit acylcarnitines as its sole carbon and nitrogen source, and this metabolic capability is widespread in Pseudomonas. We summarize frogs multiple mechanisms to filter environmental bacteria and highlight that acylcarnitines likely evolved for another function but were co-opted to provide nutritional benefits to the symbionts.

Este estudo teve como objetivo identificar a prevalência de alterações visuais em escolares. A pesquisa empregou um desenho clínico transversal, observacional, descritivo e analítico, realizando testes de triagem visual em 337 alunos entre 10 e 17 anos. Os resultados indicaram que cerca de 21,9% dos estudantes apresentavam alguma deficiência visual. Entre os que usavam lentes corretivas, 9,8% mostraram discordância entre o grau dos óculos e o grau encontrado na refração automática associado a baixa acuidade visual. Observou-se correlação significativa entre hereditariedade e a necessidade de óculos. Além disso, 17,9% das crianças sem sintomas oculares tenderam a negligenciar consultas oftalmológicas. Os resultados destacam a importância da triagem visual nas escolas para a detecção precoce de problemas oculares, essencial para o desenvolvimento biopsicossocial dos alunos. Este estudo enfatiza a necessidade de programas de triagem e acompanhamento visual para garantir o bem-estar dos estudantes.

Abstract Metabolic plasticity is a hallmark of cancer, and metabolic alterations represent a promising therapeutic target. Since cellular metabolism is controlled by membrane traffic at multiple levels, we investigated the involvement of TBC1 domain-containing proteins (TBC1Ds) in the regulation of cancer metabolism. These proteins are characterized by the presence of a RAB-GAP domain, the TBC1 domain, and typically function as attenuators of RABs, the master switches of membrane traffic. However, a number of TBC1Ds harbor mutations in their catalytic residues, predicting biological functions different from direct regulation of RAB activities. Herein, we report that several genes encoding for TBC1Ds are expressed at higher levels in triple-negative breast cancers (TNBC) vs. other subtypes of breast cancers (BC), and predict prognosis. Orthogonal transcriptomics/metabolomics analysis revealed that the expression of prognostic TBC1Ds correlates with elevated glycolytic metabolism in BC cell lines. In-depth investigations of the three top hits from the previous analyses (TBC1D31, TBC1D22B and TBC1D7) revealed that their elevated expression is causal in determining a glycolytic phenotype in TNBC cell lines. We further showed that the impact of TBC1D7 on glycolytic metabolism of BC cells is independent of its known participation in the TSC1/TSC2 complex and consequent downregulation of mTORC1 activity. Since TBC1D7 behaves as an independent prognostic biomarker in TNBC, it could be used to distinguish good prognosis patients who could be spared aggressive therapy from those with a poor prognosis who might benefit from anti-glycolytic targeted therapies. Together, our results highlight how TBC1Ds connect disease aggressiveness with metabolic alterations in TNBC. Given the high level of heterogeneity among this BC subtype, TBC1Ds could represent important tools in predicting prognosis and guiding therapy decision-making.

Acupuncture involves stimulating points with lower electrical impedance (EI). Understanding EI changes with needle and exercise stimuli can elucidate acupuncture mechanisms. This study included 60 subjects, divided into control (C) and acupuncture (A) groups. EI was assessed at four points: 0 (before procedures), I (after handgrip protocol [HGP]), II (after 20 minutes of rest), and III (after 20 minutes of rest in C or stimulation in A, followed by HGP in both groups). Statistical significance was set at p < 0.05. In the A group, EI was significantly reduced at HT3, shown by increased % microampere when comparing assessments I, II, and III with assessment 0 (p < 0.005). Intergroup comparisons revealed a reduced % microampere when comparing assessments II (p < 0.02) and III (p < 0.0001). Furthermore, the stimulation of an acupoint over a motor nerve branch changes the EI.

La investigación presenta el desarrollo de un componente para la firma digital de documentos en línea en la Plataforma GAPID, el cual desempeña un papel crucial en la gestión de Programas y Proyectos de Ciencia, Tecnología e Innovación. Se ha identificado la necesidad de fortalecer ciertos aspectos del sistema para garantizar la autenticidad, integridad y no repudio de los documentos digitales que se gestionan en el mismo. Actualmente, los usuarios dependen de métodos tradicionales que necesitan de un proceso de impresión y el escaneo para firmar documentos, así como de herramientas externas que dificultan la eficiencia del proceso documental. El objetivo principal de esta investigación es desarrollar un componente de firma digital en línea que garantice la autenticidad, integridad y no repudio de los documentos emitidos en el sistema GAPID, eliminando la dependencia de métodos tradicionales y herramientas externas. Para ello, se utilizó como tecnología principal Next.js para el desarrollo del sistema, destacándose por su eficiencia y escalabilidad. Los métodos utilizados para la investigación permitieron el análisis de soluciones similares, especificación de requisitos, prototipos de interfaz de usuario, de los diferentes conceptos. La solución propuesta involucra la integración de una firma digital robusta dentro de GAPID, mejorando la confiabilidad y seguridad de los procesos administrativos y financieros. La incorporación de este componente al sistema GAPID no solo elimina la necesidad de herramientas externas, sino que también aumenta la seguridad en la gestión de documentos digitales, beneficiando a todas las partes involucradas en los proyectos y programas suscritos.

ABSTRACT: The objective of this study was to evaluate the effects of supplementing monensin (19.8 g/Mg DM TMR; MON) and Saccharomyces cerevisiae CNCM I-1077 live-cell yeasts (Saccharomyces cerevisiae CNCM I-1077; 1 × 1010 cfu/head per day; LCY) on lactation performance, feeding behavior, and total-tract nutrient digestibility of high-producing dairy cows. Sixty-four multiparous Holstein cows (3.2 ± 1.5 lactations; 97 ± 16 DIM, and 724 ± 68 kg of BW at covariate period initiation) and 32 gate feeders were enrolled in a study with a completely randomized design and a 2 × 2 factorial arrangement. Cows and gate feeders were randomly assigned to treatments (16 cows and 8 gate feeders per treatment). Cows were allowed 2 wk to acclimate to feeding gates followed by a 2-wk covariate period. During the acclimation and covariate periods, all cows were fed a diet containing MON and LCY. Following the covariate period, cows were enrolled in a 10-wk treatment period during which cows were randomly assigned to 1 of 4 treatments: (1) a combination of MON and LCY (MON-LCY), (2) MON-CON, (3) CON-LCY, or (4) neither MON nor LCY (CON-CON). Data were analyzed using a mixed model with week as a repeated measure and fixed effects of MON, LCY, week, and all their interactions. Cow (treatment) was included as a random effect. The average covariate period value of each variable was used as a covariate. Three-way interactions were observed for DMI and feed efficiency. Dry matter intake decreased from wk 4 to 5 and wk 8 to 10 in MON-LCY cows compared with CON-CON. No treatment differences were observed for actual or component-corrected milk yield or milk components, except for a tendency for LCY to decrease milk fat yield. Feed efficiency was greater for MON-LCY relative to CON-CON in 4 of 10 wk. Interactions between MON and LCY were observed for dry matter and organic matter digestibility, where both were lower for CON-CON than other treatments. Under the conditions of the present study, feeding dairy cows in a high feed bunk density a combination of MON and LCY can decrease intake and improve feed efficiency without affecting milk production or components. Additionally, monensin and live-cell yeasts may each improve total-tract digestibility based on improvements in DM and OM digestibility.

Introduction Almost half of patients discharged from hospital are readmitted or return to the emergency department (ED) within 90 days. Non-adherence to medication changes made during hospitalisation and the use of potentially inappropriate medications (PIMs) both contribute to postdischarge adverse events. We developed Smart About Meds (SAM), a patient-centred mobile application that targets medication non-adherence and PIMs use. This protocol describes a randomised controlled trial (RCT) to evaluate SAM.Methods and analysis A pragmatic, stratified RCT will evaluate SAM among 3250 adult patients discharged from hospital. At discharge, consenting participants will be randomised 1:1 to usual care or SAM. SAM integrates novel patient-centred features with pharmacist monitoring to manage non-adherence to new medication regimens. SAM also notifies patients of PIMs in their regimen, with advice to discuss with their physician.Following discharge, patients will be followed for 90 days to measure the primary composite outcome of ED visits, hospital readmissions and death. Secondary outcomes will include primary adherence to medication changes, secondary adherence to disease-modifying medications, patient empowerment and health-related quality of life.The primary outcome will be analysed according to intention-to-treat. Multivariable logistic regression will estimate differences between treatment groups in the proportion of patients experiencing the primary outcome and will assess modification of intervention effects by hospital, unit, age, sex and comorbidity burden. With a sample size of 3250, the study will have 80% power to detect a 5% absolute reduction in the primary outcome. Binary and continuous secondary outcomes will be assessed using multivariable logistic and linear regression, respectively.Ethics and dissemination The Research Ethics Board of the McGill University Health Centre in Montréal, Canada has approved this study. Results will be submitted for publication in a peer-reviewed journal and presented at scientific conferences. If effective, SAM will be made available in app stores.Trial registration number NCT05371548.

Using pure hydrogen (H2) or mixtures of H2 and natural gas in gas-fired power plants represents a viable route to decarbonize electric power generation. This study models a system designed to cool the air at the compressor inlet to 8.8 °C, achieve a flue gas oxygen percentage of 11.46 %, and produce 44.4 MW with a fuel mix ranging from 0 to 100 % H2 operating in tropical climates, where temperatures exceed 30 °C and relative humidity exceeds 80 %. The analysis is based on energy, exergy, and exergoeconomic balance to obtain performance indicators that characterize plant operations. The results show that with 100 % H2, the PCI increases by 144 % compared to 100 % natural gas. Furthermore, the energy analysis indicates that for every 10 % volume increase in the H2 fuel mix, the CO2 concentration decreased by 34 kg/m³, the NOx concentration increased by 1 kg/m³, the dew point temperature increased by 0.5 °C, the energy efficiency improved by 4.5 percentage points, the heat rate decreased by 7 %, and the specific fuel consumption decreased by 8.5 %. Furthermore, the total exergy destruction increased by 14.83 %, and the total exergy efficiency decreased by 2.7 percentage points. The exergoeconomic analysis shows that the specific cost of electric energy per GJ decreases by 10 % for H2 contents higher than 80 % by volume. This work demonstrates that generating energy from gas turbine power plants with lower CO2 equivalent emissions is possible. On the other hand, the effects of moisture content in exhaust gases and NOX are known due to the greater presence of H2 and higher temperature combustion.

Introduction: Serious postoperative complications lead to reinterventions, which increase the risk of further complications and death. There are 2 methods for performing abdominal reintervention: Open surgery (OS) or laparoscopic surgery (LS). Objective: To compare the results of laparoscopic surgery and open surgery in reinterventions of patients with serious postoperative complications. Method: Quasi-experimental study in 155 patients with severe postoperative complications. Two groups were compared: CL (n= 71) and CA (n= 84) regarding (preoperative): cause of reintervention, mean arterial pressure, heart rate and time to reintervention; and (postoperative): Complications, further reinterventions and death. Results: Before reintervention, mean arterial pressure was similar in both groups (experimental 91.3 mmHg; control 89.5 mmHg); The percentage of cases with previous OS in the experimental group was 67.6 %, and in this group anastomotic leak (42.65 %) and postoperative peritonitis (25 %) predominated. After reintervention, surgical site infection (59.7 % vs. 16.2 %) and external intestinal fistulas (22.6 %) were higher in the control group. There were more deaths in the control group (27.4 % vs. 8.5 %) and 23 patients with new reinterventions were reported in this group, vs. 6 patients in the experimental group. Conclusions: Laparoscopic surgery showed better results than open surgery in the reintervention of patients with serious postoperative complications; there was less use of blood products, fewer reinterventions, complications and death.