Mesenchymal Stem/Stromal Cells Derived from Dental Tissues Mediate the Immunoregulation of T Cells through the Purinergic Pathway.

Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to bone marrow-derived mesenchymal stem cells (BM-MSCs) for potential clinical applications because of their accessibility and anti-inflammatory capacity. We previously demonstrated that DT-MSCs from dental pulp (DP-MSCs), periodontal ligaments (PDL-MSCs), and gingival tissue (G-MSCs) show immunosuppressive effects similar to those of BM, but to date, the DT-MSC-mediated immunoregulation of T lymphocytes through the purinergic pathway remains unknown. In the present study, we compared DP-MSCs, PDL-MSCs, and G-MSCs in terms of CD26, CD39, and CD73 expression; their ability to generate adenosine (ADO) from ATP and AMP; and whether the concentrations of ADO that they generate induce an immunomodulatory effect on T lymphocytes. BM-MSCs were included as the gold standard. Our results show that DT-MSCs present similar characteristics among the different sources analyzed in terms of the properties evaluated; however, interestingly, they express more CD39 than BM-MSCs; therefore, they generate more ADO from ATP. In contrast to those produced by BM-MSCs, the concentrations of ADO produced by DT-MSCs from ATP inhibited the proliferation of CD3+ T cells and promoted the generation of CD4+CD25+FoxP3+CD39+CD73+ Tregs and Th17+CD39+ lymphocytes. Our data suggest that DT-MSCs utilize the adenosinergic pathway as an immunomodulatory mechanism and that this mechanism is more efficient than that of BM-MSCs.

Socioeconomic determinants of small and medium-sized dairy farms in the Ecuador-Colombia border area.

The socioeconomic factors influencing small-scale dairy producers in the border area between Ecuador and Colombia were meticulously identified. Employing a non-experimental design, the study leveraged multivariate statistical analysis to discern key determinants. Data processing was executed using the statistical software SPSS v27, facilitating comprehensive analysis. A random survey was administered to 532 small and medium-scale dairy producers in the Carchi province of Ecuador, employing a structured questionnaire supplemented with a Likert scale for nuanced insights. Based on 35 original variables, seven determining factors were identified in dairy farms: political representation, adequate housing, equipment, innovation, empathy, profitability, social welfare, which combined explain 60.95% of the system's variability. Such factors affect production, the level of household income, as well as their effect on the standard of living of households. Three groups were formed, the first with a low perception of economic development (Traditionalists 33.3%); the second with a better expectation of economic development (Modernizers 27.6%); and the third, identified with greater economic development (Innovators 10.3%). Each group presents cases with a low to high standard of living perspective. The groups have peculiarities in terms of their performance that can be applied to the entire population. A significant relation was established between socioeconomic factors and standard of living.

Gut Microbiota and DTI Microstructural Brain Alterations in Rodents Due to Morphine Self-Administration.

The opioid epidemic is an evolving health crisis in need of interventions that target all domains of maladaptive changes due to chronic use and abuse. Opioids are known for their effects on the opioid and dopaminergic systems, in addition to neurocircuitry changes that mediate changes in behavior; however, new research lines are looking at complementary changes in the brain and gut. The gut-brain axis (GBA) is a bidirectional signaling process that permits feedback between the brain and gut and is altered in subjects with opioid use disorders. In this work, we determine longitudinal, non-invasive, and in-vivo complementary changes in the brain and gut in rodents trained to self-administer morphine for two weeks using MRI and 16S rDNA analysis of fecal matter. We assess the changes occurring during both an acute phase (early in the self-administration process, after two days of self-administration) and a chronic phase (late in the self-administration process, after two weeks of self-administration), with all measurements benchmarked against baseline (naïve, non-drug state). Rats were surgically implanted with an intravenous jugular catheter for self-administration of morphine. Rats were allowed to choose between an active lever, which delivers a single infusion of morphine (0.4 mg/kg/infusion), or an inactive lever, which had no consequence upon pressing. Animals were scanned in a 7T MRI scanner three times (baseline, acute, and chronic), and before scanning, fecal matter was collected from each rat. After the last scan session, a subset of animals was euthanized, and brains were preserved for immunohistochemistry analysis. We found early changes in gut microbiota diversity and specific abundance as early as the acute phase that persisted into the chronic phase. In MRI, we identified alterations in diffusivity indices both within subjects and between groups, showing a main effect in the striatum, thalamus, and somatosensory cortex. Finally, immunohistochemistry analyses revealed increased neuroinflammatory markers in the thalamus of rats exposed to morphine. Overall, we demonstrate that morphine self-administration shapes the brain and gut microbiota. In conclusion, gut changes precede the anatomical effects observed in MRI features, with neuroinflammation emerging as a crucial link mediating communication between the gut and the brain. This highlights neuroinflammation as a potential target in addressing the impacts of opioid use.

Association between personality traits, eating behaviors, and the genetic polymorphisms FTO-rs9939609 and MAO-A 30 bp u-VNTR with obesity in Mexican Mayan children.

Introduction: Genetic variants that control dopamine have been associated with obesity in children through loss of control of satiety and impulses, the manifestation of addictive eating behaviors, and specific personality traits. The variants include FTO-rs9939609 and the MAO-A 30 pb u-VNTR low-transcription alleles (LTA). Objective: To evaluate the genetic association of FTO-rs9939609 and the MAO-A LTA, along with personality traits and eating behavior with obesity in Mayan children from Mexico. Methods: We cross-sectionally evaluated 186 children (70 with obesity and 116 with normal weight) 6-12 years old from Yucatan, Mexico. Nutritional status was defined with body mass index (BMI) percentiles. Personality traits were evaluated with the Conners and TMCQ tests; eating behavior was evaluated with the CEBQ test. Genotyping with real-time PCR and TaqMan probes was used for FTO-rs9939609, whereas PCR amplification was used for MAO-A u-VNTR. Results: High-intensity pleasure (p = 0.013) and moderate appetite (p = 0.032) differed according to nutritional status. Heterozygous FTO-rs9939609 T/A children showed higher mean scores of low-intensity pleasure (p = 0.002) and moderate appetite (p = 0.027) than homozygous T/T. Hemizygous boys having MAO-A LTA showed significantly higher mean scores of anxiety (p = 0.001) and impulsivity (p = 0.008). In multivariate models, only LTA alleles of MAO-A explained obesity in boys (OR = 4.44; 95% CI = 1.18-16.63). Conclusion: In the present study, MAO-A u-VNTR alleles were associated with obesity in multivariate models only in boys. These alleles might also have a role in personality traits such as anxiety and impulsivity, which secondly contribute to developing obesity in Mayan boys.

Pharmacophore Identification and Structure-Activity Relationship Analysis of a Series of Substituted Azaindoles as Inhibitors of Trypanosoma brucei.

Human African trypanosomiasis is among the World Health Organization's designated neglected tropical diseases. Repurposing strategies are often employed in academic drug discovery programs due to financial limitations, and in this instance, we used human kinase inhibitor chemotypes to identify substituted 4-aminoazaindoles, exemplified by 1. Structure-activity and structure-property relationship analysis, informed by cheminformatics, identified 4s as a potent inhibitor of Trypanosoma brucei growth. While 4s appeared to be fast acting and cidal in the in vitro assays, it failed to cure a murine model of infection. Preliminary efforts to identify the potential mechanism of action of the series pointed to arginine kinase, though, as we demonstrate, this does not appear to be the sole target of our compounds. This comprehensive approach to drug discovery, encompassing cheminformatics, structure-potency and structure-property analysis, and pharmacophore identification, highlights our multipronged efforts to identify novel lead compounds for this deadly disease.

Lipase activity of recombinant KmYJR107Wp and KmLIP3p enzymes expressed in Saccharomyces cerevisiae BY4742 from Kluyveromyces marxianus L2029.

Lipases are used in many food, energy, and pharmaceutical processes. Thus, new systems have been sought to synthesize alternative lipases with potential biotechnological applications. Kluyveromyces marxianus is a yeast with recognized lipase activity; at least ten putative lipases/esterases in its genome have been detected, and two of them possess a signal peptide for extracellular secretion. The study of extracellular lipases becomes more relevant since they usually have higher activity rates than intracellular lipases and simpler purification mechanisms. For these reasons, this study aimed to characterize the production and lipase activity of the putative extracellular lipases of the K. marxianus L-2029 strain, encoded in the genes LIP3 and YJR107W. Both genes were heterologously expressed in Saccharomyces cerevisiae BY4742 (yeast strain without extracellular lipase activity) using a pYES2.1/V5-His-TOPO® plasmid. Herein, we show evidence that the strain transformed with the LIP3 gene did not show lipase activity during flask galactose induction. On the other hand, the strain transformed with the YJR107W gene showed a specific activity of 0.397 U/mg, with an optimum temperature of 37 °C and pH 6. For maximum cell production, glucose and yeast extract concentrations were evaluated by a 22 factorial design, followed by the validation of the best concentrations predicted by a statistical model; a 22 factorial design was also carried out to evaluate the concentration of the inducer galactose on the transformed strains, and the intracellular and extracellular lipase specific activities were quantified. Finally, the biomass and lipase production were determined for each strain, which was grown in a stirred tank bioreactor with a working volume of 1.5 L. The specific activities of the transformed strains obtained in the bioreactor were 1.36 U/mg for the LIP3 transformant and 1.25 U/mg for the YJR107W transformant, respectively.

[Bioethical issues of Covid-19 in Spain. A systematic review]. / Cuestiones bioéticas de la pandemia Covid-19 en España. Revisión sistemática.

During the COVID-19 pandemic, bioethical concerns were raised and there was even a ″resurgence of bioethics. ″ In this work, we review the scientific articles published by Spanish authors in relation to bioethical issues in the three years following the declaration of the pandemic. Seventy publications have been selected. Of all of them, the topic that lent itself to the most debate was that of prioritization in the use of health resources. A consensus was reached that ruled out that age could be considered as a sole exclusion criterion in healthcare or in a possible admission to the ICU. And the importance of taking special care of the most vulnerable and adapting care to the conditions of each patient without excluding anyone was recalled. Other relevant topics were the contrast between autonomy and the common good, the immune passport, vaccination, rigor in research and the publication of results, the professionalism of health personnel, misinformation, care for nursing homes, telemedicine, and the importance of the exercise of virtues. After the experience of both vulnerability and the need to exercise solidarity, many works raise the desire and the possibility of being able to overcome the pandemic being better.

Differential impacts of furfural and acetic acid on the bioenergetics and fermentation performance of Scheffersomyces stipitis.

Lignocellulosic material is a leading carbon source for economically viable biotechnological processes; however, compounds such furfural and acetic acid exhibit toxicity to yeasts. Nonetheless, research about the molecular mechanism of furfural and acetic acid toxicity is still scarce in yeasts like Scheffersomyces stipitis. Thus, this study aims to elucidate the impact of furfural and acetic acid on S. stipitis regarding bioenergetic and fermentation parameters. Here, we provide evidence that furfural and acetic acid induce a delay in cell growth and extend the lag phase. The mitochondrial membrane potential decreased in all treatments with no significant differences between inhibitors or concentrations. Interestingly, reactive oxygen species increased when the inhibitor concentrations were from 0.1 to 0.3 % (v/v). The glycolytic flux was not significantly (p > 0.05) altered by acetic acid, but furfural caused different effects. Ethanol production decreased significantly (4.32 g·L-1 in furfural and 5.06 g·L-1 in acetic acid) compared to the control (26.3 g·L-1). In contrast, biomass levels were not significantly different in most treatments compared to the control. This study enhances our understanding of the effects of furfural and acetic acid at the mitochondrial level in a pentose-fermenting yeast like S. stipitis.

The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in type 2 diabetes patients (TROPHIES): resource use and costs of treatment in clinical practice in France, Germany, and Italy.

AIMS: To describe healthcare resource utilization (HCRU) and associated costs after initiation of injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy by adult patients with type 2 diabetes (T2D) in the prospective, observational, 24-month TROPHIES study in France, Germany, and Italy. MATERIALS AND METHODS: HCRU data for cost calculations were collected by treating physicians during patient interviews at baseline and follow-up visits approximately 6, 12, 18, and 24 months after GLP-1 RA initiation with once-weekly dulaglutide or once-daily liraglutide. Costs were evaluated from the national healthcare system (third-party payer) perspective and updated to 2018 prices. RESULTS: In total, 2,005 patients were eligible for the HCRU analysis (1,014 dulaglutide; 991 liraglutide). Baseline patient characteristics were generally similar between treatment groups and countries. The largest proportions of patients using ≥2 oral glucose-lowering medications (GLMs) at baseline (42.9-43.4%) and month 24 (44.0-45.1%) and using another injectable GLM at month 24 (15.3-23.2%) were in France. Mean numbers of primary and secondary healthcare contacts during each assessment period were highest in France (range = 4.0-10.7) and Germany (range = 2.9-5.7), respectively. The greatest proportions (≥60%) of mean annualized costs per patient comprised medication costs. Mean annualized HCRU costs per patient varied by treatment cohort and country: the highest levels were in the liraglutide cohort in France (€909) and the dulaglutide cohort in Germany (€883). LIMITATIONS: Limitations included exclusion of patients using insulin at GLP-1 RA initiation and collection of HCRU data by physician, not via patient-completed diaries. CONCLUSIONS: Real-world HCRU and costs associated with the treatment of adults with T2D with two GLP-1 RAs in TROPHIES emphasize the need to avoid generalization with respect to HCRU and costs associated with a particular therapy when estimating the impact of a new treatment in a country-specific setting.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become frequent treatments of hyperglycemia in type-2 diabetes (T2D). Not all types of clinical study provide information about the cost of these treatments or the effects they might have on use of other medicines and equipment to control T2D or the need for visits to a doctor or nurse and different types of treatment in hospital. This study collected this information during the regular care of adults in France, Germany, or Italy who were prescribed either dulaglutide or liraglutide (both types of GLP-1 RAs) by their family doctor or a specialist in T2D. There were differences in costs and the need for other medicines and medical services between people using either dulaglutide or liraglutide and for people who were using the same GLP-1 RA in each of the three countries. The information from this study could be used to more accurately understand the overall costs and medical care needed when patients use dulaglutide or liraglutide in France, Germany, or Italy.

Medicinal Orchids of Mexico: A Review.

Some species of the Orchidaceae family are used in Mexican traditional medicine. However, there are no current and critical compilations of the medicinal uses and pharmacological effects of the members of the Orchidaceae family. This review provides a current, critical, and comprehensive analysis of the traditional medicinal uses, pharmacological reports, and active compounds isolated from Mexican orchids. A total of 62 Mexican orchids with medicinal potential have been recorded, of which 14 have scientific evidence. The remaining 48 plant species have ethnomedicinal information but have not been validated with scientific studies. These orchids are distributed in 14 states of the Mexican Republic, mainly in the southern region of Mexico. The most common pharmacological activities reported are anti-inflammatory, vasorelaxant, antinociceptive, antioxidant, spasmolytic, antihypertensive, and hallucinogenic activities. It is necessary to increase the number of pharmacological, phytochemical, and toxicological studies with medicinal orchids from Mexico because there are scientific studies on only 22.5% of these species. In further studies, it will be possible to evaluate the pharmacological effects of Mexican orchids in clinical trials. In addition, the mechanisms of action by which plant extracts and their active compounds exert medicinal effects remain to be studied. Plant extracts from orchids and their active compounds show promising antinociceptive and spasmolytic effects, respectively.

Abnormal open states patterns in the ATXN2 DNA sequence depends on the CAG repeats length.

Hereditary ataxias are one of the «anticipation diseases¼ types. Spinocerebral ataxia type 2 occurs when the number of CAG repeats in the coding region of the ATXN2 gene exceeds 34 or more. In healthy people, the CAG repeat region in the ATXN2 gene usually consists of 22-23 CAG trinucleotides. Mutations that increase the length of CAG repeats can cause severe neurodegenerative and neuromuscular disorders known as trinucleotide repeat expansion diseases. The mechanisms causing such diseases are associated with non-canonical configurations that can be formed in the CAG repeat region during replication, transcription or repair. This makes it relevant to study the zones of open states that arise in the region of CAG repeats under torque. The purpose of this work is to study, using mathematical modeling, zones of open states in the region of CAG repeats of the ATXN2 gene, caused by torque. It has been established that the torque effect on the 1st exon of the ATXN2 gene, in addition to the formation of open states in the promoter region, can lead to the formation of additional various sizes open states zones in the CAG repeats region. Moreover, the frequency of additional large zones genesis increases with increasing number of CAG repeats. The inverse of this frequency correlates with the dependence of the disease onset average age on the CAG repeats length. The obtained results will allow us to get closer to understanding the genetic mechanisms that cause trinucleotide repeat diseases.

Psychosocial risk and protective factors for youth problem behavior are associated with food addiction in the Generation Z.

Objective: Food Addiction (FA) and other well-known risk behavior as substance misuse tend to co-occur and may share similar risk and protective factors. The aim of this study was to assess the association between the diagnosis/severity of FA and psychosocial domains typically related to risk behavior syndrome in a large, nationally representative community sample of Generation Z underage Italian students. Method: The sample consisted of 8,755 students (3,623 from middle schools, 5,132 from high schools). A short version of the Yale Food Addiction Scale 2.0 was administered to evaluate FA. Risk and protective factors related to demographic, personality, behavior, and family variables were examined. Stepwise multivariate logistic and linear regressions were conducted. Results: The prevalence of FA was 30.8%. Female gender, social anxiety and depression symptoms, social withdrawal risk, Internet gaming disorder, social media addiction, current substance use, social challenge engagement and experienced doxing boosted the chance of FA diagnosis, whereas eating fruit and vegetables, playing competitive sports and an average sleep duration of 7-8 h per night reduced these odds. FA severity was significantly and positively associated with trait impulsiveness, social anxiety and depressive symptoms, risk of social withdrawal, recent substance use, social media, and gaming addiction, doxing suffered and risky social challenges participation. Negative associations between the severity of FA and fruit and vegetable diet habits were found. Conclusion: Our findings confirm that FA is widespread among Italian adolescents. The associations between the diagnosis and severity of FA and psychosocial risk factors for health, including, addictive and deviant behaviors related to digital misuse, suggest its belonging to the risk behavior constellation. Health promotion schemes based on a multicomponent strategy of intervention should consider the inclusion of FA and its psychosocial correlates.

Bacterioplankton taxa compete for iron along the early spring-summer transition in the Arctic Ocean.

Microbial assemblages under the sea ice of the Dease Strait, Canadian Arctic, were sequenced for metagenomes of a small size fraction (0.2-3 µm). The community from early March was typical for this season, with Alpha- and Gammaproteobacteria as the dominant taxa, followed by Thaumarchaeota and Bacteroidetes. Toward summer, Bacteroidetes, and particularly the genus Polaribacter, became increasingly dominant, followed by the Gammaproteobacteria. Analysis of genes responsible for microbial acquisition of iron showed an abundance of ABC transporters for divalent cations and ferrous iron. The most abundant transporters, however, were the outer membrane TonB-dependent transporters of iron-siderophore complexes. The abundance of iron acquisition genes suggested this element was essential for the microbial assemblage. Interestingly, Gammaproteobacteria were responsible for most of the siderophore synthesis genes. On the contrary, Bacteroidetes did not synthesize siderophores but accounted for most of the transporters, suggesting a role as cheaters in the competition for siderophores as public goods. This cheating ability of the Bacteroidetes may have contributed to their dominance in the summer.

First Bioprospecting Study of Skin Host-Defense Peptides in Odontophrynus americanus.

The adaptation of amphibians to diverse environments is closely related to the characteristics of their skin. The complex glandular system of frog skin plays a pivotal role in enabling these animals to thrive in both aquatic and terrestrial habitats and consists of crucial functions such as respiration and water balance as well as serving as a defensive barrier due to the secretion of bioactive compounds. We herein report the first investigation on the skin secretion of Odontophrynus americanus, as a potential source of bioactive peptides and also as an indicator of its evolutionary adaptations to changing environments. Americanin-1 was isolated and identified as a neutral peptide exhibiting moderate antibacterial activity against E. coli. Its amphipathic sequence including 19 amino acids and showing a propensity for α-helix structure is discussed. Comparisons of the histomorphology of the skin of O. americanus with other previously documented species within the same genus revealed distinctive features in the Patagonian specimen, differing from conspecifics from other Argentine provinces. The presence of the Eberth-Katschenko layer, a prevalence of iridophores, and the existence of glycoconjugates in its serous glands suggest that the integument is adapted to retain skin moisture. This adaptation is consistent with the prevailing aridity of its native habitat.

Impacto de ejercicios bilaterales y unilaterales en la potenciación aguda del salto horizontal en futbolistas profesionales / Impact of Bilateral and Unilateral Exercises on Acute Enhancement of Horizontal Jump Performance in Professional Soccer Player / Impacto dos Exercícios Bilaterais e Unilaterais no Aumento Agudo do Desempenho do Salto Horizontal em Jogadores Profissionais de Futebol

Resumen Objetivo: Analizar el efecto de una activación realizada a través de ejercicios de fuerza y pliometría ejecutados de forma bilateral o unilateral sobre el rendimiento en salto horizontal. Metodología: En el estudio participaron 15 futbolistas masculinos, altamente entrenados (edad, 24.7 ± 3.1 años; altura, 181.2 ± 4.7 cm; peso, 79.7 ± 3.4 kg) pertenecientes al mismo equipo, que competía en liga nacional. Su rutina de entrenamiento regular constaba de 4 sesiones y 1 partido competitivo por semana. Los participantes llevaron a cabo 1 protocolo control (CON) y 3 protocolos de activación, siguiendo un diseño contrabalanceado, basados en ejercicios específicos de fútbol (SIN), ejercicios de fuerza y pliometría ejecutados de forma bilateral (BIL) y unilateral (UNI). Después de cada protocolo los jugadores realizaron la prueba de salto horizontal (HZB). Resultados: Los resultados de la prueba ANOVA de medidas repetidas mostraron efectos positivos significativos sobre el HZB de los protocolos SIN (p<0.01; dif = 2.95(2.00)%), BIL (p<0.01; dif = 3.22(2.61) %); y UNI (p<0.01; dif = 6.80(3.40) %) con respecto a CON. Además, HZB fue, significativamente, mayor después del protocolo UNI que del SIN (p<0.01; dif = 3.74(2.62) %) y BIL (p<0.01; dif = 3.47(1.94) %). El análisis de la respuesta individual reflejó efectos positivos en HZB de los protocolos SIN, BIL y UNI respecto al CON, mientras que el 89 % de los jugadores tuvieron mejor rendimiento en HZB después de UNI que de BIL. Conclusiones: Una activación que incorpora estímulos de fuerza y pliometría ejecutados, de forma unilateral, tiene un efecto positivo mayor sobre la capacidad de salto horizontal, que una activación que involucra ejercicios generales, específicos de fútbol y de ejecución bilateral.

Abstract Objective: To analyze the effect of activation through bilateral or unilateral strength and plyometric exercises on horizontal jump performance. Methodology: The study involved 15 highly trained male soccer players (age, 24.7 ± 3.1 years; height, 181.2 ± 4.7 cm; weight, 79.7 ± 3.4 kg) from the same team competing in the national league. Their regular training routine consisted of 4 sessions and 1 competitive match per week. Participants performed 1 control protocol (CON) and 3 activation protocols following a counterbalanced design based on specific soccer exercises (SIN), bilateral (BIL), and unilateral (UNI) strength and plyometric exercises. After each protocol, players underwent the horizontal jump test (HZB). Results: The repeated measures ANOVA revealed significant positive effects on HZB for the SIN (p<0.01; diff = 2.95(2.00) %), BIL (p<0.01; diff = 3.22(2.61) %), and UNI (p<0.01; diff = 6.80(3.40) %) protocols compared to CON. Furthermore, HZB was significantly higher after the UNI protocol than after SIN (p<0.01; diff = 3.74(2.62) %) and BIL (p<0.01; diff = 3.47(1.94) %). Individual response analysis reflected positive effects on HZB for SIN, BIL, and UNI compared to CON, while 89 % of players showed better HZB performance after UNI than after BIL. Conclusions: Activation incorporating unilateral strength and plyometric stimuli has a greater positive effect on horizontal jump capacity than activation involving general, soccer-specific, and bilateral exercises.

Resumo Objetivo: Analisar o efeito da ativação por meio de exercícios de força e pliométricos bilaterais ou unilaterais no desempenho do salto horizontal. Metodologia: O estudo envolveu 15 jogadores de futebol masculinos altamente treinados (idade, 24.7 ± 3.1 anos; altura, 181.2 ± 4.7 cm; peso, 79.7 ± 3.4 kg) da mesma equipe competindo na liga nacional. Sua rotina de treinamento regular consistia em 4 sessões e 1 jogo competitivo por semana. Os participantes realizaram 1 protocolo de controle (CON) e 3 protocolos de ativação seguindo um desenho contrabalanceado com base em exercícios específicos de futebol (SIN), exercícios de força e pliométricos bilaterais (BIL) e unilaterais (UNI). Após cada protocolo, os jogadores foram submetidos ao teste de salto horizontal (HZB). Resultados: A ANOVA de medidas repetidas revelou efeitos positivos significativos no HZB para os protocolos SIN (p<0.01; diff = 2.95(2.00) %), BIL (p<0.01; diff = 3.22(2.61) %) e UNI (p<0.01; diff = 6.80(3.40) %) em comparação com CON. Além disso, o HZB foi significativamente maior após o protocolo UNI do que após SIN (p<0.01; diff = 3.74(2.62) %) e BIL (p<0.01; diff = 3.47(1.94) %). A análise de resposta individual refletiu efeitos positivos no HZB para SIN, BIL e UNI em comparação com CON, enquanto 89 % dos jogadores mostraram melhor desempenho de HZB após UNI do que após BIL. Conclusões: A ativação incorporando estímulos de força e pliométricos unilaterais tem um efeito positivo maior na capacidade de salto horizontal do que a ativação envolvendo exercícios gerais, específicos do futebol e bilaterais.

Morphofunctional Assessment beyond Malnutrition: Fat Mass Assessment in Adult Patients with Phenylketonuria-Systematic Review.

Morphofunctional assessment was developed to evaluate disease-related malnutrition. However, it can also be used to assess cardiometabolic risk, as excess adiposity increases this risk. Phenylketonuria (PKU) is the most prevalent inherited metabolic disease among adults, and obesity in PKU has recently gained interest, although fat mass correlates better with cardiometabolic risk than body mass index. In this systematic review, the objective was to assess whether adult patients with PKU have higher fat mass than healthy controls. Studies of adult PKU patients undergoing dietary treatment in a metabolic clinic reporting fat mass were included. The PubMed and EMBASE databases were searched. Relevance of articles, data collection, and risk of bias were evaluated by two independent reviewers. Ten articles were evaluated, six with a control group, including 310 subjects with PKU, 62 with mild hyperphenylalaninemia, and 157 controls. One study reported a significant and four a tendency towards an increased fat mass in all patients or only females with PKU. Limitations included not having a healthy control group, not reporting sex-specific results and using different techniques to assess fat mass. Evaluation of fat mass should be included in the morphofunctional assessment of cardiometabolic risk in adult patients with PKU.

Paraneoplastic leukocytosis secondary to carcinosarcoma: a report of two cases and literature review.

BACKGROUND: Neutrophilia is an increase in the number of neutrophils over 7.5×103/µL. An increase in leukocytes over 50×103/µL is called a leukemoid reaction; and when it is associated with a solid tumor, it is considered a paraneoplastic syndrome called paraneoplastic leukemoid reaction (PLR). It is a very rare clinical condition and it is very unusual for it to be associated with carcinosarcoma. We present two cases of a leukemoid reaction observed in the Medical Oncology Department of the University Hospital of Salamanca between May and September 2023. The main objectives of our article are to describe the unusual appearance of paraneoplastic leukocytosis at the diagnosis of carcinosarcoma carcinosarcoma, explain in a detailed way its diagnostic procedure and to show the poor prognosis to which it is associated. CASE DESCRIPTION: In our presentation, we describe two similar cases: first of all, a 60-year-old woman without relevant medical history. She was referred by her primary physician to the Department of Internal Medicine in August 2023 with asthenia, lumbar pain, and weight loss of 12 kg of 3 months of evolution. The physical examination revealed a palpable hypogastric mass. An abdominal, pelvic, and thoracic computed tomography (CT) scan revealed a heterogenous solid mass with necrotic areas originating in the uterus. The anatomopathological diagnosis was carcinosarcoma. The patient showed a progressive worsening in her renal function associated with hyperviscosity secondary to hyperleukocytosis caused by 170×103/µL neutrophils. In the second case we describe the diagnosis of a PLR secondary to a kidney carcinosarcoma. When the patient started chemotherapy, he presented 55.08×103/µL leukocytes, 53.16×103/µL neutrophils. Eight days after receiving chemotherapy, the patient was admitted as an emergency with oligoanuria and decreased consciousness. He presented creatinine 6.25 mg/dL, phosphate 12.4 mg/dL, leukocytes 1.05×103/µL, and neutrophils 0.71×103/µL. The clinical diagnosis was acute exacerbation of multifactorial mixed (renal and prerenal) chronic kidney disease associated with tumor lysis syndrome and grade 3 neutropenia. The patient presented a poor evolution, dying after 2 months. CONCLUSIONS: PLR is a severe paraneoplastic syndrome associated with different types of solid tumors. Its appearance at the time of diagnosis of a tumor implies a poor vital prognosis.

GNN Codon Adjacency Tunes Protein Translation.

The central dogma treats the ribosome as a molecular machine that reads one mRNA codon at a time as it adds each amino acid to its growing peptide chain. However, this and previous studies suggest that ribosomes actually perceive pairs of adjacent codons as they take three-nucleotide steps along the mRNA. We examined GNN codons, which we find are surprisingly overrepresented in eukaryote protein-coding open reading frames (ORFs), especially immediately after NNU codons. Ribosome profiling experiments in yeast revealed that ribosomes with NNU at their aminoacyl (A) site have particularly elevated densities when NNU is immediately followed (3') by a GNN codon, indicating slower mRNA threading of the NNU codon from the ribosome's A to peptidyl (P) sites. Moreover, if the assessment was limited to ribosomes that have only recently arrived at the next codon, by examining 21-nucleotide ribosome footprints (21-nt RFPs), elevated densities were observed for multiple codon classes when followed by GNN. This striking translation slowdown at adjacent 5'-NNN GNN codon pairs is likely mediated, in part, by the ribosome's CAR surface, which acts as an extension of the A-site tRNA anticodon during ribosome translocation and interacts through hydrogen bonding and pi stacking with the GNN codon. The functional consequences of 5'-NNN GNN codon adjacency are expected to influence the evolution of protein coding sequences.

Knowledge and practices regarding prostate cancer screening in Spanish men: The importance of personal and clinical characteristics (PROSHADE study).

INTRODUCTION: Patients' decisions on prostate cancer (PCa) opportunistic screening may vary. This study aimed to assess how demographic and health-related characteristics may influence knowledge and decisions regarding PCa screening. METHODS: A cross-sectional survey was conducted among men aged over 40, randomly sampled from the Spanish population, 2022. The survey underwent development and content validation using a modified Delphi method and was administered via telephone. Binomial logistic regression was used to explore the relationship between respondents' characteristics and participants' knowledge and practices concerning PCa and the PSA test. RESULTS: Out of 1,334 men, 1,067 (80%) respondents were interviewed with a mean age of 58.6 years (sd 11.9). Most had secondary or university studies (787, 73.8%) and 61 (5.7%) self-reported their health status as bad or very bad. Most of the respondents (1,018, 95.4%) had knowledge regarding PCa with nearly 70% expressed significant concern about its potential development (720, 70.8%), particularly among those under 64 years (p = 0.001). Out of 847 respondents, 573 (67.7%) reported that they have knowledge regarding the PSA test: 374 (65.4%) reported receiving information from a clinicians, 324 (86.6%) information about the benefits of the test and 189 (49,5%) about its risks, with differences based on educational background. In a multivariable analysis (adjusted for age, educational level and previous prostate problems), respondents with higher levels of education were more likely to have higher knowledge regarding the PSA test (OR 1.75, 95%CI 1.24-2.50, p<0.001). CONCLUSIONS: Although most of the patients reported to have knowledge regarding PCa, half of the interviewed men reported knowledge about PSA test. Differences in knowledge prostate cancer screening and undesirable consequences highlight the need to develop and provide tailored information for patients.