SLCO1B1 and ABCG2 genotype-informed phenotypes are related to variation in ramipril exposure.

Ramipril is an angiotensin-converting enzyme inhibitor used for hypertension and heart failure management. To date, scarce literature is available on pharmacogenetic associations affecting ramipril. The goal of this study was to investigate the effect of 120 genetic variants in 34 pharmacogenes (i.e., genes encoding for enzymes like CYPs or UGTs and transporters like ABC or SLC) on ramipril pharmacokinetic variability and adverse drug reaction (ADR) incidence. Twenty-nine healthy volunteers who had participated in a single-dose bioequivalence clinical trial of two formulations of ramipril were recruited. A univariate and multivariate analysis searching for associations between genetic variants and ramipril pharmacokinetics was performed. SLCO1B1 and ABCG2 genotype-informed phenotypes strongly predicted ramipril exposure. Volunteers with the SLCO1B1 decreased function (DF) phenotype presented around 1.7-fold higher dose/weight-corrected area under the curve (AUC/DW) than volunteers with the normal function (NF) phenotype (univariate p-value [puv] < 0.001, multivariate p-value [pmv] < 0.001, ß = 0.533, R2 = 0.648). Similarly, volunteers with ABCG2 DF + poor function (PF) phenotypes presented around 1.6-fold higher AUC/DW than those with the NF phenotype (puv = 0.011, pmv < 0.001, ß = 0.259, R2 = 0.648). Our results suggest that SLCO1B1 and ABCG2 are important transporters to ramipril pharmacokinetics, and their genetic variation strongly alters its pharmacokinetics. Further studies are required to confirm these associations and their clinical relevance.

Demographic evolution and natural increase projection of the Yanomami indigenous population in Brazil.

The Yanomami population, residing in Brazil's largest indigenous reserve in the Amazon Rainforest, face significant health challenges exacerbated by external threats such as infectious diseases, malnutrition, and mercury contamination from illegal mining. These issues, coupled with inadequate healthcare provision, have led to an alarming increase in mortality rates and potentially threaten the long-term survival of the Yanomami community. This ecological study utilized demographic data from the Special Secretariat of Indigenous Health to explore the demographic evolution and natural increase of the Yanomami Indigenous population in Brazil from 2003 to 2022. Employing population pyramids, crude rates of natural increase, the Mann-Kendall test for trend analysis, and linear regression modeling, the study analyzed vital statistics to forecast demographic trends, with analysis conducted using the R statistical software. Our findings showed a substantial growth of the Yanomami population, yet with a decreasing natural increase rate (τ = -0.33; p = 0.047), suggesting a shift toward population stagnation or decline within the next century. These results call for urgent, coordinated actions to address the complex demographic trends and health challenges faced by Yanomami Indigenous people, ensuring their demographic sustainability and the preservation of their traditional ways of life amidst ongoing environmental and health crises.

Clinical and radiographic outcomes of a two-piece ceramic implant: one year results from a prospective clinical trial.

OBJECTIVE: To describe the clinical and radiographic performance and survival rate of a new two-piece ceramic implant system after at least 12 months of follow-up. MATERIALS AND METHODS: Sixty-five implants were placed and followed up for at least 12 months (12.3 ± 1.5), in 50 patients. The implants were installed both in fresh extraction sockets and in healed sites and received provisional restoration when the clinical insertion torque was greater than 35Ncm. The primary results describe the survival rate of these implants. Clinical performance was evaluated through the evaluation of the Pink Esthetic Score (PES) and the degree of satisfaction of the patients. Bone loss was measured through radiographic measurements of the marginal bone loss in the mesial (MBLM) and distal (MBLD) sites. RESULTS: The survival rate was 98.5%. The average MBLM was 0.24 mm (± 0.53) and the MBLD was 0.27 mm (± 0.57). A statistical difference was observed only when comparing immediate implants with delayed ones (MBLM - p = 0.046 and MBLD - p = 0.028) and when they received immediate provisionalization or not (MBLM - p = 0.009 and MBLD - p = 0.040). The PES before the intervention (T0) was 13.4 (± 0.8) and the PES at T2 (12-month follow-up) was 12.9 (± 1.5) (p = 1.14). CONCLUSION: The new two-piece ceramic implant used in the present study showed predictable and reliable results, similar to those found with titanium implants after one year of follow-up. CLINICAL RELEVANCE: These implants can be used as an alternative to titanium implants in terms of the marginal bone loss and the degree of patient satisfaction.

Genetic variation in UGT1A1 is not associated with altered liver biochemical parameters in healthy volunteers participating in bioequivalence trials.

Introduction: Bioequivalence clinical trials are conducted in healthy volunteers whose blood tests should be within normal limits; individuals with Gilbert syndrome (GS) are excluded from these studies on suspicion of any liver disease, even if the change is clinically insignificant. GS is a benign genetic disorder characterized by elevated bilirubin levels, the primary cause of which is the presence of polymorphisms in UGT1A1 gene. In this work, subjects with UGT1A1 intermediate (IM) or poor (PM) metabolizer genotype-informed phenotypes were investigated to determine whether they have a higher incidence of liver disease or other biochemical parameters. Methods: The study population comprised 773 healthy volunteers who underwent biochemical analysis at baseline and at the end of the study which were genotyped for UGT1A1*80 (rs887829), as an indicator of UGT1A1*80+*28 (rs887829 and rs3064744), and UGT1A1*6 (rs4148323). Results: Bilirubin levels were higher in subjects IMs and PMs compared to normal metabolizers (NMs). Decreased uric acid levels was observed in PMs compared to NMs. No associations were observed in liver enzyme levels according to UGT1A1 phenotype. Discussion: Considering that there is no hepatic toxicity in subjects with UGT1A1 IM or PM phenotype, who are more likely to develop GS, this study suggests that they could be included in bioequivalence clinical trials as their biochemical parameters are not affected outside normal ranges.

Tumor-induced osteomalacia: A systematic literature review.

Introduction: Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast growth factor 23 (FGF23) by a tumor. Material and methods: We conducted a systematic review to identify all case reports of TIO, focusing on those associated with mesenchymal tumors. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) consensus, and we included patients with a diagnosis of TIO and histological confirmation of phosphaturic mesenchymal tumors or resolution of the condition after treatment of the tumor. Bibliographical searches were carried out until December 2023 in the Cochrane Library, Medline and Embase, as well as congress abstracts online. Results: We identified 769 articles with 1979 cases reported. Most patients were adults, with a higher incidence on men. Disease duration before diagnosis is a mean of 4.8 years. Most tumors were histologically classified as PMT. Lower limbs were the predominant location. Hypophosphatemia was present in 99.8 % of patients. The FGF23 was elevated at diagnosis in 95.5 %. Resection of the tumor was the treatment of choice in most of patients. After resection, there was a clinical improvement in 97.6 % of cases, and serum phosphorus and FGF23 levels returned to normal ranges in 91.5 % and 81.4 % of the patients, respectively. Conclusion: TIO is usually misdiagnosed with rheumatological or musculoskeletal disorders. The diagnosis should be suspected in patients with hypophosphatemic osteomalacia, and the measurement of serum FGF23 can be useful for diagnosis and management.

Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver.

Olanzapine (OLA) is a highly obesogenic second-generation antipsychotic (SGA). Recently we demonstrated that, contrarily to OLA oral treatment, intraperitoneal (i.p.) administration resulted in weight loss and absence of hepatic steatosis in wild-type (WT) and protein tyrosine phosphatase 1B (PTP1B)-deficient (KO) male mice. This protection relied on two central-peripheral axes connecting hypothalamic AMPK with brown/inguinal white adipose tissue (BAT/iWAT) uncoupling protein-1 (UCP-1) and hypothalamic JNK with hepatic fatty acid synthase (FAS). Herein, we addressed OLA i.p. treatment effects in WT and PTP1B-KO female mice. Contrarily to our previous results in WT females receiving OLA orally, the i.p. treatment did not induce weight gain or hyperphagia. Molecularly, in females OLA failed to diminish hypothalamic phospho-AMPK or elevate BAT UCP-1 and energy expenditure (EE) despite the preservation of iWAT browning. Conversely, OLA i.p. treatment in ovariectomized mice reduced hypothalamic phospho-AMPK, increased BAT/iWAT UCP-1 and EE, and induced weight loss as occurred in males. Pretreatment of hypothalamic neurons with 17ß-estradiol (E2) abolished OLA effects on AMPK. Moreover, neither hypothalamic JNK activation nor hepatic FAS upregulation were found in WT and PTP1B-KO females receiving OLA via i.p. Importantly, this axis was reestablished upon ovariectomy. In this line, E2 prevented OLA-induced phospho-JNK in hypothalamic neurons. These results support the role of estrogens in sex-related dimorphism in OLA treatment. This study evidenced the benefit of OLA i.p. administration in preventing its obesogenic effects in female mice that could offer clinical value.

Inspiratory Muscle Training in Phase 1 and 2 Postoperative Cardiac Rehabilitation Following Coronary Artery Bypass Graft Surgery: Systematic Review with Meta-Analysis.

OBJECTIVE: This study aimed to determine the effects of inspiratory muscle training (IMT) on exercise capacity, respiratory muscle strength, length of hospital stay (LOS), and quality of life (QOL) following coronary artery bypass graft surgery. METHODS: The search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Cochrane Handbook and included the databases MEDLINE, EMBASE, CINAHL, Scopus, and CENTRAL. The review included randomized controlled trials utilizing IMT during phase 1 or 2 postoperative cardiac rehabilitation (PoCR) versus alternative treatment (active or passive control) in patients following coronary artery bypass graft surgery. RESULTS: Fifteen studies were included (11 phase 1 studies, 4 phase 2 studies) with no reported adverse events. In phase 1 PoCR, IMT reduced the LOS (-1.02 days; 95% CI = -2.00 to -0.03) and increased exercise capacity (6-minute walk distance [6MWD]).(+75.46 m; 95% CI = 52.34 to 98.57), and maximal inspiratory pressure (MIP) (10.46 cm H2O; 95% CI = 2.83 to 18.10), but had no effect on maximal expiratory pressure. In phase 2 PoCR, IMT increased 6MWD (45.84 m; 95% CI = 10.89 to 80.80), MIP (-23.19 cm H2O; 95% CI = -31.31 to -15), maximal expiratory pressure (20.18 cm H2O; 95% CI = 9.60 to 30.76), and QOL (-11.17; 95% CI = -17.98 to -4.36), with no effect on peak oxygen uptake. There was a high risk of bias for MIP (75% of the phase 1 studies) and 6MWT (1 of 4 phase 2 studies). The quality of the evidence ranged from very low to moderate. CONCLUSIONS: IMT significantly improves exercise capacity, respiratory muscle strength, LOS, and QOL in phase 1 and 2 PoCR. IMPACT: IMT may benefit patients during phase 1 and 2 of PoCR, considering the safety, low cost, and potential benefits.

Impact of STAT6 Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis.

Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their association with disease features. Peak eosinophil count (PEC) and the endoscopic reference score (EREFS) were determined before and after an eight-week PPI course in 28 EoE patients. The impact of the signal transducer and activator of transcription 6 (STAT6), CYP2C19, CYP3A4, CYP3A5, and ABCB1 genetic variations on baseline PEC and EREFS, their reduction and histological response, and on EoE symptoms and comorbidities was analyzed. PEC reduction was higher in omeprazole-treated patients (92.5%) compared to other PPIs (57.9%, p = 0.003). STAT6 rs12368672 (g.18453G>C) G/G genotype showed higher baseline PEC values compared to G/C and C/C genotypes (83.2 vs. 52.9, p = 0.027). EREFS reduction in STAT6 rs12368672 G/G and G/C genotypes was higher than in the C/C genotype (36.7% vs. -75.0% p = 0.011). However, significance was lost after Bonferroni correction. Heartburn incidence was higher in STAT6 rs167769 (g.27148G>A) G/G patients compared to G/A (54.55% vs. 11.77%, p = 0.030). STAT6 rs12368672G>C and rs167769G>A variants might have a relevant impact on EoE status and PPI response. Further research is warranted to clarify the clinical relevance of these variants.

Spatiotemporal transmission of SARS-CoV-2 lineages during 2020-2021 in Pernambuco-Brazil.

SARS-CoV-2 virus emerged as a new threat to humans and spread around the world, leaving a large death toll. As of January 2023, Brazil is among the countries with the highest number of registered deaths. Nonpharmacological and pharmacological interventions have been heterogeneously implemented in the country, which, associated with large socioeconomic differences between the country regions, has led to distinct virus spread dynamics. Here, we investigate the spatiotemporal dispersion of SARS-CoV-2 lineages in the Pernambuco state (Northeast Brazil) throughout the distinct epidemiological scenarios that unfolded in the first 2 years of the pandemic. We generated a total of 1,389 new SARS-CoV-2 genomes from June 2020 to August 2021. This sampling captured the arrival, communitary transmission, and the circulation of the B1.1, B.1.1.28, and B.1.1.33 lineages; the emergence of the former variant of interest P.2; and the emergence and fast replacement of all previous variants by the more transmissible variant of concern P.1 (Gamma). Based on the incidence and lineage spread pattern, we observed an East-to-West to inner state pattern of transmission, which is in agreement with the transmission of more populous metropolitan areas to medium- and small-size country-side cities in the state. Such transmission patterns may be partially explained by the main routes of traffic across municipalities in the state. Our results highlight that the fine-grained intrastate analysis of lineages and incidence spread can provide actionable insights for planning future nonpharmacological intervention for air-borne transmissible human pathogens.IMPORTANCEDuring the COVID-19 pandemic, Brazil was one of the most affected countries, mainly due its continental-size, socioeconomic differences among regions, and heterogeneous implementation of intervention methods. In order to investigate SARS-CoV-2 dynamics in the state of Pernambuco, we conducted a spatiotemporal dispersion study, covering the period from June 2020 to August 2021, to comprehend the dynamics of viral transmission during the first 2 years of the pandemic. Throughout this study, we were able to track three significant epidemiological waves of transmission caused by B1.1, B.1.1.28, B.1.1.33, P.2, and P.1 lineages. These analyses provided valuable insights into the evolution of the epidemiological landscape, contributing to a deeper understanding of the dynamics of virus transmission during the early years of the pandemic in the state of Pernambuco.

Genetic Algorithm for Feature Selection Applied to Financial Time Series Monotonicity Prediction: Experimental Cases in Cryptocurrencies and Brazilian Assets.

Since financial assets on stock exchanges were created, investors have sought to predict their future values. Currently, cryptocurrencies are also seen as assets. Machine learning is increasingly adopted to assist and automate investments. The main objective of this paper is to make daily predictions about the movement direction of financial time series through classification models, financial time series preprocessing methods, and feature selection with genetic algorithms. The target time series are Bitcoin, Ibovespa, and Vale. The methodology of this paper includes the following steps: collecting time series of financial assets; data preprocessing; feature selection with genetic algorithms; and the training and testing of machine learning models. The results were obtained by evaluating the models with the area under the ROC curve metric. For the best prediction models for Bitcoin, Ibovespa, and Vale, values of 0.61, 0.62, and 0.58 were obtained, respectively. In conclusion, the feature selection allowed the improvement of performance in most models, and the input series in the form of percentage variation obtained a good performance, although it was composed of fewer attributes in relation to the other sets tested.

The first Neolithic boats in the Mediterranean: The settlement of La Marmotta (Anguillara Sabazia, Lazio, Italy).

Navigation in the Mediterranean in the Neolithic is studied here through the boats that were used, the degree of technical specialisation in their construction and, above all, their chronology. After a brief explanation of the exceptional site of La Marmotta, the characteristics and chronology of the five canoes found at the settlement and one of the nautical objects linked to Canoe 1 are discussed. This will allow a reflection on the capability of Neolithic societies for navigation owing to their high technological level. This technology was an essential part in the success of their expansion, bearing in mind that in a few millennia they occupied the whole Mediterranean from Cyprus to the Atlantic seaboard of the Iberian Peninsula.

Catalase and Uric Acid Prevent Morphological Damage to the Sperm Flagella of Colossoma macropomum During 96 Hours at Low Storage Temperatures.

Oxidative stress is one of the main causes of loss of sperm function during chilled storage. The aim of the current study was to evaluate the effects of a fructose-based extender, which was supplemented with catalase or uric acid, on the motility, viability, morphological integrity, and lipid peroxidation (LPO) of Colossoma macropomum spermatozoa. Sperm was diluted in extenders containing catalase (0; 0.1; 0.8; and 1.5 kU/L) or uric acid (0; 0.25; 0.5; and 1.0 mmol/L) and then stored at 4.3 ± 0.6°C for 96 hours. The chilling storage time had more significant and pronounced effects on practically all the measured sperm quality parameters than the different concentrations of both antioxidants added to the extenders. This was true for sperm motility, motility duration, sperm viability, and the percentage of normal spermatozoa. In fact, for all these parameters, values were higher in the extenders supplemented with catalase or uric acid, than those not supplemented with these antioxidants, especially after 96 hours. The LPO process showed an antioxidant-dependent response. In catalase-supplemented extenders thiobarbituric acid reactive substance (TBARS) levels increased gradually and significantly with time, but remained stable during the 96 hours of chilled storage in all samples in which uric acid was added. Despite this, TBARS levels were lower in the extenders supplemented with both catalase and uric acid than in those not having these antioxidants. Inverse correlations were found between sperm motility and the damage in sperm flagella. Our findings suggest that the supplementation of an extender with catalase or uric acid is beneficial and protects fish sperm membranes from damage caused by oxidative stress during low-temperature storage. The extenders containing 0.1 kU/L of catalase and 0.25 mmol/L of uric acid provided effective antioxidant protection for the spermatozoa of this important Amazonian fish.

Success-driven opinion formation determines social tensions.

Polarization is common in politics and public opinion. It is believed to be shaped by media as well as ideologies, and often incited by misinformation. However, little is known about the microscopic dynamics behind polarization and the resulting social tensions. By coupling opinion formation with the strategy selection in different social dilemmas, we reveal how success at an individual level transforms to global consensus or lack thereof. When defection carries with it the fear of punishment in the absence of greed, as in the stag-hunt game, opinion fragmentation is the smallest. Conversely, if defection promises a higher payoff and also evokes greed, like in the prisoner's dilemma and snowdrift game, consensus is more difficult to attain. Our research thus challenges the top-down narrative of social tensions, showing they might originate from fundamental principles at individual level, like the desire to prevail in pairwise evolutionary comparisons.

ORTHOSTATIC SUPPORT IN PARAPLEGIC AND AMPUTEE PATIENTS: A CONTROLLED TRIAL.

Introduction: Functional incapacity caused by physical alterations leads to significant limitations in daily activities and has a major impact on the return of people with disabilities to the social space and the workplace. This calls for an evaluation of the long-term influence of the use of a device specially developed for orthostatic posture on the physiological, biomechanical and functional parameters of amputees and spinal cord patients. Objective: The objective was evaluate the effect of postural support device use on function, pain, and biomechanical and cardiologic parameters in spinal cord injury and amputees patients compared to a control group. Methods: The orthostatic device was used by the participants for a period of ten consecutive days, for three cycles of 50 minutes each day, and a 15-day follow-up. Participants were positioned and stabilized using adjustable straps on the shoulders, trunk, and hips. The primary outcome was brief pain inventory. Fifteen participants were included the control group, 15 in the amputee group, and 15 in the spinal cord group. Results: Our results demonstrate that the use of the device allows the orthostatic position of amputees and spinal cord patients evaluated for ten days, leading to improved functionality and pain in the spinal cord and amputee groups compared to the control group. In addition, no changes were observed for secondary outcomes, indicating that the use of the device did not cause harm interference to patients. Conclusion: The long-term use of the orthostatic device is beneficial for improving functionality, reduce pain in amputees and spinal cord injury patients. Level of evidence II; Therapeutic Studies - Investigating the results of treatment.

Introdução: A incapacidade funcional causada por alterações físicas leva a limitações significativas nas atividades diárias e gera um grande impacto no retorno das pessoas com deficiência ao espaço social e ao local de trabalho, demandando a avaliação da influência em longo prazo do uso de um dispositivo especialmente desenvolvido para a postura ortostática nos parâmetros fisiológicos, biomecânicos e funcionais de pacientes amputados e com medula espinhal. Objetivo: O objetivo foi avaliar o efeito do uso do dispositivo de suporte postural na função, dor e parâmetros biomecânicos e cardiológicos em pacientes com lesão medular e amputados em comparação com um grupo controle. Métodos: O aparelho ortostático foi utilizado pelos participantes por um período de dez dias consecutivos, em três ciclos de 50 minutos diários, com acompanhamento de 15 dias. Os participantes foram posicionados e estabilizados por meio de alças ajustáveis nos ombros, tronco e quadris. O desfecho primário foi o questionário Breve Inventário de Dor. Quinze participantes foram incluídos no grupo controle, 15 no grupo amputado e 15 no grupo medular. Resultados: Nossos resultados demonstram que o uso do dispositivo permite a posição ortostática de amputados e pacientes com lesão medular avaliados por dez dias, levando a melhora da funcionalidade e dor nos grupos de amputados e medula espinhal em relação ao grupo controle. Além disso, não foram observadas alterações nos resultados secundários, indicando que o uso do dispositivo não causou interferência prejudicial aos pacientes. Conclusão: O uso prolongado do dispositivo ortostático é benéfico para melhorar a funcionalidade, reduzir a dor em amputados e pacientes com lesão medular. Nível de Evidência II; Estudos Terapêuticos - Investigação dos resultados de tratamento.

Evaluation of protective efficacy, serological responses, and cytokine modulation induced by polyvalent Leptospira vaccines in hamsters.

Whole-cell inactivated vaccines (bacterins) are the only licensed vaccines available for leptospirosis prevention and control, especially in domestic and farm animals. However, despite their widespread use, inconsistencies in their efficacy have been reported. Because immunity induced by bacterins is mainly mediated by antibodies against leptospiral lipopolysaccharides, the involvement of cellular responses is not well-known. The aim of this study was to investigate the efficacy and characterize the humoral and cellular immune responses induced by whole-cell inactivated leptospirosis bacterin formulations containing serovars Bratislava, Canicola, Copenhageni, Grippotyphosa, Hardjoprajitno, and Pomona. For the potency test, hamsters were immunized with one dose of polyvalent bacterins (either commercial or experimental) and then challenged with a virulent Pomona strain. Serological (MAT and IgM and IgG-ELISA) and cellular (cytokine transcription in blood evaluated by RT-qPCR) analyses were performed. The results revealed that vaccination with either bacterin formulation was able to protect 90-100% of the hamsters infected with the Pomona serovar, although most of the surviving animals remained as renal carriers. Specific agglutinating antibodies and significant levels of IgM, IgG, and IgG2 (P < 0.05) that were able to react with the six serovars present in the vaccine formulations were produced, indicating that the vaccines can potentially provide immunity against all strains. The protective immunity of these vaccines was mainly mediated by balanced a Th1/Th2 response, characterized by increased IFN-γ, IL-10 and IL-α transcription. These data support the importance of characterizing immunological responses involved in bacterin efficacy and investing in the improvement of these vaccine formulations.

Immunomodulatory effect of Lacticaseibacillus casei CB054 supplementation in calves vaccinated against infectious bovine rhinotracheitis.

Probiotics are live microorganisms that, confer health benefits to the host when supplemented in adequate amounts. They can promote immunomodulation by inducing phagocyte activity, leukocyte proliferation, antibody production, and cytokine expression. Lactic acid bacteria (BAL) are important probiotic specimens with properties that can improves ruminant nutrition, productivity and immunity. The aim of the present study was to evaluate the immunomodulatory effect of the supplementation with Lacticaseibacillus casei CB054 in calve vaccinated against bovine infectious rhinotracheitis (IBR). Calve were vaccinated with a commercial IBR vaccine, on day 0 and received a booster dose on day 21. L. casei CB054 was orally administered (4 ×109 UFC) for 35 days, while a non-supplemented control group received Phosphate Buffer Saline (PBS). Stimulation of bovine splenocytes with L. casei CB054 markedly enhanced mRNA transcription levels of cytokines IL2, IL4, IL10 and IL17 genes. Calves supplemented with L. casei CB054 showed significantly higher (p < 0.05) specific anti-BoHV-1 IgG levels, higher serum neutralization, as well as higher mRNA transcription for IL2, IL4, IL10 and IL17 genes in Peripheral Blood Mononuclear Cells (PBMCs) comparing with control calves. Supplemented calve had an average weight gain of ∼14 kg more than non-supplemented during the experimental period. These results suggest that L. casei CB054 supplementation increase immunogenicity of a commercial IBR vaccine in cattle and improve weight gain.

Estimated Energy Expenditure in Youth While Playing Active Video Games: A Systematic Review.

Sedentary behavior and inadequate energy expenditure are serious global public health concerns among youngsters. The exponential growth in technology emerges as a valuable opportunity to foster physical activity, particularly through active video games. We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in PubMed, Web of Science, Cochrane, and Scopus to provide a comprehensive view of the literature on energy expenditure levels among adolescents while playing active video games. Among the 574 manuscripts identified at the first screening stage, 23 were retained for analysis. Ten studies were characterized by longitudinal and thirteen by cross-sectional designs. The results showed that short-term active video games elicited energy expenditure values comparable to moderate-intensity physical activity (3-6 METs). However, in intervention programs (with at least six weeks) the results indicate no significant effects of active video games on youngsters' energy expenditure levels and physical activity profiles between baseline and follow-up assessments. Overall, active video games based on sports and dance were the most used, and boys tended to achieve higher energy expenditure than girls. The diversity of methods implemented limits comparing results and drawing generalized conclusions. However, considering its attractiveness to youth, active video games might emerge as a complementary tool to traditional physical activities promoted in schools and local communities. Details regarding gender differences and contradictory results of longitudinal approaches should be considered in future research based on standardized methods.

Forage cactus as an additive in corn without the cob silages of feedlot sheep diets.

This study aimed to assess the impact of adding forage cactus as an additive to the production of corn silage without the cob on the performance of feedlot sheep and subsequent silage losses. The experimental design was completely randomized, consisting of three treatments: corn silage without cob; 0% = 100% corn plant without the cob; 10% = 90% corn plant without cob + 10% forage cactus; 20% = 80% corn plant without cob + 20% forage cactus. Significant effects were observed for dry matter intake (P = 0.0201), organic matter (P = 0.0152), ether extract (P = 0.0001), non-fiber carbohydrates (P = 0.0007). Notably, nutrient digestibility showed significant differences in organic matter (P = 0.0187), ether extract (P = 0.0095), neutral detergent fiber (P = 0.0005), non-fiber carbohydrates (P = 0.0001), and metabolizable energy (P = 0.0001). Performance variables, including total weight gain (P = 0.0148), average daily weight gain (P = 0.0148), feeding efficiency, and rumination efficiency of dry matter (P = 0.0113), also exhibited significant effects. Consequently, it is recommended to include 20% forage cactus in corn silage, which, based on natural matter, helps meet animals' water needs through feed. This inclusion is especially vital in semi-arid regions and aids in reducing silage losses during post-opening silo disposal.

Evolution of a theory of mind.

Even though the Theory of Mind in upper primates has been under investigation for decades, how it may evolve remains an open problem. We propose here an evolutionary game theoretical model where a finite population of individuals may use reasoning strategies to infer a response to the anticipated behavior of others within the context of a sequential dilemma, i.e., the Centipede Game. We show that strategies with bounded reasoning evolve and flourish under natural selection, provided they are allowed to make reasoning mistakes and a temptation for higher future gains is in place. We further show that non-deterministic reasoning co-evolves with an optimism bias that may lead to the selection of new equilibria, closely associated with average behavior observed in experimental data. This work reveals both a novel perspective on the evolution of bounded rationality and a co-evolutionary link between the evolution of Theory of Mind and the emergence of misbeliefs.

The art of compensation: How hybrid teams solve collective-risk dilemmas.

It is widely known how the human ability to cooperate has influenced the thriving of our species. However, as we move towards a hybrid human-machine future, it is still unclear how the introduction of artificial agents in our social interactions affect this cooperative capacity. In a one-shot collective risk dilemma, where enough members of a group must cooperate in order to avoid a collective disaster, we study the evolutionary dynamics of cooperation in a hybrid population. In our model, we consider a hybrid population composed of both adaptive and fixed behavior agents. The latter serve as proxies for the machine-like behavior of artificially intelligent agents who implement stochastic strategies previously learned offline. We observe that the adaptive individuals adjust their behavior in function of the presence of artificial agents in their groups to compensate their cooperative (or lack of thereof) efforts. We also find that risk plays a determinant role when assessing whether or not we should form hybrid teams to tackle a collective risk dilemma. When the risk of collective disaster is high, cooperation in the adaptive population falls dramatically in the presence of cooperative artificial agents. A story of compensation, rather than cooperation, where adaptive agents have to secure group success when the artificial agents are not cooperative enough, but will rather not cooperate if the others do so. On the contrary, when risk of collective disaster is low, success is highly improved while cooperation levels within the adaptive population remain the same. Artificial agents can improve the collective success of hybrid teams. However, their application requires a true risk assessment of the situation in order to actually benefit the adaptive population (i.e. the humans) in the long-term.