Differential Activation States of Direct Pathway Striatal Output Neurons during l-DOPA-Induced Dyskinesia Development.

l-DOPA-induced dyskinesia (LID) is a debilitating motor side effect arising from chronic dopamine (DA) replacement therapy with l-DOPA for the treatment of Parkinson's disease. LID is associated with supersensitivity of striatal dopaminergic signaling and fluctuations in synaptic DA following each l-DOPA dose, shrinking the therapeutic window. The heterogeneous composition of the striatum, including subpopulations of medium spiny output neurons (MSNs), interneurons, and supporting cells, complicates the identification of cell(s) underlying LID. We used single-nucleus RNA sequencing (snRNA-seq) to establish a comprehensive striatal transcriptional profile during LID development. Male hemiparkinsonian mice were treated with vehicle or l-DOPA for 1, 5, or 10 d, and striatal nuclei were processed for snRNA-seq. Analyses indicated a limited population of DA D1 receptor-expressing MSNs (D1-MSNs) formed three subclusters in response to l-DOPA treatment and expressed cellular markers of activation. These activated D1-MSNs display similar transcriptional changes previously associated with LID; however, their prevalence and transcriptional behavior were differentially influenced by l-DOPA experience. Differentially expressed genes indicated acute upregulation of plasticity-related transcription factors and mitogen-activated protein kinase signaling, while repeated l-DOPA-induced synaptic remodeling, learning and memory, and transforming growth factor-ß (TGF-ß) signaling genes. Notably, repeated l-DOPA sensitized Inhba, an activin subunit of the TGF-ß superfamily, in activated D1-MSNs, and its pharmacological inhibition impaired LID development, suggesting that activin signaling may play an essential role in LID. These data suggest distinct subsets of D1-MSNs become differentially l-DOPA-responsive due to aberrant induction of molecular mechanisms necessary for neuronal entrainment, similar to processes underlying hippocampal learning and memory.

Quantitative Analysis of Glutathione and Carnosine Adducts with 4-Hydroxy-2-nonenal in Muscle in a hSOD1G93A ALS Rat Model.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the dysfunction and death of motor neurons through multifactorial mechanisms that remain unclear. ALS has been recognized as a multisystemic disease, and the potential role of skeletal muscle in disease progression has been investigated. Reactive aldehydes formed as secondary lipid peroxidation products in the redox processes react with biomolecules, such as DNA, proteins, and amino acids, resulting in cytotoxic effects. 4-Hydroxy-2-nonenal (HNE) levels are elevated in the spinal cord motor neurons of ALS patients, and HNE-modified proteins have been identified in the spinal cord tissue of an ALS transgenic mice model, suggesting that reactive aldehydes can contribute to motor neuron degeneration in ALS. One biological pathway of aldehyde detoxification involves conjugation with glutathione (GSH) or carnosine (Car). Here, the detection and quantification of Car, GSH, GSSG (glutathione disulfide), and the corresponding adducts with HNE, Car-HNE, and GS-HNE, were performed in muscle and liver tissues of a hSOD1G93A ALS rat model by reverse-phase high-performance liquid chromatography coupled to electrospray ion trap tandem mass spectrometry in the selected reaction monitoring mode. A significant increase in the levels of GS-HNE and Car-HNE was observed in the muscle tissue of the end-stage ALS animals. Therefore, analyzing variations in the levels of these adducts in ALS animal tissue is crucial from a toxicological perspective and can contribute to the development of new therapeutic strategies.

Selective visuoconstructional impairment following mild COVID-19 with inflammatory and neuroimaging correlation findings.

People recovered from COVID-19 may still present complications including respiratory and neurological sequelae. In other viral infections, cognitive impairment occurs due to brain damage or dysfunction caused by vascular lesions and inflammatory processes. Persistent cognitive impairment compromises daily activities and psychosocial adaptation. Some level of neurological and psychiatric consequences were expected and described in severe cases of COVID-19. However, it is debatable whether neuropsychiatric complications are related to COVID-19 or to unfoldings from a severe infection. Nevertheless, the majority of cases recorded worldwide were mild to moderate self-limited illness in non-hospitalized people. Thus, it is important to understand what are the implications of mild COVID-19, which is the largest and understudied pool of COVID-19 cases. We aimed to investigate adults at least four months after recovering from mild COVID-19, which were assessed by neuropsychological, ocular and neurological tests, immune markers assay, and by structural MRI and 18FDG-PET neuroimaging to shed light on putative brain changes and clinical correlations. In approximately one-quarter of mild-COVID-19 individuals, we detected a specific visuoconstructive deficit, which was associated with changes in molecular and structural brain imaging, and correlated with upregulation of peripheral immune markers. Our findings provide evidence of neuroinflammatory burden causing cognitive deficit, in an already large and growing fraction of the world population. While living with a multitude of mild COVID-19 cases, action is required for a more comprehensive assessment and follow-up of the cognitive impairment, allowing to better understand symptom persistence and the necessity of rehabilitation of the affected individuals.

Genomic analysis of genotype-environment interaction in age at first calving of Murrah buffaloes.

Age at first calving (AFC) is a measure of sexual maturity associated with the start of productive life of dairy animals. Additionally, a lower AFC reduces the generation interval and early culling of females. However, AFC has low heritability, making it a trait highly influenced by environmental factors. In this scenario, one way to improve the reproductive performance of buffalo cows is to select robust animals according to estimated breeding value (EBV) using models that include genotype-environment interaction (GEI) with the application of reaction norm models (RNMs). This can be achieved by understanding the genomic basis related to GEI of AFC. Thus, in this study, we aimed to predict EBV considering GEI via the RNM and identify candidate genes related to this component in dairy buffaloes through genome-wide association studies (GWAS). We used 1795 AFC records from three Murrah buffalo herds and formed environmental gradients (EGs) from contemporary group solutions obtained from genetic analysis of 270-day cumulative milk yield. Heritability estimates ranged from 0.15 to 0.39 along the EG. GWAS of the RNM slope parameter identified important genomic regions. The genomic window that explained the highest percentage of genetic variance of the slope (0.67%) was located on BBU1. After functional analysis, five candidate genes were detected, involved in two biological processes. The results suggested the existence of a GEI for AFC in Murrah buffaloes, with reclassification of animals when different environmental conditions were considered. The inclusion of genomic information increased the accuracy of breeding values for the intercept and slope of the reaction norm. GWAS analysis suggested that important genes associated with the AFC reaction norm slope were possibly also involved in biological processes related to lipid metabolism and immunity.

Genetic Mutations and Mitochondrial Redox Signaling as Modulating Factors in Hypertrophic Cardiomyopathy: A Scoping Review.

Hypertrophic cardiomyopathy (HCM) is a heart condition characterized by cellular and metabolic dysfunction, with mitochondrial dysfunction playing a crucial role. Although the direct relationship between genetic mutations and mitochondrial dysfunction remains unclear, targeting mitochondrial dysfunction presents promising opportunities for treatment, as there are currently no effective treatments available for HCM. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews guidelines. Searches were conducted in databases such as PubMed, Embase, and Scopus up to September 2023 using "MESH terms". Bibliographic references from pertinent articles were also included. Hypertrophic cardiomyopathy (HCM) is influenced by ionic homeostasis, cardiac tissue remodeling, metabolic balance, genetic mutations, reactive oxygen species regulation, and mitochondrial dysfunction. The latter is a common factor regardless of the cause and is linked to intracellular calcium handling, energetic and oxidative stress, and HCM-induced hypertrophy. Hypertrophic cardiomyopathy treatments focus on symptom management and complication prevention. Targeted therapeutic approaches, such as improving mitochondrial bioenergetics, are being explored. This includes coenzyme Q and elamipretide therapies and metabolic strategies like therapeutic ketosis. Understanding the biomolecular, genetic, and mitochondrial mechanisms underlying HCM is crucial for developing new therapeutic modalities.

Pendular mechanism determinants and elastic energy usage during walking of obese and non-obese children.

The mechanical and metabolic responses of walking by obese children are not yet well understood. The objectives of this study were (1) to compare the pendular mechanism (recovery, phase shift by α and ß values, and ratio between forward and vertical mechanical work), the maximum possible elastic energy usage and the bilateral coordination during walking between non-obese and obese children, and (2) to verify if the bilateral coordination could contribute to understanding the pendular mechanism and elastic energy usage in these populations. Nine obese (six female, 8.7 ± 0.5 years, 1.38 ± 0.04 m, 44.4 ± 6.3 kg and 24.1 ± 3.50 kg/m2 ) and eight non-obese (four female, 7.4 ± 0.5 years, 1.31 ± 0.08 m, 26.6 ± 2.1 kg and 16.4 ± 1.40 kg/m2 ) children were analysed during walking on a treadmill at five speeds: 1, 2, 3, 4 and 5 km/h. The results indicated that although the mechanical energy response of the centre of mass during walking is similar between obese and non-obese children, the obese children showed a lower pendulum-like mechanism and greater elastic energy usage during level walking. Therefore, obese children seem to use more elastic energy during walking compared to non-obese children, which may be related to their apparent higher positive work production during the double support phase. Finally, bilateral coordination presented high values at slow speeds in both groups and requires further attention due to its association with falls. NEW FINDINGS: What is the central question of this study? Are there any differences of the pendular and elastic mechanisms and bilateral coordination during walking between non-obese and obese children? What is the main finding and its importance? To our knowledge, this study is the first to analyse the mechanical energy usage and the bilateral coordination of obese and non-obese children during walking. Obese children had a lower pendular recovery mechanism and used more elastic energy compared to non-obese children. The bilateral coordination was higher at slow speeds in both groups and requires further attention due to its association with falls.

Signatures of selection in Nelore cattle revealed by whole-genome sequencing data.

Nelore cattle breed was farmed worldwide due to its economic importance in the beef market and adaptation to the tropics. In Brazil, purebred Nelore animals (PO) receive a certificate from the breeders' association based on the animal's genealogy and morphological characterization. The top 20 to 30% of the superior animals are eligible to receive the Special Certificate of Identification and Production (CEIP), meaning animals from this category were selected and evaluated in a breeding program to improve economically important traits. We used whole-genome sequencing and approaches based on haplotype differentiation and allelic differentiation to detect regions of selection signatures in Nelore cattle by comparing animals from PO and CEIP categories. From a total of 150 animals, a hierarchical clustering analysis was performed to choose the more unrelated animals from each category (16 PO and 40 CEIP). The hapFLK statistic was performed, and extensions of hapFLK values were investigated considering continuous regions with significant q-values. The Weir and Cockerham's Fst estimator (wcFst) was computed using the GPAT++ software library. The total of 82,326 SNPs with hapFLK values passed the FDR control (q-value<0.05), and 718 segments were target as signatures of selection. A total of 1713 highly differentiated genomic regions were identified based on the segmentFst approach. The signatures of selection were spread across the genome. Annotation of overlapping selection signature regions between the two methods revealed 118 genes in common. A variant located within the 3' region of the BOLA-DRB3 gene was found as a promising candidate polymorphism. Within genomic regions that deserves attention, we found genes previously associated with adaptation to tropical environments (HELB), growth and navel size (HMGA2), fat deposition and domestication (IRAK3), and feed efficiency and postmortem carcass traits (GABRG3). The genes BOLA-DQA2, BOLA-DQB, BOLA-DQA5, BOLA-DQA1, BOLA-DRB3, ENSBTAG00000038397 on chromosome 23 are part of the Bovine Major Histocompatibility Complex (MHC) Class II gene family, representing good candidates for immune response and adaptation to tropical conditions. The BoLA family genes and the interaction of ROBO1 with SLIT genes appeared in the enrichment results. Genomic regions located in intronic regions were also identified and might play a regulatory role in traits under selection in PO and CEIP subpopulations. The regions here identified contribute to our knowledge regarding genes and variants that have an important role in complex traits selected in this breed.

Genomic inbreeding estimation, runs of homozygosity, and heterozygosity-enriched regions uncover signals of selection in the Quarter Horse racing line.

With the advent of genomics, significant progress has been made in the genetic improvement of livestock species, particularly through increased accuracy in predicting breeding values for selecting superior animals and the possibility of performing a high-resolution genetic scan throughout the genome of an individual. The main objectives of this study were to estimate the individual genomic inbreeding coefficient based on runs of homozygosity (FROH ), to identify and characterize runs of homozygosity and heterozygosity (ROH and ROHet, respectively; length and distribution) throughout the genome, and to map selection signatures in relevant chromosomal regions in the Quarter Horse racing line. A total of 336 animals registered with the Brazilian Association of Quarter Horse Breeders (ABQM) were genotyped. One hundred and twelve animals were genotyped using the Equine SNP50 BeadChip (Illumina, USA), with 54,602 single nucleotide polymorphisms (SNPs; 54K). The remaining 224 samples were genotyped using the Equine SNP70 BeadChip (Illumina, USA) with 65,157 SNPs (65K). To ensure data quality, we excluded animals with a call rate below 0.9. We also excluded SNPs located on non-autosomal chromosomes, as well as those with a call rate below 0.9 or a p-value below 1 × 10-5 for Hardy-Weinberg equilibrium. The results indicate moderate to high genomic inbreeding, with 46,594 ROH and 16,101 ROHet detected. In total, 30 and 14 candidate genes overlap with ROH and ROHet regions, respectively. The ROH islands showed genes linked to crucial biological processes, such as cell differentiation (CTBP1, WNT5B, and TMEM120B), regulation of glucose metabolic process (MAEA and NKX1-1), heme transport (PGRMC2), and negative regulation of calcium ion import (VDAC1). In ROHet, the islands showed genes related to respiratory capacity (OR7D19, OR7D4G, OR7D4E, and OR7D4J) and muscle repair (EGFR and BCL9). These findings could aid in selecting animals with greater regenerative capacity and developing treatments for muscle disorders in the QH breed. This study serves as a foundation for future research on equine breeds. It can contribute to developing reproductive strategies in animal breeding programs to improve and preserve the Quarter Horse breed.

Natural levels of Rhipicephalus microplus infestation and Anaplasma marginale infection in Angus and Ultrablack calves.

Infections by Anaplasma marginale and infestations by Rhipicephalus microplus occur endemically in Brazil, representing an obstacle to expanding the use of taurine breeds, which are more susceptible. In this study, the levels of infection by A. marginale and infestation by R. microplus were monitored in 31 calves that were either purebred or had a high degree of taurine blood: 17 Angus (100% taurine) and 14 Ultrablack (ca. 82% taurine and 18% Zebu). The animals were evaluated on 13 occasions at 12-day intervals. The levels of A. marginale infection were determined by quantification of DNA copy number (CN) by qPCR, and ticks were monitored by two methods: counting adult females (≥ 4.5 mm) and scoring the level of tick infestation considering all visible instars in the animals' bodies. No significant effects were observed between the means of CN of A. marginale, tick counts and scores among Angus and Ultrablack animals. The repeatability estimates for CN of A. marginale, tick counts and tick scores were 0.53, 0.12 and 0.16, respectively. The correlations between CN and tick counts and scores were close to zero, whereas the correlations between tick assessment methods were 0.57. The absence of differences between the two genetic groups indicates, under the conditions of the present study, that the low degree of Zebu blood did not influence the levels of infection by A. marginale or infestation by R. microplus. The results also suggest that the evaluation of the levels of infestation by ticks using scores can provide information closer to the real infestation rate considering that it uses all the visible instars of the parasites.

A multiple criteria approach for building a pandemic impact assessment composite indicator: The case of COVID-19 in Portugal.

The COVID-19 pandemic has caused major damage and disruption to social, economic, and health systems (among others). In addition, it has posed unprecedented challenges to public health and policy/decision-makers who have been responsible for designing and implementing measures to mitigate its strong negative impact. The Portuguese health authorities have used decision analysis techniques to assess the impact of the pandemic and implemented measures for counties, regions, or across the entire country. These decision tools have been subject to some criticism and many stakeholders requested novel approaches. In particular, those which considered the dynamic changes in the pandemic's behaviour due to new virus variants and vaccines. A multidisciplinary team formed by researchers from the COVID-19 Committee of Instituto Superior Técnico at the University of Lisbon (CCIST analyst team) and physicians from the Crisis Office of the Portuguese Medical Association (GCOM expert team) collaborated to create a new tool to help politicians and decision-makers to fight the pandemic. This paper presents the main steps that led to the building of a pandemic impact assessment composite indicator applied to the specific case of COVID-19 in Portugal. A multiple criteria approach based on an additive multi-attribute value theory aggregation model was used to build the pandemic assessment composite indicator. The parameters of the additive model were devised based on an interactive socio-technical and co-constructive process between the CCIST and GCOM team members. The deck of cards method was the adopted technical tool to assist in the assessment the value functions as well as in the assessment of the criteria weights. The final tool was presented at a press conference and had a powerful impact on the Portuguese media and on the main health decision-making stakeholders in the country. In this paper, a completed mathematical and graphical description of this tool is presented.

Estimation of genetic parameters for the tick and hemoparasite burden in Angus cattle.

The study was conducted with the objective of estimating genetic and phenotypic parameters for tick (CRM) and Babesia bigemina (IBBi), Babesia bovis (IBBo), and Anaplasma marginale (IAM) burden in Angus female breed in Brazil. The sample group was composed of Angus females raised in herds located in a region of endemic instability for cattle tick fever in the state of Rio Grande Sul (RS), Brazil. The variance components were estimated using Bayesian inference and Gibbs sampling algorithm, considering a multi-trait animal model. Heritability estimates showed values of low magnitude, ranging from 0.03 (IBBo) to 0.16 (CRM), while repeatability estimates ranged between 0.07 (IBBo) and 0.21 (CRM). Regarding the genetic correlation estimates, the values showed low (-0.01 for IBBo × IAM) to moderate (0.55 between IBBi × IAM) magnitudes. The results indicate that it is possible to use tick count and hemoparasite infection levels as selection criteria, with small genetic gains.

How long does the mRNA remains stable in untreated whole bovine blood?

BACKGROUND: High quality and quantity of messenger RNA (mRNA) are required for accuracy of gene expression studies and other RNA-based downstream applications. Since RNA is considered a labile macromolecular prone to degradation, which may result in falsely altered gene expression patterns, several commercial stabilizing reagents have been developed aiming to keep RNA stable for long period. However, for studies involving large number of experimental samples, the high costs related to these specific reagents may constitute a barrier. METHODS AND RESULTS: In this context the present study was designed aiming to evaluate the stability of mRNA in whole bovine blood collected in EDTA tubes during storage at common fridge (4 °C). Whole blood samples were collected from six Holstein calves and submitted to RNA extraction in each different interval: immediately after blood sampling (< 2 h), at 1-day post-sampling (dps), 2 dps, 3 dps, 7 dps and 14dps intervals. RNA integrity and purity were evaluated, and RT-qPCR assays were run using seven different genes (B2M, ACTB, PPIA, GAPDH, YWHAZ, CD4 and IFN-γ) aiming to evaluate the presence of altered gene transcription during storage. All extracted RNA samples presented high purity, while optimal integrity and unaltered gene expression were observed in whole experimental group up to 3 days of storage. CONCLUSION: Bovine blood RNA remained stable in K3EDTA tubes for 3 days stored at common fridge and can be successfully and accurately used for gene expression studies.

Assessment of redox state and biochemical parameters of salivary glands in rats treated with anti-obesity drug sibutramine hydrochloride.

OBJECTIVES: To investigate the effects of anti-obesity drug sibutramine hydrochloride (SB) on redox state and biochemical parameters in the salivary glands. MATERIALS AND METHODS: Adult male Wistar rats were randomly divided into the following groups (n = 8 per group): control rats treated with vehicle (C) and rats treated with SB (10 mg/kg/day) by intragastric gavage for 28 days. The parotid (PG) and submandibular (SMG) glands were processed using histomorphometric analysis, and total protein, amylase, mucin, and oxidative damage to lipids were determined by measuring the formation of thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC), uric acid (UA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and AKT phosphorylation. RESULTS: SB decreased the acinar area, and increased the stromal area in PG, while no effect on the morphometric parameters was observed in SMG. SB also increased oxidative damage to lipids (TBARs). The SB group showed lower total protein, amylase, TAC, UA, tGSH, SOD, CAT, and GPx than the C group in PG, while in SMG, SB decreased total protein, mucin, tGSH, SOD, CAT, and GPx. However, increased AKT phosphorylation observed in both salivary glands suggests that SB exerts low-intensity oxidative stress. CONCLUSIONS: SB impaired enzymatic and non-enzymatic antioxidant defenses in the salivary glands of rats. CLINICAL RELEVANCE: Chronic treatment with SB could mitigate salivary gland dysfunction due to disturbance of redox state.

Stressful events, depressive symptoms, and frailty associated to older adults' survival and mortality.

This study analyzed factors associated with survival and mortality risk of community-dwelling older adults, considering the intensity of stressful life events, depressive symptoms, insomnia, frailty, multimorbidity, and sociodemographic factors. This is a longitudinal study on survival of older adults interviewed between 2008-2009, with follow-up after 8 years. Survival and mortality risks were analyzed using the Kaplan-Meier curve, Log Rank test, and Cox proportional-hazards model (p < 0.05). Stressful events affecting older adults' children or grandchildren were associated with higher mortality risk; depressive symptoms and frailty were associated with lower survival. Comprehensive care for older adults must involve events regarding their family relationships, especially those affecting their progeny, due to the impact they can have on older adults' survival, besides evaluating depressive symptoms and frailty.

Stress as worsening of the signs and symptoms of the geographic tongue during the COVID-19 pandemic: a pilot study.

BACKGROUND: Geographic Tongue (GT) is a benign inflammatory disorder of unknown etiology, which is characterized by the loss of epithelium due to the atrophy of filiform papillae. It usually occurs on the dorsum of the tongue and may extend to its lateral edges. It appears as an erythematous area surrounded by whitish and slightly elevated margins. In most cases, the condition is asymptomatic, although some individuals may report symptoms that include a burning sensation of the tongue. OBJECTIVE: Assess whether there was a change in the clinical aspect of Geographic Tongue (GT) during the COVID-19 pandemic. METHODS: Thirty-two participants were recruited from Dentistry School Universidade Federal Fluminense. Anamnesis and oral examination were performed to collect medical history. The participants were split into two groups: control group (no GT) n = 20 and test group (with GT) n = 12. In the second step, nine participants from a 12 (75%) of the test group were contacted by phone and answered a questionnaire about changes in the signs and symptoms of GT during the pandemic. The subjects were subdivided into two groups: GT with and without signs and symptoms exacerbation. RESULTS: In the first phase of the research, no statistical difference between control and test groups was observed regarding clinical criteria such as age (p + 0.72), gender (p = 0.24), and systemic diseases (p = 0.58). In the second phase, there was a statistical difference between GT groups with or without symptom exacerbation in terms of age and stress as a factor of the oral symptoms (p = 0.3 and 0.2), respectively. Younger patients showed a worsening of the oral lesions related to GT (p = 0.3) and reported stress during the pandemic (p = 0.02). CONCLUSION: Younger patients were more susceptible to stress and presented more exacerbation of the oral lesions related to GT.

Selection effect for growth traits on energy requirements in beef Nelore steers.

Growth data of 77,372 Nelore steers were used to estimate the selection effect on energy requirements considering two beef production systems: cow-calf and slaughter cycles. All the animals had measures from 120 days to 7 years old. The parameters necessary to evaluate the selection effect on energy requirements were obtained by random regression analysis using Legendre polynomials. The models included additive direct and maternal effects, and animal and maternal permanent environmental effects as random terms. Contemporary group and dam age at calving (linear and quadratic effect) were included as fixed effects, and orthogonal Legendre polynomials of animal age (cubic regression) were considered random covariables. The coefficients from the model M3353_5 were used to calculate the genetic gains necessary to predict the increase in phenotypes. The selection was simulated for body weight (BW) and weight gain (WG) at different ages and energy requirements were calculated using NRC equations. The cost of feed was calculated for a cow-calf and slaughter cycle of production considering a system of Brachiaria decumbens pasture without supplementation. In slaughter system, the selection for weight of 365 days of age is the best option. In cow-calf systems, the selection W120 is the best choice.

Genome-wide scans for signatures of selection in Mangalarga Marchador horses using high-throughput SNP genotyping.

BACKGROUND: The detection of signatures of selection in genomic regions provides insights into the evolutionary process, enabling discoveries regarding complex phenotypic traits. In this research, we focused on identifying genomic regions affected by different selection pressures, mainly highlighting the recent positive selection, as well as understanding the candidate genes and functional pathways associated with the signatures of selection in the Mangalarga Marchador genome. Besides, we seek to direct the discussion about genes and traits of importance in this breed, especially traits related to the type and quality of gait, temperament, conformation, and locomotor system. RESULTS: Three different methods were used to search for signals of selection: Tajima's D (TD), the integrated haplotype score (iHS), and runs of homozygosity (ROH). The samples were composed of males (n = 62) and females (n = 130) that were initially chosen considering well-defined phenotypes for gait: picada (n = 86) and batida (n = 106). All horses were genotyped using a 670 k Axiom® Equine Genotyping Array​ (Axiom MNEC670). In total, 27, 104 (chosen), and 38 candidate genes were observed within the signatures of selection identified in TD, iHS, and ROH analyses, respectively. The genes are acting in essential biological processes. The enrichment analysis highlighted the following functions: anterior/posterior pattern for the set of genes (GLI3, HOXC9, HOXC6, HOXC5, HOXC4, HOXC13, HOXC11, and HOXC10); limb morphogenesis, skeletal system, proximal/distal pattern formation, JUN kinase activity (CCL19 and MAP3K6); and muscle stretch response (MAPK14). Other candidate genes were associated with energy metabolism, bronchodilator response, NADH regeneration, reproduction, keratinization, and the immunological system. CONCLUSIONS: Our findings revealed evidence of signatures of selection in the MM breed that encompass genes acting on athletic performance, limb development, and energy to muscle activity, with the particular involvement of the HOX family genes. The genome of MM is marked by recent positive selection. However, Tajima's D and iHS results point also to the presence of balancing selection in specific regions of the genome.

Systematic review and meta-analysis of the efficacy of Unna boot in the treatment of venous leg ulcers.

This systematic review determined the effectiveness of the Unna boot in the treatment of venous leg ulcers (VLUs) by assessing the quality of the available evidence. A systematic search of studies published between August 2019 and February 2020 was conducted using the PubMed, PubMed/PMC, BVS/BIREME, CINAHL, Web of Science, MEDLINE, Embase, Cochrane, ProQuest, BDTD, CAPES Thesis and Dissertation, OPEN THESIS, Centre for Reviews and Dissemination and SciELO databases. Studies were eligible if they reported primary studies, controlled clinical trials, quasi-experimental studies or observational studies (cross-sectional studies or cohort studies). We identified 302 articles. After screening and critical appraisal, eight articles were included in this review, while six articles were included in the meta-analysis. Four studies were included in the outcome of complete ulcer healing rate with a weighted estimate of the odds ratio of 0.43 (95% CI = 0.188-1.01). No evidence of the presence of considerable heterogeneity was observed (p = 0.35, I2 = 32%). Two studies were assigned to the outcome time to complete ulcer healing (days) with a weighted estimated mean difference of 41.3 days (95% CI = 21.62-61.04). Evidence of the presence of considerable heterogeneity was observed (p = 0.01, I2 = 85%). The results showed a moderate degree of evidence that there is no difference in the healing rates of VLUs with the use of the Unna boot. For the time to complete ulcer healing, the low number of studies and low classification impaired the reporting at any level of evidence.

Psychometric properties of the WHOQOL-BREF(PT) in a sample of elderly citizens.

BACKGROUND: The goal of this article was to research the psychometric properties of the WHOQOL-BREF(PT) instrument in a sample of elderly citizens residing in a rural area in their own homes or at family members' or friends' homes and to compare the results: (i) to those reported by the team of Portuguese researchers that undertaken the instrument's translation/validation to the Portuguese language and (ii) to those reported internationally by the World Health Organization Quality of Life group. An overall quality of life scoring (QOL24-all facets) is also proposed in this article as novelty. The correlation level between QOL24 and the instrument's general facet was also investigated. METHODS: This was a cross-sectional study with a sample of 351 elderly citizens (46.4% males and 53.6% females) randomly selected from the official dataset of the Local Health Unit of Baixo Alentejo. All the data were collected by health professionals at the participants' homes following the structured interview methodology and using the WHOQOL-BREF(PT) instrument. Three different structural equation models were developed: (i) a first-order confirmatory factor analysis, to assess the instrument's psychometric properties; (ii) a hierarchical second-order confirmatory factor analysis model, to allow determining the QOL24 scoring; and (iii) a more generic structural equation model, to investigate the correlation level between QOL24 and the instrument's general facet. RESULTS: The WHOQOL-BREF(PT) showed an "almost very good" goodness of fit (comparative fit index of 0.949 and Tucker-Lewis index of 0.943), an adequate internal consistency (Cronbach's alpha: from 0.64 to 0.90; composite reliability: from 0.59 to 0.88) and tolerable convergent validity (average variance extracted: from 0.374 to 0.614). However, discriminant validity was not reached because strong correlations between the first-order factors (four QOL domains) were obtained, together with low values of the average variance extracted. The scoring of QOL domains and QOL24, determined as weighted averages (proposed in this article as novelty) were significantly different than those determined as unweighted averages. The standardized correlation coefficient between QOL24 and the instrument's general facet was of 0.89 (statistically highly significant). CONCLUSIONS: The WHOQOL-BREF(PT) is a psychometrically sound instrument to assess the QOL of the considered population sample. However, the QOL domains were found strongly intertwined. More studies are necessary to validate the weighted average scoring strategy of QOL domains and QOL24. Concurrent validity between QOL24 and the instrument's general facet was considered as "strong".

Imputation accuracy to whole-genome sequence in Nellore cattle.

BACKGROUND: A cost-effective strategy to explore the complete DNA sequence in animals for genetic evaluation purposes is to sequence key ancestors of a population, followed by imputation mechanisms to infer marker genotypes that were not originally reported in a target population of animals genotyped with single nucleotide polymorphism (SNP) panels. The feasibility of this process relies on the accuracy of the genotype imputation in that population, particularly for potential causal mutations which may be at low frequency and either within genes or regulatory regions. The objective of the present study was to investigate the imputation accuracy to the sequence level in a Nellore beef cattle population, including that for variants in annotation classes which are more likely to be functional. METHODS: Information of 151 key sequenced Nellore sires were used to assess the imputation accuracy from bovine HD BeadChip SNP (~ 777 k) to whole-genome sequence. The choice of the sires aimed at optimizing the imputation accuracy of a genotypic database, comprised of about 10,000 genotyped Nellore animals. Genotype imputation was performed using two computational approaches: FImpute3 and Minimac4 (after using Eagle for phasing). The accuracy of the imputation was evaluated using a fivefold cross-validation scheme and measured by the squared correlation between observed and imputed genotypes, calculated by individual and by SNP. SNPs were classified into a range of annotations, and the accuracy of imputation within each annotation classification was also evaluated. RESULTS: High average imputation accuracies per animal were achieved using both FImpute3 (0.94) and Minimac4 (0.95). On average, common variants (minor allele frequency (MAF) > 0.03) were more accurately imputed by Minimac4 and low-frequency variants (MAF ≤ 0.03) were more accurately imputed by FImpute3. The inherent Minimac4 Rsq imputation quality statistic appears to be a good indicator of the empirical Minimac4 imputation accuracy. Both software provided high average SNP-wise imputation accuracy for all classes of biological annotations. CONCLUSIONS: Our results indicate that imputation to whole-genome sequence is feasible in Nellore beef cattle since high imputation accuracies per individual are expected. SNP-wise imputation accuracy is software-dependent, especially for rare variants. The accuracy of imputation appears to be relatively independent of annotation classification.