Nutrition and Sexual Development in Bulls.

This manuscript provides an overview of the effects of nutrition during different stages of bull sexual development. Nutrition during the prepubertal period can modulate the hypothalamic GnRH pulse generator. Increased nutrition results in greater LH secretion, earlier puberty, and greater testicular mass in yearling bulls, whereas low nutrition has opposite effects. Targeting average daily gain from birth to 24 weeks of age to > 1.2 kg/d and limiting gain after 24 weeks of age to < 1.6 kg/d is recommended to optimize bull sexual development.

Different vehicles containing CaneCPI-5 reduce erosive dentin wear in situ.

OBJECTIVE: This study evaluated the protective capacity of a sugarcane-derived cystatin (CaneCPI-5) in different vehicles (1-solution and 2-chitosan gel) against erosive dentin wear in situ. METHODS: In part-1, 15 volunteers participated in a crossover protocol (solutions): Water; Elmex™ and CaneCPI-5. The volunteers wore an appliance with 4 dentin samples for 5 days. These samples were treated with a drop of the solutions for 1 min (4X/d), then the acquired pellicle (AP) was formed and the samples were subjected to erosive challenges (EROSION: citric acid, for 90 s, 4X/day). 2X/day, half of the samples were also abraded for 15 s (ABRASION). In part-2, 16 volunteers participated in a crossover protocol (gel): No gel, Chitosan gel, Chitosan gel + NaF and Chitosan gel + CaneCPI-5. The volunteers also wore an appliance. The samples were treated once/day with the gel or not for 4 min, then the AP was formed and the samples were subjected to erosive and abrasive challenges, as reported in part-1. Dentin wear was measured by profilometry. Data were analyzed by two-way RM-ANOVA and Sidak's tests (p < 0.05). RESULTS: Part-1: Elmex™ and CaneCPI-5 significantly reduced dentin loss in comparison with Water for the EROSION/ABRASION conditions (p < 0.05). Part-2, all the treated groups significantly reduced the dentin loss in comparison to the No gel. The greatest reduction was found for the gel + CaneCPI-5 group for the EROSION/ABRASION (p < 0.05). CONCLUSION: The solution and chitosan gel containing CaneCPI-5 protected against erosive dentin wear in situ. CLINICAL RELEVANCE: These different vehicles are probably sufficient for protecting people with high risk of developing erosive dentin wear.

Update on the treatment of chemotherapy and radiotherapy-induced buccal mucositis: a systematic review.

Oral mucositis (OM) is a frequent complication in cancer patients who are undergoing chemotherapy or radiotherapy. It manifests as an inflammation of the oral mucosa, sometimes provoking severe consequences such as eating limitations, difficulty in speaking, and possibly superinfection. Aim: The aim of this review was to update the evidence published during the last five years on the treatment of oral mucositis induced by radiotherapy and/or chemotherapy in patients with cancer. Materials and Method: A search was conducted in Pubmed, Scielo and Scopus, using the search terms mucositis, stomatitis, therapy, treatment, oral cancer, oral squamous cell carcinoma, head and neck cancer and head and neck carcinoma, with Mesh terms and free terms, from 2017 to January 2023. The systematic review was conducted in accordance with the PRISMA guidelines. Results: A total 287 articles were retrieved, of which 86 were selected by title and abstract, and 18 were included after full-text analysis. The most frequently assessed variables were OM severity, pain intensity and healing time. Treatment types were diverse, and included drugs, mouthwashes, medicines based on plant extracts, cryotherapy and low-intensity laser therapies. Conclusion: Dentoxol mouthwashes, Plantago major extract, thyme honey extract, zinc oxide paste, vitamin B complex combined with GeneTime, and the consumption of L-glutamine are effective in diminishing the severity of OM. Pain intensity was lower with doxepin mouthwashes and diphenhydramine-lidocaine-antacid mouthwashes.

La mucositis oral (MO) es una complicación frecuente en pacientes oncológicos sometidos a quimioterapia o radioterapia. Se manifiesta como una inflamación de la mucosa oral, provocando en ocasiones graves consecuencias como limitaciones en la alimentación, dificultad para hablar y posiblemente sobreinfección. Objetivo: El objetivo de esta revisión fue actualizar la evidencia publicada durante los últimos cinco años sobre el tratamiento de la mucositis oral inducida por radioterapia y/o quimioterapia, en pacientes con cáncer. Materiales y Método: Se realizó una búsqueda en Pubmed, Scielo y Scopus, con las palabras de búsqueda mucositis, stomatitis, therapy, treatment, oral cancer, oral squamous cell carcinoma, head and neck cancer and head and neck carcinoma, utilizando términos Mesh y libres, de 2017 a enero de 2023. La revisión sistemática se realizó de acuerdo con los lineamientos de declaración del PRISMA. Resultados: Se obtuvieron un total de 287 artículos, de los cuales 86 fueron seleccionados por título y resumen y finalmente 18 fueron incluidos por texto completo. Las variables evaluadas con mayor frecuencia fueron la severidad de la MO, la intensidad del dolor y el tiempo de cicatrización. Los tipos de tratamientos fueron diversos, desde medicamentos, colutorios bucales, medicamentos a base de extractos de plantas, crioterapia y terapias con láser de baja intensidad. Conclusiones: Los enjuagues bucales de Dentoxol, extracto de Plantago major, extracto de miel de tomillo, pasta de óxido de zinc, mezcla de compuestos de vitamina B combinados con GeneTime y el consumo de L-glutamina son efectivos para disminuir la severidad de la MO. La intensidad del dolor fue menor con los colutorios de doxepina y también con los colutorios de difenhidramina-lidocaína-antiácido.

The fusiform gyrus exhibits differential gene-gene co-expression in Alzheimer's disease.

Alzheimer's Disease (AD) is an irreversible neurodegenerative disease clinically characterized by the presence of ß-amyloid plaques and tau deposits in various regions of the brain. However, the underlying factors that contribute to the development of AD remain unclear. Recently, the fusiform gyrus has been identified as a critical brain region associated with mild cognitive impairment, which may increase the risk of AD development. In our study, we performed gene co-expression and differential co-expression network analyses, as well as gene-expression-based prediction, using RNA-seq transcriptome data from post-mortem fusiform gyrus tissue samples collected from both cognitively healthy individuals and those with AD. We accessed differential co-expression networks in large cohorts such as ROSMAP, MSBB, and Mayo, and conducted over-representation analyses of gene pathways and gene ontology. Our results comprise four exclusive gene hubs in co-expression modules of Alzheimer's Disease, including FNDC3A, MED23, NRIP1, and PKN2. Further, we identified three genes with differential co-expressed links, namely FAM153B, CYP2C8, and CKMT1B. The differential co-expressed network showed moderate predictive performance for AD, with an area under the curve ranging from 0.71 to 0.76 (+/- 0.07). The over-representation analysis identified enrichment for Toll-Like Receptors Cascades and signaling pathways, such as G protein events, PIP2 hydrolysis and EPH-Epherin mechanism, in the fusiform gyrus. In conclusion, our findings shed new light on the molecular pathophysiology of AD by identifying new genes and biological pathways involved, emphasizing the crucial role of gene regulatory networks in the fusiform gyrus.

Update on the treatment of chemotherapy and radiotherapy-induced buccal mucositis: a systematic review / Actualización en el tratamiento de la mucositis oral inducida por quimioterapia y radioterapia: una revisión sistemática

ABSTRACT Oral mucositis (OM) is a frequent complication in cáncer patients who are undergoing chemotherapy or radiotherapy. It manifests as an inflammation of the oral mucosa, sometimes provoking severe consequences such as eating limitations, difficulty in speaking, and possibly superinfection. Aim: The aim of this review was to update the evidence published during the last five years on the treatment of oral mucositis induced by radiotherapy and/or chemotherapy in patients with cancer. Materials and Method: A search was conducted in Pubmed, Scielo and Scopus, using the search terms mucositis, stomatitis, therapy, treatment, oral cancer, oral squamous cell carcinoma, head and neck cancer and head and neck carcinoma, with Mesh terms and free terms, from 2017 to January 2023. The systematic review was conducted in accordance with the PRISMA guidelines. Results: A total 287 articles were retrieved, of which 86 were selected by title and abstract, and 18 were included after full-text analysis. The most frequently assessed variables were OM severity, pain intensity and healing time. Treatment types were diverse, and included drugs, mouthwashes, medicines based on plant extracts, cryotherapy and low-intensity laser therapies. Conclusión: Dentoxol mouthwashes, Plantago major extract, thyme honey extract, zinc oxide paste, vitamin B complex combined with GeneTime, and the consumption of L-glutamine are effective in diminishing the severity of OM. Pain intensity was lower with doxepin mouthwashes and diphenhydramine-lidocaine-antacid mouthwashes.

RESUMEN La mucositis oral (MO) es una complicación frecuente en pacientes oncológicos sometidos a quimioterapia o radioterapia. Se manifiesta como una inflamación de la mucosa oral, provocando en ocasiones graves consecuencias como limitaciones en la alimentación, dificultad para hablar y posiblemente sobreinfección. Objetivo: El objetivo de esta revisión fue actualizar la evidencia publicada durante los últimos cinco años sobre el tratamiento de la mucositis oral inducida por radioterapia y/o quimioterapia, en pacientes con cáncer. Materiales y Método: Se realizó una búsqueda en Pubmed, Scielo y Scopus, con las palabras de búsqueda mucositis, stomatitis, therapy, treatment, oral cancer, oral squamous cell carcinoma, head and neck cancer and head and neck carcinoma, utilizando términos Mesh y libres, de 2017 a enero de 2023. La revisión sistemática se realizó de acuerdo con los lineamientos de declaración del PRISMA. Resultados: Se obtuvieron un total de 287 artículos, de los cuales 86 fueron seleccionados por título y resumen y finalmente 18 fueron incluidos por texto completo. Las variables evaluadas con mayor frecuencia fueron la severidad de la MO, la intensidad del dolor y el tiempo de cicatrización. Los tipos de tratamientos fueron diversos, desde medicamentos, colutorios bucales, medicamentos a base de extractos de plantas, crioterapia y terapias con láser de baja intensidad. Conclusiones: Los enjuagues bucales de Dentoxol, extracto de Plantago major, extracto de miel de tomillo, pasta de óxido de zinc, mezcla de compuestos de vitamina B combinados con GeneTime y el consumo de L-glutamina son efectivos para disminuir la severidad de la MO. La intensidad del dolor fue menor con los colutorios de doxepina y también con los colutorios de difenhidramina-lidocaína-antiácido. Palabras clave: mucositis bucal;cáncer;quimioterapia;radioterapia;tratamiento

Use of Reflectometer Optipen to assess the preventive effect of a sugarcane cystatin on initial dental erosion in vivo.

The sugarcane cystatin 5 (CaneCPI-5) showed protection against erosion and erosive tooth wear (ETW) under several protocols. However, evaluating these conditions in vivo is hard due to the lack of a suitable device. The aim of this study was to use clinically the relative surface reflection intensity (%SRI) by the Reflectometer Optipen to assess the acquired pellicle engineering with CaneCPI-5 rinse for the prevention of initial erosion in vivo. Nine volunteers were distributed in three cross-over phases, according to the rinse used, as follows: 1) Deionized water (negative control); 2) Elmex® (800 ppm Sn2+, 500 ppm F-; positive control); 3) 0.1 mg/mL CaneCPI-5. The following experimental steps were performed: Initially, the volunteers received prophylaxis and the initial %SRI was performed. Subsequently, they rinsed with the solutions (10 mL; 1min), followed by the formation of the acquired enamel pellicle (AEP; 120min). After, the erosive challenge with citric acid 1%, pH 2.5 (10 µL; 10s) was performed (in isolation) on the buccal surface of the maxillary central incisors (right and left). The calcium present in the acid was analyzed by Arsenazo III method. Finally, the final %SRI was performed. Data were analyzed by Kruskal-Wallis/Dunn's tests and Spearman's correlation were used (p < 0.05). For both variables, the negative control led to significantly less protection (lower reflectivity and higher calcium release) in comparison with the other groups. The best protection (higher reflectivity and lower calcium release) was observed for the Elmex® and the CaneCPI-5 groups, with no significant differences between them (p < 0.05). There was a significant correlation between both analyzes. The Reflectometer Optipen demonstrated to be a good device to assess clinically. Moreover, CaneCPI-5 rinse proved effective through acquired pellicle engineering against initial erosion in vivo.

Penicillin and amikacin mixture has bactericidal activity equivalent to gentamicin, tylosin, lincomycin and spectinomycin mixture in equine frozen semen.

Neat stallion semen can contain a variety of microorganisms, some of which may impair sperm quality and/or cause infection of the mares' reproductive tract. For this reason, antibiotics are commonly added to semen extenders. A combination of gentamicin, tylosin, lincomycin and spectinomycin (GTLS) has been recommended for use, but there are no reports on the use of this mixture in equine semen extender. Penicillin and amikacin (PA) are safe for preserving sperm quality while effectively controlling bacterial growth in equine cooled stored semen, but data on frozen semen are scarce. Therefore, a bioequivalence study was performed to assess the bactericidal activity of GTLS and PA in equine frozen semen. Nine mature, healthy stallions were used in the study. Split ejaculates were processed using media without antibiotics (Control) or with different antibiotics. For the GTLS group, centrifugation medium and freezing extender were prepared with gentamicin 250 µg/ml, tylosin 50 µg/ml, lincomycin 150 µg/ml and spectinomycin 300 µg/ml. For the PA group, the centrifugation medium was prepared with potassium penicillin G (PPG) 1200 units/ml and the freezing extender was prepared with PPG 1200 units/ml and amikacin 500 µg/ml. Semen processed in extenders without antibiotics had higher (p < .005) bacterial loads throughout all cryopreservation processing steps than semen samples processed using antibiotics. There were no differences in semen bacterial load after centrifugation, 15 and 30 min after final extension, and after thawing between GTLS and PA groups, but PA had faster (p < .05) kill-time kinetics than GTLS. Only minor differences in sperm kinetic parameters were observed among groups. In conclusion, this study demonstrated bioequivalence between GTLS and PA in mitigating end-point bacterial loads. Prudent concentrations of the antibiotic mixtures evaluated in this study can be considered both effective and sperm-safe for equine frozen semen.

DeepHP: A New Gastric Mucosa Histopathology Dataset for Helicobacter pylori Infection Diagnosis.

Emerging deep learning-based applications in precision medicine include computational histopathological analysis. However, there is a lack of the required training image datasets to generate classification and detection models. This phenomenon occurs mainly due to human factors that make it difficult to obtain well-annotated data. The present study provides a curated public collection of histopathological images (DeepHP) and a convolutional neural network model for diagnosing gastritis. Images from gastric biopsy histopathological exams were used to investigate the performance of the proposed model in detecting gastric mucosa with Helicobacter pylori infection. The DeepHP database comprises 394,926 histopathological images, of which 111 K were labeled as Helicobacter pylori positive and 283 K were Helicobacter pylori negative. We investigated the classification performance of three Convolutional Neural Network architectures. The models were tested and validated with two distinct image sets of 15% (59K patches) chosen randomly. The VGG16 architecture showed the best results with an Area Under the Curve of 0.998%. The results showed that CNN could be used to classify histopathological images from gastric mucosa with marked precision. Our model evidenced high potential and application in the computational pathology field.

Preventive effect of chitosan gel containing CaneCPI-5 against enamel erosive wear in situ.

OBJECTIVE: This study evaluated the preventive effect of a chitosan gel containing CaneCPI-5 against enamel erosion and erosion + abrasion in situ. METHODS: Sixteen volunteers participated in a crossover, double-blind protocol, comprising 4 phases: (1) no treatment (Nt); (2) chitosan gel (Cg); (3) chitosan gel + 12,300 ppm NaF (Cg + NaF); and (4) chitosan gel + 0.1 mg/mL CaneCPI-5 (Cg + Cane). Volunteers wore an appliance containing 4 specimens. Once/day, they applied the gel (except for Nt) (4 min/specimen). Erosive challenges were performed extra-orally (0.1% citric acid, 90 s, 4 × /day; ERO). Specimens were also abraded (toothbrush, 15 s/specimen, 2 × /day; ERO + ABR). Enamel wear was assessed by profilometry and relative surface reflection intensity (%SRI). Two-way RM-ANOVA/Sidak's tests and Spearman's correlation were used (p < 0.05). RESULTS: For profilometry, ERO + ABR promoted significantly greater wear when compared with ERO. There was a significant difference among all treatments. The lowest enamel loss occurred for Cg + Cane, followed by Cg + NaF, Cg, and Nt (p < 0.05). The %SRI was significantly lower for ERO + ABR when compared to ERO, only for the Nt group. The greatest %SRI was found for the Cg + NaF and Cg + Cane groups, which did not differ significantly, regardless of the conditions. The lowest %SRI was found for the Nt and Cg groups, which did not differ from each other, regardless of the conditions. The Nt group did not differ significantly from the Cg + NaF (ERO). There was a significant correlation between both analyses. CONCLUSION: The incorporation of CaneCPI-5 in the chitosan gel prevented erosive wear in situ. CLINICAL RELEVANCE: These results open a new perspective for the use of CaneCPI-5 in other application vehicles, such as chitosan gel.

Mitochondrial Genetics Reinforces Multiple Layers of Interaction in Alzheimer's Disease.

Nuclear DNA has been the main source of genome-wide loci association in neurodegenerative diseases, only partially accounting for the heritability of Alzheimer's Disease (AD). In this context, mitochondrial DNA (mtDNA) is gaining more attention. Here, we investigated mitochondrial genes and genetic variants that may influence mild cognitive impairment and AD, through an integrative analysis including differential gene expression and mitochondrial genome-wide epistasis. We assessed the expression of mitochondrial genes in different brain tissues from two public RNA-Seq databases (GEO and GTEx). Then, we analyzed mtDNA from the ADNI Cohort and investigated epistasis regarding mitochondrial variants and levels of Aß1-42, TAU, and Phosphorylated TAU (PTAU) from cognitively healthy controls, and both mild cognitive impairment (MCI) and AD cases. We identified multiple differentially expressed mitochondrial genes in the comparisons between cognitively healthy individuals and AD patients. We also found increased protein levels in MCI and AD patients when compared to healthy controls, as well as novel candidate networks of mtDNA epistasis, which included variants in all mitochondrially-encoded oxidative phosphorylation complexes, 12S rRNA and MT-DLOOP. Our results highlight layers of potential interactions involving mitochondrial genetics and suggest specific molecular alterations as potential biomarkers for AD.

AmazonForest: In Silico Metaprediction of Pathogenic Variants.

ClinVar is a web platform that stores ∼789,000 genetic associations with complex diseases. A partial set of these cataloged genetic associations has challenged clinicians and geneticists, often leading to conflicting interpretations or uncertain clinical impact significance. In this study, we addressed the (re)classification of genetic variants by AmazonForest, which is a random-forest-based pathogenicity metaprediction model that works by combining functional impact data from eight prediction tools. We evaluated the performance of representation learning algorithms such as autoencoders to propose a better strategy. All metaprediction models were trained with ClinVar data, and genetic variants were annotated with eight functional impact predictors cataloged with SnpEff/SnpSift. AmazonForest implements the best random forest model with a one hot data-encoding strategy, which shows an Area Under ROC Curve of ≥0.93. AmazonForest was employed for pathogenicity prediction of a set of ∼101,000 genetic variants of uncertain significance or conflict of interpretation. Our findings revealed ∼24,000 variants with high pathogenic probability (RFprob≥0.9). In addition, we show results for Alzheimer's Disease as a demonstration of its application in clinical interpretation of genetic variants in complex diseases. Lastly, AmazonForest is available as a web tool and R object that can be loaded to perform pathogenicity predictions.

Identificação de competências necessárias aos médicos da Atenção Primária à Saúde para a entrega de cuidados paliativos ao paciente com insuficiência cardíaca / Identification of competencies needed by primary health care physicians to deliver palliative care to patients with heart failure / Identificación de las competencias que necesitan los médicos de atención primaria de salud para brindar cuidados paliativos a pacientes con insuficiencia cardíaca

Introdução: A insuficiência cardíaca (IC) tem prevalência crescente no mundo e já existe maior proporção de pacientes com essa doença necessitando de cuidados paliativos (CP) em relação a outras patologias, como o câncer. Apesar disso, há uma iniquidade na oferta e no reconhecimento da necessidade de CP nos indivíduos com IC. A identificação das competências necessárias para o médico que ofertará esse cuidado é essencial para a melhoria da atenção prestada a esses pacientes. Objetivo: Identificar, por meio de revisão da literatura, as competências requeridas aos médicos da atenção primária para oferecer cuidados paliativos aos pacientes com insuficiência cardíaca. Métodos: Foi utilizado o acrônimo SPIDER para a construção da pergunta e, com base nela, buscou-se identificar as competências necessárias para médicos da atenção primária à saúde na atuação em CP na IC. As bases buscadas foram United States National Library of Medicine (PubMed), Scientific Electronic Library Online (SciELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) e Medical Literature Analysis and Retrieval System Online (Medline), usando descritores e suas variações registradas, guiados pela pergunta. Nos estudos primários relevantes localizados pela estratégia de busca também se procurou por mais estudos elegíveis nos artigos citados. Resultados: De 127 estudos encontrados, oito foram selecionados para extração de dados e avaliados pela metodologia de síntese temática. A competência mais prevalente nos trabalhos selecionados foi a de ofertar CP ao paciente com IC em estágio avançado. Outras competências apontadas foram coordenar o cuidado e ofertar cuidado multidisciplinar ao paciente com IC. Conclusão: Esta revisão revelou conhecimentos e habilidades requeridos na formação do médico da APS para atingir as principais competências na promoção dos CP ao paciente com IC.

Introduction: Heart failure (HF) has an increasing prevalence in the world and there is already a greater proportion of patients with this disease in need of palliative care (PC) in relation to other pathologies, such as cancer. Despite this, there is an inequity in the provision and recognition of the need for PC in individuals with HF. The identification of the necessary competencies for the physician who will offer this care is essential for improving the care provided to these patients. Objective: To identify, through a literature review, the necessary competencies to primary care physicians to provide care to patients with heart failure. Methods: The acronym SPIDER was used to construct the question and, based on it, we sought to identify the necessary skills for primary health care physicians to work in PC in HF. The bases searched were PubMed, SciELO, Lilacs, and Medline, using descriptors and their registered variations, guided by the question. In the relevant primary studies identified by the search strategy, more eligible studies were also searched in their cited articles. Results: Of 127 identified studies, 8 were selected for data extraction and evaluated by the thematic synthesis methodology. The most prevalent competence in the selected studies was to offer PC to patients with advanced stage HF. Other competencies pointed out were coordinating care and offering multidisciplinary care to patients with HF. Conclusions: This review evidenced the knowledge and skills required in the training of the PHC physician to achieve the main competencies in the promotion of PC to patients with HF.

Introducción: La insuficiencia cardíaca (IC) tiene una prevalencia creciente en el mundo y ya existe una mayor proporción de pacientes con esta enfermedad que necesitan cuidados paliativos (CP) en relación con otras patologías, como el cáncer. A pesar de eso, existe una inequidad en la provisión y reconocimiento de la necesidad de CP en individuos con IC y la identificación de las habilidades necesarias del médico que ofrecerá esa atención es fundamental para mejorar la atención brindada a esos pacientes. Objetivo: Identificar, a través de una revisión de la literatura, las competencias requeridas por los médicos de atención primaria para brindar atención a pacientes con insuficiencia cardíaca. Métodos: Se utilizó la sigla SPIDER para construir la pregunta y, con base en ella, se buscó identificar las competencias necesarias para que los médicos de atención primaria de salud actúen en CP en IC. Las bases buscadas fueron PubMed, SciELO, Lilacs y Medline utilizando descriptores y sus variaciones registradas, guiados por la pregunta. En los estudios primarios relevantes identificados por la estrategia de búsqueda, también se buscaron estudios más elegibles en los artículos citados. Resultados: De los 127 estudios identificados, 8 fueron seleccionados para la extracción de datos y evaluados por la metodología de síntesis temática. La competencia más prevalente en los estudios seleccionados fue ofrecer CP a pacientes con IC en estadio avanzado. Otras competencias señaladas fueron coordinar la atención y ofrecer atención multidisciplinar a los pacientes con IC. Conclusiones: Esta revisión evidenció los conocimientos y habilidades requeridas en la formación del médico de AP para alcanzar las principales competencias en la promoción de CP a pacientes con IC.

Effectiveness of testosterone replacement in men with obesity: a systematic review and meta-analysis.

OBJECTIVE: This systematic review evaluated the effect of testosterone replacement therapy (TRT) in men with obesity having low testosterone levels (LTLs). DESIGN AND METHODS: Search strategies were performed in MEDLINE, Embase, LILACS, and CENTRAL databases. Two reviewers selected the studies, assessed the risk of bias, and extracted data from the included studies. A random-effects model was used to pool results across studies, and the Grading of Recommendations Assessment, Development, and Evaluation was used to evaluate the certainty of evidence. RESULTS: A total of 16 randomized controlled trials were included. With moderate certainty of the evidence, no difference was found between TRT and placebo regarding total adverse events, TRT led to a 2-kg lean body mass gain and slightly improved low-density lipoprotein (LDL), without effects on the blood pressure. Due to imprecision/heterogeneity, effects in cardiovascular events (relative risk: 0.52, 95% CI: 0.26 to 1.05, 7 trials, 583 participants), high-density lipoprotein, hematocrit, prostate-specific antigen, HbA1c, and quality of life were unclear. TRT was effective for waist circumference and BMI; however, large between-study heterogeneity was found, with 95% prediction intervals crossing the null effect line. Meta-regression revealed that the average age of participants was a significant modifier for both outcomes. CONCLUSION: TRT slightly improved the lean body mass and LDL in men with obesity having LTLs but did not affect the blood pressure. The effects of TRT on cardiovascular events, HbA1c, and quality of life are unclear. The mean age of participants significantly modified the effect of TRT on weight loss.

Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation.

BACKGROUND: Next generation sequencing (NGS) has been a handy tool in clinical practice, mainly due to its efficiency and cost-effectiveness. It has been widely used in genetic diagnosis of several inherited diseases, and, in clinical oncology, it may enhance the discovery of new susceptibility genes and enable individualized care of cancer patients. In this context, we explored a pan-cancer panel in the investigation of germline variants in Brazilian patients presenting clinical criteria for hereditary cancer syndromes or familial history. METHODS: Seventy-one individuals diagnosed or with familial history of hereditary cancer syndromes were submitted to custom pan-cancer panel including 16 high and moderate penetrance genes previously associated with hereditary cancer syndromes (APC, BRCA1, BRCA2, CDH1, CDKN2A, CHEK2, MSH2, MSH6, MUTYH, PTEN, RB1, RET, TP53, VHL, XPA and XPC). All pathogenic variants were validated by Sanger sequencing. RESULTS: We identified a total of eight pathogenic variants among 12 of 71 individuals (16.9%). Among the mutation-positive subjects, 50% were diagnosed with breast cancer and had mutations in BRCA1, CDH1 and MUTYH. Notably, 33.3% were individuals diagnosed with polyposis or who had family cases and harbored pathogenic mutations in APC and MUTYH. The remaining individuals (16.7%) were gastric cancer patients with pathogenic variants in CDH1 and MSH2. Overall, 54 (76.05%) individuals presented at least one variant uncertain significance (VUS), totalizing 81 VUS. Of these, seven were predicted to have disease-causing potential. CONCLUSION: Overall, analysis of all these genes in NGS-panel allowed the identification not only of pathogenic variants related to hereditary cancer syndromes but also of some VUS that need further clinical and molecular investigations. The results obtained in this study had a significant impact on patients and their relatives since it allowed genetic counselling and personalized management decisions.

Nasal septum deviation and inferior nasal concha bone hypertrophy in class III facial deformity / Desviación del septum nasal e hipertrofia de la concha nasal inferior en deformidad facial clase III

SUMMARY: The aim of this research was to analyze the morphology of the nasal septum and inferior nasal concha bone in class III facial deformities prior to orthodontic treatment in orthognathic surgery candidates. 40 subjects were included in this research. The inclusion criteria were an Angle class III, negative overjet and SNA angle less than 80º. Patients with facial asymmetry, facial trauma or who had undergone maxillofacial or ENT procedures were excluded. CBCT images were obtained for all the patients and the nasal septum deviation, morphology of inferior nasal concha bone and ostium of the maxillary sinus were analyzed and related to the complexity of the facial deformity expressed by the ANB angle and dental relations. The measurement was standardized by ICC and the data was analyzed using a chi square test and Spearman's coefficient with a p value < 0.005 for statistical significance. Nasal septal deviation was observed in 77.5 %. The deviation angle was 13.28º (±4.68º) and the distance from the midline to the most deviated septum was 5.56 mm (±1.8 mm) with no statistical relation to the complexity of the facial deformity. The deviated nasal septum showed inferior nasal concha bone hypertrophy on the concave side of the nasal septum deviation (p=0.049). The open or closed condition of the maxillary sinus ostium was not related to any conditions in the septum or complexity of the facial deformity. Inferior nasal concha bone hypertrophy could be related to nasal septal deviation. The nasal condition in a class III facial deformity could not differ from the general population; careful in orthognathic surgery as to be assume in the Le Fort I Osteotomy and nasal approach related to nasal septum deviation and inferior nasal concha bone.

RESUMEN: El objetivo de esta investigación fue analizar la morfología del septum y la concha nasal inferior en sujetos con deformidad facial clase III previo al tratamiento de ortodoncia preparatorio para cirugía ortognática. Fueron incluidos 40 sujetos en esta investigación. Los criterios de inclusión fueron la de presentar una clase III de Angle, overjet negativo y ángulo SNA menor que 80º. Sujetos con asimetría facial, trauma facial o quienes presentaron algún tipo de procedimiento maxilofacial o de otorrinolaringología fueron excluidos. Tomografía computadorizada cone beam (CBCT) fueron obtenidas para todos los sujetos donde le morfología del septum nasal, morfología de la concha nasal inferior y el ostium del seno maxilar fueron analizados y relacionados con la complejidad de la deformidad facial expresada como ángulo ANB y relaciones dentales. Las medidas fueron estandarizadas por el ICC y los datos fueron analizados utilizando la prueba chi cuadrado y coeficiente de Spearman con un valor de p<0,05 para obtener relaciones significativas. La desviación del septum nasal se observó en el 77,5 %; el ángulo de desvío fue de 13,28º (±4,68º) y la distancia de desvío del septum desde la línea media fue de 5,56 mm (±1,8 mm) sin diferencias estadísticas en relación a la complejidad de la deformidad. El desvío de septum nasal demostró hipertrofia de la concha nsal inferior en el lado cóncavo del septum desviado (p=0,049). La condición de ostium abierto o cerrado no fue relacionado con ninguna condición del septum nasal o complejidad de la deformidad facial. La hipertrofia de la concha nasal inferior se relacionó con el desvío de septum nasal. La condición nasal en deformidad facial de clase III no es diferente de la observada en la población general; cuidados deben ser realizados en cirugía ortognática para el desarrollo de la osteotomía de Le Fort I y aproximación nasal en relación al desvío de septum y probable alteración de la concha nasal inferior.

Novel insights toward human stroke-related epigenetics: circular RNA and its impact in poststroke processes.

Aim: Circular RNAs (circRNAs) are dysregulated in complex diseases, so we investigated their global expression profile in stroke. Material & methods: Public RNA-Seq data of human ischemic stroke lesion tissues and controls were used to perform the global expression analysis. Target RNA binding proteins and microRNAs were predicted in silico. Functional enrichment analysis was performed to infer the circRNAs' potential roles. Results: We found that circRNAs are potentially involved in synaptic components and transmission, inflammation and ataxia. An integrative analysis revealed that hsa_circ_0078299 and FXN may be major players in the molecular stroke-context. Conclusion: Our results suggest a broad involvement of circRNAs in some stroke-related processes, indicating their potential as therapeutic targets to allow neuroprotection and brain recovery.

Differential Expression and miRNA-Gene Interactions in Early and Late Mild Cognitive Impairment.

Mild cognitive impairment (MCI) and Alzheimer's Disease (AD) are complex diseases with their molecular architecture not elucidated. APOE, Amyloid Beta Precursor Protein (APP), and Presenilin-1 (PSEN1) are well-known genes associated with both MCI and AD. Recently, epigenetic alterations and dysregulated regulatory elements, such as microRNAs (miRNAs), have been reported associated with neurodegeneration. In this study, differential expression analysis (DEA) was performed for genes and miRNAs based on microarray and RNA-Seq data. Global gene profile of healthy individuals, early and late mild cognitive impairment (EMCI and LMCI, respectively), and AD was obtained from ADNI Cohort. miRNA global profile of healthy individuals and AD patients was extracted from public RNA-Seq data. DEA performed with limma package on ADNI Cohort data highlighted eight differential expressed (DE) genes (AGER, LINC00483, MMP19, CATSPER1, ARFGAP1, GPER1, PHLPP2, TRPM2) (false discovery rate (FDR) p-value < 0.05) between EMCI and LMCI patients. Previous molecular studies showed associations between these genes with dementia and neurological-related pathways. Five dysregulated miRNAs were identified by DEA performed with RNA-Seq data and edgeR (FDR p-value < 0.002). All reported miRNAs in AD interact with the aforementioned genes. Our integrative transcriptomic analysis was able to identify a set of miRNA-gene interactions that may be involved in cognitive and neurodegeneration processes.

3-D airway analysis related to facial morphology / Análisis 3-D de la vía aerea relacionado con la morfología facial

The aim of this investigation was to define the volume and area of the airway in subjects with Class II and Class III skeletal deformity. A cross-sectional study was designed including subjects with facial deformity defined by Steiner's analysis in subjects with indication of orthognathic surgery who presented diagnosis by cone beam computerised tomography. We determined the measurements of maximum area, minimum area and volume of the airway. The data were compared using Spearman's test, with statistical significance defined as p<0.05. 115 subjects were included: 61.7 % Class II and 38.3 % Class III, mean age 27.8 years (± 11.6). A significant difference was observed in the area and volume measurements in the groups studied, with significantly smaller measurements found in Class II (p=0.034). The minimum area was 10.4 mm2 smaller in Class II patients than in Class III, while the general volume of the airway was 4.1 mm3 smaller in Class II than in Class III. We may conclude that Class II subjects present a smaller airway volume than Class III subjects.

El objetivo de esta investigación de definir el volumen y área de vía aérea en sujetos con deformidad esqueletal clase II y III. Se diseñó un estudio de corte transversal incluyendo sujetos con deformidad facial definida según análisis de Stainer en sujetos con indicación de cirugía ortognática que presentaran una tomografía computadorizada de haz cónico como elemento diagnóstico; en este examen se determinaron medidas de área mayor, menor de vía aérea y volumen presente; los datos fueron comparados utilizando pruebas estadísticas con el test de spearman considerando el valor de p<0,05 para definir significancia estadística. 115 sujetos fueron incluidos, siendo 61,7 % de tipo clase II y 38,3 % de sujetos clase III, con una edad promedio de 27,8 años (± 11,6). Se observó una diferencia significativa en mediciones de area y volumen en los grupos estudiados, siendo el grupo de clase II significativamente menor (p=0,034). El área de menor tamaño fue 10,4 mm2 en pacientes clase II que en pacientes clase III, mientras que el volumen general de la vía área fue 4,1 menor en los clase II que en los clase III. Es posible concluir que los sujetos de clase II presentan menor volumen de vía área que los sujetos clase III.

Nível de ansiedade e fatores associados: Estudantes de Farmácia de uma faculdade privada / Anxiety Level and Associated Factors: Pharmacy Students from a Private College

Objetivo: Avaliar o perfil de ansiedade de estudantes do curso de Farmácia em uma Instituição particular do Distrito Federal e verificar fatores associados. Método: Trata-se de um estudo transversal, realizado, entre novembro de 2018 a abril de 2019, com 200 estudantes de graduação do curso de Farmácia de uma faculdade particular do Distrito Federal. O instrumento utilizado foi o Inventário de Ansiedade de Beck (BAI), validado no Brasil, composto por 21 perguntas de múltipla escolha, referentes ao estado emocional, fisiológico e cognitivo da última semana. Foram também avaliados dados sociodemográficos e hábitos de vida. Resultados: A amostra foi constituída por maioria mulheres (76%), sem companheiro (64%), com baixa classe econômica (62%), baixa ingesta de álcool (59%), estado nutricional (56% sobrepeso), inatividade física (66%) e percepção de saúde regular (32%). A maioria dos estudantes apresentaram elevado nível de ansiedade, sendo relacionado com sexo (p=0,02), estado civil (p=0,04), etilismo (0<0,01) e atividade física (p=0,03). Os estudantes que apresentaram o maior nível de ansiedade foram os etilistas, os inativos fisicamente e com sobrepeso. Conclusão: Os alunos de farmácia apresentaram elevados níveis de ansiedade e hábitos de vida inadequados. Assim, são necessárias intervenções que propiciem uma melhora desses níveis, impactando positivamente a formação acadêmica e a qualidade de vida dos estudantes

Objective: To evaluate the anxiety profile of students of the Pharmacy course in a private institution of the Federal District and to verify associated factors. Methods: This is a cross-sectional study, carried out between November 2018 and April 2019, with 200 undergraduate students of the Pharmacy course of a private college in the Federal District. The instrument used was the Beck Anxiety Inventory (BAI), validated in Brazil, composed of 21 multiple-choice questions concerning the emotional, physiological and cognitive state of last week. Sociodemographic data and life habits were also evaluated. Results: The sample consisted of a majority of women (76%), with no partner (64%), low economic class (62%), low alcohol intake (59%), nutritional status (56% overweight), physical inactivity 66%) and regular health perception (32%). (P = 0.02), marital status (p = 0.04), alcoholism (0 <0.01) and physical activity (p = 0.03) . The students who presented the highest level of anxiety were the alcoholics, the physically inactive and overweight. Conclusion: Pharmacy students presented high levels of anxiety and inadequate life habits. Thus, interventions are necessary to improve these levels, positively impacting the academic formation and quality of life of the students.