Validation of qPCR reference genes in the endangered annual killifish Austrolebias charrua considering different tissues, gender and environmental conditions.

The annual killifish Austrolebias charrua is an endangered species, endemic to the southern region of South America, which inhabits temporary ponds that emerges in the rainy season. The main anthropogenic threat driving the extinction of A. charrua stems from extensive agriculture, primarily due to the widrespread use of glyphosate-based herbicides near their habitats. Annual killifishes have been used as models for ecotoxicological studies but, up to now, there are no studies about reference genes in any Austrolebias species. This represents an obstacle to the use of qPCR-based technologies, the standard method for gene expression quantification. The present study aimed to select and validate potential reference genes for qPCR normalization in the annual killifish Austrolebias charrua considering different tissues, gender and environmental conditions. The candidate reference genes 18 s, actb, gapdh, ef1a, shox, eif3g, and the control gene atp1a1 were evaluated in male and female individuals in three different tissues (brain, liver, and gills) under two experimental conditions (control and acute exposition to Roundup Transorb®). The collected tissues were submitted to RNA extraction, followed by cDNA synthesis, cloning, sequencing, and qPCR. Overall, 18 s was the most stable reference gene, and 18 s and ef1a were the most stable combination. Otherwise, considering all variables, gapdh and shox were the least stable candidate genes. Foremost, suitable reference genes were validated in A. charrua, facilitating accurate mRNA quantification in this species, which might be useful for developing molecular tools of ecotoxicological assessment based on gene expression analysis for environmental monitoring of annual killifish.

Treatment with Blackberry Extract and Metformin in Sporadic Alzheimer's Disease Model: Impact on Memory, Inflammation, Redox Status, Phosphorylated Tau Protein and Insulin Signaling.

Natural products offer promising potential for the development of new therapies for Alzheimer's disease (AD). Blackberry fruits are rich in phytochemical compounds capable of modulating pathways involved in neuroprotection. Additionally, drug repurposing and repositioning could also accelerate the development of news treatments for AD. In light of the reduced brain glucose metabolism in AD, an alternative approach has been the use of the drug metformin. Thus, the aim of this study was to evaluate the effect of treatment with blackberry extract in a model of AD induced by streptozotocin (STZ) and compare it with metformin treatment. Male rats were divided into groups: I - Control; II - STZ; III - STZ + blackberry extract (100 mg/kg); IV - STZ + blackberry extract (200 mg/kg) and V - STZ + metformin (150 mg/kg). The animals received intracerebroventricular injection of STZ or buffer. Seven days after the surgical procedure, the animals were treated orally with blackberry extract or metformin for 21 days. Blackberry extract and metformin prevented the memory impairment induced by STZ. In animals of group II, an increase in acetylcholinesterase activity, phosphorylated tau protein, IL-6, oxidative damage, and gene expression of GSK-3ß and Nrf2 was observed in the hippocampus. STZ induced a decrease in IL-10 levels and down-regulated the gene expression of Akt1, IRS-1 and FOXO3a. Blackberry extract and metformin prevented the alterations in acetylcholinesterase activity, IL-6, GSK3ß, Nrf2, and oxidative damage. In conclusion, blackberry extract exhibits multi-target actions in a model of AD, suggesting new therapeutic potentials for this neurodegenerative disease.

Patentometric analysis of the technological development of biotechnology for health in higher education institutions in Rio Grande do Sul.

Biotechnology offers solutions and opportunities to meet various societal demands, thereby contributing to significant scientific advancements. This study aimed to characterize the technological development of biotechnology in the healthcare sector in the state of Rio Grande do Sul, Brazil, from 2016 to 2022 by analyzing patents filed by and granted to public and private Higher Education institutions. For data collection, a quantitative exploratory approach was employed using statistical methods and a patent analysis of institutions in the patent database of the Brazilian National Institute of Industrial Property (INPI), focusing on patents related to the healthcare field. Data were collected in October, November, and December. A total of 580 patent records were collected from the INPI, belonging to Sections A and C of the International Patent Classification (IPC) related to educational institutions. Furthermore, this study highlighted that higher education institutions have a higher number of patents in the healthcare field. These results provide an understanding of the strategic areas for technological development in biotechnology in Rio Grande do Sul, Brazil.

Developing a Nomogram for Prioritizing Hysteroscopy in Endometrial Cancer Diagnosis: A Case-Control Study.

(1) Background: The pandemic led to significant healthcare disruptions, resulting in postponed surgeries and extended waiting times for non-urgent treatments, including hysteroscopies essential for diagnosing endometrial cancer. This study aims to formulate a risk stratification model to enhance the prioritization of hysteroscopy procedures in Brazil; (2) Methods: A case-control study was conducted at Vila Santa Catarina Hospital in São Paulo, analyzing the medical records of 2103 women who underwent hysteroscopy between March 2019 and March 2022. We used bivariate analysis and multivariate linear regression to identify risk factors associated with endometrial cancer and formulate a nomogram; (3) Results: The findings revealed a 5.5% incidence of pre-invasive and invasive endometrial disease in the study population, with an average waiting time of 120 days for hysteroscopy procedures. The main risk factors identified were hypertension, diabetes, postmenopausal bleeding, and obesity; (4) Conclusions: This research highlights the urgent need for efficient prioritization of hysteroscopy procedures in the wake of the pandemic. The developed nomogram is an innovative tool for identifying patients at higher risk of endometrial cancer, thus facilitating timely diagnosis and treatment and improving overall patient outcomes in a strained healthcare system.

Expression of sperm microRNAs related to bull fertility: A systematic review.

In this study we proposed to address the following question: "Are there differentially expressed sperm microRNAs related to fertility in bulls?". A systematic review of scientific literature until November 2022 was performed, in accordance with PRISMA guidelines. The main outcome was differentially expressed sperm microRNA from bulls with low versus high fertility profiles identified by using different methods such as field fertility evaluation and sperm laboratory analysis. Were identified 786 documents, of which 13 were selected for qualitative analysis. A total of 182 unique differentially expressed miRNAs were identified, among these, 49 miRNAs were found in common between at least two studies. It is believed that from these 49 miRNAs, it is possible that miRNAs such as miR-10a, -10b, -103, -15b, -122, -125b, -126-5p, -151-5p, -193a-5p, -196a, -27a-5p and -99b could be potential universal biomarkers to assess the reproductive potential of males.

Assessment of oxidative stress biomarkers in the threatened annual killifish Austrolebias charrua exposed to Roundup.

This study aimed to analyze the toxic effects of Roundup Transorb® on the endangered Neotropical annual killifish Austrolebias charrua through the assessment of molecular and biochemical biomarkers. The fish were collected in temporary ponds and exposed to environmentally realistic concentrations of the herbicide (5 mg.L-1 for 96 h). The production of ROS, lipid peroxidation, DNA damage, and membrane fluidity were evaluated in the blood cells by flow cytometry. The mRNA expression of the antioxidant-related genes sod2, cat, gstα, atp1a1, gclc, and ucp1 across the brain, liver, and gills was quantified. The acute exposure of annual killifish to Roundup significantly increased ROS production, lipid peroxidation, and DNA damage in their erythrocytes. Likewise, Roundup Transorb® decreased membrane fluidity in the blood cells of the exposed fish. Gene expression analysis revealed that Roundup exposure alters the relative expression of genes associated with oxidative stress and antioxidant defense. Our results give rise to new insights into adaptive mechanisms of A. charrua in response to Roundup. Since Brazilian annual killifishes strongly risk extinction, this study paves the way for developing novel biotechnologies applied to environmental monitoring and aquatic toxicology assessment.

Direct interhemispheric cortical communication via thalamic commissures: a new white matter pathway in the primate brain.

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported and named the thalamic commissures (TCs) as an additional interhemispheric axonal fiber pathway connecting the cortex to the contralateral thalamus in the rodent brain. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted MRI, viral axonal tracing, and fMRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as a vital fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.

Predictors of chronic joint pain after Chikungunya virus infection in the INOVACHIK prospective cohort study.

BACKGROUND: Chikungunya can cause persistent chronic joint pain. Knowledge of the risk factors for disease progression is important for preventing and controlling complications. This study aimed to identify factors associated with chronic joint pain. METHODS: This prospective cohort study was conducted at a reference center in Rio de Janeiro. Men and women (aged ≥ 18 years) in the acute phase of Chikungunya were included. Clinical data and samples were collected over three months. Risk factors were evaluated using multivariate and logistic regression analyses. RESULTS: A total of 107 patients were followed up. The incidence rate of joint tenderness was 61.7 %. Female sex (adjusted odds ratio [AOR] 3.24, 95 % confidence interval [CI]:1.07-9.77), diarrhea (AOR 5.08, 95 % CI:1.55-16.67), severe joint pain (AOR 4.26, 95 % CI:1.06-17.06), and CHIKV real-time reverse transcription polymerase chain reaction positivity up to 5 days after the onset of symptoms in urine or saliva (AOR 4.56, 95 % CI:1.41-14.77) were identified as predictors of persistent chronic pain. CONCLUSIONS: In a predominantly female population, musculoskeletal symptoms are not the sole determinant of chronic pain, and careful evaluation of CHIKV detection in alternative body fluids (such as saliva and urine) during the early phase of the disease is warranted.

Validation of deep learning techniques for quality augmentation in diffusion MRI for clinical studies.

The objective of this study is to evaluate the efficacy of deep learning (DL) techniques in improving the quality of diffusion MRI (dMRI) data in clinical applications. The study aims to determine whether the use of artificial intelligence (AI) methods in medical images may result in the loss of critical clinical information and/or the appearance of false information. To assess this, the focus was on the angular resolution of dMRI and a clinical trial was conducted on migraine, specifically between episodic and chronic migraine patients. The number of gradient directions had an impact on white matter analysis results, with statistically significant differences between groups being drastically reduced when using 21 gradient directions instead of the original 61. Fourteen teams from different institutions were tasked to use DL to enhance three diffusion metrics (FA, AD and MD) calculated from data acquired with 21 gradient directions and a b-value of 1000 s/mm2. The goal was to produce results that were comparable to those calculated from 61 gradient directions. The results were evaluated using both standard image quality metrics and Tract-Based Spatial Statistics (TBSS) to compare episodic and chronic migraine patients. The study results suggest that while most DL techniques improved the ability to detect statistical differences between groups, they also led to an increase in false positive. The results showed that there was a constant growth rate of false positives linearly proportional to the new true positives, which highlights the risk of generalization of AI-based tasks when assessing diverse clinical cohorts and training using data from a single group. The methods also showed divergent performance when replicating the original distribution of the data and some exhibited significant bias. In conclusion, extreme caution should be exercised when using AI methods for harmonization or synthesis in clinical studies when processing heterogeneous data in clinical studies, as important information may be altered, even when global metrics such as structural similarity or peak signal-to-noise ratio appear to suggest otherwise.

Direct interhemispheric cortical communication via thalamic commissures: a new white-matter pathway in the primate brain.

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported an additional commissural pathway in rodents, termed the thalamic commissures (TCs), as another interhemispheric axonal fiber pathway that connects cortex to the contralateral thalamus. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted magnetic resonance imaging, viral axonal tracing, and functional MRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as an important fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.

Retinopatia hipertensiva - relação com o tempo de diagnóstico da hipertensão arterial sistêmica / Hypertensive retinopathy - relation with time of diagnosis of hypertension / Retinopatía hipertensiva - relación con el tiempo de diagnóstico de hipertensión arterial sistémica

Introdução: Hipertensão arterial sistêmica é uma condição em que a pressão do sangue contra as paredes das artérias é muito elevada. O olho, diretamente envolvido no aumento da resistência vascular periférica, é orgão-alvo quando a retinopatia hipertensiva se faz presente. O controle da hipertensão arterial sistêmica desempenha papel fundamental na evolução da retinopatia hipertensiva, considerando o tempo de duração e a idade dos pacientes. Fundoscopia é o exame mais importante para visualizar esses pequenos vasos, sendo possível detectar alterações e classificar a hipertensão arterial sistêmica para uma melhor conduta terapêutica. As alterações vasculares retinianas visualizadas no fundo do olho são classificadas na hipertensão arterial sistêmica em arterioescleróticas e hipertensivas. Objetivo: Identificar os principais fatores relacionados à retinopatia hipertensiva e a relação com o tempo de diagnóstico de hipertensão arterial sistêmica. Método: Estudo transversal, observacional e descritivo. Fundoscopia e Retinografia foram realizados em pacientes do ambulatório de oftalmologia de um hospital-escola no interior paulista, com diagnóstico de hipertensão arterial sistêmica, para avaliar o grau de comprometimento vascular retiniano. Resultados: Foram examinados 236 olhos de 118 pacientes, a maioria do sexo feminino (58,5%), com idade média de 61 anos. Questionados sobre o controle da sua hipertensão arterial sistêmica, as respostas obtidas foram: 48 pacientes (40,7%) souberam responder que sua pressão era controlada com medicação; 60 (50,9%) afirmaram descontrole da pressão sistêmica e 10 (8,4%) não souberam responder. Dos 103 pacientes (88%) que apresentaram alterações na Fundoscopia, 70% apresentaram alterações relacionadas a arteriosclerose e 76 (64%) relacionados à retinopatia hipertensiva. Dos pacientes com arteriosclerose, 74,7% apresentaram alteração no cruzamento arteriovenoso, enquanto os pacientes com retinopatia hipertensiva 51,3% apresentaram vasoconstrição arteriolar espástica. A abordagem terapêutica da HAS é baseada na tentativa de controle dos valores pressóricos e a adesão ao tratamento é um fator fundamental para o manejo de condições e a prevenção de complicações decorrentes delas. Conclusão: Os fatores diagnósticos relacionados à retinopatia hipertensiva foram: o tempo diagnóstico, as alterações vasculares de arterioloesclerose e o descontrole pressórico. As alterações na retinografia servem para auxiliar na gravidade de hipertensão arterial sistêmica bem como alertar e estimular à ter um melhor controle de PA. O envolvimento de toda a equipe de saúde também é necessário para uma visão multidisciplinar do problema, já que a adesão ao tratamento é importante no controle da hipertensão arterial sistêmica

Introduction: Systemic arterial hypertension is a condition in which blood pressure against the walls of the arteries is very high. The eye, directly involved in increasing peripheral vascular resistance, is the target organ when hypertensive retinopathy is present. The control of systemic arterial hypertension plays a fundamental role in the evolution of hypertensive retinopathy, considering the duration and age of the patients. Fundoscopy is the most important exam to visualize these small vessels, making it possible to detect changes and classify systemic arterial hypertension for better therapeutic management. Retinal vascular changes seen in the fundus of the eye are classified in systemic arterial hypertension into arteriosclerotic and hypertensive. Objective: To identify the main factors related to hypertensive retinopathy and the relationship with the time of diagnosis of systemic arterial hypertension. Method: Cross-sectional, observational and descriptive study. Fundoscopy and retinography were performed on patients at the ophthalmology outpatient clinic of a teaching hospital in the interior of São Paulo, diagnosed with systemic arterial hypertension, to assess the degree of retinal vascular compromise. Results: 236 eyes of 118 patients were examined, the majority of them female (58.5%), with a mean age of 61 years. When asked about the control of their systemic arterial hypertension, the answers obtained were: 48 patients (40.7%) were able to answer that their pressure was controlled with medication; 60 (50.9%) stated that they had uncontrolled systemic pressure and 10 (8.4%) were unable to answer. Of the 103 patients (88%) who presented changes on Fundoscopy, 70% presented changes related to arteriosclerosis and 76 (64%) related to hypertensive retinopathy. Of the patients with arteriosclerosis, 74.7% presented changes in arteriovenous crossing, while 51.3% of patients with hypertensive retinopathy presented spastic arteriolar vasoconstriction. The therapeutic approach to SAH is based on trying to control blood pressure values and adherence to treatment is a fundamental factor in managing conditions and preventing complications resulting from them. Conclusion: The diagnostic factors related to hypertensive retinopathy were: time of diagnosis, vascular alterations of arteriolosclerosis and lack of blood pressure control. Changes in retinography serve to help with the severity of systemic arterial hypertension as well as alert and encourage better BP control. The involvement of the entire healthcare team is also necessary for a multidisciplinary view of the problem, as adherence to treatment is important in controlling systemic arterial hypertension

Introducción: La hipertensión arterial sistémica es una condición en la que la presión arterial contra las paredes de las arterias es muy alta. El ojo, directamente implicado en el aumento de la resistencia vascular periférica, es el órgano diana cuando hay retinopatía hipertensiva. El control de la hipertensión arterial sistémica juega un papel fundamental en la evolución de la retinopatía hipertensiva, considerando la duración y edad de los pacientes. La fundoscopia es el examen más importante para visualizar estos pequeños vasos, permitiendo detectar cambios y clasificar la hipertensión arterial sistémica para un mejor manejo terapéutico. Los cambios vasculares retinianos observados en el fondo del ojo se clasifican en la hipertensión arterial sistémica en arteriosclerótica e hipertensiva. Objetivo: Identificar los principales factores relacionados con la retinopatía hipertensiva y la relación con el momento del diagnóstico de la hipertensión arterial sistémica. Método: Estudio transversal, observacional y descriptivo. Se realizaron fundoscopia y retinografía a pacientes del ambulatorio de oftalmología de un hospital universitario del interior de São Paulo, diagnosticados con hipertensión arterial sistémica, para evaluar el grado de compromiso vascular retiniano. Resultados: Se examinaron 236 ojos de 118 pacientes, la mayoría del sexo femenino (58,5%), con una edad media de 61 años. Al preguntarles sobre el control de su hipertensión arterial sistémica, las respuestas obtenidas fueron: 48 pacientes (40,7%) pudieron responder que su presión estaba controlada con medicamentos; 60 (50,9%) afirmaron tener presión sistémica descontrolada y 10 (8,4%) no supieron responder. De los 103 pacientes (88%) que presentaron cambios en la fundoscopia, el 70% presentó cambios relacionados con arteriosclerosis y 76 (64%) relacionados con retinopatía hipertensiva. De los pacientes con arteriosclerosis, el 74,7% presentó cambios en el cruce arteriovenoso, mientras que el 51,3% de los pacientes con retinopatía hipertensiva presentaron vasoconstricción arteriolar espástica. El abordaje terapéutico de la HAS se basa en intentar controlar los valores de presión arterial y la adherencia al tratamiento es un factor fundamental para el manejo de las afecciones y la prevención de complicaciones derivadas de las mismas. Conclusión: Los factores diagnósticos relacionados con la retinopatía hipertensiva fueron: momento del diagnóstico, alteraciones vasculares de la arteriolosclerosis y falta de control de la presión arterial. Los cambios en la retinografía sirven para ayudar con la gravedad de la hipertensión arterial sistémica, así como para alertar y fomentar un mejor control de la PA. También es necesaria la implicación de todo el equipo sanitario para una visión multidisciplinar del problema, ya que la adherencia al tratamiento es importante en el control de la hipertensión arterial sistémica

MicroRNA qPCR normalization in Nile tilapia (Oreochromis niloticus): Effects of acute cold stress on potential reference targets.

The Nile tilapia (Oreochromis niloticus) is one of the most important cultured fish worldwide, but tilapia culture is largely affected by low temperatures. Recent studies suggest that microRNAs (miRNAs) regulate cold tolerance traits in fish. In general, qPCR-based methods are the simplest and most accurate forms of miRNA quantification. However, qPCR data heavily depends on appropriate normalization. Therefore, the aim of the present study is to determine whether the expression of previously tested, stably expressed miRNAs are affected by acute cold stress in Nile tilapia. For this purpose, one small nuclear RNA (U6) and six candidate reference miRNAs (miR-23a, miR-25-3, Let-7a, miR-103, miR-99-5, and miR-455) were evaluated in four tissues (blood, brain, liver, and gills) under two experimental conditions (acute cold stress and control) in O. niloticus. The stability of the expression of each candidate reference miRNA was analyzed by four independent methods (the delta Ct method, geNorm, NormFinder, and BestKeeper). Further, consensual comprehensive ranking of stability was built with RefFinder. Overall, miR-103 was the most stable reference miRNA in this study, and miR-103 and Let-7a were the best combination of reference targets. Equally important, Let-7a, miR-23a, and miR-25-3 remained consistently stable across different tissues and experimental groups. Considering all variables, U6, miR-99-5, and miR-455 were the least stable candidates under acute cold stress. Most important, suitable reference miRNAs were validated in O. niloticus, facilitating further accurate miRNA quantification in this species.

Accuracy Study of Kato-Katz and Helmintex Methods for Diagnosis of Schistosomiasis Mansoni in a Moderate Endemicity Area in Sergipe, Northeastern Brazil.

Schistosomiasis is a neglected tropical disease (NTD) caused by blood flukes from the genus Schistosoma. Brazil hosts the main endemic area in the Americas, where Schistosoma mansoni is the only species causing the disease. Kato-Katz (KK) thick smear is the WHO recommended screening test for populational studies, but there is growing evidence for the sensitivity limitations associated with KK, especially in areas with low parasite loads. Helmintex (HTX) is another highly sensitive egg-detection method, based on the magnetic properties of S. mansoni eggs and their isolation in a magnetic field. The objective of this study is to evaluate both KK and HTX in a moderate endemic locality, Areia Branca, located in the municipality of Pacatuba, in the state of Sergipe in northeastern Brazil. From 234 individual fecal samples, two KK thick smears were prepared and evaluated for each sample. Similarly, 30 g of each fecal sample was processed by HTX protocol. Eggs were detected in 80 (34.18%) residents. Twenty-three (9.83%) samples were positive for eggs (only by KK), and 77 (32.91%) samples showed positive for eggs (only by HTX). Sensitivity, specificity, and accuracy estimates gave values of 28.75%, 100% and 75.64%, respectively, for KK, and 96.25%, 100% and 98.72% respectively, for HTX. The positive predictive value was 100% for both methods, while the negative predictive value was 72.99% for KK and 98.09% for HTX. Overall, HTX presented a superior performance compared to the one sample, two slides KK examination. The study confirms the role of HTX as a reference method for the definition of true-positive samples in comparative accuracy studies and its potential role in the late stages when the certification of schistosomiasis transmission interruption is required. Diagnostic tests are important tools for the elimination of this NTD, besides the effective implementation of safe water, basic sanitation, snail control, and the treatment of infected populations.

A Short Review of Antimalarial Compounds with Sulfonamide Moiety.

Malaria is a public health problem that causes thousands of deaths, primarily in children in African regions. Artemisinin-based combination therapies (ACTs) have helped to save thousands of lives; however, due to Plasmodium's resistance to available treatments, there is a need to search for new low-cost drugs that act through different mechanisms of action to contain this disease. This review shows that compounds with sulfonamide moiety, possibly, act as inhibitors of P. falciparum carbonic anhydrases, moreover, when linked to a variety of heterocycles potentiate the activities of these compounds and may be used in the design of new antimalarial drugs.

An Overview of Treatment Guidelines and Methods of Synthesis of Drugs Used in Leprosy Chemotherapy.

Leprosy is a Neglected Tropical Disease (NTDs) caused by Mycobacterium leprae (M. leprae). The treatment is considered effective, however, the high dose Multidrug Therapy (MDT) for a long period and its adverse effects result in the abandonment of the treatment by patients. Indeed, antimicrobial resistance is still an obstacle that must be overcome in the treatment of leprosy. In the present article, we reviewed the WHO guidelines for the chemotherapy of leprosy and the methods of synthesis of these drugs.

Vitamin B12 sources in non-animal foods: a systematic review.

Interest in plant-based diets and vegetarianism is increasing worldwide, however, a concern for total vegetarians is vitamin B12 (B12) deficiency. We conducted a systematic review to investigate non-animal food sources of B12. Databases were PubMed, LILACS, Cochrane, Embase and Google Scholar, up to September 9, 2020. Quality of the eligible studies were assessed. We identified 25 studies which assessed B12 content in seaweeds, mushrooms, plants and fermented foods. Initial studies were microbiological bioassay, ELISA and HPLC. In the last decade, more sensitive method for real B12 determination was used, the liquid chromatography-electrospray ionization tandem mass spectrometry chromatograms. Real B12 content varied from mean (SD) mcg/portion size of seaweed hijiki 3 × 10-3/7 g to nori 1.03 - 2.68/sheet; mushroom white button cap 2 × 10-3(7 × 10-4)/20 g dry weight (dw) to shiitake 0.79(0.67)-1.12 (0.78)/20 g dw; and fermented foods from soy yogurt 20/cup. It is possible that daily recommendations for B12 can be met by a varied diet containing non-animal B12 food sources. Future research should consider different methods of storage, preparation, fermented foods and standardization of the production of certain foods.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2053057.

Dietary weight loss intervention provides improvement of gastroesophageal reflux disease symptoms-A randomized clinical trial.

To evaluate the effect of dietary interventions aimed at weight loss in gastroesophageal reflux disease (GERD) symptoms and general health-related quality of life (HRQL) in overweight and obese patients. A population of GERD patients were randomized into two groups: the intervention group received individualized dietary counselling on scheduled appointments throughout 6 months of follow-up (n = 31) and the control group received only informative dietary guidelines on baseline (n = 31). Anthropometric data were monthly collected, and the HRQL score for GERD (GERD-HRQL) and the Health Survey (SF-36) questionnaires were applied on baseline and reevaluated at the end of follow-up. Dietary intervention led to an average weight loss of 4.4 kg (±5.3) and an average BMI reduction of 1.7 kg/m2 (±2.9) compared to an increase in weight of 2.1 kg (±4.4) (p < .001) and an increase in BMI of 1.3 (±6.3) (p = 0.023) in the control group. Individuals in the intervention group had a mean decrease in symptoms of 6.8 (±5.5) points while the control group had worsening of their symptoms with an increase of 3.3 (±4) points (p < .001) in the disease-specific questionnaire. There was a positive association between weight loss and reduction of symptoms as measured by the GERD-HRQL score (r = .49; p < .001). Dietary intervention for 6 months with an individualized low-calorie diet program produces weight loss and a significant improvement in GERD-related symptoms, as well as in HRQL.

A Purine Derivative Containing an Organoselenium Group Protects Against Memory Impairment, Sensitivity to Nociception, Oxidative Damage, and Neuroinflammation in a Mouse Model of Alzheimer's Disease.

In the present study, the effect of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) was tested against memory impairment and sensitivity to nociception induced by intracerebroventricular injection of amyloid-beta peptide (Aß) (25-35 fragment), 3 nmol/3 µl/per site in mice. Memory impairment was determined by the object recognition task (ORT) and nociception by the Von-Frey test (VFT). Aß caused neuroinflammation with upregulation of glial fibrillary acidic protein (GFAP) (in hippocampus), nuclear factor-κB (NF-κB), and the proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in cerebral cortex and hippocampus. Additionally, Aß increased oxidant levels and lipid peroxidation in cerebral cortex and hippocampus, but decreased heme oxygenase-1 (HO-1) and peroxiredoxin-1 (Prdx1) expression in the hippocampus. Anti-neuroinflammatory effects of FSP were demonstrated by a decrease in the expression of GFAP and NF-κB in the hippocampus, as well as a decrease in proinflammatory cytokines in both the hippocampus and cerebral cortex FSP protected against oxidative stress by decreasing oxidant levels and lipid peroxidation and by increasing HO-1 and Prdx1 expressions in the hippocampus of mice. Moreover, FSP prevented the activation of nuclear factor erythroid 2-related factor 2 (Nrf-2) in the hippocampus of mice induced by Aß. In conclusion, treatment with FSP attenuated memory impairment, nociception sensitivity by decreasing oxidative stress, and neuroinflammation in a mouse model of Alzheimer's disease.

Blueberry Extract Modulates Brain Enzymes Activities and Reduces Neuroinflammation: Promising Effect on Lipopolysaccharide-Induced Depressive-Like Behavior.

Major depressive disorder (MDD) is one of the most common neuropsychiatric disorders with high rates of prevalence and mortality. MDD is pathophysiologically complex, and treatment options are limited. Blueberries are rich in polyphenols and have neuroprotective potential. The aim of this study was to investigate the effects of blueberry extract on neuroinflammatory and neuroplasticity parameters, as well as Na+/K+-ATPase, monoamine oxidase-A (MAO-A), and acetylcholinesterase (AChE) activities in the cerebral cortex and hippocampus of mice subject to lipopolysaccharide (LPS)-induced depressive-like behavior. We also analyzed the interaction between anthocyanins and indoleamine 2 3-dioxygenase (IDO). Male Swiss mice (60-day-old) received vehicle, fluoxetine (20 mg/kg), or blueberry extract (100 or 200 mg/kg) intragastrically for 7 days before intraperitoneal LPS (0.83 mg/kg) injection. Twenty-four hours after LPS administration, the mice were subjected to behavioral tests. Both fluoxetine and blueberry extract (200 mg/kg) decreased the immobility time in the forced swim test, without affecting locomotor activity. Fluoxetine attenuated the decrease of Na+/K+-ATPase in the cerebral cortex, while blueberry extract promoted this same effect in the hippocampus. Additionally, fluoxetine and blueberry extract attenuated the decrease in the activity of MAO-A in the hippocampus. Blueberry extract (200 mg/kg) also prevented LPS-induced increase in AChE activity in the hippocampus as well as LPS upregulation of relative mRNA expression of tumor necrosis factor alpha, interleukin (IL)-1ß, and IL-10 in the cerebral cortex. Molecular docking analysis revealed binding sites for malvidin 3-galactoside (- 7.8 kcal/mol) and malvidin 3-glucoside (- 7.9 kcal/mol) residues with IDO. Taken together, these results indicate that blueberry extract improved depression-like behavior and attenuated the neurochemical and molecular changes in the brains of mice challenged with LPS.

Massive gastrointestinal bleeding as a clinical manifestation of miliary tuberculosis

Tuberculosis is still a public health problem today and can have acute and chronic manifestations challenging clinics for various medical specialties. Because it's a disease of multisystem potential, it is often overlooked when outside the respiratory clinical context. As a result, a clinical case report was carried out at the Hospital de Clínicas de Porto Alegre, in 2020, of a patient with voluminous gastrointestinal bleeding as severe acute clinical manifestation of Miliary and Intestinal Tuberculosis. Due to the potential severity of undiagnosed and untreated tuberculosis, high suspicion is suggested at all levels of health systems (whether public or private) with a view to early diagnosis, treatment and prevention of complications resulting from the disease.