Platinum Deposition in the Central Nervous System: A Novel Insight into Oxaliplatin-induced Peripheral Neuropathy in Young and Old Mice.

Numerous factors can contribute to the incidence or exacerbation of peripheral neuropathy induced by oxaliplatin (OXA). Recently, platinum accumulation in the spinal cord of mice after OXA exposure, despite the efficient defenses of the central nervous system, has been demonstrated by our research group, expanding the knowledge about its toxicity. One hypothesis is platinum accumulation in the spinal cord causes oxidative damage to neurons and impairs mitochondrial function. Thus, the main aim of this study was to investigate the relationship between aging and OXA-induced neuropathic pain and its comorbidities, including anxious behavior and cognitive impairment. By using an OXA-induced peripheral neuropathy model, platinum and bioelement concentrations and their influence on oxidative damage, neuroprotection, and neuroplasticity pathways were evaluated in Swiss mice, and our findings showed that treatment with OXA exacerbated pain and anxious behavior, albeit not age-induced cognitive impairment. Platinum deposition in the spinal cord and, for the first time, in the brain of mice exposed to OXA, regardless of age, was identified. We found that alterations in bioelement concentration, oxidative damage, neuroprotection, and neuroplasticity pathways induced by aging contribute to OXA-induced peripheral neuropathy. Our results strive to supply a basis for therapeutic interventions for OXA-induced peripheral neuropathy considering age specificities.

Tannic acid: A possible therapeutic agent for hypermethioninemia-induced neurochemical changes in young rats.

This study explores the therapeutic benefits of tannic acid (TnA) in an experimental protocol of chronic hypermethioninemia in rats. Rats were categorized into four groups: Group I - control, Group II - TnA 30 mg/kg, Group III - methionine (Met) 0.2-0.4 g/kg + methionine sulfoxide (MS) 0.05-0.1 g/kg, Group IV - TnA/Met + MS. Saline was administered by subcutaneous pathway into groups I and II twice daily from postnatal day 6 (P6) to P28, whereas those in groups III and IV received Met + MS. From P28 to P35, groups II and IV received TnA orally. Animals from group III presented cognitive and memory impairment assessed through object recognition and Y-maze tests (p < 0.05). Elevated levels of reactive species, lipid peroxidation, and nitrites followed by a decline in sulfhydryl content, catalase activity, and superoxide dismutase activity were observed in animals treated with Met + MS (p < 0.05). However, TnA treatment reversed all these effects (p < 0.05). In group III, there was an increase in acetylcholinesterase activity and IL-6 levels, coupled with a reduction in Na+/K+-ATPase activity (p < 0.05). TnA was able to protect against these effects (p < 0.05). The gene expression of catalase, brain-derived neurotrophic factor, and nuclear factor erythroid 2-related factor 2 was decreased in the hippocampus and striatum from group III (p < 0.05). TnA reversed almost all of these alterations (p < 0.05). These findings suggest that TnA is a therapeutic target for patients with hypermethioninemia.

Selection of references for quantitative real-time PCR analysis of microRNAs in Nile tilapia (Oreochromis niloticus) under osmotic stress.

MicroRNAs play crucial regulatory roles in various aspects of development and physiology, including environmental adaptation and stress responses in teleosts. RT-qPCR is the most commonly used method for studying microRNA expression, with the accuracy and reliability of results depending on the use of an appropriate reference gene for normalization. This study aimed to evaluate seven miRNAs (U6, Let-7a, miR-23a, miR-25-3, miR-103, miR-99-5, and miR-455) expression stability in different tissues of Nile tilapia subjected to osmotic stress. Fish were divided into two groups: a control and an experimental group, raised in 0 and 12 ppt salinity water respectively. After 21 days, brain, gills, liver, and posterior intestine were collected for analysis. Different mathematical algorithms (geNorm, NormFinder, BestKeeper, and the comparative ΔCt method) were employed to identify the most suitable reference miRNAs. The results indicate that the miR-455/miR-23a combination is a robust reference for normalizing miRNA expression levels in studies of osmotic stress responses in Nile tilapia. The stability of miRNA expression can vary depending on specific stress conditions and biological processes, underscoring the necessity of selecting appropriate normalizing miRNAs for each experimental context. This study identifies reliable reference genes for future RT-qPCR analyses of miRNA expression, thereby enhancing our understanding of molecular responses in fish to environmental challenges. These insights are fundamental to the development of new technologies for the improved management and sustainability of aquaculture practices.

Assessing reproductive effects and epigenetic responses in Austrolebias charrua exposed to Roundup Transorb®: Insights from miRNA profiling and molecular interaction analysis.

This study examines the effects of Roundup Transorb® (RDT) exposure on reproductive functions and ovarian miRNA expression in Austrolebias charrua. Exposure to RDT (at 0.065 or 5 mg. L-1 for 96 h) significantly disrupts fertility, evidenced by changes in fertilization rates and egg diameter. Profiling of ovarian miRNAs identified a total 205 miRNAs in A. charrua. Among these, three miRNAs were upregulated (miR-10b-5p, miR-132-3p, miR-100-5p), while ten miRNAs were downregulated (miR-499-5p, miR-375, miR-205-5p, miR-206-3p, miR-203a-3p, miR-133b-3p, miR-203b-5p, miR-184, miR-133a-3p, miR-2188-5p) compared to non-exposed fish. This study reveals that differentially expressed miRNAs are linked to molecular pathways such as steroid hormone biosynthesis, lipid and carbohydrate metabolism, bioenergetics, and antioxidant defense. It also analyzes molecular interactions between miRNAs and target genes during RDT exposure in annual killifish, providing insights into biomarkers in ecotoxicology. Moreover, it provides scope for developing environmental health assessment models based on epigenomic endpoints, supporting the protection of biodiversity and ecosystem services through the quantification of stress responses in living organisms exposed to pesticides.

A Pilot Study of Gene Expression Modulation from Antioxidant System of Killifish Austrolebias charrua After Exposure to Roundup Transorb®.

Roundup Transorb® (RDT) is the most popular glyphosate-based herbicide (GHB) used in agriculture, and its impact extends to non-target organisms. The annual killifish Austrolebias charrua is an endangered species endemic to southern South America and inhabits temporary ponds. This study evaluates the effects of RDT concentrations (0.065 and 5 mg/L GAE) on A. charrua exposed for 96 h. Gene expression of cat, sod2, gstα, gclc, and ucp1 was evaluated on the liver and gills. Highlighting that even at low concentrations permitted by Brazilian legislation, the RDT can have adverse effects on A. charrua.

MicroRNA Transcriptomes Reveal Prevalence of Rare and Species-Specific Arm Switching Events During Zebrafish Ontogenesis.

In metazoans, microRNAs (miRNAs) are essential regulators of gene expression, affecting critical cellular processes from differentiation and proliferation, to homeostasis. During miRNA biogenesis, the miRNA strand that loads onto the RNA-induced Silencing Complex (RISC) can vary, leading to changes in gene targeting and modulation of biological pathways. To investigate the impact of these "arm switching" events on gene regulation, we analyzed a diverse range of tissues and developmental stages in zebrafish by comparing 5p and 3p arms accumulation dynamics between embryonic developmental stages, adult tissues, and sexes. We also compared variable arm usage patterns observed in zebrafish to other vertebrates including arm switching data from fish, birds, and mammals. Our comprehensive analysis revealed that variable arm usage events predominantly take place during embryonic development. It is also noteworthy that isomiR occurrence correlates to changes in arm selection evidencing an important role of microRNA distinct isoforms in reinforcing and modifying gene regulation by promoting dynamics switches on miRNA 5p and 3p arms accumulation. Our results shed new light on the emergence and coordination of gene expression regulation and pave the way for future investigations in this field.

Significant and distinct impacts of sleeve gastrectomy and Roux-en-Y gastric bypass on esophageal acid exposure, esophageal motility, and endoscopic findings: a systematic review and meta-analysis.

BACKGROUND: The lack of standardized objective assessment of esophageal physiology and anatomy contributes to controversies regarding the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on gastroesophageal reflux disease. This study aimed to investigate esophageal acid exposure, esophageal motility, and endoscopic findings before and after SG and RYGB. METHODS: This was a systematic review and meta-analysis of studies reporting at least 1 objective measure of esophageal physiology and/or esophagogastroduodenoscopy (EGD) at baseline and after SG or RYGB. The changes in pH test, manometry, and EGD parameters were summarized. RESULTS: Acid exposure time (AET) and DeMeester score (DMS) significantly increased after SG (mean difference [MD]: 2.1 [95% CI, 0.3-3.9] and 8.6 [95% CI, 2.0-15.2], respectively). After RYGB, both AET and DMS significantly decreased (MD: -4.2 [95% CI, -6.1 to -2.3] and -16.6 [95% CI, -25.4 to -7.8], respectively). Lower esophageal sphincter resting pressure and length significantly decreased after SG (MD: -2.8 [95% CI, -4.6 to -1.1] and -0.1 [95% CI, -0.2 to -0.02], respectively). There were no significant changes in esophageal manometry after RYGB. The relative risks of erosive esophagitis were 2.3 (95% CI, 1.5-3.5) after SG and 0.4 (95% CI, 0.2-0.8) after RYGB. The prevalence rates of Barrett esophagus changed from 0% to 3.6% after SG and from 2.7% to 1.4% after RYGB. CONCLUSION: SG resulted in the worsening of all objective parameters, whereas RYGB resulted in the improvement in AET, DMS, and EGD findings. Determining the risk factors associated with these outcomes can help in surgical choice.

Chemical activation of mammalian oocytes and its application in camelid reproductive biotechnologies: A review.

Mammalian oocyte activation is a critical process occurring post-gamete fusion, marked by a sequence of cellular events initiated by an upsurge in intracellular Ca2+. This surge in calcium orchestrates the activation/deactivation of specific kinases, leading to the subsequent inactivation of MPF and MAPK activities, alongside PKC activation. Despite various attempts to induce artificial activation using distinct chemical compounds as Ca2+ inducers and/or Ca2+-independent agents, the outcomes have proven suboptimal. Notably, incomplete suppression of MPF and MAPK activities persists, necessitating a combination of different agents for enhanced efficiency. Moreover, the inherent specificity of activation methods for each species precludes straightforward extrapolation between them. Consequently, optimization of protocols for each species and for each technique, such as PA, ICSI, and SCNT, is required. Despite recent strides in camelid biotechnologies, the field has seen little advancement in chemical activation methods. Only a limited number of chemical agents have been explored, and the effects of many remain unknown. In ICSI, despite obtaining blastocysts with different chemical compounds that induce Ca2+ and calcium-independent increases, viable offspring have not been obtained. However, SCNT has exhibited varying outcomes, successfully yielding viable offspring with a reduced number of chemical activators. This article comprehensively reviews the current understanding of the physiological activation of oocytes and the molecular mechanisms underlying chemical activation in mammals. The aim is to transfer and apply this knowledge to camelid reproductive biotechnologies, with emphasis on chemical activation in PA, ICSI, and SCNT.

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.

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.

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.

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.