Perfil lipídico e fatores de risco para doenças cardiovasculares em idosos acompanhados na atenção primária à saúde / Lipid profile and risk factors for cardiovascular diseases in older people seen in primary health care / Perfil lipídico y factores de riesgo de enfermedades cardiovasculares en ancianos seguidos en la atención primaria de salud

Introdução: As dislipidemias estão entre os fatores de riscos mais importantes para o desenvolvimento de doenças cardiovasculares (DCV), além de estarem relacionadas a outras patologias que predispõem às DCV. Em função da elevada prevalência e da incidência de complicações associadas à cronicidade da doença, as dislipidemias representam elevados custos ao setor da saúde e da previdência social. Diante disso, ressalta-se a importância do Sistema Único de Saúde, representado pela Atenção Primária à Saúde (APS), em prover práticas de prevenção, diagnóstico e acompanhamento dos pacientes dislipidêmicos, a fim de desonerar o sistema financeiro e promover o envelhecimento saudável. Objetivo: Descrever a prevalência de perfil lipídico alterado entre os idosos. Além disso, pretendeu-se caracterizar a amostra quanto aos aspectos sociodemográficos, de saúde e de comportamento, bem como analisar os fatores associados à distribuição do perfil lipídico alterado e às características da amostra. Métodos: Estudo transversal com dados secundários, obtidos de agosto de 2021 a julho de 2022, tendo como população pacientes idosos em acompanhamento na APS do município de Marau (RS). Todos os dados foram coletados dos prontuários eletrônicos da rede de APS e, após dupla digitação e validação dos dados, a amostra foi caracterizada por meio de estatística descritiva. Foi calculada a prevalência de perfil lipídico alterado com intervalo de confiança de 95% (IC95%) e foi verificada sua distribuição conforme as variáveis de exposição, empregando-se o teste do χ2 e admitindo-se erro tipo I de 5%. Resultados: A prevalência de dislipidemia proporcional entre os sexos foi maior no feminino (33%). A cor de pele predominante foi a branca (76,7%). Cerca de 20% dos pacientes apresentavam colesterol total, colesterol HDL-c e triglicerídeos alterados, enquanto cerca de 15% apresentavam o colesterol HDL-c anormal. Constatou-se que os pacientes dislipidêmicos apresentam mais diabetes e hipertensão em relação aos não dislipidêmicos, ocorrendo a sinergia de fatores de risco para as DCV. Conclusões: A caracterização exercida neste estudo serve de base científica para a compreensão da realidade local e, também, para o direcionamento de políticas públicas na atenção primária que atuem de forma efetiva na prevenção e no controle das dislipidemias e demais fatores de risco cardiovascular.

Introduction: Dyslipidemias are among the most important risk factors for the development of cardiovascular diseases (CVD), in addition to being related to other pathologies that predispose to CVD. Because of the high prevalence and incidence of complications associated with the chronicity of the disease, dyslipidemias represent high costs for the health and social security sector. This highlights the importance of the Unified Health System, represented by primary health care (PHC), in providing prevention, diagnosis and follow-up practices for dyslipidemic patients to relieve the financial system and promote healthy aging. Objective: The study aimed to describe the prevalence of altered lipid profile among older people. In addition, we sought to characterize the sample in terms of sociodemographic, health and behavioral aspects, as well as to analyze the factors associated with the distribution of the altered lipid profile and the characteristics of the sample. Methods: We conducted a cross-sectional study with secondary data, from August 2021 to July 2022, with older patients being followed up at the PHC in the city of Marau (RS) as the study population. All data were collected from the electronic medical records of the PHC network, and after double-typing and validation, the sample was characterized using descriptive statistics. The prevalence of altered lipid profile was determined with a 95% confidence interval (95%CI), and its distribution was verified according to the exposure variables, using the chi-square test and a type I error of 5%. Results: The prevalence of proportional dyslipidemia between sexes was higher in females (33%). The predominant skin color was white (76.7%). About 20% of the patients had altered total cholesterol, HDL-C and triglycerides, while about 15% had abnormal HDL-C. It was found that more dyslipidemic patients had diabetes and hypertension than non-dyslipidemic patients, with a synergy of risk factors for CVD. Conclusions: The characterization carried out in this study serves as a scientific basis for understanding the local reality and also for directing public policies in PHC that act effectively in the prevention and control of dyslipidemia and other cardiovascular risk factors.

Introducción: las dislipidemias se encuentran entre los factores de riesgo más importantes para el desarrollo de enfermedades cardiovasculares (ECV), además de estar relacionadas con otras patologías que predisponen a ECV. Debido a la alta prevalencia e incidencia de complicaciones asociadas a la cronicidad de la enfermedad, las dislipidemias representan altos costos para los sectores de salud y seguridad social. Frente a eso, se destaca la importancia del Sistema Único de Salud, representado por la Atención Primaria de Salud (APS), en la provisión de prácticas de prevención, diagnóstico y seguimiento de pacientes dislipidémicos, con el fin de descongestionar el sistema financiero y promover el envejecimiento saludable. Objetivo: El estudio tiene como objetivo describir la prevalencia del perfil lipídico alterado entre los ancianos. Además, se pretende caracterizar la muestra en cuanto a aspectos sociodemográficos, de salud y conductuales, así como analizar los factores asociados a la distribución del perfil lipídico alterado y las características de la muestra. Métodos: estudio transversal con datos secundarios, de agosto de 2021 a julio de 2022, con pacientes ancianos en seguimiento en la APS del municipio de Marau (RS) como población. Todos los datos fueron recolectados de la historia clínica electrónica de la red de la APS y, luego de doble digitación y validación, la muestra fue caracterizada mediante estadística descriptiva. Se calculó la prevalencia de perfil lipídico alterado con un intervalo de confianza del 95% (IC95%) y se verificó su distribución según las variables de exposición, utilizando la prueba de chi-cuadrado y admitiendo un error tipo I del 5%. Resultados: la prevalencia de dislipidemia proporcional entre sexos fue mayor en el sexo femenino (33%). El color de piel predominante fue el blanco (76,7%). Alrededor del 20% de los pacientes tenían colesterol total, colesterol HDL-C y triglicéridos alterados, mientras que alrededor del 15% tenían colesterol HDL-C anormal. Se encontró que los pacientes dislipidémicos tienen más diabetes e hipertensión que los pacientes no dislipidémicos, con una sinergia de factores de riesgo para ECV. Conclusiones: la caracterización realizada en este estudio sirve de base científica para comprender la realidad local y también para orientar políticas públicas en atención primaria que actúen de manera efectiva en la prevención y control de la dislipidemia y otros factores de riesgo cardiovascular.

Immune checkpoint expression as prognostic biomarker candidates in non-small cell lung carcinoma patients.

BACKGROUND: Cancer immunotherapy has had an important role in oncologic therapeutics for patients with non-small cell lung cancer (NSCLC) using checkpoint inhibitors. We will explore the possible prognosis biomarker candidates such as: soluble OX40 (sOX40), OX40L (sOX40L), Glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR), and their ligand (GITRL), 4-1BB or tumor necrosis factor receptor superfamily 9 (TNFRS9) and inducible T cell co-stimulator (ICOS) in peripheral blood of NSCLC patients. METHODS: Fifty-eight patients were diagnosed with advanced NSCLC between January 2019 and March 2020. RESULTS: High sOX40 and low s4-1BB levels in smokers compared non-smoker NSCLC patients. Lower sOX40L levels were found in the male than female (p < 0.05). High sOX40 and sGITRL in stage III compared to the stage IV (p < 0.05). With follow-up at 21.4 months, 44.1% and 91.1% were alive in the sGITRhigh and sGITRlow groups, respectively (p = 0.02), and 73.3% and 27.7% were alive in the sGITRLhigh and sGITRLlow groups, respectively (p = 0.02). At 22 months, 38.7% and 92.3% were alive in the sOX40Lhigh and sOX40Llow groups, respectively (p = 0.01). CONCLUSION: sGITR, sGITRL, and sOX40L levels were potential prognostic biomarkers and could have an important role as new targets of immunotherapy in NSCLC patients. sGITR, sGITRL, sOX40L, and sOX40 levels were associated with smoking, sex, stage, and age in NSCLC.

Acute effects of atrazine on the immunoexpressions of sertoli and germ cells molecular markers, cytokines, chemokines, and sex hormones levels in mice testes and epididymides.

Atrazine is currently one of the most commonly used agrochemicals in the United States and elsewhere. Here, we studied the immunoexpression of molecular markers of mammalian testicular functions: androgen receptor (AR), promyelocytic leukemia zinc finger (PLZF), GDNF family receptor alpha-1 (GFRA1), VASA/DDX4 (DEAD-Box Helicase 4) as well as the levels of intratesticular and intra-epididymal estradiol (E2) and dihydrotestosterone (DHT), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukins (IL-1ß and IL-6, IL-10) and testicular chemokines (CXCL-1, CCL-2 and CCL3) in BalB/c mice after a sub-acute gavage treatment with a gonado-toxin, atrazine (50 mg/kg body wt.) for three days. We found high numbers of AR immunopositive Sertoli cells and low numbers of GFRA1, PLZF and VASA/DDX4-positive germ cells in the seminiferous tubule regions of the testes. While TNF-α level in the testes fell and remained unchanged in the epididymides, IFN-γ levels in the testes remained constant but increased in the epididymides. E2 and DHT concentrations remained unaltered in the testes but were changed in the epididymides. There were no significant changes in the levels of interleukins in the testis and epididymis. Intratesticular chemokines were also not significantly altered, except for CCL-4, which was increased in the testis. Light microscopy of the epididymis showed detached epithelium and some detached cells in the lumen. It is concluded that atrazine changed the inflammatory status of the gonads and highlighted Sertoli and undifferentiated spermatogonia as important targets for atrazine's toxic effects in the testis of mice. Concerning the epididymis, atrazine altered the epididymal hormonal concentrations and promoted histopathological modifications in its parenchyma.

Subchronic intake of arsenic at environmentally relevant concentrations causes histological lesions and oxidative stress in the prostate of adult Wistar rats.

The prostate gland is one of the main sites of hyperplasia and cancer in elderly men. Numerous factors have been demonstrated to disrupt prostate homeostasis, including exposure to environmental pollutants. Arsenic is a metalloid found ubiquitously in soil, air, and water, which favors human poisoning through the involuntary intake of contaminated drinking water and food and has harmful effects by increasing the oxidative stress response. This study aimed to investigate the effects of prolonged exposure to arsenic at environmentally relevant concentrations on the prostate biology of adult Wistar rats. Thirty 80-day-old male rats were divided into three experimental groups. Rats from the control group received filtered water, whereas animals from the arsenic groups ingested 1 mg L-1 and 10 mg L-1 of arsenic, in the form of sodium arsenite, daily. The arsenic solutions were provided ad libitum in the drinking water for eight weeks. Our results showed that 1 mg L-1 and 10 mg L-1 of arsenic made the prostate susceptible to evolving benign and premalignant histopathological changes. While the ingestion of 1 mg L-1 of arsenic reduced SOD activity only, 10 mg L-1 diminished SOD and CAT activity in the prostate tissue, culminating in high MDA production. These doses, however, did not affect the intraprostatic levels of DHT and estradiol. In conclusion, exposure to arsenic at environmentally relevant concentrations through drinking water induces histological and oxidative stress-related changes in the prostate of adult rats, strengthening the between arsenic exposure and prostate disorders.

The toxicity of superparamagnetic iron oxide nanoparticles induced on the testicular cells: In vitro study.

Superparamagnetic iron oxide nanoparticles (SPIONs) have gained significant attention in biomedical research due to their potential applications. However, little is known about their impact and toxicity on testicular cells. To address this issue, we conducted an in vitro study using primary mouse testicular cells, testis fragments, and sperm to investigate the cytotoxic effects of sodium citrate-coated SPIONs (Cit_SPIONs). Herein, we synthesized and physiochemically characterized the Cit_SPIONs and observed that the sodium citrate diminished the size and improved the stability of nanoparticles in solution during the experimental time. The sodium citrate (measured by thermogravimetry) was biocompatible with testicular cells at the used concentration (3%). Despite these favorable physicochemical properties, the in vitro experiments demonstrated the cytotoxicity of Cit_SPIONs, particularly towards testicular somatic cells and sperm cells. Transmission electron microscopy analysis confirmed that Leydig cells preferentially internalized Cit_SPIONs in the organotypic culture system, which resulted in alterations in their cytoplasmic size. Additionally, we found that Cit_SPIONs exposure had detrimental effects on various parameters of sperm cells, including motility, viability, DNA integrity, mitochondrial activity, lipid peroxidation (LPO), and ROS production. Our findings suggest that testicular somatic cells and sperm cells are highly sensitive and vulnerable to Cit_SPIONs and induced oxidative stress. This study emphasizes the potential toxicity of SPIONs, indicating significant threats to the male reproductive system. Our findings highlight the need for detailed development of iron oxide nanoparticles to enhance reproductive nanosafety.

Impact of Neurological Complications on Long-Term Outcomes in Patients with Infective Endocarditis.

Neurological complications are frequent during the active course of infective endocarditis (IE), and they are associated with high in-hospital mortality rates. However, limited data exist on the prognostic value of these complications for late outcomes. This study aimed to assess the long-term impact of neurological complications in patients surviving an IE episode. A total of 263 consecutive IE patients admitted to a tertiary care center between 2007 and 2022 were prospectively included. Neurological complications at admission included transient ischemic attack (TIA), ischemic stroke, hemorrhagic stroke, intracerebral abscess, and meningitis. The primary outcome was a composite of overall mortality or heart valve surgery. Of the patients, 34.2% died in the hospital, leaving 173 survivors for long-term follow-up. Over a median of 3.5 years, 29 patients died, and 13 (9%) underwent cardiac surgery, resulting in an overall adverse event rate of 30%. Neurological complications independently predicted long-term adverse outcomes (hazard ratio (HR) 2.237; 95% CI 1.006-4.976), after adjusting for age, chronic kidney disease (CKD), and heart failure (HF) development. In an IE patient cohort, neurological complications at admission, which is a complication directly related to the IE process, were independent predictors of long-term outcomes.

Determination of speed and assessment of conditioning in horses submitted to a lactate minimum test-alternative approaches.

The maximal lactate steady state (MLSS) is a well-known gold standard method for determining the aerobic capacity of athletic horses. Owing to its high cost and complex execution, there is a search for standardized exercise tests that can predict this value in a single session. One of the methods described for this purpose is the lactate minimum test (LMT), which could be more accurate despite being adequate to predict MLSS. This study aimed to examine the impact of training on the speed corresponding to lactate minimum speed (LMS) and to apply new mathematical methods to evaluate the fitness level of horses based on the curve obtained by the LMT. Ten Arabian horses underwent a 6-week training program based on LMS calculated by second-degree polynomial regression (LMSP). In addition, the LMS was also determined by visual inspection (LMSV), bi-segmented linear regression (LMSBI) and spline regression (LMSS). From the curve obtained during the LMT, it was possible to calculate angles α, ß and ω, as well as the total area under the curve (AUCTOTAL) before (AUCPRELMS) and after (AUCPOSLMS) the LMS. The methods for determining the LMS were evaluated by ANOVA, intraclass correlation coefficient (ICC) and effect size (ES) by Cohen's d test. The Pearson correlation coefficient (r) between the proposed LMS determination methods and other mathematical methods was also calculated. Despite showing a good correlation (ICC >0.7), the LMS determination methods differed from each other (p < 0.05), albeit without a significant difference resulting from conditioning. There were reductions in α:ß ratio, angle α, and AUCPOSTLMS, with the latter indicating lower lactate accumulation in the incremental phase of LMT after conditioning, in addition to an improvement in the animals' aerobic capacity. Considering that the most common methods for determining the LMS are applicable yet with low sensitivity for conditioning assessment, the approaches proposed herein can aid in analyzing the aerobic capacity of horses subjected to LMT. The mathematical models presented in this paper have the potential to be applied in human lactate-guided training program trials with a comparable study basis.

Immunotherapy Combining Mimotopes Selected by Phage Display Plus Amphotericin B Is Effective for Treatment Against Visceral Leishmaniasis.

The treatment for visceral leishmaniasis (VL) causes toxicity in patients, entails high cost and/or leads to the emergence of resistant strains. No human vaccine exists, and diagnosis presents problems related to the sensitivity or specificity of the tests. Here, we tested two phage clones, B1 and D11, which were shown to be protective against Leishmania infantum infection in a murine model as immunotherapeutics to treat mice infected with this parasite species. The phages were used alone or with amphotericin B (AmpB), while other mice received saline, AmpB, a wild-type phage (WTP) or WTP/AmpB. Results showed that the B1/AmpB and D11/AmpB combinations induced polarised Th1-type cellular and humoral responses, which were primed by high levels of parasite-specific IFN-γ, IL-12, TNF-α, nitrite and IgG2a antibodies, which reflected in significant reductions in the parasite load in distinct organs of the animals when analyses were performed 1 and 30 days after the treatments. Reduced organic toxicity was also found in these animals, as compared with the controls. In conclusion, preliminary data suggest the potential of the B1/AmpB and D11/AmpB combinations as immunotherapeutics against L. infantum infection.

Effects of superparamagnetic iron oxide nanoparticles (SPIONS) testicular injection on Leydig cell function and sperm production in a murine model.

In the domain of medical advancement, nanotechnology plays a pivotal role, especially in the synthesis of biocompatible materials for therapeutic use. Superparamagnetic Iron Oxide Nanoparticles (SPIONs), known for their magnetic properties and low toxicity, stand at the forefront of this innovation. This study explored the reproductive toxicological effects of Sodium Citrate-functionalized SPIONs (Cit_SPIONs) in adult male mice, an area of research that holds significant potential yet remains largely unknown. Our findings reveal that Cit_SPIONs induce notable morphological changes in interstitial cells and the seminiferous epithelium when introduced via intratesticular injection. This observation is critical in understanding the interactions of nanomaterials within reproductive biological systems. A striking feature of this study is the rapid localization of Cit_SPIONs in Leydig cells post-injection, a factor that appears to be closely linked with the observed decrease in steroidogenic activity and testosterone levels. This data suggests a possible application in developing nanostructured therapies targeting androgen-related processes. Over 56 days, these nanoparticles exhibited remarkable biological distribution in testis parenchyma, infiltrating various cells within the tubular and intertubular compartments. While the duration of spermatogenesis remained unchanged, there were many Tunel-positive germ cells, a notable reduction in daily sperm production, and reduced progressive sperm motility in the treated group. These insights not only shed light on the intricate mechanisms of Cit_SPIONs interaction with the male reproductive system but also highlight the potential of nanotechnology in developing advanced biomedical applications.

Multilevel analysis of social determinants of advanced stage colorectal cancer diagnosis.

The advanced stage at diagnosis of colorectal cancer (CRC) may be related to individual factors, socioeconomic conditions, and healthcare service availability. The objective of the study was to analyze the prevalence of advanced stage CRC at the time of diagnosis and its association with individual, contextual, socioeconomic, and healthcare service indicators. An observational, cross-sectional study was conducted, analyzing cases of malignant neoplasms of the colon and rectum in individuals of both sexes, aged between 18 and 99 years, diagnosed between 2010 and 2019 in Brazil (n = 69,047). Data were collected from the Hospital Cancer Registry (HCR), Atlas of Human Development in Brazil, and from the National Registry of Health Institutions (NRHI). A Multilevel Poisson Regression model with random intercept was used. The prevalence of advanced stage CRC at diagnosis was 65.6%. Advanced stage was associated with older age groups prevalence ratio (PR) 4.40 and younger age groups (PR 1.84), low Human Development Index (HDI) (PR 1.22), and low density of family health strategy teams (PR 1.10). The study highlights the unequal distribution of social determinants of health in the diagnosis CRC in Brazil, revealing the need to evaluate and redirect public policies aimed at improving early detection and prevention of CRC in the country.

Effect of hormone therapy on blood pressure and hypertension in postmenopausal women: a systematic review and meta-analysis.

IMPORTANCE: Menopausal hormone therapy (HT) includes a wide variety of hormonal compounds, and its effect on blood pressure is still uncertain. OBJECTIVE: The aim of this study was to assess evidence regarding the effect of HT on blood pressure in postmenopausal women and its association with arterial hypertension. EVIDENCE REVIEW: This systematic review and meta-analysis included randomized clinical trials and prospective observational studies. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and the incidence of hypertension were assessed. All stages were independently performed by two reviewers. For blood pressure outcome, standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated as effect measures. Heterogeneity was assessed using the I2 statistic. The results are presented based on the HT type. The incidence of hypertension was compared using descriptive analyses. FINDINGS: Eleven studies were included with 81,041 women evaluated, of which 29,812 used HT. The meta-analysis, conducted with 8 studies and 1,718 women, showed an increase in SBP with the use of oral conjugated equine estrogens plus progestogen (SMD = 0.60 mm Hg, 95% CI = 0.19 to 1.01). However, oral or transdermal use of estradiol plus progestogen (SMD = -2.00 mm Hg, 95% CI = -7.26 to 3.27), estradiol alone, and tibolone did not show any significant effect. No significant effect on DBP was observed for any formulation. Women who used oral estrogen plus progestogen had a higher risk of incident hypertension than those who never used it. CONCLUSIONS AND RELEVANCE: The effect of HT on blood pressure is influenced by the formulation used, especially the type of estrogen. The combined formulations of conjugated equine estrogens plus progestogen increased SBP and the risk of hypertension, which was not observed among estradiol plus progestogen, estradiol alone, and tibolone users.

Intracardiac echography-guided fluoroless ablation versus conventional fluoroscopy-guided ablation for cardiac arrhythmias: a systematic review and meta-analysis

BACKGROUND: Intracardiac echocardiography (ICE) has improved catheter ablation procedures, reducing reliance on fluoroscopy. Yet, the efficacy and safety of zero-fluoroscopy (ZF) procedures remain uncertain. METHODS: We conducted a systematic review and meta-analysis comparing ZF ablation procedures guided by ICE vs. conventional techniques regarding efficacy and safety outcomes. PubMed, Cochrane, and embase were searched. A random-effects model was used to calculate risk ratios (RRs), odds ratios (OR) and mean differences (MDs) with 95% confidence intervals (CI). RESULTS: We includedfourteen studies with 1,919 patients of whom 1,023 (58.72%) performed ZF ablation using ICE. We found a significant reduced ablation time (SMD -0.18; 95% CI -0.31;-0.04; p=0.009), procedure time (MD -7.54; 95% CI -14.68;-0.41; p=0.04), fluoroscopic time (MD -2.52; 95% CI -3.20;-1.84; p<0.001) in patients treated with ZF approach compared with NZF approach. However, there was no significant difference between the two groups in acute success rate (RR 1.00; 95% CI 0.99-1.01; p=0.85), long-term success rate (RR 0.99; 95% CI 0.93-1.05; p=0.77) and complications (RR 0.84, 95% CI: 0.48-1.46; p = 0.54). CONCLUSION: Our findings suggest that among patients undergoing arrhythmia ablation, fluoroscopy-free ICE-guided technique reduces procedure time and radiation exposure with comparable short and long-term success rates and complications.

Novel Fe3O4 Nanoparticles with Bioactive Glass-Naproxen Coating: Synthesis, Characterization, and In Vitro Evaluation of Bioactivity.

Immune response to biomaterials, which is intimately related to their surface properties, can produce chronic inflammation and fibrosis, leading to implant failure. This study investigated the development of magnetic nanoparticles coated with silica and incorporating the anti-inflammatory drug naproxen, aimed at multifunctional biomedical applications. The synthesized nanoparticles were characterized using various techniques that confirmed the presence of magnetite and the formation of a silica-rich bioactive glass (BG) layer. In vitro studies demonstrated that the nanoparticles exhibited bioactive properties, forming an apatite surface layer when immersed in simulated body fluid, and biocompatibility with bone cells, with good viability and alkaline phosphatase activity. Naproxen, either free or encapsulated, reduced nitric oxide production, an inflammatory marker, while the BG coating alone did not show anti-inflammatory effects in this study. Overall, the magnetic nanoparticles coated with BG and naproxen showed promise for biomedical applications, especially anti-inflammatory activity in macrophages and in the bone field, due to their biocompatibility, bioactivity, and osteogenic potential.

The scaffolding protein AKAP12 regulates mRNA localization and translation.

Regulation of subcellular messenger (m)RNA localization is a fundamental biological mechanism, which adds a spatial dimension to the diverse layers of post-transcriptional control of gene expression. The cellular compartment in which mRNAs are located may define distinct aspects of the encoded proteins, ranging from production rate and complex formation to localized activity. Despite the detailed roles of localized mRNAs that have emerged over the past decades, the identity of factors anchoring mRNAs to subcellular domains remains ill-defined. Here, we used an unbiased method to profile the RNA-bound proteome in migrating endothelial cells (ECs) and discovered that the plasma membrane (PM)-associated scaffolding protein A-kinase anchor protein (AKAP)12 interacts with various mRNAs, including transcripts encoding kinases with Actin remodeling activity. In particular, AKAP12 targets a transcript coding for the kinase Abelson Tyrosine-Protein Kinase 2 (ABL2), which we found to be necessary for adequate filopodia formation and angiogenic sprouting. Moreover, we demonstrate that AKAP12 is necessary for anchoring ABL2 mRNA to the PM and show that in the absence of AKAP12, the translation efficiency of ABL2 mRNA is reduced. Altogether, our work identified a unique post-transcriptional function for AKAP12 and sheds light into mechanisms of spatial control of gene expression.

Congenital Zika virus infection impacts on male mouse offspring's reproductive biology.

In brief: Congenital ZIKV infection promotes alarming effects on male offspring's reproductive biology. This study showed the presence of the ZIKV antigen in the testis parenchyma, decreased testosterone levels, and sperm abnormalities in male offspring born to infected mothers. Abstract: Infection with ZIKV during pregnancy is associated with fetal developmental problems. Although neurological issues are being explored more in experimental studies, limited research has focused on the reproductive health consequences for offspring born to infected mothers. In this context, this study aimed to assess the impact of ZIKV infection during pregnancy on the testes and sperm of adult male offspring. Female mice were intraperitoneally inoculated with a Brazil strain of ZIKV during the 5.5th day of embryonic gestation. The offspring were evaluated 12 weeks after birth to analyze cellular and molecular changes in the testes and sperm. A novel approach combining variable-angle spectroscopic ellipsometry and machine learning modeling was also introduced for sperm sample analysis. The study revealed the presence of ZIKV protein in the testis parenchyma of adult male offspring born to infected mothers. It was shown that the testes exhibited altered steroidogenesis and inflammatory mediators, in addition to significant issues with spermiogenesis that resulted in sperm with DNA fragmentation, head defects, and protamination failure. Additionally, sperm dielectric properties and artificial intelligence showed potential for rapid identification and classification of sperm samples from infected mice. These findings provide crucial insights into the reproductive risks for men born from ZIKV-infected pregnant women.

Preventive effects of hesperidin in an experimental model ofs acute lung inflammation.

In this study, we hypothesized that long-term administration of hesperidin can modulate the inflammatory response and oxidative stress in animals submitted to mechanical ventilation (MV). Twenty-five C57BL/6 male mice were divided into 5 groups: control, MV, animals receiving hesperidin in three doses 10, 25 and 50 mg/kg. The animals received the doses of hesperidin for 30 days via orogastric gavage, and at the end of the period the animals were submitted to MV. In animals submitted to MV, increased lymphocyte, neutrophil and monocyte/macrophage cell counts were observed in the blood and airways. Associated to this, MV promoted an increase in inflammatory cytokine levels such as CCL2, IL-12 and TNFα. The daily administration of hesperidin in the three doses prevented the effects caused by MV, which was observed by a lower influx of inflammatory cells into the airways, a reduction in inflammatory markers and less oxidative damage.

Avian iPSC Derivation to Recover Threatened Wild Species: A Comprehensive Review in Light of Well-Established Protocols.

Induced pluripotent stem cells (iPSCs) were first generated by Yamanaka in 2006, revolutionizing research by overcoming limitations imposed by the use of embryonic stem cells. In terms of the conservation of endangered species, iPSC technology presents itself as a viable alternative for the manipulation of target genetics without compromising specimens. Although iPSCs have been successfully generated for various species, their application in nonmammalian species, particularly avian species, requires further in-depth investigation to cover the diversity of wild species at risk and their different protocol requirements. This study aims to provide an overview of the workflow for iPSC induction, comparing well-established protocols in humans and mice with the limited information available for avian species. Here, we discuss the somatic cell sources to be reprogrammed, genetic factors, delivery methods, enhancers, a brief history of achievements in avian iPSC derivation, the main approaches for iPSC characterization, and the future perspectives and challenges for the field. By examining the current protocols and state-of-the-art techniques employed in iPSC generation, we seek to contribute to the development of efficient and species-specific iPSC methodologies for at-risk avian species. The advancement of iPSC technology holds great promise for achieving in vitro germline competency and, consequently, addressing reproductive challenges in endangered species, providing valuable tools for basic research, bird genetic preservation and rescue, and the establishment of cryobanks for future conservation efforts.

Bovine serum albumin nanoparticles containing Poly (I:C) can enhance the neutralizing antibody response induced by envelope protein of Orthoflavivirus zikaense.

Since the Orthoflavivirus zikaense (ZIKV) has been considered a risk for Zika congenital syndrome development, developing a safe and effective vaccine has become a high priority. Numerous research groups have developed strategies to prevent ZIKV infection and have identified the domain III of the ZIKV envelope protein (zEDIII) as a promising target. Subunit antigens are often poorly immunogenic, necessitating the use of adjuvants and/or delivery systems to induce optimal immune responses. The subject of nanotechnology has substantial expansion in recent years in terms of research and applications. Nanoparticles could be used as drug delivery systems and to increase the immunogenicity and stability of a given antigen. This work aims to characterize and validate the potential of a vaccine formulation composed of domain zEDIII and bovine serum albumin nanoparticles containing polyinosinic-polycytidylic acid (NPPI). NPPI were uptake in vitro by immature bone marrow dendritic cells and histological analysis of the skin of mice treated with NPPI showed an increase in cellularity. Immunization assay showed that mice immunized with zEDIII in the presence of NPPI produced neutralizing antibodies. Through the passive transfer of sera from immunized mice to ZIKV-infected neonatal mice, it was demonstrated that these antibodies provide protection, mitigating weight loss, clinical or neurological signs induced by infection, and significantly increased survival rates. Protection was further substantiated by the reduction in the number of viable infectious ZIKV, as well as a decrease in inflammatory cytokines and tissue alterations in the brains of infected mice. Taken together, data presented in this study shows that NPPI + zEDIII is a promising vaccine candidate for ZIKV.

The bladder microbiota is not significantly altered by intravesical BCG therapy.

INTRODUCTION: Bladder microbiota dysbiosis has been associated with several urological disorders. However, dysbiosis markers in bladder cancer have not been identified and little is known about the effect of Bacillus Calmette-Guérin (BCG) intravesical therapy on the bladder microbiota. In this study, we compared the bladder microbiota of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy to nononcological controls. We also longitudinally analyzed the impact of BCG therapy on the bladder microbiota of NMIBC patients and addressed whether bladder microbiota is associated with BCG efficacy. METHODS: We collected catheterized urine samples from males with intermediate/high-risk NMIBC (cancer group, n = 32) or benign prostatic hyperplasia (control group, n = 41). The cancer group also provided urine samples during and after BCG induction. We used 16S rRNA gene sequencing to characterize the bladder microbiota. Bladder microbiota parameters, such as diversity and taxonomic composition, were compared between groups and associated with clinicopathological data and BCG efficacy. RESULTS: We observed no significant differences between the bladder microbiota of NMIBC patients and controls. BCG intravesical instillations did not significantly alter the bladder microbiota of NMIBC patients, and BCG was rarely detected in the bladder during and after BCG therapy. Microbiota diversity and overall composition before BCG induction did not influence disease persistence at 3 months. However, higher abundance of Lactobacillus, Streptococcus, and Cutibacterium in the pre-BCG bladder microbiota was associated with BCG effectiveness. CONCLUSION: We were unable to identify markers of bladder microbiota dysbiosis among male NMIBC patients. Moreover, we demonstrated for the first time using longitudinally collected samples that BCG cannot persist in the bladder microbiota nor significantly alter its diversity and composition. The associations found between bladder microbes and BCG efficacy highlight the potential of microbial-based therapeutic and risk-stratification strategies in the intermediate/high-risk NMIBC setting.