Bioinformatics analysis to identify the relationship between human papillomavirus-associated cervical cancer, toll-like receptors and exomes: A genetic epidemiology study.

INTRODUCTION: Genetic variants may influence Toll-like receptor (TLR) signaling in the immune response to human papillomavirus (HPV) infection and lead to cervical cancer. In this study, we investigated the pattern of TLR expression in the transcriptome of HPV-positive and HPV-negative cervical cancer samples and looked for variants potentially related to TLR gene alterations in exomes from different populations. MATERIALS AND METHODS: A cervical tissue sample from 28 women, which was obtained from the Gene Expression Omnibus database, was used to examine TLR gene expression. Subsequently, the transcripts related to the TLRs that showed significant gene expression were queried in the Genome Aggregation Database to search for variants in more than 5,728 exomes from different ethnicities. RESULTS: Cancer and HPV were found to be associated (p<0.0001). TLR1(p = 0.001), TLR3(p = 0.004), TLR4(221060_s_at)(p = 0.001), TLR7(p = 0.001;p = 0.047), TLR8(p = 0.002) and TLR10(p = 0.008) were negatively regulated, while TLR4(1552798_at)(p<0.0001) and TLR6(p = 0.019) were positively regulated in HPV-positive patients (p<0.05). The clinical significance of the variants was statistically significant for TLR1, TLR3, TLR6 and TLR8 in association with ethnicity. Genetic variants in different TLRs have been found in various ethnic populations. Variants of the TLR gene were of the following types: TLR1(5_prime_UTR), TLR4(start_lost), TLR8(synonymous;missense) and TLR10(3_prime_UTR). The "missense" variant was found to have a risk of its clinical significance being pathogenic in South Asian populations (OR = 56,820[95%CI:40,206,80,299]). CONCLUSION: The results of this study suggest that the variants found in the transcriptomes of different populations may lead to impairment of the functional aspect of TLRs that show significant gene expression in cervical cancer samples caused by HPV.

Modulation of sHLA-G, PD-1, and PD-L1 Expression in Cervical Lesions Following Imiquimod Treatment and Its Association with Treatment Success.

(1) Background: Cervical intraepithelial neoplasia (CIN) is a precancerous condition linked to human papillomavirus (HPV) infection, often necessitating surgical interventions carrying the risk of subsequent preterm births. This study explores the potential of imiquimod (IMQ), as a non-invasive alternative treatment. The focus is on understanding IMQ impact on immune checkpoint molecules, particularly PD-1, PD-L1, and sHLA-G, which play pivotal roles in shaping immune responses and cancer progression. (2) Methods: Forty-three patients diagnosed with a high-risk squamous intraepithelial lesion (HSIL, p16-positive) self-applied 5% IMQ encapsulated in sachets containing 250 g of cream into the vaginal cavity three times a week for 16 weeks. The impact of IMQ therapy on cervical lesion regression was assessed through immunohistochemistry (IHC), examining changes in sHLA-G, PD-L1, and PD-1 levels. The antiviral activity of IMQ was evaluated through HPV-E7 immunofluorescence. Ethical considerations were adhered to, and the research methods were based on a previously approved clinical trial (clinicaltrials.gov Identifier: NCT04859361). (3) Results: IMQ treatment demonstrated efficacy, leading to lesion regression. sHLA-G levels in CIN before starting IMQ application were associated with unsuccessful treatment (p = 0.0036). IMQ did not significantly alter the expression of PD-1. We observed a decrease in PD-L1 levels in those who were successfully treated (p = 0.0509) and a reduction in HPV burden. (4) Conclusions: IMQ exhibits promise as a non-invasive treatment for CIN, emphasising its potential to modulate the immune microenvironment. Baseline sHLA-G levels emerge as potential predictors of treatment response. Understanding the nuanced dynamics of immune checkpoints sheds light on IMQ mechanism of action. Further exploration is warranted to decipher the intricate mechanisms underlying IMQ treatment in the context of cervical lesions.

Influence of sociodemographic and obstetric factors on maternal mortality in Brazil from 2011 to 2021.

BACKGROUND: Obstetric causes are classified as direct (complications of pregnancy, childbirth or the puerperium) or indirect (caused by pregnancy but not directly caused by it). This study aimed to analyze maternal mortality from obstetric causes in Brazil from 2011 to 2021. METHODS: This was an ecological study on mortality and live births. The outcomes were the specific risk of mortality from direct and indirect cause adjustment and death during pregnancy and the puerperium. Binary and multiple linear logistic regressions were used to assess the influence of sociodemographic factors and maternal and child health indicators on maternal mortality and time of death (pregnancy and puerperium). RESULTS: Regarding mortality during pregnancy and during the puerperium, increased (p = 0.003) and decreased (p = 0.004) mortality over the years, respectively; residing in the northern region was associated with lower (p < 0.05) and greater (p = 0.035) odds; and the Maternal Mortality Committee was the primary and least active source of investigation, respectively (p < 0.0001). The number of deaths from indirect causes increased with age (p < 0.001) and in the northern region (p = 0.011) and decreased in the white (< 0.05) and stable union (0.002) regions. Specifically, for mortality risk, the age group [women aged 15-19 years presented an increase in cesarean section (p < 0.001) was greater than that of women who had < 4 antenatal visits (p < 0.001)], education [women who completed high school (8 to 11 years) was greater when they had < 4 prenatal visits (p = 0.018)], and marital status [unmarried women had more than 4 antenatal visits (p < 0.001); cesarean birth (p = 0.010) and < 4 antenatal visits (p = 0.009) were predictors of marriage; and women in a stable union who had < 4 prenatal visits and live births to teenage mothers (p < 0.001) were predictors]. Women who had no education (p = 0.003), were divorced (p = 0.036), had cesarean deliveries (p < 0.012), or lived in the north or northeast (p < 0.008) had higher indirect specific mortality risk. CONCLUSIONS: Sociodemographic factors and maternal and child health indicators were related to different patterns of obstetric mortality. Obstetric mortality varied by region, marital status, race, delivery, prenatal care, and cause of death.

Impacts of Sociodemographic Factors, Screening, and Organization of Health Services on Breast Cancer Mortality in Brazil: An Ecological Study of 20 Years.

Background: Breast cancer mortality is increasing in Brazil. This study examines the impact of sociodemographic factors, screening procedures, and primary healthcare (PHC) on breast cancer mortality. Methods: An ecological study analyzed secondary data of women diagnosed with breast cancer who died between 2000 and 2019. Sociodemographic factors, screening procedures, and PHC were examined in relation to breast cancer mortality. Statistical analyses included normality tests, Kruskal-Wallis and one-way ANOVA tests with post hoc comparisons, Pearson and Spearman correlation tests, age-period-cohort analysis, Kaplan-Meier analysis, and Cox regression analysis. Significance was set at p < 0.05. Results: Mortality rates were higher in the southeast (15.77) and south (15.97) regions compared to the north (5.07) (p < 0.0001). Survival rates were longer in the southeast (70.3 ± 0.05) and south (70.6 ± 0.09) than in the north (63.98 ± 0.053) (p ≤ 0.001). Mortality increased with age after 32 years (p ≤ 0.001). Brown and indigenous women had lower mortality and survival rates. Increased coverage of PHC, ultrasound, and biopsy did not reduce mortality. However, improved cytopathologic analysis led to a decrease in mortality. Conclusions: Sociodemographic factors, screening procedures, and PHC are specific predictors of breast cancer mortality in Brazil.

Predictors of Testicular Cancer Mortality in Brazil: A 20-Year Ecological Study.

Testicular cancer is common in young men, and early detection and multimodality treatment can lead to successful outcomes. This study aims to identify sociodemographic and risk factors associated with higher testicular cancer mortality and poorer survival rates, while examining the impact of diagnostic and treatment procedures on reducing mortality. The retrospective ecological study analyzed mortality data from testicular cancer in Brazil from 2001 to 2020. Sociodemographic variables such as marital status, age, birth period, year of death (cohort), race, and geographic region were assessed. Risk factors included cryptorchidism and pesticide exposure. Data were subjected to statistical analysis, which revealed an increasing trend in mortality after 2011 among persons born after 1976 in the 15-40 age group. Individuals in the South Region, whites, and singles had higher age-standardized mortality rates (ASMRs), while singles had lower survival rates. The Northeast region had a higher survival rate. Fungicides and insecticides increase ASMR in Brazil. Herbicides increase ASMR in the Northeast and Midwest regions and insecticides increase ASMR in the Northeast, Southeast, and Midwest regions. High rates of implementation of diagnostic procedures in the Midwest were not sufficient to reduce ASMR. No treatment procedure was associated with mortality at the national or regional level.

Sociodemographic and Clinical Factors for Microcephaly Secondary to Teratogenic Infections in Brazil: An Ecological Study.

Microcephaly is a neurological condition characterized by anomalies in the growth of the cranial circumference. This study aims to examine the association between sociodemographic and clinical variables and the occurrence of secondary microcephaly in newborns in Brazil. It also aims to investigate the association between this congenital anomaly and teratogenic infections. This research adopts an observational approach with an ecological, descriptive, and analytical design. The sample includes infants aged ≤28 days and registered in the country's Live Births Information System from January 2015 to December 2021. Newborns were categorized into G1, consisting of newborns with one of the three infections (Zika, toxoplasmosis, or syphilis), and G2, consisting of newborns with two of the three infections. A total of 1513 samples were analyzed and divided into two groups: one infection (syphilis n = 423; toxoplasmosis n = 295; or Zika n = 739) and two infections (n = 56). The northeastern region of Brazil has the highest prevalence of microcephaly. Regarding the population profile, the Zika virus infection is more common among white mothers, while the syphilis infection is more common among black mothers. Among newborns with microcephaly, boys have a lower prevalence of toxoplasmosis infection, while girls have a lower prevalence of Zika virus infection. This study provides pertinent information on each infection and contributes to the epidemiologic understanding of the association between teratogenic infections and microcephaly.

Aspects of Sexuality in Quilombola Communities' Young Adults in Eastern Brazilian Amazon.

Quilombola communities are descended from African slaves who escaped in resistance to imperial rule in Brazil. Today, these communities suffer from inadequate health care and health promotion programs due to socioeconomic, geographic, and political factors. This generates greater vulnerability among these groups because they have limited information about prevention to improve their quality of life. This research aimed to analyze the sexuality of young quilombola adults and the impact on their quality of life through an observational, cross-sectional, quantitative study with descriptive and inferential analyses. Our study is the first to address these issues among quilombolas in the Eastern Amazon region. The participants were 79 individuals of both sexes, aged between 18 to 35 years, belonging to seven communities in the state of Pará. The questionnaires were designed to assess sexual behavior and satisfaction, values and beliefs about sexuality, prejudice regarding sexual and gender diversity, knowledge about sexually transmitted infections (STIs), beliefs about maternity, and quality of life. Women reported greater sexual dissatisfaction and lower quality of life than men. Men reported no dysfunctions; however, they were highly prejudiced towards sexual and gender diversity. Low education negatively impacts the health of quilombola populations, as knowledge about STIs and values and beliefs influence sexual behavior, exposing individuals to diseases. The research also confirms that, both among quilombolas and other groups, factors such as sexual satisfaction, values and beliefs about reproduction, and affectivity directly influence the quality of life.

Contribution of HLA-G and FOXP3 genes and proteins in the severity of cervical intraepithelial neoplasia during HPV infection.

Human Papillomavirus (HPV) persistence leads to the chronification of cervical inflammation, where HLA-G and Foxp3; immunomodulatory molecules, may contribute to the aggravation of the lesion and cancerization. Here, we evaluated the synergic effect of these two molecules in the worsening of the lesion in presence of HPV infection. Hundred and eighty (180) women cervical cells and biopsies were collected for (i) HLAG Sanger sequencing and gene expression, and (ii) HLA-G and Foxp3 molecule expressions by immunohistochemistry. 53 women were HPV+ against 127 women HPV-. HPV+ women were more at risk of having cytological changes (p ≤ 0.0123), histological changes (p < 0.0011), and cervical lesion (p = 0.0004). The HLA-G + 3142CC genotype predisposed women to infection (p = 0.0190), while HLA-G + 3142C and +3035 T alleles were associated with HLA-G5 transcript expression. Both sHLA-G (p = 0.030) and Foxp3 (p = 0.0002) proteins were higher in cervical lesion as well as in high-grade lesion. In addition, sHLA-G+ cells were positively correlated to Foxp3+ cells in presence of HPV infection and in cervical grade II/III injuries. In conclusion, HPV may use HLA-G and Foxp3 as a way of host immune escape contributing to the persistence of infection and inflammation, leading to the cervical lesion and the worsening of lesions.

Social, Genetics and Histopathological Factors Related to Titin (TTN) Gene Mutation and Survival in Women with Ovarian Serous Cystadenocarcinoma: Bioinformatics Analysis.

Several factors may increase the risk of development of ovarian cancer. In this study, we investigated the relationship between social, genetic, and histopathologic factors in women with ovarian serous cystadenocarcinoma and titin (TTN) mutations, whether the TTN gene mutation may be a predictor, and its impact on mortality and survival in these patients. A total of 585 samples from patients with ovarian serous cystadenocarcinoma were collected from The Cancer Genome Atlas and PanCancer Atlas through the cBioPortal for analysis of social, genetic, and histopathological factors. Logistic regression was used to investigate whether TTN mutation could be a predictor, and the Kaplan-Meier method was applied to analyze survival time. TTN mutation frequency did not differ between age at diagnosis, tumor stage, and race, and was related to increased Buffa hypoxia score (p = 0.004), mutation count (p < 0.0001), Winter hypoxia Score (p = 0.030), nonsynonymous tumor mutation burden (TMB) (p < 0.0001), and reduced microsatellite instability sensor score (p = 0.010). The number of mutations (p < 0.0001) and winter hypoxia score (p = 0.008) were positively associated with TTN mutations, and nonsynonymous TMB (p < 0.0001) proved to be a predictor. Mutated TTN affects the score of genetic variables involved in cancer cell metabolism in ovarian cystadenocarcinoma.

COVID-19 in the Eastern Brazilian Amazon: Incidence, Clinical Management, and Mortality by Social Determinants of Health, Symptomatology, and Comorbidities in the Xingu Health Region.

This study aims to investigate the relationship between social determinants of health (SDH), incidence, and mortality to verify which sociodemographic factors, symptoms, and comorbidities predict clinical management; second, this study aims to conduct a survival analysis of individuals with COVID-19 in the Xingu Health Region. Consequently, this study adopted an ecological framework, employing secondary data of COVID-19-positive individuals from the Xingu Health Region, Pará State, Brazil. The data were obtained through the database of the State of Pará Public Health Secretary (SESPA) for the period from March 2020 to March 2021. The incidence and mortality were higher in Vitória do Xingu and Altamira. Municipalities with a higher percentage of citizens with health insurance and higher public health expenditure showed a higher incidence and mortality. A higher gross domestic product was associated with a higher incidence. Females were found to be associated with better clinical management. To live in Altamira was a risk factor for intensive care unit admission. The symptoms and comorbidities that predicted worse clinical management were dyspnea, fever, emesis, chills, diabetes, cardiac and renal diseases, obesity, and neurological diseases. There were higher incidence, mortality, and lower survival rates among the elderly. Thus, it can be concluded that SDH indicators, symptomatology, and comorbidities have implications for the incidence, mortality, and clinical management of COVID-19 in the Xingu Health Region of eastern Amazonia, Brazil.

Influence of social, demographic, and clinical factors in live births with spinal dysraphism in Brazil: an ecological study of 21 years.

OBJECTIVES: This study aimed to verify possible associations between sociodemographic and clinical factors in live births with spinal dysraphism. METHODS: An analytical (descriptive and inferential) and ecological study was carried out based on secondary data of 11,308 live births with spinal dysraphism registered in the Live Birth Information System (SINASC) in Brazil from 1999 to 2019. Demographic factors analyzed were age, education, mothers' marital status and geographic region. The clinical factors analyzed were duration, gestation period, birthweight, and number of prenatal visits performed by women who underwent medical follow-up. RESULTS: There was an increase in the number of cases of spinal dysraphism in recent years in Brazil with an annual percentage variation of 3.52%. However, the period from 2005 to 2009 showed a reduction in live births with spinal dysraphism. The regions with the highest incidence were the South and Southeast. The risk increased in mothers born after 1980, older than 30 years and with a high level of education. The risk was increased in live births of whites and blacks, born from double pregnancy and with body weight less than 3000 g. The absence of prenatal care was associated with a higher incidence. CONCLUSION: Sociodemographic and clinical factors have specific characteristics that can predict spinal dysraphism in newborns in Brazil.

Sociodemographic and clinical variables as determinants of mortality and survival in patients with acute ST-elevation myocardial infarction in the Eastern Amazon.

Background: The aim of this study was to analyze the influence of sociodemographic and clinical variables as determinants of mortality and survival in patients with ST-segment elevation acute myocardial infarction in the Eastern Amazon. Design and methods: This observational, longitudinal, and retrospective study was conducted at the Gaspar Vianna Clinical Hospital Foundation in patients hospitalized from January 2017 to June 2020. Patients were divided into two groups: those who survived (G1) (n = 646) and those who died (G2) (n = 37). Sociodemographic and clinical variables associated with mortality and survival in these two groups were analyzed. Results: Patients with STEMI who had the highest risk of death were often the oldest (G1: 61.58 ± 10.74 years; G2: 69.57 ± 9.02 years; t = -4.492; p = 0.001), with Killip III-IV classifications (OR = 0.13; 95% CI = 0.02-0.71; p = 0.03), and with diseases such as heart failure (OR = 0.07; 95% CI = 0.004-1.50; p = 0.168) or renal failure (OR = 0.03; 95% CI = 0.006-0.16; p = 0.0001). In addition, female sex (hazard ratio = 2.073; 95% CI = 1.413-5.170), Killip III-IV classifications (hazard ratio = 4.041; 95% CI = 1.703-18.883) and the presence of heart failure (hazard ratio = 34.102; 95% CI = 4.410-263.684) or renal failure (hazard ratio = 14.278; 95% CI = 3.275-62.248) shortened in-hospital survival. Conclusions: Specific sociodemographic and clinical aspects influenced mortality and survival in patients with acute ST -elevation myocardial infarction.

Chemokine receptors on human regulatory T cells during cutaneous leishmaniasis.

The aim of this work was to define the population of regulatory T cells (Tregs) which are circulating in the blood of Leishmania infected individuals clinically displaying a lesion (active disease-AD) and sub-clinical (SC) ones. We have individually collected blood samples, processed the PBMC and stained with fluorochrome-conjugated antibodies against CD3, CD4, Foxp3, CD25, CTLA-4, Ki-67, CCR4, CCR5, and CCR7. Cells were analyzed by flow cytometry. Our results suggest that CD25 and CTLA-4 are upregulated in Tregs of AD patients when compared to SC and uninfected (UN) controls. Moreover, Tregs proliferate upon infection based on Ki-67 nuclear antigen staining. Finally, we have observed that these Tregs of SC and AD patients upregulate CCR4, but not CCR5 and CCR7. There is an increase in the number of circulating Tregs in the blood of Leishmania infected individuals. These cells are potentially more suppressive based on the increased upregulation of CD25 and CTLA-4 during clinical infection (AD) when compared to SC infection. Tregs of both SC and AD cohorts are proliferating and express CCR4, which potentially guide them to the skin, but do not upregulate CCR5 and CCR7.

Strength and Bioelectrical Activity of the Pelvic Floor Muscles and Sexual Function in Women with and without Stress Urinary Incontinence: An Observational Cross-Sectional Study.

Stress urinary incontinence (SUI) results from an increase in intravesical pressure, which exceeds the pressure at which the urethra remains closed. Symptoms cause social and sexual intercourse discomfort directly or indirectly, which affect health-related quality of life and are associated with pelvic floor muscle (PFM) dysfunction. We aimed to verify the variation in strength and PFM bioelectrical activity and sexual function in women with SUI. Additionally, we analyzed the impact of this dysfunction on quality of life. This was an observational cross-sectional study. Women aged 25−55 years with frequent sexual intercourse were included. Women with SUI were included in a study group (G2, n = 17), and those without any type of incontinence were included in a control group (G1, n = 16). Primary outcomes were level of strength and PFM bioelectrical activity and sexual function as determinants of worse SUI in the control group. Secondary outcomes were associated between the primary outcomes and severity of urinary loss, impact on daily life, and quality of life in women with SUI. In the domains evaluated in the Female Sexual Function Index (FSFI), only sexual desire was lower in women with SUI (G2) than in the controls (p = 0.033). During analysis of G1 variables, a positive and moderate correlation was observed between power/myoeletric activation and maximum voluntary contraction (MVC) (p < 0.01), peak (p < 0.01), and mean amplitudes (p = 0.017). There was a high positive correlation between sexual arousal and other variables, including vaginal lubrication, sexual orgasm, and total FSFI value (p < 0.001 for all analyses). During evaluation of G2 variables, the MVC was positively correlated with the peak and mean amplitudes (p < 0.0001). Additionally, there was a high and positive correlation between the mean amplitudes (%MVC) and personal relationships (KHQ) (p = 0.001); the same was observed between the total (ICIQ) and activities of daily living (ICIQ) (p < 0.0001). Therefore, women with SUI presented with lower sexual desire and bioelectric activity but were not related to PFM strength. Additionally, the domains of sexual function and certain variables of quality of life are aggravated by SUI.

Effect of benznidazole on cerebral microcirculation during acute Trypanosoma cruzi infection in mice.

Central nervous system alterations was described in Chagas disease in both human and experimental models, leading to meningoencephalitis, stroke and cognitive impairment. Recently, our group demonstrated that acute infection by Trypanossoma cruzi leads to cerebral microvasculophaty in mice with endothelial dysfunction, capillary rarefaction, increased rolling and leukocyte adhesion. Only benznidazole and nifurtimox are available for clinical treatment, they have an efficiency of 80% in the acute phase and less than 20% in chronic phase. However, the effect of these drugs on brain microcirculation has not yet been evaluated. We hypothesized that early treatment with benznidazole could protect brain microcirculation during acute experimental Chagas disease. Swiss Webster mice were inoculated with 104 trypomastigotes forms of T. cruzi, and after 24 h they were treated with 50 or 100 mg/kg/day of benznidazole for 14 consecutive days. In untreated infected mice, we observed cerebral microvascular rarefaction, increase in leukocyte rolling and adhesion, reduced cerebral blood flow, and increased CD3+ and F4-80+ cells in brain tissue. Early treatment with benznidazole at 100 mg/kg/day and 50 mg/kg/day prevented the occurrence of the alterations mentioned. Here, we show that BZ is able to protect the microcirculation and reduced brain inflammation in acute experimental Chagas disease.

Association between Sociodemographic Factors, Coverage and Offer of Health Services with Mortality Due to Oral and Oropharyngeal Cancer in Brazil: A 20-Year Analysis.

To investigate the association between sociodemographic factors and variables related to oral health services in oral and oropharyngeal cancer mortality in Brazil, between 2000 and 2019. This study had an ecological design. Standardized mortality rates were compared between age group, sex, and regions. Age-Period-Cohort analysis was applied. Oral health services variables were analyzed in correlation tests. Survival analysis included Kaplan-Meier estimators, log-rank tests, and Cox regression. The mortality rate increased with age and was higher in men. Southeast and south regions had the highest rates for men, and the northeast and southeast had it for women. Age-Period-Cohort analysis showed a slight increase in female deaths and an increasing trend in the annual percent change in mortality for men over age 55. In survival analysis, males, Black individuals and southern residents were more strongly associated with death. The correlation between oral health teams' coverage was high and negative, while the number of dental specialty centers and soft tissue biopsies had a high and positive correlation. Mortality and survival patterns were dependent on sex, age, geographic region and race/ethnicity. It was observed that preventive and diagnostic procedures were not being performed, which may be related to the increase in mortality.

Ivabradine treatment lowers blood pressure and promotes cardiac and renal protection in spontaneously hypertensive rats.

Hypertension is linked to hyperpolarization-activated cyclic nucleotide-gated (HCN) function, expressed in excitable and non-excitable cells. Considering that the reduction in heart rate (HR) improves coronary perfusion and cardiac performance, ivabradine (IVA) emerged as an important drug for the treatment of cardiovascular diseases. AIM: Evaluate if IVA chronic treatment effect can mitigate hypertension and reverse the cardiac and renal damage in SHR. MAIN METHODS: Rats were divided into 4 groups treated for 14 days with PBS (1 ml/kg; i.p) or IVA (1 mg/kg; i.p): 1) WKY PBS; 2) SHR PBS; 3) WKY IVA; and 4) SHR IVA. The systolic blood pressure (SBP) was measured, indirectly, before and during the treatment period with IVA (day 0, 1, 7 and 11). Rats were subjected to artery cannulation for direct blood pressure (BP) measurement. Morphofunctional and gene expression were evaluated in the heart and kidneys. KEY FINDINGS: IVA reduced SBP only in SHR on the 7th day. Direct blood pressure measurement showed that IVA chronic treatment reduced HR in the SHR. Interestingly, mean arterial pressure (MAP) was reduced in SHR IVA when compared to SHR PBS. Serum and urinary biochemical data were not altered by IVA. Moreover, IVA reduced the renal inflammatory infiltrates and increased glomerular density, besides preventing the cardiac inflammatory and hypertrophic responses. SIGNIFICANCE: IVA treatment lowered blood pressure, improved cardiac remodeling and inflammation, as well as decreasing renal damage in SHR. Further, IVA increased renal HCN2 mRNA and reduced cardiac HCN4 mRNA.

Impact of sociodemographic factors and screening, diagnosis, and treatment strategies on colorectal cancer mortality in Brazil: A 20-year ecological study.

Colorectal cancer (CRC) caused 261,060 deaths in Brazil over a 20-year period, with a tendency to increase over time. This study aimed to verify the sociodemographic factors predicting higher mortality caused by CRC and survival rates. Moreover, we aimed to verify whether the performance of screening, diagnostic and treatment procedures had an impact on mortality. Ecological observational study of mortality due to CRC was conducted in Brazil from 2000-2019. The adjustment variable was age, which was used to calculate the age-standardized mortality rate (ASMR). The exposure variables were number of deaths and ASMR. Outcome variables were age-period-cohort, race classification, marital status, geographic region, and screening, diagnostic, and treatment procedures. Age-period-cohort analysis was performed. ANOVA and Kruskal-Wallis test with post hoc tests were used to assess differences in race classification, marital status, and geographic region. Multinomial logistic regression was used to test for interaction among sociodemographic factors. Survival analysis included Kaplan-Meier plot and Cox regression analysis were performed. Multivariate linear regression was used to test prediction using screening, diagnosis, and treatment procedures. In Brazil, mortality from CRC increased after age 45 years. The highest adjusted mortality rates were found among white individuals and in the South of the country (p < 0.05). Single, married, and widowed northern and northeastern persons had a higher risk of death than legally separated southern persons (p < 0.05). Lower survival rates were observed in brown and legally separated individuals and residents from the North (p < 0.05). An increase in first-line chemotherapy and a decrease in second-line chemotherapy were associated with high mortality in the north (p<0.05). In the south, second-line chemotherapy and abdominoperineal rectal resection were associated with high mortality (p < 0.05). Regional differences in sociodemographic factors and clinical procedures can serve as guidelines for adjusting public health policies.

Vitamin D3 supplementation may attenuate morphological and molecular abnormalities of the olfactory bulb in a mouse model of Down syndrome.

Individuals with Down syndrome (DS) exhibit impaired olfactory function and are at a higher risk of developing Alzheimer's disease (AD). Olfactory dysfunction may be an early clinical symptom of AD. Recent studies have demonstrated that vitamin D3 (VD3) exerts neuroprotective effects in mouse models of AD. In this study, we investigated the effects of VD3 on the morphology, immunolocalization, and markers involved in neuropathogenic processes, apoptosis, proliferation, cell survival, and clearance of amyloid peptides, along with neuronal markers in the olfactory bulb (OB) of an adult female mouse model of DS. Morphological and molecular analyses revealed that trisomic mice exhibited a volume reduction in the external plexiform layer, a decrease in the number of mitral and granule cells, and an increase in the expression of amyloid-ß 42, caspase-3 p12, and P-glycoprotein. VD3 reversed certain morphological abnormalities in the OB of control trisomic mice (Ts(CO)) and decreased the levels of caspase-3 p12 and methylenetetrahydrofolate reductase in the treated groups. The results demonstrated that trisomy factor causes morphofunctional abnormalities in the OB of Ts(CO) mice. Moreover, VD3 could represent a therapeutic target to attenuate morphological and molecular alterations in OB.

Factors associated with 5-min APGAR score, death and survival in neonatal intensive care: a case-control study.

BACKGROUND: The 5-minute APGAR score is clinically used as a screening tool to assess how the newborn has reacted to previous care, remaining relevant for predicting neonatal survival. This study aimed to analyze the determinants of the 5th minute APGAR score, and the factors associated with the death and survival of newborns with low APGAR scores hospitalized in the neonatal intensive care unit (NICU) at a referral public hospital in North Brazil. METHODS: This was a hospital-based retrospective case-control study with 277 medical records. Newborns who presented with a 1-minute APGAR score < 7 followed by a 5-minute APGAR score < 7 were considered cases, while a score ≥ 7 was categorized as controls. Univariate and multivariable logistic regression analyses were used to establish the determinant factors of the low APGAR score and death outcome in this group. Survival curves were obtained using the Kaplan-Meier estimator, and then univariate and multivariate Cox regression was performed. RESULTS: After adjusted analysis, the factor associated with low APGAR scores was vaginal delivery (OR = 3.25, 95%CI = 1.60-6.62, p = 0.001). Birth injury (OR = 0.39, 95%CI = 0.19-0.83, p = 0.014) was associated with upper APGAR scores. No significant independent associations were observed between the variables analyzed and death in the low APGAR score group. The Kaplan-Meier curve showed that individuals who presented Cesarean delivery had a shorter survival time in the ICU. CONCLUSION: In this setting, a 5-minute Apgar score < 7 was associated with the occurrence of vaginal delivery and birth injury with a 5-minute Apgar score ≥ 7. Survival in ICU was lower in newborns that were delivered via cesarean section.