Acute toxicity and genotoxicity of Schinus molle L. aqueous extract/ethanol-soluble fraction in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Schinus molle L. is a medicinal species belonging to the Anacardiaceae family. It is commonly referred to as "aroeira" and its leaves and roots are utilized for treating different pathological conditions. However, despite its widespread use in traditional medicine, there is a lack of in-depth toxicological studies. AIM: To evaluate the acute toxicity and genotoxicity of S. molle aqueous extract/ethanol-soluble fraction in rats. MATERIAL AND METHODS: First, a purified aqueous extract was obtained from the leaves of S. mole through infusion (referred to as EESM) and its compounds were identified using LC-DAD-MS data. Female rats were then subjected to acute oral toxicity tests using doses of 5, 50, 300, and 2000 mg/kg of ESSM. Studies on genetic material, including the micronucleus test and comet assay, were conducted on male and female Wistar rats using the same doses as in the acute toxicity test. For both assays, ESSM was administered orally. RESULTS: The main metabolites annotated from ESSM were dimeric proanthocyanidins, phenylpropanoids acids, flavan-3-ols, simple organic acids (C6-C1), a flavonol di-O-glycosylated (rutin), and O-glycosylated megastigmane. The ESSM did not exhibit any acute toxic effects, such as changes in biochemical, hematologic, or histopathological analysis. Furthermore, no changes were observed in comet assay or micronucleus tests when rats were given doses of 5, 50, 300, or 2000 mg/kg of ESSM. CONCLUSION: The results showed that the ESSM does not induce acute toxicity or exhibit genotoxicity up to a dose of 2000 mg/kg.

Maternal nutrition and its effects on fetal neurodevelopment.

Herein, we present a thorough examination of the impact of maternal nutrition on fetal and infant neurodevelopment, focusing on specific nutrients and their critical roles in perinatal and pediatric health. Through a comprehensive narrative review of the literature, this study highlights the importance of a balanced maternal diet rich in nutrients like eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), folic acid, iron, and iodine in shaping children's neurological functions. Key findings underscore the influence of maternal nutrition during pregnancy and the peri-gestational period on children's cognitive, motor, speech, and socio-emotional development. Deficiencies in essential nutrients, such as DHA, are linked to adverse long-lasting outcomes such as premature birth and intrauterine growth restriction, where a suitable intake of iron and folic acid is vital to prevent neural tube defects and promote healthy brain development. We highlight areas requiring further investigation, particularly regarding iodine's impact and the risks associated with alcohol consumption during pregnancy. In conclusion, this research sheds light on our current understanding of maternal nutrition and child neurodevelopment, offering valuable insights for health professionals and researchers.

Geography and public health: analysis of the epidemiological dynamics of meningitis in Brazil, between 2010 and 2019.

OBJECTIVE: To analyze the spatiotemporal epidemiological dynamics of meningitis in Brazil, between 2010 and 2019. METHODS: Descriptive ecological study with cases and deaths due to meningitis in Brazil (2010-2019) in the National Notifiable Diseases Information System (Sistema de Informações de Agravos de Notificação - SINAN). The following analyses were performed: (I) frequency analyses of cases and deaths, prevalence rates, mortality, lethality, Fisher's exact test, and chi-square test; (II) Prais-Winstein regression; and (III) Global, Local Moran's index, and Kernel density. RESULTS: 182,126 cases of meningitis were reported in Brazil, of which 16,866 (9.26%) resulted in death, with prevalence rates of 9.03/100,000 inhabitants, mortality of 0.84/100,000 inhabitants, and lethality of 9.26%. There was a noted trend of decreasing prevalence rates (-9.5%, 95% confidence interval - 95%CI -13.92; -4.96, p<0.01) and mortality (-11.74%, 95%CI -13.92; -9.48, p<0.01), while lethality remained stable (-2.08%, 95%CI -4.9; 0.8; p<0.1941). The majority of cases were viral meningitis (45.7%), among 1-9 years old (32.2%), while the highest proportion of deaths was due to bacterial meningitis (68%), among 40-59 years old (26.3%). In the Moran and Kernel maps of prevalence and mortality rates, municipalities in the South, Southeast, and the capital of Pernambuco in the Northeast stood out with high rates; as for lethality, the North, Northeast, and Southeast coastal areas were highlighted. CONCLUSION: A decrease in meningitis cases and deaths was found in this study; however, the lethality rate was higher in areas with lower prevalence, emphasizing the need to enhance actions for identifying, monitoring, and providing health care for cases, as well as expanding vaccination coverage.

A nationwide study on immunosenescence biomarkers profile in older adults: ELSI-Brazil.

Immunosenescence is a phenomenon caused by changes in the immune system, and part of these changes involves an increase in circulating immunological biomarkers, a process known as "Inflammaging." Inflammaging can be associated with many diseases related to older people. As the older population continues to grow, understanding changes in the immune system becomes essential. While prior studies assessing these alterations have been conducted in countries with Caucasian populations, this investigation marks a pioneering effort. The object of the study is to describe for the first time that the distribution of cytokines, chemokines, and growth factors serum levels, assessed by Luminex platform, has been examined in a Brazilian population-based study of older adult females and males by age. Blood samples from 2111 participants (≥50 years old) were analyzed at the baseline (2015/2016) of the ELSI-Brazil study. The exploratory variables considered in the study were age, sex, educational level, residence area, geographic region, alcohol and smoking consumption, physical activity, and self-reported medical diagnoses of hypertension, diabetes, asthma, arthritis, and cancer. The association between serum biomarker levels and age was assessed by a quantile regression model adjusted in the total population and stratified by sex. The significance level considered in the analysis was 0.05. The mean age of the participants was 62.9 years, with a slight majority of female (52.7 %). Differences were found between the sexes in the median circulating levels of the CCL11, CXCL10, and FGF biomarkers. Eight biomarkers showed significant associations with age, including the pro-inflammatory CXCL10, TNF-α, IL-6, IL-17, and IL-2; and type 2/regulatory CCL11 and IL-4, showing positive associations, and anti-inflammatory IL-1Ra showing a negative association. The results suggest similar associations between the sexes, revealing an inflammatory profile characterized by types 1 and 2. Remarkably, these findings reinforce the concept of the Inflammaging process in Brazilian population. These findings add novel insights to about the immunosenescence aspects in middle-income countries and help define biomarkers capable of monitoring inflammation in older adults.

Therapeutic itineraries in health care in Quilombola communities. / Itinerários terapêuticos no cuidado em saúde em comunidades quilombolas.

This article aimed to map therapeutic itineraries in health care within rural Quilombola communities in the north of Minas Gerais, Brazil. This is a section of a qualitative research conducted in six visited communities. The data was collected through 18 individual interviews, analyzed using the theoretical-methodological framework of Therapeutic Itineraries, and organized into three empirical themes. The narratives allowed for understanding the paths taken in health care by the Quilombola population, identifying the components of the popular subsystem (natural resources, the use of teas and home remedies), the family subsystem (transmission of knowledge and cultural heritage of care), and the professional subsystem (hospital level, medical care, primary and specialized attention). The difficulties of access are not only due to geographical distances, but also broader aspects of social determination, such as institutional racism, low availability of services, the need for payment for transportation and medical procedures. In this sense, it is necessary to have an approach and interventions from public policies to address ethnic-racial, economic, and access inequalities in health care services.

Este artigo teve como objetivo mapear os itinerários terapêuticos no cuidado em saúde em comunidades quilombolas rurais no norte de Minas Gerais, Brasil. Trata-se de um recorte de uma pesquisa qualitativa realizada em seis comunidades visitadas. Os dados foram produzidos por meio de 18 entrevistas individuais, analisados pelo referencial teórico-metodológico dos itinerários terapêuticos e organizados em três temas empíricos. As narrativas permitiram a compreensão dos percursos trilhados no cuidado em saúde pela população quilombola, a identificação dos componentes do subsistema popular (recursos naturais, o uso de chás e remédios caseiros), do subsistema familiar (transmissão de conhecimentos e herança cultural de cuidados), e do subsistema profissional (nível hospitalar, cuidados médicos, atenção primária e especializada). As dificuldades de acesso não decorrem apenas das distâncias geográficas, envolvem aspectos mais amplos da determinação social, como o racismo institucional, a baixa oferta de serviços, a necessidade de pagamento para deslocamentos e procedimentos médicos. Nesse sentido, fazem-se necessárias uma abordagem e intervenções das políticas públicas frente às desigualdades étnico-raciais, econômicas e de acesso aos serviços de cuidado em saúde.

Insect residues as an alternative and promising source for the extraction of chitin and chitosan.

This work aimed to obtain and characterize chitin and chitosan extracted from the rearing residues of Tenebrio molitor, Zophobas morio, and Blaptica dubia insects in different growth stages in the same rearing cycles chitin and chitosan yielded 11.21 %-20.89 % and 6.26 %-7.07 %, respectively. The deacetylation degrees of chitosan ranged from 75.75 %-89.21 %, and the solubilities from 69.88 %-94.39 %. Infrared spectroscopy corroborated the acquisition of chitin and chitosan and can be used as a semi-quantitative technique for determining the degree of chitosan deacetylation. The X-ray diffraction profiles revealed the presence of α-chitin, and the relative crystalline indices ranged from 65.9 %-89.2 %. Typical TG profiles with two thermal events are observed for chitin and chitosan samples with different residue contents from the extraction procedure. The chitosan solutions exhibited pseudoplastic behavior, with apparent viscosities ranging from 195.96 to 249.86 mPa.s. The characterization results of the biopolymers extracted from insect residues were similar to those obtained from conventional sources. The growth stage influenced the chitin yield and crystallinity index. The results of this study reinforce the feasibility of using alternative sources of chitin and chitosan, providing the use of waste from insect farms and contributing to sustainability and a circular economy.

Geography and public health: analysis of the epidemiological dynamics of meningitis in Brazil, between 2010 and 2019 / Geografia e saúde coletiva: análise da dinâmica epidemiológica das meningites no Brasil, entre os anos de 2010 e 2019

ABSTRACT Objective: To analyze the spatiotemporal epidemiological dynamics of meningitis in Brazil, between 2010 and 2019. Methods: Descriptive ecological study with cases and deaths due to meningitis in Brazil (2010-2019) in the National Notifiable Diseases Information System (Sistema de Informações de Agravos de Notificação - SINAN). The following analyses were performed: (I) frequency analyses of cases and deaths, prevalence rates, mortality, lethality, Fisher's exact test, and chi-square test; (II) Prais-Winstein regression; and (III) Global, Local Moran's index, and Kernel density. Results: 182,126 cases of meningitis were reported in Brazil, of which 16,866 (9.26%) resulted in death, with prevalence rates of 9.03/100,000 inhabitants, mortality of 0.84/100,000 inhabitants, and lethality of 9.26%. There was a noted trend of decreasing prevalence rates (−9.5%, 95% confidence interval — 95%CI −13.92; −4.96, p<0.01) and mortality (−11.74%, 95%CI −13.92; −9.48, p<0.01), while lethality remained stable (−2.08%, 95%CI −4.9; 0.8; p<0.1941). The majority of cases were viral meningitis (45.7%), among 1-9 years old (32.2%), while the highest proportion of deaths was due to bacterial meningitis (68%), among 40-59 years old (26.3%). In the Moran and Kernel maps of prevalence and mortality rates, municipalities in the South, Southeast, and the capital of Pernambuco in the Northeast stood out with high rates; as for lethality, the North, Northeast, and Southeast coastal areas were highlighted. Conclusion: A decrease in meningitis cases and deaths was found in this study; however, the lethality rate was higher in areas with lower prevalence, emphasizing the need to enhance actions for identifying, monitoring, and providing health care for cases, as well as expanding vaccination coverage.

RESUMO Objetivo: Analisar a dinâmica epidemiológica espaçotemporal das meningites no Brasil, entre os anos de 2010 e 2019. Métodos: Estudo ecológico descritivo com os casos e óbitos por meningites no Brasil (2010-2019) no Sistema de Informações de Agravos de Notificação. Realizaram-se (I) análises de frequências dos casos e óbitos, taxas de prevalência, mortalidade, letalidade, testes de exato de Fisher e qui-quadrado; (II) regressão de Prais-Winsten; e (III) índice de Moran global, local e densidade de Kernel. Resultados: Notificaram-se 182.126 casos de meningites no Brasil, dos quais 16.866 (9,26%) evoluíram para óbito, com taxas de prevalência de 9,03/100.000/habitantes, mortalidade de 0,84/100.000/habitantes e letalidade de 9,26%. Destaca-se a tendência de decrescimento das taxas de prevalência (−9,5%, intervalo de confiança de 95% — IC95% −13,92; −4,96, p<0,01) e mortalidade (−11,74%, IC95% −13,92; −9,48, p<01,01), enquanto a letalidade se manteve estacionária (−2,08%, IC95% −4,9; 0,8; p<0,1941). A maioria dos casos foi de meningites virais (45,7%), entre 1 e 9 anos (32,2%), enquanto a maior parcela dos óbitos foi por meningites bacterianas (68%), entre 40 e 59 anos (26,3%). Nos mapas de Moran e Kernel das taxas de prevalência e mortalidade, destacaram-se com altas taxas os municípios do sul, sudeste e a capital de Pernambuco, no nordeste; já na letalidade, evidenciaram-se o norte, o nordeste e o litoral do sudeste. Conclusão: Encontrou-se decréscimo dos casos e óbitos por meningites neste estudo, entretanto a taxa de letalidade foi maior em áreas com menor prevalência, reforçando a necessidade do aprimoramento das ações de identificação, vigilância e assistência em saúde dos casos, bem como da ampliação da cobertura vacinal.

Itinerários terapêuticos no cuidado em saúde em comunidades quilombolas / Therapeutic itineraries in health care in Quilombola communities

Resumo Este artigo teve como objetivo mapear os itinerários terapêuticos no cuidado em saúde em comunidades quilombolas rurais no norte de Minas Gerais, Brasil. Trata-se de um recorte de uma pesquisa qualitativa realizada em seis comunidades visitadas. Os dados foram produzidos por meio de 18 entrevistas individuais, analisados pelo referencial teórico-metodológico dos itinerários terapêuticos e organizados em três temas empíricos. As narrativas permitiram a compreensão dos percursos trilhados no cuidado em saúde pela população quilombola, a identificação dos componentes do subsistema popular (recursos naturais, o uso de chás e remédios caseiros), do subsistema familiar (transmissão de conhecimentos e herança cultural de cuidados), e do subsistema profissional (nível hospitalar, cuidados médicos, atenção primária e especializada). As dificuldades de acesso não decorrem apenas das distâncias geográficas, envolvem aspectos mais amplos da determinação social, como o racismo institucional, a baixa oferta de serviços, a necessidade de pagamento para deslocamentos e procedimentos médicos. Nesse sentido, fazem-se necessárias uma abordagem e intervenções das políticas públicas frente às desigualdades étnico-raciais, econômicas e de acesso aos serviços de cuidado em saúde.

Abstract This article aimed to map therapeutic itineraries in health care within rural Quilombola communities in the north of Minas Gerais, Brazil. This is a section of a qualitative research conducted in six visited communities. The data was collected through 18 individual interviews, analyzed using the theoretical-methodological framework of Therapeutic Itineraries, and organized into three empirical themes. The narratives allowed for understanding the paths taken in health care by the Quilombola population, identifying the components of the popular subsystem (natural resources, the use of teas and home remedies), the family subsystem (transmission of knowledge and cultural heritage of care), and the professional subsystem (hospital level, medical care, primary and specialized attention). The difficulties of access are not only due to geographical distances, but also broader aspects of social determination, such as institutional racism, low availability of services, the need for payment for transportation and medical procedures. In this sense, it is necessary to have an approach and interventions from public policies to address ethnic-racial, economic, and access inequalities in health care services.

Multi targets of cannabidiol (CBD) on skeletal mammalian and avian neuromuscular preparations.

Cannabidiol (CBD) has been used in diseases that affect the central nervous system. Its effects on the peripheral synapses are of great interest, since endocannabinoid receptors are expressed in muscles. CBD (0.3 mM) was analysed using mammalian and avian neuromuscular preparations, through myographic techniques in complementary protocols. Mammalian cells were examined by light microscopy while exogenous acetylcholine (40 µM) and potassium chloride (100 mM) were added into avian preparations, before and at the end of experiments. Pharmacological tools such as atropine (2 µM), polyethylene glycol (PEG 400, 20 µM), Ca2+ (1.8 mM), F55-6 (20 µg/mL), and nifedipine (1.3 mM) were assessed with CBD. In mice, CBD causes a facilitatory effect and paralysis, whereas in avian, paralysis. Concluding, CBD is responsible for activated or inhibited channels, for ACh release via muscarinic receptor modulation, and by the inhibition of nicotinic receptors leading to neuromuscular blockade, with no damage to striated muscle cells.

Vasodilator Responses of Perivascular Adipose Tissue-Derived Hydrogen Sulfide Stimulated with L-Cysteine in Pregnancy Hypertension-Induced Endothelial Dysfunction in Rats.

Endothelium-derived nitric oxide (NO)-induced vasodilation is impaired in pregnancy hypertension. However, the role of perivascular adipose tissue (PVAT)-derived hydrogen sulfide (H2S), as an alternative for counteracting vascular dysfunction, is incompletely clear in hypertensive disorders of pregnancy. Therefore, PVAT-derived H2S-induced vasodilation was investigated in pregnancy hypertension-induced endothelial dysfunction. Non-pregnant (Non-Preg) and pregnant (Preg) rats were submitted (or not) to the deoxycorticosterone (DOCA)-salt protocol and assigned as follows (n = 10/group): Non-Preg, Non-Preg+DOCA, Preg, and Preg+DOCA groups. Systolic blood pressure (SBP), angiogenesis-related factors, determinant levels of H2S (PbS), NO (NOx), and oxidative stress (MDA) were assessed. Vascular changes were recorded in thoracic aortas with PVAT and endothelium (intact and removed layers). Vasorelaxation responses to the substrate (L-cysteine) for the H2S-producing enzyme cystathionine-γ-lyase (CSE) were examined in the absence and presence of CSE-inhibitor DL-propargylglycine (PAG) in thoracic aorta rings pre-incubated with cofactor for CSE (pyridoxal-5 phosphate: PLP) and pre-contracted with phenylephrine. Hypertension was only found in the Preg+DOCA group. Preg+DOCA rats showed angiogenic imbalances and increased levels of MDA. PbS, but not NOx, showed increased levels in the Preg+DOCA group. Pre-incubation with PLP and L-cysteine elevated determinants of H2S in PVAT and placentas of Preg-DOCA rats, whereas no changes were found in the aortas without PVAT. Aortas of Preg-DOCA rats showed that PVAT-derived H2S-dependent vasodilation was greater compared to endothelium-derived H2S, whereas PAG blocked these responses. PVAT-derived H2S endogenously stimulated with the amino acid L-cysteine may be an alternative to induce vasorelaxation in endothelial dysfunction related to pregnancy hypertension.

Rhythmic profile of memory T and B-cells along childhood and adolescence.

Immunobiography describes the life-long effects of exogenous or endogenous stimuli on remodeling of immune cell biology, including the development of memory T and B-cells. The present study aimed at investigating the rhythms of changes in phenotypic features of memory T and B-cells along childhood and adolescence. A descriptive-observational investigation was conducted including 812 healthy volunteers, clustered into six consecutive age groups (9Mths-1Yr; 2Yrs; 3-4Yrs; 5-7Yrs; 8-10Yrs; 11-18Yrs). Immunophenotypic analysis of memory T-cell (CD4+ and CD8+) and B-cell subsets were performed by flow cytometry. The results pointed out that memory-related biomarkers of T and B-cells displayed a bimodal profile along healthy childhood and adolescence, regardless of sex. The first stage of changes occurs around 2Yrs, with predominance of naive cells, while the second and more prominent wave occurs around the age 8-10Yrs, with the prevalence of memory phenotypes. The neighborhood connectivity profile analysis demonstrated that the number of correlations reaches a peak at 11-18Yrs and lower values along the childhood. Males presented higher and conserved number of correlations when compared to females. Altogether, our results provide new insights into immunobiography and a better understanding of interactions among the cellular subsets studied here during childhood and adolescence.

Sodium Nitrite Attenuates Reduced Activity of Vascular Matrix Metalloproteinase-2 and Vascular Hyper-Reactivity and Increased Systolic Blood Pressure Induced by the Placental Ischemia Model of Preeclampsia in Anesthetized Rats.

Preeclampsia is a maternal hypertension disorder associated with vascular dysfunction and fetal and placental growth restrictions. Placental ischemia is suggested as the primary trigger of preeclampsia-associated impairments of both endothelium-derived nitric oxide (NO) and the vascular activity of extracellular matrix metalloproteinase-2 (MMP-2). Reduced uteroplacental perfusion pressure (RUPP) is a placental ischemia model of preeclampsia. Reduction of sodium nitrite to NO may occur during ischemic conditions. However, sodium nitrite effects in the RUPP model of preeclampsia have not yet been investigated. Pregnant rats were divided into four groups: normotensive pregnant rats (Norm-Preg), pregnant rats treated with sodium nitrite (Preg + Nitrite), preeclamptic rats (RUPP), and preeclamptic rats treated with sodium nitrite (RUPP + Nitrite). Maternal blood pressure and fetal and placental parameters were recorded. Vascular function, circulating NO metabolites, and the gelatinolytic activity of vascular MMP-2 were also examined. Sodium nitrite attenuates increased blood pressure, prevents fetal and placental weight loss, counteracts vascular hyper-reactivity, and partially restores NO metabolites and MMP-2 activity. In conclusion, sodium nitrite reduction to NO may occur during RUPP-induced placental ischemia, thereby attenuating increased blood pressure, fetal and placental growth restriction, and vascular hyper-reactivity associated with preeclampsia and possibly restoring NO and MMP-2 activity, which underlie the blood pressure-lowering effects.

Pregnancy hypertension-associated endothelial dysfunction is attenuated by isoflurane anesthesia: Evidence of protective effect related to increases in nitric oxide.

AIMS: Pregnancy hypertension-induced endothelial dysfunction associated with impairment of nitric oxide (NO) bioavailability and hemodynamic derangements is a challenging for urgent procedures requiring maternal anesthesia. The volatile anesthetic isoflurane has demonstrated NO-associated protective effects. However, this isoflurane-induced effect is still unclear in pregnancy hypertension. Therefore, the present study examined the potential protective effects of isoflurane anesthesia on endothelial dysfunction and hemodynamic changes induced by hypertensive pregnancy associated with fetal and placental growth restrictions. MATERIALS AND METHODS: Animals were distributed into four groups: normotensive pregnant rats (Preg), anesthetized pregnant rats (Preg+Iso), hypertensive pregnant rats (HTN-Preg), and anesthetized hypertensive pregnant rats (HTN-Preg+Iso). Systolic and diastolic pressures, mean arterial pressure (MAP), heart rate, fetal and placental weights, vascular contraction, endothelium-derived NO-dependent vasodilation, and NO levels were assessed. The vascular endothelial growth factor (VEGF) levels and endothelial NO synthase (eNOS) Serine (1177) phosphorylation (p-eNOS) expression were also examined. KEY FINDINGS: Isoflurane produced more expressive hypotensive effects in the HTN-Preg+Iso versus Preg+Iso group, with respective reductions in MAP by 50 ± 13 versus 25 ± 4 mmHg (P < 0.05). Also, HTN-Preg+Iso compared to the HTN-Preg group showed (respectively) preventions against the weight loss of the fetuses (4.0 ± 0.6 versus 2.8 ± 0.6 g, P < 0.05) and placentas (0.37 ± 0.06 versus 0.30 ± 0.06 mg, P < 0.05), hyper-reactive vasocontraction response (1.8 ± 0.4 versus 2.8 ± 0.6 g, P < 0.05), impaired endothelium-derived NO-dependent vasodilation (84 ± 8 versus 50 ± 17 %, P < 0.05), reduced VEGF levels (147 ± 46 versus 25 ± 13 pg/mL, P < 0.05), and decreased p-eNOS expression (0.24 ± 0.07 versus 0.09 ± 0.05 arbitrary units, P < 0.05). SIGNIFICANCE: Isoflurane anesthesia protects maternal endothelial function in pregnancy hypertension, and possibly endothelium-derived NO is involved.

Sildenafil attenuates oxidative stress and endothelial dysfunction in lead-induced hypertension.

Lead (Pb) reduces NO bioavailability, impairs the antioxidant system, and increases the generation of reactive oxygen species (ROS). Pb-induced oxidative stress may be responsible for the associated endothelial dysfunction. Sildenafil has shown nitric oxide (NO)-independent action, including antioxidant effects. Therefore, we examined the effects of sildenafil on oxidative stress, reductions of NO and endothelial dysfunction in Pb-induced hypertension. Wistar rats were distributed into three groups: Pb, Pb + sildenafil and Sham. Blood pressure and endothelium-dependent vascular function were recorded. We also examined biochemical determinants of lipid peroxidation and antioxidant function. ROS levels, NO metabolites and NO levels in human umbilical vein endothelial cells (HUVECs) were also evaluated. Sildenafil prevents impairment of endothelium-dependent NO-mediated vasodilation and attenuates Pb-induced hypertension, reduces ROS formation, enhances superoxide dismutase (SOD) activity and antioxidant capacity in plasma and increases NO metabolites in plasma and HUVECs culture supernatants, while no changes were found on measurement of NO released from HUVECs incubated with plasma of the Pb and Pb + sildenafil groups compared with the sham group. In conclusion, sildenafil protects against ROS-mediated inactivation of NO, thus preventing endothelial dysfunction and attenuating Pb-induced hypertension, possibly through antioxidant effects.

Spatial patterns of new leprosy cases in a northeastern state of Brazil, 2011-2021.

OBJECTIVE: To analyze the spatial patterns of leprosy in Pernambuco from 2011 to 2021. METHODS: This is an ecological epidemiological study, carried out with data from the Notifiable Diseases Information System, based on new cases of leprosy among inhabitants of Pernambuco, between 2011-2021. An empirical Bayesian analysis of local and spatial dependence was performed with the global and local Moran indices. RESULTS: 25,008 new cases of leprosy were registered with an annual case detection rate in the general population of 16.51 cases/100,000 inhabitants - which is considered high. Among those younger than 15 years of age, there were 5.16 cases/100,000 inhabitants (high) and 0.89/100,000 inhabitants with degree II of physical disability (low); there were also many high-risk cases with an overall Moran index of 0.33 (p<0.001), active transmission (0.26; p<0.001), and subsequent diagnosis of the disease (0.12; p<0.006), as well as distribution in macro-region 1 and macro-region 4. CONCLUSION: There was a heterogeneous spatial distribution in the state, showing two overviews, the first being the presence of municipalities with high risk of disease transmission and the second with clusters of silent municipalities, reinforcing the character of leprosy neglect as a major public health problem. This study brings reflections for leprosy control actions, due to the identification of priority areas to combat this disease in Pernambuco.

Spatial patterns of new leprosy cases in a northeastern state of Brazil, 2011-2021 / Padrões espaciais dos casos novos de hanseníase em um estado nordestino do Brasil, 2011-2021

ABSTRACT Objective: To analyze the spatial patterns of leprosy in Pernambuco from 2011 to 2021. Methods: This is an ecological epidemiological study, carried out with data from the Notifiable Diseases Information System, based on new cases of leprosy among inhabitants of Pernambuco, between 2011-2021. An empirical Bayesian analysis of local and spatial dependence was performed with the global and local Moran indices. Results: 25,008 new cases of leprosy were registered with an annual case detection rate in the general population of 16.51 cases/100,000 inhabitants — which is considered high. Among those younger than 15 years of age, there were 5.16 cases/100,000 inhabitants (high) and 0.89/100,000 inhabitants with degree II of physical disability (low); there were also many high-risk cases with an overall Moran index of 0.33 (p<0.001), active transmission (0.26; p<0.001), and subsequent diagnosis of the disease (0.12; p<0.006), as well as distribution in macro-region 1 and macro-region 4. Conclusion: There was a heterogeneous spatial distribution in the state, showing two overviews, the first being the presence of municipalities with high risk of disease transmission and the second with clusters of silent municipalities, reinforcing the character of leprosy neglect as a major public health problem. This study brings reflections for leprosy control actions, due to the identification of priority areas to combat this disease in Pernambuco.

RESUMO Objetivo: Analisar os padrões espaciais da hanseníase em Pernambuco no período de 2011 a 2021. Métodos: Trata-se de um estudo epidemiológico ecológico, realizado com dados do Sistema de Informações de Agravos de Notificação com base nos casos novos de hanseníase em residentes de Pernambuco, entre 2011-2021. Foi realizada uma análise bayesiana empírica local e de dependência espacial com os índices de Moran global e local. Resultados: Foram registrados 25.008 casos novos de hanseníase com coeficiente médio anual de detecção de casos novos na população geral de 16,51 casos/100 mil habitantes — classificado como alto. Na população menor de 15 anos, ocorreu 5,16 casos/100 mil habitantes (muito alto) e 0,89/100 mil habitantes com grau II de incapacidade física (baixo) com aglomerados de alto risco para ocorrência com índice global de Moran de 0,33 (p<0,001), transmissão ativa (0,26; p<0,001) e diagnóstico tardio da doença (0,12; p<0,006), localizados na macrorregião 1 e na macrorregião 4. Conclusão: Houve uma distribuição espacial heterogênea no estado, evidenciando dois panoramas, o primeiro, a presença de municípios com alto risco de transmissão da doença e, o segundo, aglomerados de municípios silenciosos reforçando o caráter de negligência da hanseníase como grande problema de saúde pública. Este estudo traz reflexões para ações de controle da hanseníase, dada a identificação de áreas prioritárias para o enfrentamento dess/a doença em Pernambuco.

Effect of ouabain on calcium signaling in rodent brain: A systematic review of in vitro studies.

The Na+/K+-ATPase is an integral membrane ion pump, essential to maintaining osmotic balance in cells in the presence of cardiotonic steroids; more specifically, ouabain can be an endogenous modulator of the Na+/K+-ATPase. Here, we conducted a systematic review of the in vitro effects of cardiotonic steroids on Ca2+ in the brain of rats and mice. Methods: The review was carried out using the PubMed, Virtual Health Library, and EMBASE databases (between 12 June 2020 and 30 June 2020) and followed the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Results: in total, 829 references were identified in the electronic databases; however, only 20 articles were considered, on the basis of the inclusion criteria. The studies demonstrated the effects of ouabain on Ca2+ signaling in synaptosomes, brain slices, and cultures of rat and mouse cells. In addition to the well-known cytotoxic effects of high doses of ouabain, resulting from indirect stimulation of the reverse mode of the Na+/Ca2+ exchanger and increased intracellular Ca2+, other effects have been reported. Ouabain-mediated Ca2+ signaling was able to act increasing cholinergic, noradrenergic and glutamatergic neurotransmission. Furthermore, ouabain significantly increased intracellular signaling molecules such as InsPs, IP3 and cAMP. Moreover treatment with low doses of ouabain stimulated myelin basic protein synthesis. Ouabain-induced intracellular Ca2+ increase may promote the activation of important cell signaling pathways involved in cellular homeostasis and function. Thus, the study of the application of ouabain in low doses being promising for application in neurological diseases. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020204498, identifier CRD42020204498.

Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach.

Amyotrophic lateral sclerosis (ALS) is a multi-system neurodegenerative disease that affects both upper and lower motor neurons, resulting from a combination of genetic, environmental, and lifestyle factors. Usually, the association between single-nucleotide polymorphisms (SNPs) and this disease is tested individually, which leads to the testing of multiple hypotheses. In addition, this classical approach does not support the detection of interaction-dependent SNPs. We applied a two-step procedure to select SNPs and pairwise interactions associated with ALS. SNP data from 276 ALS patients and 268 controls were analyzed by a two-step group LASSO in 2000 iterations. In the first step, we fitted a group LASSO model to a bootstrap sample and a random subset of predictors (25%) from the original data set aiming to screen for important SNPs and, in the second step, we fitted a hierarchical group LASSO model to evaluate pairwise interactions. An in silico analysis was performed on a set of variables, which were prioritized according to their bootstrap selection frequency. We identified seven SNPs (rs16984239, rs10459680, rs1436918, rs1037666, rs4552942, rs10773543, and rs2241493) and two pairwise interactions (rs16984239:rs2118657 and rs16984239:rs3172469) potentially involved in nervous system conservation and function. These results may contribute to the understanding of ALS pathogenesis, its diagnosis, and therapeutic strategy improvement.

Effect of dietary inclusion of licuri cake on intake, feeding behavior, and performance of feedlot cull cows.

Licuri cake (LC) is an interesting alternative nutritional component for high-grain diets for ruminants due to its high protein (21.6% CP), fat (12.0% EE), and fiber (62.8% NDF) contents. We investigated the effect of increasing levels of LC inclusion on the intake, digestibility, feeding behavior, performance, and carcass traits of cull cows fed high-grain diets. Forty Zebu cows with an initial weight of 318 ± 38.1 kg, at 105 months of age, were confined in collective stalls and fed (ad libitum) a diet containing 0, 50, 100, or 150 g/kg LC on a diet dry matter (DM) basis. Licuri cake inclusion induced quadratic responses (P < 0.05) in the intakes of DM (9.57 kg/day at 97.8 g/kg LC), crude protein (CP; 1.02 kg/day at 91.7 g/kg LC), and total digestible nutrients (6.68 kg/day at 75.2 g/kg LC). The digestibility of DM, CP, and non-fibrous carbohydrates decreased linearly (P < 0.05). Neutral detergent fiber (NDF) intake and rumination efficiencies increased linearly (P < 0.05) with the inclusion of LC in the diet. The inclusion of LC did not influence (P > 0.05) on daily weight gain, hot carcass weight, or back fat thickness in the carcass. Therefore, we recommend the inclusion of up to 150 g/kg LC in high-grain diets for feedlot cull cows.