Trilobatin contributes to the improvement of myopathy in a mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) occurs due to genetic mutations that lead to a deficiency in dystrophin production and consequent progressive degeneration of skeletal muscle fibres, through oxidative stress and an exacerbated inflammatory process. The flavonoid trilobatin (TLB) demonstrates antioxidant and anti-inflammatory potential. Its high safety profile and effective action make it a potent therapy for the process of dystrophic muscle myonecrosis. Thus, we sought to investigate the action of TLB on damage in a DMD model, the mdx mouse. Eight-week-old male animals were treated with 160 mg/kg/day of trilobatin for 8 weeks. Control animals were treated with saline. Following treatment, muscle strength, serum creatine kinase (CK) levels, histopathology (necrotic myofibres, regenerated fibres/central nuclei, Feret's diameter and inflammatory area) and the levels of catalase and NF-κB (western blotting) of the quadriceps (QUA), diaphragm (DIA) and tibialis anterior (TA) muscles were measured. TLB was able to significantly increase muscle strength and reduce serum CK levels in dystrophic animals. The QUA of mdx mice showed a reduction in catalase and the number of fibres with a centralized nucleus after treatment with TLB. In the DIA of dystrophic animals, TLB reduced the necrotic myofibres, inflammatory area and NF-κB and increased the number of regenerated fibres and the total fibre diameter. In TA, TLB increased the number of regenerated fibres and reduced catalase levels in these animals. It is concluded that in the mdx experimental model, treatment with TLB was beneficial in the treatment of DMD.

In vitro results with minimal blood toxicity of a combretastatin A4 analogue.

Cancer is a disease caused by uncontrolled cell growth that is responsible for several deaths worldwide. Breast cancer is the most common type of cancer among women and is the leading cause of death. Chemotherapy is the most commonly used treatment for cancer; however, it often causes various side effects in patients. In this study, we evaluate the antineoplastic activity of a parent compound based on a combretastatin A4 analogue. We test the compound at 0.01 mg mL- 1, 0.1 mg mL- 1, 1.0 mg mL- 1, 10.0 mg mL- 1, 100.0 mg mL- 1, and 1,000.0 mg mL- 1. To assess molecular antineoplastic activity, we conduct in vitro tests to determine the viability of Ehrlich cells and the blood mononuclear fraction. We also analyze the cytotoxic behavior of the compound in the blood and blood smear. The results show that the molecule has a promising antineoplastic effect and crucial anticarcinogenic action. The toxicity of blood cells does not show statistically significant changes.

Antioxidant defense of children and adolescents with atopic dermatitis: Association with disease severity.

BACKGROUND: Atopic dermatitis (AD) is a relapsing, chronic cutaneous inflammatory disease with onset, in general, in early childhood. Chronic skin inflammation is associated with overproduction of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide. Oxidative stress, an imbalance between the production of free radicals and antioxidant defense, results in tissue inflammation due to the upregulation of genes that encode inflammatory cytokines. This condition plays an important role in the pathogenesis of AD. OBJECTIVE: To compare the antioxidant defense in children and adolescents with AD with that of healthy individuals and to verify the association of antioxidant defense with disease severity and nutritional status. METHODS: Cross-sectional study that evaluated 48 children and adolescents with AD and 25 controls for nutritional assessment (body mass index z score [BMIZ] and height for age z score [HAZ]) and levels of vitamins A, C, E, and D, zinc (Zn), copper (Cu), antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]), high-sensitivity C-reactive protein (CRP) and interleukin 33 (IL-33). RESULTS: There was no significant difference in the comparison between AD and control groups for serum levels of vitamins (A, D, C, and E), copper, and antioxidant enzymes. Serum zinc levels were higher in the AD group (ß = 24.20; 95% CI 13.95-34.91; P < 0.001) even after adjusting the BMIZ, HAZ, gender, IL-33, and CRP. Children and adolescents with moderate or severe AD compared to mild AD (SCORAD - 36.7±17.4 vs 11.8 ± 3.9; P < 0.001) had lower values of the vitamin E/total lipid ratio (3.68 [0.29;12.63] vs 5.92 [3.27;17.37]; P = 0.013). CONCLUSION: Children and adolescents with AD had higher concentrations OF elevated levels of zinc compared to controls, a fact not observed for other biomarkers of antioxidant defense. AD in moderate or severe forms presented lower concentrations of vitamin E, a potent antioxidant fat soluble.

Acute Toxicity Assays with the Artemia salina Model: Assessment of Variables.

The use of the brine shrimp Artemia salina (Leach) in acute toxicity assays has great potential due to its simplicity, low cost and reproducibility. In the current study, some of the variables that can influence the reliability of the assay in terms of test organism survival, were evaluated as part of its implementation in our laboratory. The quality and type of water used, the buffer components and other parameters (salinity, pH and dissolved oxygen level), were all evaluated for optimisation purposes. DMSO (dimethyl sulphoxide) was used as the test substance in the toxicity assay, to evaluate the concentration limits as a solvent in sample preparation. Regarding the buffer salinity, pH and dissolved oxygen level, we found that a 25% to 30% deviation from the standard values did not affect the survival of the nauplii (the first-instar larval stage) under assay conditions. In summary, we corroborate the potential use of this model for the prediction of the toxic potential of substances, to inform future testing strategies.

Pre-analytical processing protocol of breast biopsies affects multigene panel results.

The creation of multigene panels for prognostic and predictive purposes allows a more accurate indication of adjuvant chemotherapy for patients with breast cancer. In a previous study, we reproduced a multigene panel of 21 genes based on the commercial Oncotype-DX method. We submitted 183 embedded specimens obtained from breast surgery on patients with locoregional disease (stages I to III) between 2005 and 2010 performed at the Hospitals of the Medical School of the ABC Foundation. When we analysed the correlations between the score of the multigene panel and the progression-free interval (PFI) in all patients, we did not find a statistically significant association. However, when we selected only the 71 samples that had amplification of at least eight non-housekeeping genes, we observed that those with scores above the 75th percentile had a significantly lower PFI (p = .0054). Samples processed with nonbuffered formaldehyde were associated with a worse quality of extracted RNA (p = .004) and a significantly higher multigene panel score (p = .021). We conclude that variations in the pre-analytical processing of specimens destined for multigene panel amplification can significantly affect the results, with a potential impact on clinical management.

Stroke Hospital Admissions during the COVID-19 Outbreak in São Paulo, Brazil.

BACKGROUND: Globally, stroke remains an important cause of death and long-term disability, and the impact of coronavirus disease (COVID-19) on the health system may have impaired stroke care. Previous studies suggest significant reduction in hospital admissions for stroke after COVID-19 onset as patients may hesitate seeking medical help due to fear of exposure. METHODS: This cross-sectional study included cases of hospital admissions for stroke, identified from the Hospital Information System of the Unified Health System (Sistema Único de Saúde), which contains official and public data in Brazil. Data were collected in duplicate, then categorized according to the International Classification of Diseases, tenth revision (ICD-10), considering codes I60-I69. Linear regression was used to estimate the variation in hospital admissions for stroke in the city of São Paulo (SP) - the largest and most populous city in Brazil and Latin America, between January and June of each analyzed year (2017-2020). The percentage variation between June and January 2020 was also compared. The level of significance was set at 5%, and the statistical program used was Stata, version 14.0. RESULTS: In the city of SP, during the first wave of COVID-19, from January to June 2020, there were registered decreases in absolute numbers and mean monthly admissions for stroke. Compared to January 2020, data from June 2020 showed 17% reduction in hospitalizations for intracerebral hemorrhage, 32% for cerebral infarction, 26% for stroke unspecified, and 47% for other cerebrovascular diseases. CONCLUSION: We argue for policies aimed at improving stroke care and developing awareness campaigns regarding the importance of early diagnosis and treatment, as even in less severe presentations, stroke can trigger an increase in mortality, cost, and long-term disability.

Physical inactivity level and lipid profile in traditional communities in the Legal Amazon: a cross-sectional study : Physical inactivity level in the Legal Amazon.

BACKGROUND: The practice of regular physical activity can alter the lipid profile in populations according to diverse demographic characteristics. OBJECTIVE: To evaluate the association of physical inactivity with the lipid profile among vulnerable populations. METHODS: A cross-sectional study was conducted among 349 vulnerable individuals from Tocantins state, northern Brazil. The International Physical Activity Questionnaire 7 Day short form was used to measure self-reported physical activity levels. Venous blood samples were drawn to evaluate lipid profile. Logistic regression adjusted by the socioeconomic variables was used to analyse the effects of physical inactivity on the lipidic profile. The level of significance was 5% and Stata® (StataCorp, LC) version 11 was used. RESULTS: We observe an inverse relationship between physical inactivity and HDL-C-that is, those who were sedentary or below the WHO Recommendations for physical activity were at 2.6 greater odds (IC95% 1.21, 5.67; p = 0.015) of having a lower HDL compared with those meeting or exceeding WHO physical activity recommendations. CONCLUSION: On the vulnerable populations studied, the insufficiently active or sedentary individuals (called the physical inactivity individuals) have more risk of the altered HDL-C.

Reduction on Proinflammatory Cytokines after Application of Transcutaneous Electrical Nerve Stimulation (TENS) in Patients with a Breast Cancer: A Nonrandomized, Open, and Single-Arm Study Protocol with Paired Analysis.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) has been used as analgesic therapy in many diseases. It is already known that studies that have observed the relationship between pain and cytokines have found that patients who report less severe pain have less production of proinflammatory cytokines. However, one another accepted mechanism is that decreasing proinflammatory cytokines results in decreased pain intensity. Analyzing the literature, the authors describe that, in addition to the analgesic effect, TENS has shown systemic effects, and clinically, the reduction of proinflammatory cytokines could be a protective factor against inflammation. To test the inflammatory effect of TENS, we researched the literature for clinical conditions that suggest that proinflammatory cytokines are one of the main mediators of the disease process. Chronic inflammation is one of the risk factors mentioned for the development of a new cancer; at the same time, it is indicated as an indicator of the worst prognosis. Studies also suggest that the worst prognosis of breast cancer, one of the types with the highest incidence in the world, may be related to increased inflammatory activity. Considering that inflammation is increased in breast cancer and that TENS can reduce proinflammatory cytokines even without blocking the pain pathway, our hypothesis is that the anti-inflammatory effect of TENS can bring benefits to these patients. The aim of this study will be to evaluate the effect of TENS on blood reduction of proinflammatory cytokines in breast cancer patients. METHODS: This study will evaluate at least 59 patients, over 18 years of age, diagnosed with breast cancer, but who have not yet started any treatment. All patients will be submitted to TENS intervention (Ibramed, Model Neurodyn III, parameters: VIF-turn on, frequency-2-247 Hz, pulse size-50-500 µs, and intensity (mA)-maximum tolerated by the patient), and the data will be analyzed in the pre- and postintervention of each patient. The application has a total duration of 30 minutes, and 8 ml of blood will be collected before and after the intervention. Proinflammatory (IL-1, IL-2, IL-6, IL-7, and TNF-α) and anti-inflammatory (IL-4, IL-10, IL-13, and FTCß) cytokines will be analyzed. As a primary endpoint, we will analyze the reduction in blood concentration of proinflammatory cytokines, and as secondary endpoints, we will analyze the size of the effect according to each type of proinflammatory cytokine, describe the effect size of the reduction according to the breast cancer immunohistochemistry, and analyze the effect of TENS on anti-inflammatory cytokines. This study is approved by the Research Ethics Committee (Centro Universitário FMABC, Brazil) and registered in the Brazilian Clinical Trials (Search text: RBR-10jbwh47).

Vitamin D deficiency in children and adolescents with food allergy: Association with number of allergens, sun exposure and nutritional status.

Our objective was to describe the serum vitamin D concentrations of children and adolescents with food allergy (FA) and to verify the association between the number of food allergens involved, length of sun exposure, and nutritional status. Through a cross-sectional study, 79 patients with FA, from ages 2 to 15 years, were assessed and followed up in a reference outpatient clinic, in Sao Paulo, Brazil. Clinical and biochemical data were collected for analysis of 25(OH)D, calcium, phosphorus, phosphatase, parathyroid hormone (PTH), and high-sensitivity C-reactive protein (hs-CRP). The cut-off point used for vitamin D deficiency was 25(OH)D ≤ 20 ng/mL. Vitamin D deficiency was detected in 45.6% of patients with a median age of 6.9 years (Interquartile range [IQR] 4.7; 10.2). The median serum 25(OH)D concentration was 21.1 ng/mL (IQR 17.8; 26.0). Multivariate linear regression was performed considering serum vitamin D level as a dependent variable. Allergy to multiple foods (inverse) and length of sun exposure (direct), but not nutritional status, were independently associated with serum 25(OH)D levels (P = 0.034 and P = 0.014, respectively). Patients with cow's milk allergy also showed lower vitamin D concentrations in comparison with other FA (19.1 ng/mL [IQR 16.6; 24.4] vs 22.2 ng/mL [IQR 18.1; 27.1] [P = 0.056]). Vitamin D deficiency affected about half of individuals with FA. Multiple food allergy was associated with lower vitamin D concentrations, reinforcing the importance of monitoring vitamin D status in patients with FA.

Is There an Association between Vitamin D Concentrations and Overweight in Children and Adolescents?

OBJECTIVE: To describe the 25-hydroxyvitamin D [25(OH)D] concentrations in children and adolescents and to verify the association with the body mass index z-score (ZBMI), lipid profile and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). METHOD: Cross-sectional study with 170 children and adolescents aged between 4 and 15 years (106 normal weight and 64 overweight) from a public institution in Santo André-Brazil. Weight, height and waist circumference were verified and ZBMI and waist-to-height ratio (WHtR) were calculated. Biochemical analysis: 25(OH)D levels [deficiency: 25(OH)D < 20 ng/ml]; glycemia and insulin (HOMA-IR), lipid profile and ultra-sensitive C-reactive protein. RESULTS: Mean age was 8.37 ± 3.17 years; 89 (52.4%) were male; 77 (45.3%) Caucasians and 121 (71.2%) pre-pubescent. Overweight was observed in 64 (37.6%), dyslipidemia in 108 (63.5%) and 25(OH)D deficiency in 117 (68.8%) of the individuals. ZBMI (r = -0.209; p = 0.006), WHtR (r = -0.154; p = 0.045), triglycerides (TGs) (r = -0.161; p = 0.037) and TGs/high-density lipoprotein (HDL) ratio (r = -0.168; p = 0.028) were inversely correlated with 25(OH)D concentrations. Overweight children and adolescents were four times more likely to have vitamin D deficiency (odds ratio = 4.28; 95% confidence interval 1.152 to 4.907; p = 0.019), after adjustment for pubertal development (prepubertal), sex (male), HDL-c (<45 mg/dl), non-HDL (>120 mg/dl), TG/HDL ratio (>2.0) and HOMA-IR. CONCLUSIONS: A high prevalence of vitamin D deficiency (68.8%) was observed. There was an independent association between vitamin D deficiency and overweight, not observed for dyslipidemia and insulin resistance. The data point to the need for periodic monitoring of serum concentrations of 25(OH)D and reinforcement of guidelines for combating and preventing overweight in the pediatric age group.

Immune Checkpoint Blockade via PD-L1 Potentiates More CD28-Based than 4-1BB-Based Anti-Carbonic Anhydrase IX Chimeric Antigen Receptor T Cells.

The complete regression of clear cell renal cell carcinoma (ccRCC) obtained pre-clinically with anti-carbonic anhydrase IX (CAIX) G36 chimeric antigen receptor (CAR) T cells in doses equivalent to ≅108 CAR T cells/kg renewed the potential of this target to treat ccRCC and other tumors in hypoxia. The immune checkpoint blockade (ICB) brought durable clinical responses in advanced ccRCC and other tumors. Here, we tested CD8α/4-1BB compared to CD28-based anti-CAIX CAR peripheral blood mononuclear cells (PBMCs) releasing anti-programmed cell death ligand-1 (PD-L1) IgG4 for human ccRCC treatment in vitro and in an orthotopic NSG mice model in vivo. Using a ≅107 CAR PBMCs cells/kg dose, anti-CAIX CD28 CAR T cells releasing anti-PD-L1 IgG highly decrease both tumor volume and weight in vivo, avoiding the occurrence of metastasis. This antitumoral superiority of CD28-based CAR PBMCs cells compared to 4-1BB occurred under ICB via PD-L1. Furthermore, the T cell exhaustion status in peripheral CD4 T cells, additionally to CD8, was critical for CAR T cells efficiency. The lack of hepatotoxicity and nephrotoxicity upon the administration of a 107 CAR PMBCs cells/kg dose is the basis for carrying out clinical trials using anti-CAIX CD28 CAR PBMCs cells releasing anti-PD-L1 antibodies or anti-CAIX 4-1BB CAR T cells, offering exciting new prospects for the treatment of refractory ccRCC and hypoxic tumors.

Selenium-related nutritional status in patients with common variable immunodeficiency: association with oxidative stress and atherosclerosis risk.

BACKGROUND: Common variable immunodeficiency (CVID) is an inborn errors of immunity, that leads to recurrent chronic infections and autoimmune/ inflammatory diseases and neoplasms. It is considered that these condition is related to persistent this immune-inflammatory stimulation and increased oxidative stress. A positive impact on the survival of patients with an inborn error of immunity was observed with advanced clinical care protocols, thus raising concerns about the risk of developing other associated chronic diseases, such as atherosclerosis. Studies suggest that selenium (Se) is a protective trace element against damage caused by oxidative stress. Thus, it is postulated that adequate consumption reduces the risk of some chronic diseases. RESULTS: Se median levels (ug/L) [45.6 (37.3-56.2) vs. 57.8 (46.0-66.0); p = 0.004] and GPX activity (U/L) [7682 (6548-8446) vs. 9284(8440-10,720); p = 0,002) were significantly lower in patients compared to controls. Inadequacy of Se levels was observed in 50% of the patients. There was a higher percentage of high values of C-reactive protein in the group of CVID patients compared to controls [8 (36.4%) vs. 2 (11.1%); p = 0.082]. Higher concentrations of oxidized LDL (45.3 mg/dL vs. 33.3 mg/dL; p = 0.016) and lower concentrations of Apo A-1 (98.5 mg/dL) vs. 117.0 mg/dL; p = 0.008) were observed in the CVID group compared to the control. There was a significant and positive correlation between Se plasma levels and apolipoprotein A-1 concentrations in CVID group (rho = 0.577; p = 0.001). Se values less than 46 µg / L (OR = 3.590; 95% CI 1.103 to 11.687; p = 0.034) and GPX activity below the 4th quartile (OR = 21.703; 95% CI 2.534 to 185.914; p = 0.005) were independently associated, after adjustment for age, overweight and dyslipidemia, with the CVID group (Table 5). CONCLUSION: This study showed an higher percentage of high us-CRP, lower values of plasma Se and GPX activity, higher concentrations of LDLox and lower levels of Apo A-1 in CVID patients in comparison to controls, suggesting oxidative stress and cardiovascular risk.These data point to the importance of assessing the Se status and cardiovascular risk in these patients.

Ixazomib, an oral proteasome inhibitor, exhibits potential effect in dystrophin-deficient mdx mice.

Dystrophin deficiency makes the sarcolemma fragile and susceptible to degeneration in Duchenne muscular dystrophy. The proteasome is a multimeric protease complex and is central to the regulation of cellular proteins. Previous studies have shown that proteasome inhibition improved pathological changes in mdx mice. Ixazomib is the first oral proteasome inhibitor used as a therapy in multiple myeloma. This study investigated the effects of ixazomib on the dystrophic muscle of mdx mice. MDX mice were treated with ixazomib (7.5 mg/kg/wk by gavage) or 0.2 mL of saline for 12 weeks. The Kondziela test was performed to measure muscle strength. The tibialis anterior (TA) and diaphragm (DIA) muscles were used for morphological analysis, and blood samples were collected for biochemical measurement. We observed maintenance of the muscle strength in the animals treated with ixazomib. Treatment with ixazomib had no toxic effect on the mdx mouse. The morphological analysis showed a reduction in the inflammatory area and fibres with central nuclei in the TA and DIA muscles and an increase in the number of fibres with a diameter of 20 µm2 in the DIA muscle after treatment with ixazomib. There was an increase in the expression of dystrophin and utrophin in the TA and DIA muscles and a reduction in the expression of osteopontin and TGF-ß in the DIA muscle of mdx mice treated with ixazomib. Ixazomib was thus shown to increase the expression of dystrophin and utrophin associated with improved pathological and functional changes in the dystrophic muscles of mdx mice.

What is the elephant in the room when considering new therapies for fungal diseases?

The global scenario of antimicrobial resistance is alarming, and the development of new drugs has not appeared to make substantial progress. The constraints on drug discovery are due to difficulties in finding new targets for therapy, the high cost of development, and the mismatch between the time of drug introduction in a clinic and microorganism adaptation to a drug. Policies to address neglected diseases miss the broad spectrum of mycosis. Society is not aware of the actual threat represented by fungi to human health, food security, and biodiversity. The evidence discussed here is critical for warning governments to establish effective surveillance policies for fungi.HIGHLIGHTSFungal diseases are ignored even among neglected disease classifications.There are few options to treat mycoses, which is an increasing concern regarding fungal resistance to drugs, as evidenced by the spread of Candida auris.Fungal diseases represent a real threat to human health and food security.Investment in research to investigate the potential of repurposing drugs already in use could obtain results in the short term.

Causal effects on low Apgar at 5-min and stillbirth in a malaria maternal-fetal health outcome investigation: a large perinatal surveillance study in the Brazilian Amazon.

BACKGROUND: Malaria elimination in Brazil poses several challenges, including the control of Plasmodium falciparum foci and the hidden burden of Plasmodium vivax in pregnancy. Maternal malaria and fetal health outcomes were investigated with a perinatal surveillance study in the municipality of Cruzeiro do Sul, Acre state, Brazilian Amazon. The research questions are: what are the causal effects of low birth weight on low Apgar at 5-min and of perinatal anaemia on stillbirth? METHODS: From November 2018 to October 2019, pregnant women of ≥ 22 weeks or puerperal mothers, who delivered at the referral maternity hospital (Juruá Women and Children's Hospital), were recruited to participate in a malaria surveillance study. Clinical information was obtained from a questionnaire and abstracted from medical reports. Haemoglobin level and presence of malarial parasites were tested by haematology counter and light microscopy, respectively. Low Apgar at 5-min and stillbirth were the outcomes analysed in function of clinical data and epidemiologic risk factors for maternal malaria infection using both a model of additive and independent effects and a causal model with control of confounders and use of mediation. RESULTS: In total, 202 (7.2%; N = 2807) women had malaria during pregnancy. Nearly half of malaria infections during pregnancy (n = 94) were P. falciparum. A total of 27 women (1.03%; N = 2632) had perinatal malaria (19 P. vivax and 8 P. falciparum). Perinatal anaemia was demonstrated in 1144 women (41.2%; N = 2779) and low birth weight occurred in 212 newborns (3.1%; N = 2807). A total of 75 newborns (2.7%; N = 2807) had low (< 7) Apgar scores at 5-min., and stillbirth occurred in 23 instances (30.7%; n = 75). Low birth weight resulted in 7.1 higher odds of low Apgar at 5-min (OR = 7.05, 95% CI 3.86-12.88, p < 0.001) modulated by living in rural conditions, malaria during pregnancy, perinatal malaria, and perinatal anaemia. Stillbirth was associated with perinatal anaemia (OR = 2.56, 95% CI 1.02-6.42, p = 0.0444) modulated by living in rural conditions, falciparum malaria during pregnancy, perinatal malaria, and perinatal fever. CONCLUSIONS: While Brazil continues its path towards malaria elimination, the population still faces major structural problems, including substandard living conditions. Here malaria infections on pregnant women were observed having indirect effects on fetal outcomes, contributing to low Apgar at 5-min and stillbirth. Finally, the utility of employing multiple statistical analysis methods to validate consistent trends is vital to ensure optimal public health intervention designs.

Are ovarian reserve tests reliable in predicting ovarian response? Results from a prospective, cross-sectional, single-center analysis.

OBJETIVE: Several biomarkers of ovarian reserve have been proposed as possible predictors of the response to controlled ovarian stimulation (COS). We aimed to evaluate age, FSH, AMH, antral follicle count (AFC), and ovarian response prediction index (ORPI), as potential predictors of response to COS. METHODS: Cross-sectional study enrolling of 188 infertile women who underwent the first cycle of IVF/ICSI. AFC was evaluated; serum FSH and AMH levels were measured by ELISA. ORPI was calculated as AMH x AFC/patient´s age. RESULTS: As expected, hypo-responder group had less retrieved oocytes, MII, and embryos compared to the good responders. The hyper-response patients were younger, with lower FSH, increased AMH, AFC, and ORPI values. Regarding the assessment of the predictive capacity of ovarian reserve tests, none of them individually or combined showed a good predictive capacity for hypo-response. With respect to the hyper-responder group, individually AMH was the best predictor, while in the multivariable model, ORPI demonstrated the best predictive capacity. Furthermore, patients with serum AMH < 2.09 ng/mL (p25) had fewer AFC than patients with higher AMH values. CONCLUSIONS: Our findings suggest that none of the ovarian reserve tests showed a good predictive capacity for hypo-response, while the ORPI was the strongest predictor of hyper-response in normovulatory infertile women.

White, brown, and bone marrow adipose tissue behavior in DHEA-induced PCOS mice.

METHODS: Thirty-one female C57BL/6J mice were divided into four groups: two were treated with subcutaneous dehydroepiandrosterone (DHEA) implants and divided into normal and hypercaloric diet (HFD). Two were control and divided into normal and HFD. Presence of insulin resistance, growth, and adipocyte markers expression of white and brown adipose tissues and growth and inflammatory cytokines expression of bone marrow adipose tissue were evaluated. RESULTS: Hypercaloric diet groups presented higher total weight gain and huge growth in all fat sites, except bone marrow. They also demonstrated greater expression of adipocyte markers in sites of white adipose tissue. DHEA + HFD group showed more insulin intolerance than all other groups. DHEA shows to abrogate AdipoQ expression in all fatty tissues. CONCLUSIONS: DHEA alone does not influence adipose tissue growth, but contributes to increased insulin resistance and influences the expression of adipokines. Proximal MAT showed different behavior from the other fat depot.

Examining the Relationship between Social and School Environment and Children's Caries Experience Using Primary and Secondary Data: A Cluster Analysis.

Dental caries is still prevalent worldwide, even with advances in preventive and curative measures. The aim was to examine clustering patterns of socioeconomic and environmental characteristics of schools and their associations with caries experience of schoolchildren. An epidemiological survey with cross-sectional design was conducted in 2014/2015 and included 5,213 students (aged 2-11 years) from 38 public schools of Carapicuíba (SP, Brazil). Primary data consisted of dental examinations performed at schools by 6 calibrated examiners to evaluate caries experience (dmf/DMFT index). Secondary data were extracted from the last official Demographic Census (2010) and School Census (2014 and 2015) to assess the socioeconomic and environmental characteristics of the territorial units and infrastructure of each school, respectively. Cluster analysis and ANOVA were applied to identify schools with similar social and environmental aspects and children's caries experience. A logistic regression model was used to ascertain the effects of cluster variables on the likelihood that participants have caries experience, controlling for the stage of dentition and sex. Two valid and reliable clusters were identified: cluster 1 ("advantaged group"), characterized by 33 schools with the highest percentages of children without caries experience and located in regions with better socioenvironmental indicators, and cluster 2 ("least advantaged group"), characterized by 5 schools with higher percentages of children with caries experience, lower percentages of households with sanitary sewer and water supply, higher residents/household ratio and higher percentages of families living with up to 1 minimum wage. An increase in the odds of having caries experience for each percent of houses with well water and families which live with up to 1 minimum wage was observed. By using primary and secondary data, the study draws attention to the relationship between socioeconomic and environmental indicators and caries experience, identifying least advantaged regions and helping to design strategic health plans for this target population.

Use of health services by the population living in contaminated areas in the region of the Santos and São Vicente estuarine system, Brazil.

Objective: To relate the socio-demographic profile with access to health services of the population living in environmentally degraded areas in an estuary region.Study design: A sectional field study of 8819 people, evaluating three contaminated areas of São Vicente.Methods: Households were divided by studied area. A structured and pre-tested questionnaire was applied to obtain the data. A probabilistic sample was used. The prevalence of each of the outcomes of interest by area was calculated. To verify the existence of an association between the outcomes of interest and other variables (qualitative), by area, a descriptive analysis and to compare percentages and a comparison test was used between two proportions, a Chi-square test and/or a Fisher's exact test and a Kruska-wallis and Dunn multiple comparison were used as well. The significance level was 5%.Results: Most residents (94%) reported the use of public health services at least once a year (p < 0.001), mainly through the Basic Health Units (BHU) (p < 0.001). Most of the studied population (65%) did not have private health insurance and their schooling was basically restricted to primary education (p < 0.001). The predominant family income (70%) in the three areas was between one and five minimum wages (p < 0.001), with a higher incidence of people receiving one to three minimum wages at the time. The demand for health services was not associated with education or income.Conclusion: The population of the regions analysed heavily rely on the Unified Health System - SUS, but there was no association between income and frequency of health services and there was also no association between education and use of health services.

Kidney Diseases: The Age of Molecular Markers.

Kidney diseases are conditions that increase the morbidity and mortality of those afflicted. Diagnosis of these conditions is based on parameters such as the glomerular filtration rate (GFR), measurement of serum and urinary creatinine levels and equations derived from these measurements (Wasung, Chawla, Madero. Clin Chim Acta 438:350-357, 2015). However, serum creatinine as a marker for measuring renal dysfunction has its limitations since it is altered in several other physiological situations, such as in patients with muscle loss, after intense physical exercise or in people on a high protein diet (Riley, Powers, Welch. Res Q Exerc Sport 52(3):339-347, 1981; Juraschek, Appel, Anderson, Miller. Am J Kidney Dis 61(4):547-554, 2013). Besides the fact that serum creatinine is a marker that indicates glomerular damage, it is necessary the discovery of new biomarkers that reflect not only glomerular damage but also tubular impairment. Recent advances in Molecular Biology have led to the generation or identification of new biomarkers for kidney diseases such as: Acute Kidney Failure (AKI), chronic kidney disease (CKD), nephritis or nephrotic syndrome. There are recent markers that have been used to aid in diagnosis and have been shown to be more sensitive and specific than classical markers, such as neutrophil gelatinase associated lipocalin (NGAL) or kidney injury molecule-1 (KIM-1) (Wasung, Chawla, Madero. Clin Chim Acta 438:350-357, 2015; George, Gounden. Adv Clin Chem 88:91-119, 2019; Han, Bailly, Abichandani, Thadhani, Bonventre. Kidney Int 62(1):237-244, 2002; Fontanilla, Han. Expert Opin Med Diagn 5(2):161-173, 2011). However, early diagnostic biomarkers are still necessary to assist the intervention and monitor of the progression of these conditions.