The long Filamin-A isoform is required for intestinal development and motility: implications for chronic intestinal pseudo-obstruction.

Filamin A (FLNA) is a cytoplasmic actin binding protein, recently shown to be expressed as a long and short isoform. Mutations in FLNA are associated with a wide spectrum of disorders, including an X-linked form of chronic intestinal pseudo-obstruction (CIPO). However, the role of FLNA in intestinal development and function is largely unknown. In this study, we show that FLNA is expressed in the muscle layer of the small intestine from early human fetal stages. Expression of FLNA variants associated with CIPO, blocked expression of the long flna isoform and led to an overall reduction of RNA and protein levels. As a consequence, contractility of human intestinal smooth muscle cells was affected. Lastly, our transgenic zebrafish line showed that the flna long isoform is required for intestinal elongation and peristalsis. Histological analysis revealed structural and architectural changes in the intestinal smooth muscle of homozygous fish, likely triggered by the abnormal expression of intestinal smooth muscle markers. No defect in the localization or numbers of enteric neurons was observed. Taken together, our study demonstrates that the long FLNA isoform contributes to intestinal development and function. Since loss of the long FLNA isoform does not seem to affect the enteric nervous system, it likely results in a myopathic form of CIPO, bringing new insights to disease pathogenesis.

A combinatorial panel for flow cytometry-based isolation of enteric nervous system cells from human intestine.

Efficient isolation of neurons and glia from the human enteric nervous system (ENS) is challenging because of their rare and fragile nature. Here, we describe a staining panel to enrich ENS cells from the human intestine by fluorescence-activated cell sorting (FACS). We find that CD56/CD90/CD24 co-expression labels ENS cells with higher specificity and resolution than previous methods. Surprisingly, neuronal (CD24, TUBB3) and glial (SOX10) selective markers appear co-expressed by all ENS cells. We demonstrate that this contradictory staining pattern is mainly driven by neuronal fragments, either free or attached to glial cells, which are the most abundant cell types. Live neurons can be enriched by the highest CD24 and CD90 levels. By applying our protocol to isolate ENS cells for single-cell RNA sequencing, we show that these cells can be obtained with high quality, enabling interrogation of the human ENS transcriptome. Taken together, we present a selective FACS protocol that allows enrichment and discrimination of human ENS cells, opening up new avenues to study this complex system in health and disease.

Physical performance and plasma metabolic profile as potential prognostic factors in metastatic lung cancer patients.

BACKGROUND: Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non-small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells. METHODS: This prospective cohort study included 55 metastatic NSCLC patients and seven age-matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis. RESULTS: We observed a higher survival rate in NSCLC patients with high performance in the timed up-and-go (+320%; p = .007), sit-to-stand (+256%; p = .01) and six-minute walking (+323%; p = .002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (p > .05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (-54.2%; p < .0001) and cell proliferation (-44.9%; p = .007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance. CONCLUSION: These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism.

Abnormal neurovascular control during central and peripheral chemoreceptors stimulation in heart failure patients with preserved ejection fraction.

PURPOSE: Central and peripheral chemoreceptors are hypersensitized in patients with heart failure with reduced ejection fraction. Whether this autonomic alteration occurs in patients with heart failure with preserved ejection fraction (HFpEF) remains little known. We test the hypothesis that the central and peripheral chemoreflex control of muscle sympathetic nerve activity (MSNA) is altered in HFpEF. METHODS: Patients aged 55-80 years with symptoms of heart failure, body mass index ≤ 35 kg/m2, left ventricular ejection fraction > 50%, left atrial volume index > 34 mL/m2, left ventricular early diastolic filling velocity and early diastolic tissue velocity of mitral annulus ratio (E/e' index) ≥ 13, and BNP levels > 35 pg/mL were included in the study (HFpEF, n = 9). Patients without heart failure with preserved ejection fraction (non-HFpEF, n = 9), aged-paired, were also included in the study. Peripheral chemoreceptors stimulation (10% O2 and 90% N2, with CO2 titrated) and central chemoreceptors stimulation (7% CO2 and 93% O2) were conducted for 3 min. MSNA was evaluated by microneurography technique, and forearm blood flow (FBF) by venous occlusion plethysmography. RESULTS: During hypoxia, MSNA responses were greater (p < 0.001) and FBF responses were lower in patients with HFpEF (p = 0.006). Likewise, MSNA responses during hypercapnia were higher (p < 0.001) and forearm vascular conductance (FVC) levels were lower (p = 0.030) in patients with HFpEF. CONCLUSIONS: Peripheral and central chemoreflex controls of MSNA are hypersensitized in patients with HFpEF, which seems to contribute to the increase in MSNA in these patients. In addition, peripheral and central chemoreceptors stimulation in patients with HFpEF causes muscle vasoconstriction.

Size matters: Large copy number losses in Hirschsprung disease patients reveal genes involved in enteric nervous system development.

Hirschsprung disease (HSCR) is a complex genetic disease characterized by absence of ganglia in the intestine. HSCR etiology can be explained by a unique combination of genetic alterations: rare coding variants, predisposing haplotypes and Copy Number Variation (CNV). Approximately 18% of patients have additional anatomical malformations or neurological symptoms (HSCR-AAM). Pinpointing the responsible culprits within a CNV is challenging as often many genes are affected. Therefore, we selected candidate genes based on gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics. Next, we used a zebrafish model to investigate whether loss of these genes affects enteric neuron development in vivo. This study included three groups of patients, two groups without coding variants in disease associated genes: HSCR-AAM and HSCR patients without associated anomalies (HSCR-isolated). The third group consisted of all HSCR patients in which a confirmed pathogenic rare coding variant was identified. We compared these patient groups to unaffected controls. Predisposing haplotypes were determined, confirming that every HSCR subgroup had increased contributions of predisposing haplotypes, but their contribution was highest in isolated HSCR patients without RET coding variants. CNV profiling proved that specifically HSCR-AAM patients had larger Copy Number (CN) losses. Gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics were used to determine plausible candidate genes located within CN losses. Validation in zebrafish using CRISPR/Cas9 targeting confirmed the contribution of UFD1L, TBX2, SLC8A1, and MAPK8 to ENS development. In addition, we revealed epistasis between reduced Ret and Gnl1 expression and between reduced Ret and Tubb5 expression in vivo. Rare large CN losses-often de novo-contribute to HSCR in HSCR-AAM patients. We proved the involvement of six genes in enteric nervous system development and Hirschsprung disease.

Endangered bird species of one of the last remnants of lowland Atlantic Forest in Rio de Janeiro state, Brazil: pressures and preservation measures.

The lowland Atlantic Forest, at altitudes of below 500 m, is highly fragmented, and is home to many threatened species of birds. The Brazilian state of Rio de Janeiro has a high concentration of threatened birds in the Americas and is an important residual of the dense ombrophilous formations of the Atlantic Forest, which includes the Reserva Biológica União, a high priority area for conservation of Atlantic Forest birds. This study compiled empirical and secondary records of threatened birds in this reserve and discusses potential factors determining their local occurrence. Since 2008, regular observations, including transect surveys and mist-netting, in addiction to secondary data, have provided records of 306 bird species, of which 49 appear on red lists at some level (state, national or global), including 34 listed as endangered, of which 13 are listed globally, eight of them dependent on well-conserved lowland rainforest. Future studies should include new areas of the reserve, with the aim of confirming the presence of additional threatened species. The long-term conservation of this fauna will depend not only on the adequate management of the reserve, but also the reestablishment of its connectivity with adjacent forest fragments and upland areas in the state.

Predicting attachment in Portuguese infants born very or extremely preterm: Understanding the roles of infant regulatory behavior, maternal sensitivity, and risk factors.

A growing body of research shows that early attachment relationships are foundational for children's later developmental and psychosocial outcomes. However, findings are mixed regarding whether preterm birth predicts later attachment, but insecurity is generally more prevalent among infants at higher medical and/or social/familial risk. This longitudinal study aimed to identify specific relational, familial/demographic, and perinatal predictors of attachment in a sample of 63 Portuguese infants born very or extremely preterm (VEPT, <32 gestational weeks) and their mothers from diverse socioeconomic backgrounds. One-third of the mothers had social/family risk factors (e.g., single parent, immigrant, unemployed, low education, and/or low income). At 3 months (corrected age), dyads were observed during social interaction in the Face-to-Face Still-Face paradigm (FFSF) and during free play. At 12 months, mother-infant dyads were observed in Ainsworth's Strange Situation. Over half (58.7%) of the infants were classified as insecurely attached. Social-Positive Oriented regulatory behavior pattern, higher maternal sensitivity, higher infant cooperation during free play, number of siblings and an absence of social/family risk factors were associated with attachment security. Perinatal variables were unrelated to attachment. Findings indicate that both relational and social contextual factors contribute to attachment in this biologically vulnerable sample.

Un creciente cuerpo investigativo muestra que las relaciones afectivas tempranas son fundamentales para posteriores resultados de desarrollo y sicosociales de los niños. Sin embargo, los resultados son variados acerca de si el nacimiento prematuro predice la afectividad posterior, pero la inseguridad es generalmente más prevalente entre infantes bajo más alto riesgo médico y/o social/familiar. Este estudio longitudinal se propuso identificar factores específicos de predicción de la afectividad, relacionales, familiar/demográficos y perinatales en un grupo muestra de 63 infantes portugueses nacidos muy o extremadamente prematuros (VEPT, < 32 semanas gestacionales) y sus madres de diversos niveles socioeconómicos. Un tercio de las madres tenían factores de riesgo social/familiar (v.g. madre soltera, inmigrante, desempleada, de baja educación y/o de bajos recursos económicos). A los tres meses (edad corregida), se les observó a las díadas durante la interacción social en el paradigma de Cara a Cara y Rostro Inmutable (FFSF) y durante el juego libre. A los 12 meses, se les observó a las díadas madre-infante por medio de la Situación Extraña de Ainsworth. Se clasificó más de la mitad (58.7%) de los infantes como afectivamente inseguros. Entre los factores de predicción de la afectividad segura se incluyó un patrón de conducta regulatoria con orientación social positiva durante FFSF, una sensibilidad materna más alta y la cooperación del infante durante el juego libre, así como la ausencia de factores de riesgo sociales/familiares. Las variables perinatales no estuvieron relacionadas con la afectividad. Los resultados indican que los factores contextuales, tanto relacionales como sociales contribuyen a la afectividad en este grupo biológicamente vulnerable.

Brazilian Women in Paralympic Sports: Uncovering Historical Milestones in the Summer Paralympic Games.

The journey of Brazilian female Paralympians transcends mere statistical increases in women's participation. Behind the modest athlete growth lies the reality of women who are doubly marginalized by the intersection of gender and disability in an arena tailored for able-bodied men. Our study aimed to catalyze critical discourses surrounding the historical trajectory of Paralympic women's sports. Through a comprehensive documentary analysis based on the Brazilian Paralympic Committee's official documents from 1976 to 2021, we sought to shed light on this complex scenario. Numerically, Brazil's representation comprised 229 women who, predominantly, had physical impairments and engaged in individual sports. In addition to a sporting legacy deeply entrenched in physical rehabilitation with limited opportunities for team-based sports, we observed negative influences stemming from ableist and sexist narratives. A thorough investigation into Paralympic milestones revealed a multitude of social barriers and highlighted the significant impact of societal changes in reshaping athletic opportunities and challenging traditional stereotypes.

Neurovascular and hemodynamic responses to mental stress and exercise in severe COVID-19 survivors.

Previous studies show that COVID-19 survivors have elevated muscle sympathetic nerve activity (MSNA), endothelial dysfunction, and aortic stiffening. However, the neurovascular responses to mental stress and exercise are still unexplored. We hypothesized that COVID-19 survivors, compared with age- and body mass index (BMI)-matched control subjects, exhibit abnormal neurovascular responses to mental stress and physical exercise. Fifteen severe COVID-19 survivors (aged: 49 ± 2 yr, BMI: 30 ± 1 kg/m2) and 15 well-matched control subjects (aged: 46 ± 3 yr, BMI: 29 ± 1 kg/m2) were studied. MSNA (microneurography), forearm blood flow (FBF), and forearm vascular conductance (FVC, venous occlusion plethysmography), mean arterial pressure (MAP, Finometer), and heart rate (HR, ECG) were measured during a 3-min mental stress (Stroop Color-Word Test) and during a 3-min isometric handgrip exercise (30% of maximal voluntary contraction). During mental stress, MSNA (frequency and incidence) responses were higher in COVID-19 survivors than in controls (P < 0.001), and FBF and FVC responses were attenuated (P < 0.05). MAP was similar between the groups (P > 0.05). In contrast, the MSNA (frequency and incidence) and FBF and FVC responses to handgrip exercise were similar between the groups (P > 0.05). MAP was lower in COVID-19 survivors (P < 0.05). COVID-19 survivors exhibit an exaggerated MSNA and blunted vasodilatory response to mental challenge compared with healthy adults. However, the neurovascular response to handgrip exercise is preserved in COVID-19 survivors. Overall, the abnormal neurovascular control in response to mental stress suggests that COVID-19 survivors may have an increased risk to cardiovascular events during mental challenge.

Bioactive compounds: a goldmine for defining new strategies against pathogenic bacterial biofilms?

Most human infectious diseases are caused by microorganisms growing as biofilms. These three-dimensional self-organized communities are embedded in a dense matrix allowing microorganisms to persistently inhabit abiotic and biotic surfaces due to increased resistance to both antibiotics and effectors of the immune system. Consequently, there is an urgent need for novel strategies to control biofilm-associated infections. Natural products offer a vast array of chemical structures and possess a wide variety of biological properties; therefore, they have been and continue to be exploited in the search for potential biofilm inhibitors with a specific or multi-locus mechanism of action. This review provides an updated discussion of the major bioactive compounds isolated from several natural sources - such as plants, lichens, algae, microorganisms, animals, and humans - with the potential to inhibit biofilm formation and/or to disperse established biofilms by bacterial pathogens. Despite the very large number of bioactive products, their exact mechanism of action often remains to be clarified and, in some cases, the identity of the active molecule is still unknown. This knowledge gap should be filled thus allowing development of these products not only as novel drugs to combat bacterial biofilms, but also as antibiotic adjuvants to restore the therapeutic efficacy of current antibiotics.

Quantitative expression evaluation of PRAME gene in osteosarcoma.

BACKGROUND: In a previous study, our group observed that 68% of the osteosarcoma (OS) samples presented PRAME (Preferentially Expressed Antigen in Melanoma) gene expression. In this work, we propose to investigate quantitatively gene expression of PRAME in distinct patients groups. METHODS AND RESULTS: 61 osteosarcoma samples, from 3 distinct patients groups were selected for this study: (1) Patients younger than 10 years old at diagnosis, (2) Patients that had poor evolution of disease and (3) Patients that were in remission of disease and had treatment with no intercurrences) PRAME gene expression levels were obtained using quantitative Real-Time Polymerase Chain Reaction method (qRT-PCR). Clinical parameters were collected from patient's medical charts. Results demonstrated an increase in PRAME gene expression in all samples, with high variation in expression levels, when considering all samples and when analyzed in each group. In addition, no statistical difference was found when considering clinical data collected or patients groups. CONCLUSION: PRAME gene expression quantitative investigation did not bring any complementary information beyond of what had already been observed in other qualitative investigations published by our group, there is no relation between PRAME gene expression levels and disease evolution. However, the findings in this work contribute for validation PRAME gene expression as a good biomarker to OS, which, in the future, may allow identification circulating tumor cell or molecules to contribute with early diagnostic of metastasis, a genuine problem in OS that determinate flattening in survival curves.

Similar regional-scale survival of tropical and southern temperate birds from the New World.

The general assumption that the survival patterns of tropical and southern temperate birds are similar lacks empirical data from higher latitudes. Regional comparisons of New World species are rare, and this assumption has been based on data from African studies. Here, we estimate the survival rates of 88 tropical and southern temperate bird populations (69 species) from eight localities in South America to evaluate the hypothesis that the survival of these populations is homogeneous at the regional scale. We estimated survival based on the Cormack-Jolly-Seber model and compared values from different environments. The survival estimates ranged from 0.30 to 0.80 (0.56 ± 0.12). Apparent survival did not differ significantly between low-latitude tropical environments (03°S) and the other sites from high-latitudes (between 22° and 34°S). Despite a predicted positive trend, body size was not significantly related to survival among passerines. On the other hand, phylogenetic relationships explained more than a third of the variation in bird survival. Based on the largest available database on South American bird species, our findings support the hypothesis that bird survival is homogeneous, at the regional scale, along the southern hemisphere. In particular, we reinforce the hypothesis that climatic variation has a limited influence on bird survival in the southern hemisphere.

Multi-disciplinary Insights from the First European Forum on Visceral Myopathy 2022 Meeting.

Visceral myopathy is a rare, life-threatening disease linked to identified genetic mutations in 60% of cases. Mostly due to the dearth of knowledge regarding its pathogenesis, effective treatments are lacking. The disease is most commonly diagnosed in children with recurrent or persistent disabling episodes of functional intestinal obstruction, which can be life threatening, often requiring long-term parenteral or specialized enteral nutritional support. Although these interventions are undisputedly life-saving as they allow affected individuals to avoid malnutrition and related complications, they also seriously compromise their quality of life and can carry the risk of sepsis and thrombosis. Animal models for visceral myopathy, which could be crucial for advancing the scientific knowledge of this condition, are scarce. Clearly, a collaborative network is needed to develop research plans to clarify genotype-phenotype correlations and unravel molecular mechanisms to provide targeted therapeutic strategies. This paper represents a summary report of the first 'European Forum on Visceral Myopathy'. This forum was attended by an international interdisciplinary working group that met to better understand visceral myopathy and foster interaction among scientists actively involved in the field and clinicians who specialize in care of people with visceral myopathy.

Effects of exercise on platelet reactivity after myocardial infarction: a randomized clinical trial.

Exercise training (ET) can lower platelet reactivity in patients with cardiovascular risk factors. However, the effects of ET on platelet reactivity in higher-risk patients is unknown. The aim of this study was to evaluate the effects of ET on platelet reactivity in patients with recent myocardial infarction (MI). Ninety patients were randomly assigned 1 month post-MI to the intervention (patients submitted to a supervised ET program) or control group. All patients were on dual antiplatelet therapy (DAPT). Platelet reactivity by VerifyNow-P2Y12 (measured by P2Y12 reaction units - PRUs) test was determined at baseline and at the end of 14 ± 2 weeks of follow-up at rest (primary endpoint), and multiplate electrode aggregometry (MEA) adenosine diphosphate (ADP) and aspirin (ASPI) tests were performed immediately before and after the maximal cardiopulmonary exercise test (CPET) at the same time points (secondary endpoints). Sixty-five patients (mean age 58.9 ± 10 years; 73.8% men; 60% ST elevation MI) completed follow-up (control group, n = 31; intervention group, n = 34). At the end of the follow-up, the mean platelet reactivity was 172.8 ± 68.9 PRUs and 166.9 ± 65.1 PRUs for the control and intervention groups, respectively (p = .72). Platelet reactivity was significantly increased after the CPET compared to rest at the beginning and at the end of the 14-week follow-up (among the intervention groups) by the MEA-ADP and MEA-ASPI tests (p < .01 for all analyses). In post-MI patients on DAPT, 14 weeks of supervised ET did not reduce platelet reactivity. Moreover, platelet reactivity was increased after high-intensity exercise (ClinicalTrials.gov: NCT02958657; https://clinicaltrials.gov/ct2/show/NCT02958657).

What is the context? Platelet reactivity is reduced after exercise training in healthy individuals and patients with cardiovascular risk factors, but the effect in higher-risk patients is unknown.High-intensity exercise in untrained individuals increases platelet reactivity. The effect of dual antiplatelet therapy in inhibiting exercise-induced hyperreactivity is poorly understood.What's new?Exercise training did not reduce platelet reactivity in post-myocardial infarction patients.High-intensity exercise increased platelet reactivity in post-myocardial infarction patients on dual antiplatelet therapy.Exercise training did not attenuate the exercise-induced increase in platelet reactivity.What's the impact?The study suggests that strenuous exercise, if indicated, should be applied carefully to patients with high risk of recurrent ischemic events, even if on optimal medical therapy and after being trained.

First record of the parasitoid wasp Ixodiphagus hookeri (Hymenoptera: Encyrtidae) infesting the tick Amblyomma nodosum (Acari: Ixodidae).

Ticks (Ixodida) are ecologically important ectoparasites that may impact human health and economic activities. Parasitoid wasps are natural enemies of ticks and a potential option for its biological control. In the present study, we recorded parasitism of the nymphs of the tick Amblyomma nodosum by the parasitoid wasp Ixodiphagus hookeri. The ticks, in turn, were parasitizing white-bearded manakins, Manacus manacus (Passeriformes: Pipridae) in the União Biological Reserve, one of the last major remnants of lowland rainforest in Rio de Janeiro state, southeastern Brazil. During the collection of ectoparasites from two manakins in this reserve, 20-30 parasitoid wasps hatched spontaneously from two of the ticks collected. The species of the tick nymphs and adult wasps were identified using morphological traits and molecular analyses. This record is the first documented case of I. hookeri parasitizing A. nodosum and the first time that parasitoid wasps have been found in ticks parasitizing birds in Brazil. This is also the first record of Ixodiphagus from southeastern Brazil in more than a century, with the only other record dating back to 1914. The record presented here provides valuable new information on the biology of this tick and its parasitoids, and new insights into this interspecific interaction. Further research on these vertebrate-tick-wasp interactions will be necessary to better understand the respective roles of the organisms involved in these processes.

Zebrafish as a biological model for assessing water quality along tropical hydrographic river basins in Northeast Brazil.

Tropical rivers are the main destinations for tailings from urban, industrial and agricultural activities in the region studied. The present study aimed to investigate if early stages of zebrafish (Danio rerio) development is a viable biological model to assess the toxicity of surface waters of tropical rivers, and whether that toxicity could be correlated to standard water quality indexes. Embryos were exposed to samples from 55 sites from 10 hydrographic basins of rivers in Pernambuco State, northeastern Brazil. Lethality rates, sublethal toxicity based on the general morphology score (GMS) and frequencies of abnormalities were analyzed. Significant mortality was observed in samples of 7 basins. The GMS indicated significant delay in embryo-larval development in 50% of the samples. The highest toxicity was detected in basins within Recife metropolitan area, where 61% of the samples caused sublethal toxicity. Most frequent developmental abnormalities included non-inflation of the swim bladder, delayed hatching and blood stasis. The highest frequencies of blood stasis were detected in samples with highest NH3 concentrations, corroborated by a positive correlation suggesting the existence of a causal relationship. A significant correlation was detected between water quality indexes and GMS with a greater toxic effect being observed in samples collected in areas of greater urban density and greater contamination by domestic sewage. This study demonstrates that the early stages of the zebrafish is a viable ecotoxicological model to assess the toxicity of surface waters and can contribute to a better understanding between the chemical composition and the adverse effects suffered by fish early life stage fish in tropical rivers.

Pharmacogenetics of the Primary and Metastatic Osteosarcoma: Gene Expression Profile Associated with Outcome.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. In recent decades, OS treatment has reached a plateau and drug resistance is still a major challenge. Therefore, the present study aimed to analyze the expression of the genes related to pharmacogenetics in OS. The expression of 32 target genes in 80 paired specimens (pre-chemotherapeutic primary tumor, post-chemotherapeutic primary tumor and pulmonary metastasis) obtained from 33 patients diagnosed with OS were analyzed by the real-time PCR methodology. As the calibrators (control), five normal bone specimens were used. The present study identified associations between the OS outcome and the expression of the genes TOP2A, DHFR, MTHFR, BCL2L1, CASP3, FASLG, GSTM3, SOD1, ABCC1, ABCC2, ABCC3, ABCC5, ABCC6, ABCC10, ABCC11, ABCG2, RALBP1, SLC19A1, SLC22A1, ERCC1 and MSH2. In addition, the expression of the ABCC10, GGH, GSTM3 and SLC22A1 genes were associated with the disease event, and the metastasis specimens showed a high expression profile of ABCC1, ABCC3 and ABCC4 genes and a low expression of SLC22A1 and ABCC10 genes, which is possibly an important factor for resistance in OS metastasis. Therefore, our findings may, in the future, contribute to clinical management as prognostic factors as well as possible therapeutic targets.

GSTM1 and GSTT1 polymorphisms in healthy volunteers - a worldwide systematic review.

The GSTM1 and GSTT1 genes encode homonymous enzymes, which are responsible for the detoxification of several substances potentially harmful to the human body, such as air pollution, drugs, pesticides, and tobacco. However, some individuals may present a complete deletion of these genes and, consequently, an enzyme deficiency leading to an inadequate metabolism and, therefore, a higher susceptibility to some clinical conditions. Interethnic variations have also been described for both genes, making necessary the study of the deletion frequencies of GSTM1 and GSTT1 in different populations around the world. So, the aim of this study was to enable the synthesis and discussion of the main population differences of GSTM1 and GSTT1 polymorphisms in healthy volunteers. Searches were performed in the PubMed database, including 533 articles and 178,566 individuals in the analyses. We found an overrepresentation of European individuals and studies, and an underrepresentation of non-European ethnicities. Moreover, there are significant frequency differences among distinct ethnic groups: East Asians present the highest frequencies worldwide for GSTM1 and GSTT1 deletions, which could suggest higher disorders risk for this population; in contrast, Sub-Saharan Africans presented the lowest frequency of GSTM1 worldwide, corroborating evolution inferences performed previously for other genes codifying metabolism enzymes. Also, admixture is a relevant component when analyzing frequency values for both genes, but further studies focusing on this subject are warranted.

The consumption of culinary preparations and ultra-processed food is associated with handgrip strength in teenagers.

BACKGROUND: A nutrient-poor and hypocaloric diet may be associated with lower handgrip strength (HGS), whereas a high-quality or balanced diet may be associated with higher HGS. However, no study has used the NOVA system for classifying food by their degree of processing. OBJECTIVE: To analyze the association between food consumption according to the degree of food processing and HGS in Brazilian teenagers. METHODS: This cross-sectional study included teenagers aged 18 and 19 years old from the 1997/98 São Luís' birth cohort, Maranhão, Brazil. HGS (kilogram-force) was measured via a Jamar Plus + dynamometer. Food consumption was assessed using a semiquantitative food frequency questionnaire. The energy intake of culinary preparations (unprocessed or minimally processed food and processed culinary ingredients), processed, and ultra-processed foods was evaluated in percentages and categorized in tertiles. The associations between each food group intake and HGS was estimated via crude and adjusted linear regression models. A directed acyclic graph was used to identify confounding factors. RESULTS: We evaluated 2,433 teenagers, 52.1% of which were girls. For boys, adjusted analysis showed an association between the highest HGS and the 3rd tertile of culinary preparation consumption (ß: 1.95; 95%CI: 0.80; 3.10) and between the lowest HGS and the 3rd tertile of ultra-processed food consumption (ß: -2.25; 95%CI: -3.40; -1.10). Among girls, the consumption of culinary preparations in the 3rd tertile was associated with higher HGS (ß: 0.76; 95%CI: 0.05; 1.46). CONCLUSIONS: Higher consumption of culinary preparations and lower consumption of ultra-processed foods can contribute to reduce the chance of lower HGS in adult life. Interventions to promote the development and preservation of muscle strength should include dietary recommendations.

Association between violence and depression during pregnancy with perinatal outcomes: a moderated mediation analysis.

OBJECTIVE: To assess the direct, indirect, and total effects of violence during pregnancy on perinatal outcomes, and to evaluate the effect of violence as a moderator of the mediated relationship of depression with perinatal outcomes. METHODS: Data was collected from the prenatal study and follow-ups of the BRISA cohort, São Luís, Maranhão, Brazil. The perinatal outcomes investigated were: birth weight (BW), intrauterine growth restriction (IUGR) and gestational age (GA). Violence against women was evaluated using the World Health Organization Violence against Women instrument (Violence during pregnancy - regardless of the type of violence; Physical violence during pregnancy; Psychological violence during pregnancy). Depressive symptoms during pregnancy were evaluated as a mediating variable. Moderated mediation analysis was performed to estimate the effects of violence and depression on perinatal outcomes. RESULTS: Three types of violence analyzed by depression had an indirect effect in BW and GA. None of the types of violence showed an association with IUGR. All types of violence analyzed showed a moderated mediation effect with BW and GA. Only among women who experienced violence were birth weight and gestational age lower the higher the values of depressive symptoms. CONCLUSION: Violence and depression are only associated with lower BW and GA when they occur simultaneously.