Shock drives a STAT3 and JunB-mediated coordinated transcriptional and DNA methylation response in the endothelium.

Endothelial dysfunction is a crucial factor in promoting organ failure during septic shock. However, the underlying mechanisms are unknown. Here, we show that kidney injury after lipopolysaccharide (LPS) insult leads to strong endothelial transcriptional and epigenetic responses. Furthermore, SOCS3 loss leads to an aggravation of the responses, demonstrating a causal role for the STAT3-SOCS3 signaling axis in the acute endothelial response to LPS. Experiments in cultured endothelial cells demonstrate that IL-6 mediates this response. Furthermore, bioinformatics analysis of in vivo and in vitro transcriptomics and epigenetics suggests a role for STAT, AP1 and interferon regulatory family (IRF) transcription factors. Knockdown of STAT3 or the AP1 member JunB partially prevents the changes in gene expression, demonstrating a role for these transcription factors. In conclusion, endothelial cells respond with a coordinated response that depends on overactivated IL-6 signaling via STAT3, JunB and possibly other transcription factors. Our findings provide evidence for a critical role of IL-6 signaling in regulating shock-induced epigenetic changes and sustained endothelial activation, offering a new therapeutic target to limit vascular dysfunction.

Resolvin D2-G-Protein Coupled Receptor 18 Enhances Bone Marrow Function and Limits Steatosis and Hepatic Collagen Accumulation in Aging.

Aging is associated with nonresolving inflammation and tissue dysfunction. Resolvin D2 (RvD2) is a proresolving ligand that acts through the G-protein-coupled receptor called GPR18. Unbiased RNA sequencing revealed increased Gpr18 expression in macrophages from old mice, and in livers from elderly humans, which was associated with increased steatosis and fibrosis in middle-aged (MA) and old mice. MA mice that lacked GPR18 on myeloid cells had exacerbated steatosis and hepatic fibrosis, which was associated with a decline in Mac2+ macrophages. Treatment of MA mice with RvD2 reduced steatosis and decreased hepatic fibrosis, correlating with increased Mac2+ macrophages, increased monocyte-derived macrophages, and elevated numbers of monocytes in the liver, blood, and bone marrow. RvD2 acted directly on the bone marrow to increase monocyte-macrophage progenitors. A transplantation assay further demonstrated that bone marrow from old mice facilitated hepatic collagen accumulation in young mice. Transient RvD2 treatment to mice transplanted with bone marrow from old mice prevented hepatic collagen accumulation. Together, this study demonstrates that RvD2-GPR18 signaling controls steatosis and fibrosis and provides a mechanistic-based therapy for promoting liver repair in aging.

The Effect of Gender-Affirming Hormone Therapy on the Risk of Subclinical Atherosclerosis in the Transgender Population: A Systematic Review.

OBJECTIVE: The impact of gender-affirming hormone therapy (GAHT) on cardiovascular (CV) health is still not entirely established. A systematic review was conducted to summarize the evidence on the risk of subclinical atherosclerosis in transgender people receiving GAHT. METHODS: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and data were searched in PubMed, LILACS, EMBASE, and Scopus databases for cohort, case-control, and cross-sectional studies or randomized clinical trials, including transgender people receiving GAHT. Transgender men and women before and during/after GAHT for at least 2 months, compared with cisgender men and women or hormonally untreated transgender persons. Studies reporting changes in variables related to endothelial function, arterial stiffness, autonomic function, and blood markers of inflammation/coagulation associated with CV risk were included. RESULTS: From 159 potentially eligible studies initially identified, 12 were included in the systematic review (8 cross-sectional and 4 cohort studies). Studies of trans men receiving GAHT reported increased carotid thickness, brachial-ankle pulse wave velocity, and decreased vasodilation. Studies of trans women receiving GAHT reported decreased interleukin 6, plasminogen activator inhibitor-1, and tissue plasminogen activator levels and brachial-ankle pulse wave velocity, with variations in flow-mediated dilation and arterial stiffness depending on the type of treatment and route of administration. CONCLUSIONS: The results suggest that GAHT is associated with an increased risk of subclinical atherosclerosis in transgender men but may have either neutral or beneficial effects in transgender women. The evidence produced is not entirely conclusive, suggesting that additional studies are warranted in the context of primary prevention of CV disease in the transgender population receiving GAHT. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42022323757.

Association between global leukocyte DNA methylation and cardiovascular risk in postmenopausal women.

BACKGROUND: Genetic studies to date have not provided satisfactory evidence regarding risk polymorphisms for cardiovascular disease (CVD). Conversely, epigenetic mechanisms, including DNA methylation, seem to influence the risk of CVD and related conditions. Because postmenopausal women experience an increase in CVD, we set out to determine whether global DNA methylation was associated with cardiovascular risk in this population. METHODS: In this cross sectional study carried out in a university hospital, 90 postmenopausal women without prior CVD diagnosis (55.5 ± 4.9 years, 5.8 [3.0-10.0] years since menopause) were enrolled. DNA was extracted from peripheral leukocytes and global DNA methylation levels were obtained with an ELISA kit. Cardiovascular risk was estimated by the Framingham General Cardiovascular Risk Score (10-year risk) (FRS). Clinical and laboratory variables were assessed. Patients were stratified into two CVD risk groups: low (FRS: <10 %, n = 69) and intermediate/high risk (FRS ≥10 %, n = 21). RESULTS: Age, time since menopause, blood pressure, total cholesterol, and LDL-c levels were higher in FRS ≥10 % group vs. FRS <10 % group. BMI, triglycerides, HDL-c, HOMA-IR, glucose and hsC-reactive protein levels were similar in the two groups. Global DNA methylation (% 5mC) in the overall sample was 26.5 % (23.6-36.9). The FRS ≥10 % group presented lower global methylation levels compared with the FRS <10 % group: 23.9 % (20.6-29.1) vs. 28.8 % (24.3-39.6), p = 0.02. This analysis remained significant even after adjustment for time since menopause (p = 0.02). CONCLUSIONS: Our results indicate that lower global DNA methylation is associated with higher cardiovascular risk in postmenopausal women.

A transient brain endothelial translatome response to endotoxin is associated with mild cognitive changes post-shock in young mice.

Sepsis-associated encephalopathy (SAE) is a common manifestation in septic patients that is associated with increased risk of long-term cognitive impairment. SAE is driven, at least in part, by brain endothelial dysfunction in response to systemic cytokine signaling. However, the mechanisms driving SAE and its consequences remain largely unknown. Here, we performed translating ribosome affinity purification and RNA-sequencing (TRAP-seq) from the brain endothelium to determine the transcriptional changes after an acute endotoxemic (LPS) challenge. LPS induced a strong acute transcriptional response in the brain endothelium that partially correlates with the whole brain transcriptional response and suggested an endothelial-specific hypoxia response. Consistent with a crucial role for IL-6, loss of the main regulator of this pathway, SOCS3, leads to a broadening of the population of genes responsive to LPS, suggesting that an overactivation of the IL-6/JAK/STAT3 pathway leads to an increased transcriptional response that could explain our prior findings of severe brain injury in these mice. To identify any potential sequelae of this acute response, we performed brain TRAP-seq following a battery of behavioral tests in mice after apparent recovery. We found that the transcriptional response returns to baseline within days post-challenge. Despite the transient nature of the response, we observed that mice that recovered from the endotoxemic shock showed mild, sex-dependent cognitive impairment, suggesting that the acute brain injury led to sustained, non-transcriptional effects. A better understanding of the transcriptional and non-transcriptional changes in response to shock is needed in order to prevent and/or revert the devastating consequences of septic shock.

SH2 domain-containing protein tyrosine phosphatase-2 is enriched in eyelid specimens of rosacea.

Background: Rosacea is a cutaneous disease that may secondarily affect the ocular surface. Due to the vision threatening, cosmetic, psychological, and work productivity impact, the identification of cellular targets that govern rosacea would enhance our understanding of the biology of the disease and delineate targets for therapeutic manipulation. Objective: To characterize the involvement of SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) in the pathogenesis of rosacea. Methods: Specimens from elective ectropion surgery (n = 20) were processed from patients with rosacea (n = 10) and control patients (n = 10). Immunohistochemistry (IHC) and quantitative western blotting (WB) were performed to identify and quantify the presence of SHP2 and 4G10 (a phosphotyrosine antibody) in rosacea compared to normal tissue. IHC samples were graded according to an intensity scale (0-4). Mann-Whitney statistical analyses were performed via a dedicated computerized software package. Results: On WB, SHP2 was expressed in higher concentrations in rosacea specimens (p < 0.05). On IHC, SHP2 was enriched in the epidermis in rosacea (p < 0.05), although 4G10 levels were not statistically significantly different between the two groups (p > 0.05). Conclusions: SHP2 is enriched in cutaneous specimens of rosacea, suggesting a critical role for this protein in the disease and indicating a modifiable therapeutic moiety.

Metabolic Features of Women With Polycystic Ovary Syndrome in Latin America: A Systematic Review.

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder that commonly affects women of childbearing age and has been associated with metabolic and reproductive abnormalities. Only a few studies have investigated metabolic traits in women with PCOS in Latin America. Therefore, we conducted a systematic review to provide an overview of the available evidence on the metabolic profile of Latin American women with PCOS. Methods: We searched PubMed, Cochrane Central Register of Controlled Trials, and Embase databases for cross-sectional, case-control, or cohort studies focusing on populations of countries in South and Central America and Mexico, published until October 31, 2019. We selected studies that reported the diagnostic criteria for PCOS. In the absence of a control group, we included studies if they reported relevant metabolic data. Results: The initial search yielded 4878 records, of which 41 studies were included in the systematic review. Sample sizes ranged from 10 to 288 in PCOS groups and from 10 to 1500 in control groups. The prevalence of phenotypes A and B (classic PCOS) ranged from 65.8% to 87.5% as reported in studies from Argentina, Brazil, and Chile. Metabolic syndrome ranged from 33.3% to 44.0% for phenotype A, from 15.0% to 58.0% for phenotype B, from 11.9% to 36.0% for phenotype C, and from 14.2% to 66.0% for phenotype D. Women with PCOS had higher body mass index, waist circumference, blood pressure, glucose, and homeostasis model assessment index as well as a more adverse lipid profile than those without PCOS. Conclusions: Evidence from the present systematic review suggests that anthropometric and metabolic profiles are worse in women with PCOS who live in different Latin American countries than in women without PCOS living in the same region. Additional studies assessing metabolic comorbidities, such as diabetes, and distinct PCOS phenotypes in different Latin American countries are warranted and may produce invaluable information for primary and secondary prevention of PCOS in the region. This systematic review was registered with PROSPERO under number CRD42016038537. Systematic Review Registration: PROSPERO, identifier CRD42016038537.

Metabolic profile of women with PCOS in Brazil: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease affecting women of reproductive age and associated with reproductive and metabolic dysfunction. Few studies are available regarding metabolic traits in Brazilian women with PCOS. The aim of this systematic review and meta-analysis was to summarize the available evidence regarding metabolic traits and comorbidities in Brazilian women with polycystic ovary syndrome (PCOS). METHODS: We systematically searched PubMed, Cochrane Central Register of Controlled Trials, and Embase for cross-sectional, case-control, or cohort studies focusing on populations of different regions from Brazil, published until July 31, 2019. Studies were selected if they reported PCOS diagnostic criteria. Studies without a control group were included if they presented relevant metabolic data. RESULTS: Of 4856 studies initially identified, 27 were included in the systematic review and 12 were included in the meta-analysis, for a total of 995 women with PCOS defined by Rotterdam criteria and 2275 controls from different regions of Brazil. Obesity, metabolic syndrome and IGT were prevalent, and standard mean differences for BMI (SMD 0.67, 95% CI, 0.29, 1.05), waist circumference (SMD 0.22, 95% CI 0.02, 0.41), systolic (SMD 0.66, 95% CI 0.30, 1.01) and diastolic blood pressure (SMD 0.55, 95% CI 0.24, 0.87), glucose (SMD 0.21, 95% CI 0.04, 0.38) and HOMA (SMD 0.78, 95% CI 0.52, 1.04) were significantly higher in Brazilian women with PCOS compared to controls. Lipid profile was more adverse in PCOS vs. non-PCOS women. Between-study heterogeneities were low/moderate for glucose and HOMA and moderate/high for the other variables. CONCLUSIONS: The data of this systematic review and meta-analysis indicate that Brazilian women with PCOS have a worse metabolic profile than women without PCOS with no important regional differences. The prevalence of metabolic changes is intermediate in Brazil vs. other countries.

Endothelial SOCS3 maintains homeostasis and promotes survival in endotoxemic mice.

SOCS3 is the main inhibitor of the JAK/STAT3 pathway. This pathway is activated by interleukin 6 (IL-6), a major mediator of the cytokine storm during shock. To determine its role in the vascular response to shock, we challenged mice lacking SOCS3 in the adult endothelium (SOCS3iEKO) with a nonlethal dose of lipopolysaccharide (LPS). SOCS3iEKO mice died 16-24 hours postinjection after severe kidney failure. Loss of SOCS3 led to an LPS-induced type I IFN-like program and high expression of prothrombotic and proadhesive genes. Consistently, we observed intraluminal leukocyte adhesion and neutrophil extracellular trap-osis (NETosis), as well as retinal venular leukoembolization. Notably, heterozygous mice displayed an intermediate phenotype, suggesting a gene dose effect. In vitro studies were performed to study the role of SOCS3 protein levels in the regulation of the inflammatory response. In human umbilical vein endothelial cells, pulse-chase experiments showed that SOCS3 protein had a half-life less than 20 minutes. Inhibition of SOCS3 ubiquitination and proteasomal degradation led to protein accumulation and a stronger inhibition of IL-6 signaling and barrier function loss. Together, our data demonstrate that the regulation of SOCS3 protein levels is critical to inhibit IL-6-mediated endotheliopathy during shock and provide a promising therapeutic avenue to prevent multiorgan dysfunction through stabilization of endothelial SOCS3.

C-reactive protein gene rs1205 polymorphism is associated with low-grade chronic inflammation in postmenopausal women.

BACKGROUND: Cardiovascular disease is the leading cause of death in postmenopausal women, and inflammation is a key mechanism involved in the pathogenesis of atherosclerosis. High-sensitivity C-reactive protein (hs-CRP) has been used as a biomarker of inflammation. Considering that CRP gene rs1205 polymorphism has been associated with hs-CRP circulating levels, we evaluated whether rs1205 genotypes influence the presence of low-grade chronic inflammation, acting as a marker of cardiovascular risk. METHODS: We performed a cross-sectional study with biobanked blood samples from 327 postmenopausal women with no evidence of clinical disease. Genotyping for rs1205 C > T SNP of the CRP gene was done by real-time polymerase chain reaction with allelic discrimination assays. RESULTS: Mean age was 55.6 ± 5.6 years. Mean body mass index (BMI) was 27.3 ± 4.7. Participants were divided according to hs-CRP levels: ≥3 mg/l (low-grade chronic inflammation) or < 3 mg/l. The frequency of allele C at rs1205 was 74.2% in the hs-CRP ≥ 3 mg/l group vs. 59% in the hs-CRP < 3 mg/l. In a multivariable model, higher prevalence of hs-CRP ≥ 3 mg/l was associated with CC genotype (PR 1.53; 95%CI 1.07-2.18; p = 0.018) and waist circumference ≥ 88 cm (PR 2.45; 95%CI 1.66-3.60; p < 0.001). CONCLUSIONS: CRP rs1205 CC homozygotes may be at higher risk of a low-grade chronic inflammatory status compared to individuals carrying the T allele.

Two approaches reveal a new paradigm of 'switchable or genetics-influenced allele-specific DNA methylation' with potential in human disease.

Imprinted genes are vulnerable to environmental influences during early embryonic development, thereby contributing to the onset of disease in adulthood. Monoallelic methylation at several germline imprints has been reported as DNMT1-dependent. However, which of these two epigenetic attributes, DNMT1-dependence or allelic methylation, renders imprinted genes susceptible to environmental stressors has not been determined. Herein, we developed a new approach, referred to as NORED, to identify 2468 DNMT1-dependent DNA methylation patterns in the mouse genome. We further developed an algorithm based on a genetic variation-independent approach (referred to as MethylMosaic) to detect 2487 regions with bimodal methylation patterns. Two approaches identified 207 regions, including known imprinted germline allele-specific methylation patterns (ASMs), that were both NORED and MethylMosaic regions. Examination of methylation in four independent mouse embryonic stem cell lines shows that two regions identified by both NORED and MethylMosaic (Hcn2 and Park7) did not display parent-of-origin-dependent allelic methylation. In these four F1 hybrid cell lines, genetic variation in Cast allele at Hcn2 locus introduces a transcription factor binding site for MTF-1 that may predispose Cast allelic hypomethylation in a reciprocal cross with either C57 or 129 strains. In contrast, each allele of Hcn2 ASM in J1 inbred cell line and Park7 ASM in four F1 hybrid cell lines seems to exhibit similar propensity to be either hypo- or hypermethylated, suggesting a 'random, switchable' ASM. Together with published results, our data on ASMs prompted us to propose a hypothesis of regional 'autosomal chromosome inactivation (ACI)' that may control a subset of autosomal genes. Therefore, our results open a new avenue to understand monoallelic methylation and provide a rich resource of candidate genes to examine in environmental and nutritional exposure models.

Feeding methods for children with cleft lip and/or palate: a systematic review.

INTRODUCTION: Feeding difficulties in children with cleft lip and palate (CLP) are frequent and appear at birth due to impairment of sucking and swallowing functions. The use of appropriate feeding methods for the different types of cleft and the period of the child's life is of utmost importance for their full development. OBJECTIVE: Review studies comparing feeding methods for children with CLP, pre- and postoperatively. METHODS: The search covered the period between January 1990 and August 2015 in the PubMed, LILACS, SciELO, and Google Scholar databases using the terms: cleft lip or cleft palate and feeding methods or breastfeeding or swallowing disorders and their synonyms. This systematic review was recorded in PROSPERO under number CRD42014015011. Publications that compared feeding methods and published in Portuguese, English, and Spanish were included in the review. Studies with associated syndromes, orthopedic methods, or comparing surgical techniques were not included. RESULTS: The three reviewed studies on the period prior to surgical repair showed better feeding performance with three different methods: squeezable bottle, syringe, and paladai bottle. Only one study addressed the postoperative period of cleft lip and/or palate repair, with positive results for the feeding method with suction. Likewise, the post-lip repair studies showed better results with suction methods. After palatoplasty, two studies showed better performance with alternative feeding routes, one study with suction method, and one study that compared methods with no suction showed better results with spoon. CONCLUSION: The studies show that prior to surgical repair, the use of alternative methods can be beneficial. In the postoperative period following lip repair, methods with suction are more beneficial. However, in the postoperative period of palatoplasty, there are divergences of opinion regarding the most appropriate feeding methods.

Association between rs7903146 and rs12255372 polymorphisms of transcription factor 7-like 2 gene and polycystic ovary syndrome: a systematic review and meta-analysis.

The present systematic review and meta-analysis of case-control studies examines the associations between rs7903146 and rs12255372 polymorphisms of the TCF7L2 gene and PCOS. A search of the literature published until August 2014 was carried out in PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and LILACS. There were no other limits except for the end date. We included observational studies with women of any age diagnosed with PCOS and healthy controls that analyzed polymorphisms rs7903146 and rs12255372. We included case-control or cross-sectional studies analyzing polymorphism rs7903146 or rs12255372 in women with PCOS and healthy controls. Eighteen studies were identified after the primary literature search and seven articles were included in the meta-analysis. All employed Rotterdam criteria for the diagnosis of PCOS. The genotypic distributions in the control groups were in agreement with Hardy-Weinberg equilibrium in all studies. The pooled population included Asian descendents (Chinese, Korean), Caucasians from southern Brazil, Tunisian, and European populations (British/Irish, Northern Finns, Greeks, Czechs), including 1,892 women with PCOS and 2,695 controls. There were no significant associations between PCOS and TCF7L2 rs7903146 or rs12255372 polymorphisms, irrespective of whether allele contrast, additive, dominant, or recessive models of inheritance were used. Furthermore, no significant associations were found after stratification for ethnicity (Asian or non-Asian). There was no significant heterogeneity between studies and no publication bias. The present results suggest that rs7903146 T allele or rs12255372 is not associated with risk for PCOS in non-Asian or Asian women. This systematic review and meta-analysis are registered in PROSPERO under number CRD42013005930.

First-year students' perceptions of team-based learning in a new medical genetics course / Percepção dos alunos do primeiro ano sobre a aprendizagem baseada em equipes em um novo curso de genética médica

ABSTRACT Background Medical education has evolved considerably over the last few years, especially through adoption of new technologies and active methodologies. These methodologies aim to improve learning and engage students deeply in the process. TBL is a methodology widely used in health schools, including Medical Schools. We can use it to work with large groups, divided into small teams. The students first work individually, then within teams, and finally the groups cooperate to solve applied problems. Objectives To describe students' perceptions and satisfaction about a Medical Genetics course organized into blocks of subject in which we used TBL sessions with first-year medical students. Methods A Medical Genetics course were organized into subject blocks in which a TBL session was conducted in each of these blocks to improve the learning process. At the end of the course, the students answered a questionnaire on satisfaction and perceptions. Results By the first time we described a Medical Genetics course organized into 5 blocks of subject matter on a total of 25 genetic diseases in which a TBL session was conducted in each of these blocks. We enrolled a total of 290 participants and 96% of the students were satisfied with TBL. Furthermore, 97% of students believe that TBL helped them to learn, and 87% approved of use of TBL in the future at other stages of their medical course. Conclusion Application of the TBL method during a medical genetics course was well-received by students and proved an important tool in the structures of curricula for medical education at this university.

RESUMO Introdução A educação médica evoluiu consideravelmente nos últimos anos, especialmente através da adoção de novas tecnologias e metodologias ativas. Essas metodologias visam melhorar a aprendizagem e envolver os alunos profundamente no processo. O TBL é uma metodologia amplamente utilizada em escolas de saúde, incluindo escolas médicas. Podemos usá-lo para trabalhar com grandes grupos, divididos em pequenas equipes. Primeiro, os alunos trabalham individualmente, depois dentro das equipes e, finalmente, os grupos cooperam para resolver os problemas aplicados. Objetivos Descrever as percepções e a satisfação dos alunos em relação a um curso de Genética Médica organizado em blocos de assuntos em que utilizamos sessões de TBL com estudantes de medicina do primeiro ano. Métodos Um curso de Genética Médica foi organizado em blocos de assuntos em que uma sessão de TBL foi realizada em cada um desses blocos para melhorar o processo de aprendizagem. No final do curso, os alunos responderam a um questionário sobre satisfação e percepções. Resultados Pela primeira vez nós descrevemos um curso de Genética Médica organizado em 5 blocos de assuntos, compreendendo 25 doenças genéticas, nos quais, uma sessão de TBL foi conduzida em cada um desses blocos. Participaram um total de 290 alunos, dos quais 96% estavam satisfeitos com o método de TBL. Além disso, 97% dos estudantes acreditam que o TBL os ajudou a aprender, e 87% aprovaram o uso do TBL no futuro, em outras etapas de seu curso de medicina. Conclusão A aplicação do método TBL durante um curso de genética médica foi bem recebida pelos estudantes e se mostrou uma ferramenta importante na estruturação curricular para a educação médica nesta universidade.

Polymorphisms of TCF7L2 gene in South Brazilian women with polycystic ovary syndrome: a cross-sectional study.

OBJECTIVE: To assess whether TCF7L2 single nucleotide polymorphisms rs7903146 C/T and rs11196236 C/T are associated with polycystic ovary syndrome (PCOS) in South Brazilian women. DESIGN: Cross-sectional study. METHODS: Two hundred PCOS patients and 102 non-hirsute, ovulatory controls were genotyped by real-time PCR. Haplotypes were constructed from the combination of both polymorphisms. Frequencies were inferred using the PHASE 2.1.1 software. RESULTS AND CONCLUSIONS: The distribution of rs7903146 (PCOS, 54.4% CC; 28.5% CT; 17.1% TT; controls, 51.0% CC; 37.0% CT; 12.0% TT) and rs11196236 (PCOS, 4.3% CC; 33.5% CT; 62.2% TT; controls, 3.2% CC; 35.5% CT; 61.3% TT) was similar between the groups. rs7903146 and rs11196236 were not in linkage disequilibrium (|D'|=0.34; r(2)=0.07). PCOS participants were younger, with higher age-adjusted BMI, waist circumference, blood pressure, triglycerides, insulin, homeostasis model assessment index to estimate insulin resistance and total testosterone, and lower HDL-C and sex hormone binding globulin vs controls. In PCOS, no differences between genotypes and haplotypes were found for clinical and metabolic variables. However, for each T (rs7903146) and T (rs11196236) allele added to the haplotypes, a variation of 5.87 cm in waist (P trend=0.01), 10.7 mg/dl in total cholesterol (P trend=0.03), and 10.3 mg/dl in LDL-C (P trend=0.01) was recorded. TCF7L2 variants are probably not implicated in PCOS development in South Brazilian women.

Variations in the fat mass and obesity-associated (FTO) gene are related to glucose levels and higher lipid accumulation product in postmenopausal women from southern Brazil.

OBJECTIVE: To test the association between polymorphisms rs9939609 T>A and rs8050136 A>C of the fat mass and obesity-associated (FTO) gene and metabolic and cardiovascular variables in postmenopause. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S): A total of 135 postmenopausal women (mean age 52 ± 4 years). INTERVENTION(S): Anthropometric measurements and collection of blood samples. MAIN OUTCOME MEASURE(S): Blood pressure, metabolic variables, and FTO genotype. RESULT(S): The frequency of polymorphism rs9939609 was 43.7% for the wild TT genotype, 43.0% for TA, and 13.3% for AA. The frequency of the rs8050136 polymorphism was 12.6% for the wild AA genotype, 39.3% for AC, and 48.1% for CC. The polymorphic AA genotype of the SNP rs9939609 was associated with higher glucose levels and lipid accumulation product (LAP) index, whereas the wild AA genotype of the SNP rs8050136 was associated with higher LAP. CONCLUSION(S): The rs9939609 polymorphism in the FTO gene is related to abnormal glucose levels and with LAP, a surrogate marker of diabetes and cardiovascular risk in postmenopause. Further studies are needed in different ethnic backgrounds to confirm the clinical relevance of these associations.

Feeding methods for children with cleft lip and/or palate: a systematic review / Métodos de alimentação para crianças com fissura de lábio e/ou palato: uma revisão sistemática

ABSTRACT INTRODUCTION: Feeding difficulties in children with cleft lip and palate (CLP) are frequent and appear at birth due to impairment of sucking and swallowing functions. The use of appropriate feeding methods for the different types of cleft and the period of the child's life is of utmost importance for their full development. OBJECTIVE: Review studies comparing feeding methods for children with CLP, pre- and postoperatively. METHODS: The search covered the period between January 1990 and August 2015 in the PubMed, LILACS, SciELO, and Google Scholar databases using the terms: cleft lip or cleft palate and feeding methods or breastfeeding or swallowing disorders and their synonyms. This systematic review was recorded in PROSPERO under number CRD42014015011. Publications that compared feeding methods and published in Portuguese, English, and Spanish were included in the review. Studies with associated syndromes, orthopedic methods, or comparing surgical techniques were not included. RESULTS: The three reviewed studies on the period prior to surgical repair showed better feeding performance with three different methods: squeezable bottle, syringe, and paladai bottle. Only one study addressed the postoperative period of cleft lip and/or palate repair, with positive results for the feeding method with suction. Likewise, the post-lip repair studies showed better results with suction methods. After palatoplasty, two studies showed better performance with alternative feeding routes, one study with suction method, and one study that compared methods with no suction showed better results with spoon. CONCLUSION: The studies show that prior to surgical repair, the use of alternative methods can be beneficial. In the postoperative period following lip repair, methods with suction are more beneficial. However, in the postoperative period of palatoplasty, there are divergences of opinion regarding the most appropriate feeding methods.

Resumo Introdução: As dificuldades de alimentação em crianças com fissura labiopalatina (FLP) são frequentes e surgem logo ao nascimento, devido ao comprometimento das funções de sucção e deglutição. A utilização de métodos de alimentação adequados aos diferentes tipos de fissura e ao momento da vida da criança é primordial para seu pleno desenvolvimento. Objetivo: Revisar estudos que compararam métodos de alimentação para crianças com FLP antes da correção cirúrgica e no pós-operatório. Método: A busca compreendeu o período entre janeiro de 1990 e agosto de 2015, nas bases de dados PubMed, LILACS, Scielo e Google Acadêmicos e utilizando os termos: Fenda Labial ou Fissura Palatina e Métodos de Alimentação ou Aleitamento Materno ou Transtornos de deglutição e seus sinônimos. Esta revisão sistemática foi registrada no PROSPERO sob o número CRD42014015011. Foram incluídas publicações comparando métodos de alimentação nos idiomas português, inglês e espanhol. Pesquisas com síndromes associadas, métodos ortopédicos ou comparando técnicas cirúrgicas não foram incluídas. Resultados: Os três estudos revisados sobre o período que antecede a correção cirúrgica apresentaram melhor desempenho na alimentação com três diferentes métodos: mamadeira compressível, seringa e paladai. Um único estudo abordou o pós-operatório de fissura de lábio e/ou palato, apresentando resultados positivos para a alimentação com método com sucção. Da mesma forma, no pós-queiloplastia os estudos mostraram melhores resultados com métodos com sucção. Após a palatoplastia, dois estudos apresentaram melhor desempenho com via alternativa de alimentação; um estudo com método com sucção; e outro que comparou métodos sem sucção apresentou melhores resultados com colher. Conclusão: Os estudos mostram que antes da correção cirúrgica a utilização de métodos alternativos pode apresentar benefícios. No pós-operatório de queiloplastia, os métodos com sucção são mais benéficos. Porém, no período pós-operatório de palatoplastia há divergências quanto aos métodos mais indicados.