Fecal microbiota transplantation ameliorates high-fat diet-induced memory impairment in mice.

Gut dysbiosis is linked to metabolic and neurodegenerative diseases and comprises a plausible link between high-fat diet (HFD) and brain dysfunction. Here we show that gut microbiota modulation by either antibiotic treatment for 5 weeks or a brief 3-day fecal microbiota transplantation (FMT) regimen from low-fat (control) diet-fed mice decreased weight gain, adipose tissue hypertrophy, and glucose intolerance induced by HFD in C57BL/6 male mice. Notably, gut microbiota modulation by FMT completely reversed impaired recognition memory induced by HFD, whereas modulation by antibiotics had less pronounced effect. Improvement in recognition memory by FMT was accompanied by decreased HFD-induced astrogliosis in the hippocampal cornu ammonis region. Gut microbiome composition analysis indicated that HFD diminished microbiota diversity compared to control diet, whereas FMT partially restored the phyla diversity. Our findings reinforce the role of the gut microbiota on HFD-induced cognitive impairment and suggest that modulating the gut microbiota may be an effective strategy to prevent metabolic and cognitive dysfunction associated with unfavorable dietary patterns.

Body mass trajectory from diagnosis to the end of treatment in a pediatric acute lymphoblastic leukemia cohort.

The advances in pediatric acute lymphoblastic leukemia (ALL) care have substantially increased survival, and the late effects of treatment are a growing concern. Obesity development is frequent following ALL therapy and may significantly contribute to long-term morbidity and mortality. We examined the body mass trajectory of 208 children with ALL, from the diagnosis to the completion of therapy. We found that 7.2% of children were overweight or obese at diagnosis, which increased to 19.7% at the end of induction therapy and 20.8% after completion of treatment. In a multivariable linear regression model, age at ALL diagnosis, the type of chemotherapy regimen, and body mass index (BMI) z-score at diagnosis were significant predictors of BMI z-score after induction therapy, whereas BMI z-score at diagnosis was the only significant predictor of BMI z-score at the completion of treatment. In a subgroup of 120 children, we found no association between nutrition status at diagnosis and the risk of ALL relapse or poorer overall survival. Our findings indicate that weight gain occurs early during ALL therapy and is predicted by weight status at diagnosis. Therefore, nutritional status should be assessed throughout treatment, and weight management interventions should be considered early, particularly for patients with higher weight at diagnosis.

Early-life exposure to antibiotics and excess body weight in childhood and adolescence: A systematic review and meta-analysis.

BACKGROUND: The association between early-life exposure to antibiotics and overweight/obesity is unclear. We conducted a systematic review and meta-analysis to address this issue. METHODS: We searched PubMed, Web of Science, Scopus, and grey literature from inception to August 10, 2022, for cohort studies investigating the association between early-life exposure to antibiotics and weight outcomes. Two independent reviewers screened studies for eligibility, extracted data, assessed risk of bias, and examined the certainty of the evidence. Random-effects meta-analyses was used for pooling the data. The review was registered in PROSPERO, CRD42021265417. RESULTS: We included 42 studies and data from 28 of them were pooled in the quantitative synthesis. Overall antenatal (OR 1.10, 95% CI 1.04-1.16; 518,095 children, very low certainty) and second trimester (OR 1.11, 95% CI 1.08-1.14, 248,469 children, low certainty) exposure to antibiotics were associated with increased risk of overweight/obesity in childhood/adolescence. Overall early postnatal antibiotic exposure was also associated with increased likelihood of overweight/obesity in childhood/adolescence (OR 1.09, 95% CI 1.05-1.12, 1,488,316 children, very low certainty). The magnitude of the association increased from exposure to one (OR 1.07, 95% CI 1.00-1.15, 512,954 children) to four or more courses of antibiotics (OR 1.31, 95% CI 1.17-1.46, 543,627 children). CONCLUSION: Antenatal and early postnatal exposure to antibiotics is associated increased likelihood of overweight/obesity, although the findings are limited by the very low certainty of evidence. We highlight the need for homogeneous prospective studies addressing potential confounding factors to further explore the link between exposure to antibiotics and the risk of excess body weight.

The effect of long-term exposure to nonylphenol at environmentally relevant levels on mouse liver and adipose tissue.

Exposure to the xenoestrogen nonylphenol (NP) during critical windows of development leads to metabolic abnormalities in adult life. However, less is known about NP exposure outside the developmental period on metabolic outcomes. We investigated the effect of prolonged exposure to NP after sexual maturity and at environmentally relevant concentrations below the 'no observable adverse effects level' (0.5 and 2.5 mg/kg/d). Male Swiss mice fed a normal-fat diet exposed to 2.5 mg/kg/d NP showed reduced weight gain and hepatic fat content. In male and female C57BL/6 mice fed a high-fat diet, NP exposure modified the mRNA levels of estrogen receptor α (Esr1) and adipose lineage markers in a sexually dimorphic and adipose depot-dependent pattern. Moreover, in primary female but not male stromal vascular cells from C57BL/6 mouse inguinal WAT induced to differentiate into adipocytes, NP upregulated Fabp4 expression. Low-level exposure to NP outside critical developmental windows may affect the metabolic phenotype distinctly. DATA AVAILABILITY STATEMENT: All data not included in the manuscript, such as raw results, are available upon request and should be addressed to AAA.

Unplanned pregnancy in Brazil: national study in eight university hospitals.

OBJECTIVE: To estimate the prevalence of unplanned pregnancy in eight public university hospitals, distributed in the five regions that make up Brazil. METHODS: A secondary analysis of a national multicenter cross-sectional study, carried out in eight public university hospitals between June 1 and August 31, 2020, in Brazil. Convenience sample including women who gave birth within sixty consecutive days and met the following criteria: over 18 years old; gestational age over 36 weeks at delivery; with a single and live newborn, without malformations. RESULTS: Sample composed of 1,120 postpartum women, of whom 756 (67.5%) declared that the pregnancy had not been planned. The median prevalence of unplanned pregnancy was 59.7%. The prevalence of unplanned pregnancy across hospitals differed significantly: Campinas (54.8%), Porto Alegre (58.2%), Florianópolis (59%), Teresina (61.2%), Brasília (64.3%), São Paulo (64.6%), Campo Grande (73.9%) and Manaus (95.3%) (p < 0.001). Factors significantly associated with unplanned pregnancy were maternal age, black color, lower family income, greater number of children, greater number of people living in household, and not having a partner. CONCLUSION: In the studied sample, about two thirds of the pregnancies were declared as unplanned. The prevalence of unplanned pregnancies was related to social and demographic factors and varied significantly across the university hospitals evaluated.

Early-life exposure to endocrine-disrupting chemicals and autistic traits in childhood and adolescence: a systematic review of epidemiological studies.

Aims: Exposure to endocrine-disrupting chemicals (EDCs) during critical neurodevelopmental windows has been associated with the risk of autistic traits. This systematic review of epidemiological studies examined the association between maternal exposure to EDCs during pregnancy and the risk of autism spectrum disorder (ASD) in the offspring. Methods: We searched PubMed, Web of Science, Scopus, and Google Scholar from inception to November 17, 2022, for studies investigating the association between prenatal exposure to EDCs and outcomes related to ASD. Two independent reviewers screened studies for eligibility, extracted data, and assessed the risk of bias. The review was registered in PROSPERO (CRD42023389386). Results: We included 27 observational studies assessing prenatal exposure to phthalates (8 studies), polychlorinated biphenyls (8 studies), organophosphate pesticides (8 studies), phenols (7 studies), perfluoroalkyl substances (6 studies), organochlorine pesticides (5 studies), brominated flame retardants (3 studies), dioxins (1 study), and parabens (1 study). The number of examined children ranged from 77 to 1,556, the age at the assessment of autistic traits ranged from 3 to 14 years, and most studies assessed autistic traits using the Social Responsiveness Scale. All but one study was considered to have a low risk of bias. Overall, there was no association between maternal exposure to specific ECDs during pregnancy and the occurrence of autistic traits in offspring. Conclusions: Findings from the epidemiological studies evaluated here do not support an association between prenatal exposure to ECDs and the likelihood of autistic traits in later in life. These findings should not be interpreted as definitive evidence of the absence of neurodevelopment effects of EDCs affecting ASD risk, given the limitations of current studies such as representative exposure assessment, small sample sizes, inadequacy to assess sexually dimorphic effects, or the effects of EDC mixtures. Future studies should carefully address these limitations.

Early-life metabolic dysfunction impairs cognition and mitochondrial function in mice.

The impact of overnutrition early in life is not restricted to the onset of cardiovascular and metabolic diseases, but also affects critical brain functions related to cognition. This study aimed to evaluate the relationship between peripheral metabolic and bioenergetic changes induced by a two-hit protocol and their impact on cognitive function in juvenile mice. Three-week-old male C57BL/6 mice received a high-fat diet (HFD) or control diet for 7 weeks, associated with two low doses of streptozotocin (STZ) or vehicle. Despite the absence of obesity, HFD+STZ impaired glucose metabolism and induced a trend towards cholesterol increase. The two-hit protocol impaired recognition and spatial memories in juvenile mice, without inducing a depressive-like behavior. HFD+STZ mice presented increased immunoreactivity for GFAP and a trend towards a decrease in NeuN in the hippocampus. The treatment caused a bioenergetic impairment in the hippocampus, characterized by a decrease in both O2 consumption related to ATP production and in the maximum respiratory capacity. The thermogenic capacity of brown adipose tissue was impaired by the two-hit protocol, here verified through the absence of a decrease in O2 consumption after uncoupled protein-1 inhibition and an increase in the reserve respiratory capacity. Impaired mitochondrial function was also observed in the liver of HFD+STZ juvenile mice, but not in their heart. These results indicate that exposure to HFD+STZ early in life has a detrimental impact on the bioenergetic and mitochondrial function of tissues with metabolic and thermogenic activities, which is likely related to hippocampal metabolic changes and cognitive impairment.

Unplanned pregnancy in Brazil: national study in eight university hospitals / Gravidez não planejada no Brasil: estudo nacional em oito hospitais universitários

ABSTRACT OBJECTIVE To estimate the prevalence of unplanned pregnancy in eight public university hospitals, distributed in the five regions that make up Brazil. METHODS A secondary analysis of a national multicenter cross-sectional study, carried out in eight public university hospitals between June 1 and August 31, 2020, in Brazil. Convenience sample including women who gave birth within sixty consecutive days and met the following criteria: over 18 years old; gestational age over 36 weeks at delivery; with a single and live newborn, without malformations. RESULTS Sample composed of 1,120 postpartum women, of whom 756 (67.5%) declared that the pregnancy had not been planned. The median prevalence of unplanned pregnancy was 59.7%. The prevalence of unplanned pregnancy across hospitals differed significantly: Campinas (54.8%), Porto Alegre (58.2%), Florianópolis (59%), Teresina (61.2%), Brasília (64.3%), São Paulo (64.6%), Campo Grande (73.9%) and Manaus (95.3%) (p < 0.001). Factors significantly associated with unplanned pregnancy were maternal age, black color, lower family income, greater number of children, greater number of people living in household, and not having a partner. CONCLUSION In the studied sample, about two thirds of the pregnancies were declared as unplanned. The prevalence of unplanned pregnancies was related to social and demographic factors and varied significantly across the university hospitals evaluated.

RESUMO OBJETIVO Estimar a prevalência de gestação não planejada (GNP) em oito hospitais públicos universitários, distribuídos nas cinco regiões que compõem o Brasil. MÉTODOS Análise secundária de um estudo transversal multicêntrico nacional, realizado em oito hospitais universitários públicos, entre 1º de junho e 31 de agosto de 2020, no Brasil. Amostra por conveniência incluindo mulheres que deram à luz em período de sessenta dias consecutivos e atenderam aos seguintes critérios: maiores de 18 anos; idade gestacional acima de 36 semanas no parto; com recém-nascido único e vivo, sem malformações. RESULTADOS Amostra composta por 1.120 puérperas, das quais 756 (67,5%) declararam que a gravidez não tinha sido programada. A mediana da prevalência de GNP foi de 59,7%. Observou-se diferença significativa na prevalência de GNP entre os hospitais: Campinas (54,8%), Porto Alegre (58,2%), Florianópolis (59%), Teresina (61,2%), Brasília (64,3%), São Paulo (64,6%), Campo Grande (73,9%) e Manaus (95,3%) (p < 0,001). Foram fatores significativamente associados a GNP a idade materna, cor negra, menor renda familiar, maior número de filhos, maior número de pessoas convivendo em casa e não ter parceiro. CONCLUSÃO Na amostra estudada, cerca de dois terços das gestações foram declaradas como não programadas. A prevalência de gestação não planejada teve relação com fatores sociais e demográficos e variou significativamente entre os hospitais universitários avaliados.

Thermogenic adipose tissue aging: Mechanisms and implications.

Adipose tissue undergoes significant anatomical and functional changes with aging, leading to an increased risk of metabolic diseases. Age-related changes in adipose tissue include overall defective adipogenesis, dysfunctional adipokine secretion, inflammation, and impaired ability to produce heat by nonshivering thermogenesis. Thermogenesis in adipose tissue is accomplished by brown and beige adipocytes, which also play a role in regulating energy homeostasis. Brown adipocytes develop prenatally, are found in dedicated depots, and involute in early infancy in humans. In contrast, beige adipocytes arise postnatally in white adipose tissue and persist throughout life, despite being lost with aging. In recent years, there have been significant advances in the understanding of age-related reduction in thermogenic adipocyte mass and function. Mechanisms underlying such changes are beginning to be delineated. They comprise diminished adipose precursor cell pool size and adipogenic potential, mitochondrial dysfunction, decreased sympathetic signaling, and altered paracrine and endocrine signals. This review presents current evidence from animal models and human studies for the mechanisms underlying thermogenic adipocyte loss and discusses potential strategies targeting brown and beige adipocytes to increase health span and longevity.

The association between excess body weight at diagnosis and pediatric leukemia prognosis: A systematic review and meta-analysis.

Obesity affects the prognosis of several types of cancer. However, whether excess body weight is independently associated with adverse outcomes following initial pediatric acute leukemia (AL) treatment is still unclear. We conducted a systematic review and meta-analysis to investigate the impact of overweight/obesity at diagnosis on pediatric AL prognosis following initial treatment by performing an extensive database search up to January 22, 2021. Twenty-three studies were included, providing data for 15689 children with acute lymphoblastic leukemia (ALL) and 2506 children with acute myeloid leukemia (AML). Data from 12 studies were pooled in the meta-analysis. Children with overweight/obesity at diagnosis of ALL had poorer event free-survival (random-effects hazard ratio of 1.44, 95%CI 1.16-1.79, p = 0.0008), but no difference in overall survival (random-effects hazard ratio 1.33, 95%CI 0.77-2.29, p = 0.31) when compared with healthy-weight children. Children with overweight/obesity at diagnosis of AML had no difference in event-free survival (random-effects hazard ratio of 0.88, 95%CI 0.48-1.59, p = 0.66) or overall survival (random-effects hazard ratio 1.40, 95%CI 0.78-2.49, p = 0.26), when compared with healthy-weight children. This systematic review and meta-analysis indicates that overweight/obesity negatively affects the prognosis of children with ALL. Future studies should address the best approach to consider nutritional status in their management.

Coffee Increases Post-Exercise Muscle Glycogen Recovery in Endurance Athletes: A Randomized Clinical Trial.

Coffee is one of the most widely consumed beverages worldwide and caffeine is known to improve performance in physical exercise. Some substances in coffee have a positive effect on glucose metabolism and are promising for post-exercise muscle glycogen recovery. We investigated the effect of a coffee beverage after exhaustive exercise on muscle glycogen resynthesis, glycogen synthase activity and glycemic and insulinemic response in a double-blind, crossover, randomized clinical trial. Fourteen endurance-trained men performed an exhaustive cycle ergometer exercise to deplete muscle glycogen. The following morning, participants completed a second cycling protocol followed by a 4-h recovery, during which they received either test beverage (coffee + milk) or control (milk) and a breakfast meal, with a simple randomization. Blood samples and muscle biopsies were collected at the beginning and by the end of recovery. Eleven participants were included in data analysis (age: 39.0 ± 6.0 years; BMI: 24.0 ± 2.3 kg/m2; VO2max: 59.9 ± 8.3 mL·kg-1·min-1; PPO: 346 ± 39 W). The consumption of coffee + milk resulted in greater muscle glycogen recovery (102.56 ± 18.75 vs. 40.54 ± 18.74 mmol·kg dw-1; p = 0.01; d = 0.94) and greater glucose (p = 0.02; d = 0.83) and insulin (p = 0.03; d = 0.76) total area under the curve compared with control. The addition of coffee to a beverage with adequate amounts of carbohydrates increased muscle glycogen resynthesis and the glycemic and insulinemic response during the 4-h recovery after exhaustive cycling exercise.

Exposure to endocrine disruptors and risk of breast cancer: A systematic review.

AIM: The aim of this study was to investigate the association between human exposure to endocrine disruptors (EDs) and the risk of breast cancer. METHODS: This was a systematic review conducted by searching Cochrane Library, LILACS, Livivo, PubMed, and Science Direct. Observational studies addressing the association between exposure to EDs and breast cancer risk in adults were included. Risk of bias was assessed using the National Toxicology Program's Office of Health Assessment Translation tool. RESULTS: a total of 37 studies were included. Most studies reported that exposure to organochlorine pesticides, phthalates, heavy metals, and polycyclic aromatic hydrocarbons was associated with increased breast cancer risk. CONCLUSION: qualitative analysis of observational studies indicates that human exposure to EDs is associated with increased breast cancer risk. Additional studies are needed to determine whether this association is causal.

Obesity and endocrine-disrupting chemicals.

Obesity is now a worldwide pandemic. The usual explanation given for the prevalence of obesity is that it results from consumption of a calorie dense diet coupled with physical inactivity. However, this model inadequately explains rising obesity in adults and in children over the past few decades, indicating that other factors must be important contributors. An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture that interferes with any aspect of hormone action. EDCs have become pervasive in our environment, allowing humans to be exposed daily through ingestion, inhalation, and direct dermal contact. Exposure to EDCs has been causally linked with obesity in model organisms and associated with obesity occurrence in humans. Obesogens promote adipogenesis and obesity, in vivo, by a variety of mechanisms. The environmental obesogen model holds that exposure to obesogens elicits a predisposition to obesity and that such exposures may be an important yet overlooked factor in the obesity pandemic. Effects produced by EDCs and obesogen exposure may be passed to subsequent, unexposed generations. This "generational toxicology" is not currently factored into risk assessment by regulators but may be another important factor in the obesity pandemic as well as in the worldwide increases in the incidence of noncommunicable diseases that plague populations everywhere. This review addresses the current evidence on how obesogens affect body mass, discusses long-known chemicals that have been more recently identified as obesogens, and how the accumulated knowledge can help identify EDCs hazards.

Predictors of sudomotor dysfunction in patients with type 1 diabetes without clinical evidence of peripheral neuropathy.

AIM: To investigate the frequency of foot sudomotor dysfunction determined by the electrochemical skin conductance test (ESC) and its independent predictors in individuals with type 1 diabetes mellitus (T1D) and no clinical evidence of diabetic peripheral neuropathy (DPN). METHODS: Adults with T1D for longer than 5 years and without DPN defined by the Michigan Neuropathy Screening Instrument and Neuropathy Disability Score were assessed for foot sudomotor dysfunction by ESC. Multivariate logistic regression analysis was used to examine the association between foot sudomotor dysfunction (ESC < 70 µS) and demographic, clinical, and biochemical variables. RESULTS: A total of 61 individuals with T1D were included. Their mean age was 29.5 ± 8.6 years, and mean diabetes duration was 17.8 ± 7.9 years. Foot sudomotor dysfunction was present in 16 (26.2%) participants, despite no clinical evidence of DPN. Retinopathy, hand sudomotor dysfunction and glycated haemoglobin (HbA1c) levels were identified as independent predictors of foot sudomotor dysfunction by multivariate logistic regression analysis. Retinopathy, hand sudomotor dysfunction, and every 1% increase of HbA1c increased the odds of foot sudomotor dysfunction by 2.48, 2.82, and 1.24-fold, respectively. CONCLUSION: Our findings indicate a high frequency of foot sudomotor dysfunction among individuals with T1D and no overt DPN. Factors associated with DPN, including retinopathy and higher HbA1c levels, independently predicted the occurrence of sudomotor dysfunction, suggesting that ESC assessment is a useful tool in the clinical setting to identify early small-fiber neuropathy.

Exposure to endocrine-disrupting chemicals and anthropometric measures of obesity: a systematic review and meta-analysis.

OBJECTIVE: Endocrine-disrupting chemicals (EDCs) are viewed as a major potential link between the environment and obesity development. We did a systematic review and meta-analysis to examine the association between exposure to EDCs and obesity. DATA SOURCES, DESIGN AND ELIGIBILITY CRITERIA: PubMed, Scopus and Web of Science were searched from inception to 6 June 2018 for studies primarily addressing the association between exposure to EDCs after the age of 2 years and anthropometric measures of obesity or body fat. The Newcastle-Ottawa scale was used to assess the risk of bias. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened and conducted data extraction and synthesis. A third reviewer resolved disagreements. RESULTS: A total of 73 studies investigating bisphenol A (32 286 individuals), organochlorine compounds (34 567 individuals), phthalates (21 401 individuals), polybrominated biphenyls (2937 individuals), polycyclic aromatic hydrocarbons (5174 individuals), parabens (4097 individuals), benzoic acid (3671 individuals) and polyfluoroalkyl substances (349 individuals) met our inclusion criteria. Most had a cross-sectional design and low or medium risk of bias. In qualitative analysis, bisphenol A and phthalates were consistently associated with general and abdominal obesity, in children and adults, and some studies suggested this association was age-dependent and gender-dependent. Meta-analysis indicated a significant association between exposure to bisphenol A and overweight (OR 1.254, 95% CI 1.005 to 1.564), obesity (OR 1.503, 95% CI 1.273 to 1.774) and increased waist circumference (OR 1.503, 95% CI 1.267 to 1.783) in adults, and between exposure to 2,5-dichlorophenol and obesity in children (OR 1.8, 95% CI 1.1018 to 3.184). CONCLUSION: Most observational studies supported a positive association between obesity and exposure to EDCs. Although causality cannot be determined from these data, they underscore the need to limit human exposure to EDCs in light of the evidence from animal and cell-based studies indicating the effects of these chemicals on adiposity. PROSPERO REGISTRATION NUMBER: CRD42018074548.

Factors associated with overweight and abdominal obesity in Brazilian school-aged children: a comprehensive approach.

Objective We investigated the association between demographic, socio-economic, perinatal, parental and lifestyle-related factors with general and abdominal obesity among prepubertal children aged 6 to 8 years in a Southeastern city of Brazil. Subjects and methods A total of 486 children were randomly selected from public schools in the city of Patos de Minas, and examined to determine body mass index (BMI) and waist circumference (WC). Demographic, socio-economic, perinatal, parental and lifestyle-related data were obtained and assessed as independent risk factors for overweight/obesity and abdominal obesity, using multiple regression analysis. Results Obesity/overweight (BMI percentile ≥ 85), seen in 19% of the children, was positively associated with low maternal education, being born small for gestational age, maternal BMI and screen time, whereas abdominal obesity (WC percentile > 90), seen in 9.9% of the children, was positively associated with maternal age and maternal BMI. When BMI and WC percentile were analyzed as continuous variables, birth by cesarean section, parental BMI, and lower sleep time were positively associated with BMI percentile, and birth by cesarean section, being born small for gestational age, and parental BMI were positively associated with WC percentile. Conclusion Our findings suggest that the frequency of overweight and obesity in a city in the Southeastern region of Brazil is similar to the global frequency reported by the World Health Organization. We also found that many modifiable risk factors were associated with general and abdominal obesity, and these may possibly substantiate future strategies to prevent childhood obesity and its consequences in adult life.

Intrauterine Device Insertion during Cesarean Section in Women without Prenatal Contraception Counseling: Lessons from a Country with High Cesarean Rates.

OBJECTIVE: The moment of admission for delivery may be inappropriate for offering an intrauterine device (IUD) to women without prenatal contraception counseling. However, in countries with high cesarean rates and deficient prenatal contraception counseling, this strategy may reduce unexpected pregnancies and repeated cesarean sections. METHODS: This was a prospective cohort study involving 100 women without prenatal contraception counseling. Postplacental IUD was offered after admission for delivery and placed during cesarean. The rates of IUD continuation, uterine perforation, and endometritis were assessed at 6 weeks and 6 months, and the proportion of women continuing with IUD at 6 months was assessed with respect to the number of previous cesareans. RESULTS: Ninety-seven women completed the follow-up. The rate of IUD continuation was 91% at 6 weeks and 83.5% at 6 months. The expulsion/removal rate in the first 6 weeks was not different from that between 6 weeks and 6 months (9 vs 9.1%, respectively). There were 2 cases of endometritis (2.1%), and no case of uterine perforation. Among 81 women continuing with intrauterine device after 6-months, 31% had undergone only the cesarean section in which the IUD was inserted, 44% had undergone 2 and 25% had undergone 3 or more cesarean sections. CONCLUSION: Two thirds of the women who continued with IUD at 6 months had undergone 2 or more cesarean sections. Since offering trial of labor is unusual after 2 or more previous cesareans, we believe that offering IUD after admission for delivery may reduce the risk of repeated cesarean sections and its inherent risks.

OBJETIVO: O momento da admissão para o parto pode ser considerado inapropriado para oferecer o dispositivo intrauterino (DIU) para mulheres sem aconselhamento contraceptivo pré-natal. Entretanto, em países com elevadas taxas de cesáreas e aconselhamento contraceptivo deficiente, essa estratégia pode reduzir o risco de gestações não programadas e cesáreas repetidas. MéTODOS: Estudo de coorte envolvendo 100 mulheres sem aconselhamento contraceptivo pré-natal. A inserção de DIU pós-dequitação foi oferecida após a admissão para o parto e indicação de cesárea. As taxas de continuidade com o DIU, perfuração uterina e endometrite foram avaliadas após 6 semanas e 6 meses, e a proporção de mulheres que continuaram com o DIU após 6 meses foi analisada em relação ao número de cesáreas prévias. RESULTADOS: Noventa e sete mulheres completaram o seguimento. A taxa de permanência do DIU foi de 91% em 6 semanas e 83,5% em 6 meses. A taxa de expulsão/remoção nas primeiras 6 semanas foi não foi diferente daquela observada entre 6 emanas e 6 meses (9 vs 9,1%, respectivamente). Houve dois casos de endometrite (2,1%), e nenhum caso de perfuração uterina. Entre as 81 mulheres que permaneceram com o DIU após 6 meses, 31% haviam sido submetidas a apenas uma cesárea, em que o DIU foi inserido, 44% a 2, e 25% a 3 ou mais cesáreas. CONCLUSãO: Dois terços das mulheres que continuaram com o DIU após 6 meses haviam sido submetidas a 2 ou mais cesáreas. Considerando que oferecer a tentativa de parto vaginal após duas ou mais cesáreas prévias é incomum, é possível que a oferta do DIU na admissão para o parto possa reduzir o risco de cesáreas repetidas e de seus riscos associados.

Evaluation of the hypothalamic-pituitary-adrenal axis in a case series of familial partial lipodystrophy.

BACKGROUND: Familial partial lipodystrophy (FPL) is a rare genetic disease characterized by body fat abnormalities that lead to insulin resistance (IR). Clinical conditions linked to milder IR, such as type 2 diabetes (T2D) and metabolic syndrome, are associated with abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis, but little is known about its activity in FPL. METHODS: Patients meeting the clinical criteria for FPL were subjected to anthropometric, biochemical and hormone analyses. A genetic study to identify mutations in the genes encoding peroxisome proliferator-activated receptor gamma (PPARγ) was performed. Polycystic ovary syndrome and hepatic steatosis were investigated, and the patient body compositions were analyzed via dual X-ray energy absorptiometry (DXA). The HPA axis was assessed via basal [cortisol, adrenocorticotrophic hormone (ACTH), cortisol binding globulin, nocturnal salivary cortisol and urinary free cortisol (UFC)] as well as dynamic suppression tests (cortisol post 0.5 mg and post 1 mg dexamethasone). RESULTS: Six patients (five female and one male) aged 17 to 42 years were included. In DXA analyses, the fat mass ratio between the trunk and lower limbs (FMR) was > 1.2 in all phenotypes. One patient had a confirmed mutation in the PPARγ gene: a novel heterozygous substitution of p. Arg 212 Trp (c.634C>T) at exon 5. HPA sensitivity to glucocorticoid feedback was preserved in all six patients, and a trend towards lower basal serum cortisol, serum ACTH and UFC values was observed. CONCLUSIONS: Our findings suggest that FPL is not associated with overt abnormalities in the HPA axis, despite a trend towards low-normal basal cortisol and ACTH values and lower UFC levels. These findings suggest that the extreme insulin resistance occurring in FPL may lead to a decrease in HPA axis activity without changing its sensitivity to glucocorticoid feedback, in contrast to the abnormalities in HPA axis function in T2D and common metabolic syndrome.

Supplementation Adherence and Outcomes Among Pregnant Women After Bariatric Surgery.

PURPOSE: Most patients undergoing bariatric surgery (BS) are fertile women whose postoperative (post-op) hormonal balance and weight loss increases fertility, frequently leading to pregnancy. This study aims to analyze supplementation adherence of pregnant women after BS and perinatal outcomes. MATERIALS AND METHODS: This retrospective study analyzed records from women after BS who consulted nutritionists at least twice during pregnancy. Each patient received nutritional guidance about vitamin and mineral supplementation and protein intake. Demographic data, body mass index (BMI), percentage of weight loss (%WL) at conception, maximum post-op BMI and %WL, post-op time at conception, supplementation adherence, biochemical data, possible gestational complications, and infant's birth weight were collected. RESULTS: Data was obtained from 23 women (mean age 33 ± 4 years). On average, patients became pregnant 43 months after surgery. The mean preoperative BMI was 40.2 kg/m2, the maximum post-op %WL was 36.6%, and the mean %WL at conception was 32.0%. No gestational intercurrence was related to biochemical data. Supplementation adherence was 34.7% for one multivitamin and 34.7% for two multivitamins; 43.5% for iron, 43.5% for omega 3, 39.1% for folic acid, 17.4% for B complex, and 60.8% for calcium. Mean infant birth weight was 3.0 kg, and it was not associated with maximum %WL, % WL at conception, and time since BS at conception. CONCLUSION: Our data indicate satisfactory adherence to post-op micronutrient supplementation and few gestational complications following BS. Moreover, child's birth weight was not associated with maximum %WL, %WL at conception, or time since BS.

Research Priorities and Resource Allocation in the Investigation of New Drugs for Cancer in Least Developed Countries.

Cancer incidence has increased significantly in low- and middle-income countries. The priorities of international health research are not always aligned with the global burden of cancer. This study aims to analyze global tendencies in clinical trials in oncology and discuss research priorities and resource allocation in the investigation of new drugs for cancers that significantly affect the least developed countries. This was a retrospective and analytical study that included data collected from the World Health Organization's International Clinical Trials Registry Platform (ICTRP) in 2014. According to our results, there was a tendency for clinical trials involving breast and lung cancer to be conducted in countries with a lower level of economic development. On the other hand, cervical, stomach, and liver cancer, despite the significant burden that these place on middle- and low-income countries, were studied little among the countries selected. In conclusion, the organizations that most fund research to develop new drugs for cancer treatment continue to show little interest in prioritizing resources to fund research for certain types of cancer such as those of the cervix, stomach, and liver, which have a significant impact in low- and middle-income countries.