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Haematopoietic stem cells (HSCs) home to the bone marrow (BM) via, in part, the interactions with Vascular Cell Adhesion Molecule-1 (VCAM1)(1–3). Once into the BM, HSCs are vetted by perivascular phagocytes to ensure their self-integrity. Here, we show that VCAM1 is also expressed on healthy HSCs and upregulated on leukaemic stem cells (LSCs) where it serves as a quality-control checkpoint for entry into BM by providing ‘don’t-eat-me’ stamping in the context of major histocompatibility complex (MHC) class-I presentation. While haplotype-mismatched HSCs can engraft, Vcam1 deletion, in the setting of haplotype mismatch, leads to impaired haematopoietic recovery due to HSC clearance by mononuclear phagocytes. Mechanistically, VCAM1 ‘don’t-eat-me’ activity is regulated by ß2-microglobulin MHC presentation on HSCs and paired Ig-like receptor-B (PIR-B) on phagocytes. VCAM1 is also used by cancer cells to escape immune detection as its expression is upregulated in multiple cancers, including acute myeloid leukaemia (AML), where high expression associates with poor prognosis. In AML, VCAM1 promotes disease progression while VCAM1 inhibition or deletion reduces leukaemia burden and extends survival. These results suggest that VCAM1 engagement regulates a critical immune-checkpoint gate in the BM, and offers an alternative strategy to eliminate cancer cells via modulation of the innate immune tolerance.

Purpose: To evaluate the accuracy of the uterine artery pulsatility index (PI) for the diagnosis of pubertal onset in girls. Methods: Cross-sectional study of girls with normal pubertal development. Puberty was diagnosed by the presence of Tanner breast development score ≥2. All girls underwent pelvic ultrasound and Doppler imaging of the uterine arteries. We evaluated the uterine artery PI and uterine, endometrial, and ovarian measurements. We used ROC curves with cutoffs determined by Youden index for data analysis. Results: We included 169 girls aged 5-16 years who underwent 202 pelvic ultrasound examinations. Prepubertal girls had a significantly higher mean PI (mean, 6.70; SD, 2.15) than girls in initial puberty (mean, 4.14; SD, 1.55) and in late puberty (mean, 2.81; SD, 1.05) (P3.75 cm³ had a sensitivity of 73%, specificity of 95%, PPV of 97%, and accuracy of 79% to detect initial puberty. Conclusions: The significant reduction in the PI during pubertal development combined with increasing uterine volume can be a valuable, highly specific, noninvasive tool to confirm the onset of puberty.

Objectives Achieving glycated hemoglobin (A1C) and blood pressure targets is an important strategy for preventing chronic vascular complications in diabetes. Our aim in this study was to determine the proportion of type 2 diabetes patients who meet the recommended A1C and arterial blood pressure targets and to identify the determinants of failure to do so. Methods A cross-sectional study was conducted in an outpatient endocrine clinic at a university hospital. The A1C goal was 7% in general and 8% for patients with advanced chronic complications. Regarding blood pressure, the overall expected target was 140/90 mmHg. Results A total of 602 type 2 diabetes patients were analyzed: 62% were female, 14% self-reported as black, mean age was 63±11 years, mean diabetes duration was 17±9 years and median A1C was 8.0% (interquartile range, 7.0% to 9.5%). Macrovascular disease was present in 33% of the patients, diabetic retinopathy in 47%, peripheral neuropathy in 43% and diabetic kidney disease in 56%. Regarding metabolic control, 403 (67%) patients were not at the adjusted target A1C level, and being female, black, young and an insulin user were the main determinants of poor glycemic control. Regarding blood pressure, 348 (58%) patients were not at the recommended targets, and a more advanced age was the main associated factor. Conclusions Because more than half of type 2 diabetes outpatients do not meet the recommended A1C and blood pressure target values, there is a major call to overcome the therapeutic inertia and target treatment of patients on an individual basis.

The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. It is classified as central precocious puberty when premature maturation of the hypothalamic-pituitary-gonadal axis occurs, and as peripheral precocious puberty when there is excessive secretion of sex hormones, independent of gonadotropin secretion. Precocious sexual maturation is more common in girls, generally central precocious puberty of idiopathic origin. In boys, it tends to be linked to central nervous system abnormalities. Clinical evaluation should include a detailed history and physical examination, including anthropometric measurements, calculation of growth velocity, and evaluation of secondary sexual characteristics. The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. Hormonal assessment and imaging are required for diagnosis and identification of the etiology. Genetic testing should be considered if there is a family history of precocious puberty or other clinical features suggestive of a genetic syndrome. Long-acting gonadotropin-releasing hormone analogs are the standard of care for central precocious puberty management, while peripheral precocious puberty management depends on the etiology.Conclusion: The aim of this review is to address the epidemiology, etiology, clinical assessment, and management of precocious sexual maturation. What is Known: • The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. • Long-acting gonadotropin-releasing hormone agonist (GnRHa) is the standard of care for CPP management, and adequate hormone suppression results in the stabilization of pubertal progression, a decline in growth velocity, and a decrease in bone age advancement. What is New: • Most cases of precocious sexual maturation are gonadotropin-dependent and currently assumed to be idiopathic, but mutations in genes involved in pubertal development have been identified, such as MKRN3 and DLK1. • A different preparation of long-acting GnRHa is now available: 6-month subcutaneous injection.

The prostate is a hormone-responsive organ where testicular androgens drive the proliferation and survival of prostatic cells, ensuring the development and functioning of this gland throughout life. Androgen deprivation therapy leads to apoptosis of prostatic cells and organ regression, and is a cornerstone of prostate cancer and benign prostatic hypertrophy treatment. For several decades, androgen deprivation has been used as an adjuvant to external beam radiotherapy, however, emerging data suggests that the low rates of epithelial proliferation in the castrated prostate imparts radio-resistance. As proliferating cells exhibit increased sensitivity to radiation, we hypothesized that short bursts of synchronized epithelial proliferation, which can be achieved by exogeneous testosterone supplementation prior to targeted high-dose radiation, would maximize sustained prostate ablation, while minimizing damage to surrounding tissues. To test this hypothesis, we designed a novel computed-tomography (CT)-guided stereotactic prostate radiation therapy (CT-SPRT) technique to deliver a single high-dose 25 Gy fraction of X-ray radiation. Sustained prostatic cell ablation was assessed post CT-SPRT by measuring prostate weight, epithelial cell number, and relative contributions of luminal and basal epithelial populations in control and testosterone-pretreated glands. CT-SPRT was safely delivered with no observed damage to surrounding rectal and bladder tissues. Importantly, castrated mice that received a pulse of testosterone to induce synchronous cell proliferation prior to CT-SPRT exhibited significant sustained gland ablation compared to control mice. These results provide new insights in stereotactic radiotherapy sensitivity to maximize prostatic cell ablation and improve our understanding of prostate gland regeneration that can potentially lead to improved non-invasive therapies for benign prostatic hypertrophy and prostate cancer.

The aim of this study was to establish a peptidomic profile based on LC-MS/MS and random forest (RF) algorithm to distinguish the urinary peptidomic scenario of type 2 diabetes mellitus (T2DM) patients with different stages of diabetic kidney disease (DKD). Urine from 60 T2DM patients was collected: 22 normal (stage A1), 18 moderately increased (stage A2) and 20 severely increased (stage A3) albuminuria. A total of 1080 naturally occurring peptides were detected, which resulted in the identification of a total of 100 proteins, irrespective of the patients’ renal status. The classification accuracy showed that the most severe DKD (A3) presented a distinct urinary peptidomic pattern. Estimates for peptide importance assessed during RF model training included multiple fragments of collagen and alpha-1 antitrypsin, previously associated to DKD. Proteasix tool predicted 48 proteases potentially involved in the generation of the 60 most important peptides identified in the urine of DM patients, including metallopeptidases, cathepsins, and calpains. Collectively, our study lightened some biomarkers possibly involved in the pathogenic mechanisms of DKD, suggesting that peptidomics is a valuable tool for identifying the molecular mechanisms underpinning the disease and thus novel therapeutic targets.

Estimated glomerular filtration rate (eGFR) equations accuracy has been questioned in diabetes mellitus (DM). We aimed to evaluate the performance of three equations - European Kidney Function Consortium (EKFC), Full Age Spectrum (FAS), and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) - in healthy and type 2 DM participants.This cross-sectional studycompared eGFR equations withareference method: measured GFR (mGFR) byIn the 100 healthy adults included (aged 39 ± 15 years, 67% women, mean mGFR 107 ± 15, 2021 CKD-EPI 109 ± 14, FAS 107 ± 18 and EKFC 101 ± 12 mL/min/1.73 mIn healthy Brazilian adults, 2021 CKD-EPI, FAS and EKFC are suitable to estimate GFR. However, all equations underperform in people with type 2 DM.

Diabetes mellitus is the leading cause of end-stage renal disease, and uncontrolled hyperglycemia is directly related to the increased mortality in this setting. As kidney function decreases, it becomes more challenging to control blood glucose since the risk of hypoglycemia increases. Decreased appetite, changes in glycaemia homeostasis, along with reduced renal excretion of anti-hyperglycemic drugs tend to facilitate the occurrence of hypoglycemia, despite the paradoxical occurrence of insulin resistance in advanced kidney disease. Thus, in patients using insulin and/or oral anti-hyperglycemic agents, dynamic adjustments with drug dose reduction or drug switching are often necessary. Furthermore, in addition to consider these pharmacokinetics alterations, it is of utmost importance to choose drugs with proven cardio-renal benefits in this setting, such as sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists. In this review, we summarize the indications and contraindications, titration of doses and side effects of the available anti-hyperglycemic agents in the presence of advanced diabetic kidney disease (DKD) and dialysis, highlighting the risks and benefits of the different agents. Additionally, basic renal function assessment and monitoring of glycemic control in DKD will be evaluated in order to guide the use of drugs and define the glycemic targets to be achieved.

Introduction New antihyperglycemic medications have been proven to have cardiovascular (CV) and renal benefits in type 2 diabetes mellitus (T2DM); however, an evidence-based decision tree in specific clinical scenarios is lacking. Materials and Methods Systematic review and meta-analysis of randomized controlled trials (RCTs), with trial sequential analysis (TSA). Randomized controlled trial inclusion criteria were patients with T2DM from 1 of these subgroups: elderly, obese, previous atherosclerotic CV disease (ASCVD), previous coronary heart disease (CHD), previous heart failure (HF), or previous chronic kidney disease (CKD). Randomized controlled trials describing those subgroups with at least 48 weeks of follow-up were included. Outcomes: 3-point major adverse cardiovascular events (MACE), CV death, hospitalization due to HF, and renal outcomes. We performed direct meta-analysis with the number of events in the intervention and control groups in each subset, and the relative risk of the events was calculated. Results Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) were the only antihyperglycemic agents related to a reduction in CV events in different populations. For obese and elderly populations, GLP-1 RA were associated with benefits in 3-point MACE; for patients with ASCVD, both SGLT2i and GLP-1 RA had benefits in 3-point MACE, while for patients with CHD, only SGLT2i were beneficial. Conclusions SGLT2i and GLP-1 RA reduced CV events in selected populations: SGLT2i led to a reduction in events in patients with previous CHD, ASCVD, and HF. GLP-1 RA led to a reduction in CV events in patients with ASCVD, elderly patients, and patients with obesity. Trial sequential analysis shows that these findings are conclusive. This review opens a pathway towards evidence-based, personalized treatment of T2DM. Registration PROSPERO CRD42019132807

Objective: Our objective was to evaluate gestational weight gain (GWG) patterns and their relation to birth weight. Subjects and methods: We prospectively enrolled 474 women with gestational diabetes mellitus (GDM) at a university hospital (Porto Alegre, Brazil, November 2009-May 2015). GWG was categorized according to the 2009 Institute of Medicine guidelines; birth weight was classified as large (LGA) or small (SGA) for gestational age. Adjusted relative risks (aRRs) and 95% confidence intervals (95% CIs) were determined. Results: Adequate GWG occurred in 121 women [25.5%, 95% CI: 22, 30%]; excessive, in 180 [38.0%, 95% CI: 34, 43%]; and insufficient, in 173 [36.5%, 95% CI: 32, 41%]. In women with normal body mass index (BMI), the prevalence of SGA was higher in those with insufficient compared to adequate GWG (30% vs. 0%, p < 0.001). In women with BMI ≥ 25 kg/m2, excessive GWG increased the prevalence of LGA [aRR 2.58, 95% CI: 1.06, 6.29] and protected from SGA [aRR 0.25, 95% CI: 0.10, 0.64]. Insufficient vs. adequate GWG did not influence the prevalence of SGA [aRR 0.61, 95% CI: 0.31, 1.22]; insufficient vs. excessive GWG protected from LGA [aRR 0.46, 95% CI: 0.23, 0.91]. Conclusions: One quarter of this cohort achieved adequate GWG, indicating that specific ranges have to be tailored for GDM. To prevent inadequate birth weight, excessive GWG in women with higher BMI and less than recommended GWG in normal BMI women should be avoided; less than recommended GWG may be suitable for overweight and obese women. Arch Endocrinol Metab. 2018;62(1):48-56

Aims Maturity-Onset Diabetes of the Young (MODY) comprises a heterogeneous group of monogenic forms of diabetes caused by mutations in at least 14 genes, but mostly by mutations in Glucokinase ( GCK ) and hepatocyte nuclear factor-1 homeobox A ( HNF1A ). This study aims to establish a national registry of MODY cases in Brazilian patients, assessing published and unpublished data. Methods 311 patients with clinical characteristics of MODY were analyzed, with unpublished data on 298 individuals described in 12 previous publications and 13 newly described cases in this report. Results 72 individuals had GCK mutations, 9 described in Brazilian individuals for the first time. One previously unpublished novel GCK mutation, Gly178Ala, was found in one family. 31 individuals had HNF1A mutations, 2 described for the first time in Brazilian individuals. Comparisons of GCK probands vs HNF1A : age 16 ± 11 vs 35 ± 20 years; age at diagnosis 11 ± 8 vs 21 ± 7 years; BMI 19 ± 6 vs 25 ± 6 kg/m 2 ; sulfonylurea users 5 vs 83%; insulin users 5 vs 17%; presence of arterial hypertension 0 vs. 33%, all p Conclusions Most MODY cases in Brazil are due to GCK mutations. In agreement with other studied populations, novel mutations are common. Only 14% of patients with familial diabetes carry a HNF1A mutation. Diagnosis of other rare forms of MODY is still a challenge in Brazilian population, as well as adequate strategies to screen individuals for molecular diagnosis.

Background Maturity‐onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. To date, mutations in 11 genes have been frequently associated with this phenotype. In Brazil, few cohorts have been screened for MODY, all using a candidate gene approach, with a high prevalence of undiagnosed cases (MODY‐X). Methods We conducted a next‐generation sequencing target panel (tNGS) study to investigate, for the first time, a Brazilian cohort of MODY patients with a negative prior genetic analysis. One hundred and two patients were selected, of which 26 had an initial clinical suspicion of MODY‐GCK and 76 were non‐GCK MODY. Results After excluding all benign and likely benign variants and variants of uncertain significance, we were able to assign a genetic cause for 12.7% (13/102) of the probands. Three rare MODY subtypes were identified (PDX1/NEUROD1/ABCC8), and eight variants had not been previously described/mapped in genomic databases. Important clinical findings were evidenced in some cases after genetic diagnosis, such as MODY‐PDX1/HNF1B. Conclusion A multiloci genetic approach allowed the identification of rare MODY subtypes, reducing the large percentage of MODY‐X in Brazilian cases and contributing to a better clinical, therapeutic, and prognostic characterization of these rare phenotypes., Maturity‐onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance and, to date, mutations in 11 genes have been frequently associated with this phenotype. We have conducted a NGS target panel (tNGS) study to investigate, for the first time, a Brazilian cohort of MODY patients with a negative prior genetic analysis. One hundred and two patients were selected and we were able to assign a genetic cause for 12.7% (13/102) of the probands, with three rare MODY subtypes were identified (PDX1/NEUROD1/ABCC8).

The accuracy of estimated glomerular filtration rate (eGFR) equations in diabetes mellitus (DM) patients has been extensively questioned. We evaluated the performance of cystatin C-based equations alone or in combination with creatinine to estimate GFR in DM patients. A PRISMA-compliant systematic review was performed in the MEDLINE and Embase databases, with “diabetes mellitus” and “cystatin C” as search terms. Studies comparing cystatin C-based eGFR equations with measured GFR (mGFR) in DM patients were eligible. Accuracies P10, P15, P20, and P30 indicated the proportion of eGFR results within 10, 15, 20, and 30% of mGFR. Single-arm meta-analyses were conducted, and the Quality of Diagnostic Accuracy Studies-II tool (QUADAS-2) was applied. Twenty-three studies comprising 7065 participants were included, and 24 equations were analyzed in a broad range of GFRs. Meta-analyses were completed for 10 equations. The mean P30 accuracies of the equations ranged from 41% to 87%, with the highest values found with both CKD-EPI equations. Mean P10-P15 achieved 35% in the best scenario. A sensitivity analysis to evaluate different mGFR methods did not change results. In conclusion, cystatin C-based eGFR equations represent measured GFR fairly at best in DM patients, with high variability among the several proposed equations.

We tested whether individuals with autism spectrum disorder (ASD) are impaired in visuospatial working memory or in the use of the semantic system, in particular in categorization processes at the service of working memory. The performance of high-functioning individuals with ASD (N = 21) in a visual same-different task adapted from Lachmann and van Leeuwen [e.g., Lachmann, T.,van Leeuwen, C. (2010). Representational economy, not processing speed, determines preferred processing strategy of visual patterns. Acta Psychologica, 134(3), 290-298] was compared to those of typically developed controls (N = 25). In a categorical identity task, two successive patterns had to be judged as the same if they belonged to the same equivalence set (cf. Garner, W. R.,Clement, D. E. (1963). Goodness of pattern and pattern uncertainty. Journal of Verbal Learning and Verbal Behavior, 2, 446-452), including all possible rotation and reflection transformations (RR category), and as different otherwise. In a physical identity task, only patterns that matched in both shape and orientation had to be responded to as the same; all others, including category matches, had to be classified as different. Equivalence sets had different sizes (ESS). Earlier studies showed an increase in reaction time (RT) with increasing ESS and, for the physical identity task, a response conflict for category matching. Both of these effects were interpreted as evidence for a categorical code by which individual patterns are mentally represented. Assuming that categorization processes are deficient in individuals with ASD, we expected no ESS effects and, in the physical identity task, absence of a response conflict for these individuals. In contrast, we found individuals with ASD to be generally as sensitive to ESS as controls, and they showed a response conflict in the physical identity task. Thus, categorical processing seems to be intact in ASD. However, a strong overall group effect was found in RTs: Individuals with ASD are considerably slower than controls.

Thirty-two patients with diabetes negative for point mutations in GCK and HNF1A underwent further molecular screening of GCK, HNF1A, HNF4A, and HNF1B by MLPA analysis. We described the first Brazilian case of MODY5 due to a heterozygous whole-gene deletion in HNF1B, who developed rapidly progressive renal failure and death.

Haematopoietic stem cells (HSCs) are maintained by bone marrow niches in vivo

In the present study, we aimed to evaluate the hypothesis that the reported discrepancy in the performance of verbal fluency in individuals with autism spectrum disorder (ASD), characterized by an overall word productivity impairment with normal clustering and switching abilities, may be due to an initiation deficit. In the present study, we evaluated the temporal dynamics of both letter and semantic verbal fluency tasks in a sample of 20 young adults with high-functioning ASD compared with a sample of 20 gender-, age-, education-, and verbal-IQ-matched participants. We first compared both the word productivity and the qualitative analysis of clustering and switching abilities during the entire task to replicate the discrepancy reported in the literature. Importantly, we next analyzed both word productivity and clustering and switching abilities in two time intervals (0-30 s and 31-60 s), as it was our primary interest to evaluate the functioning of the initial component of word retrieval. Directly supporting the idea that the discrepancy found between an impairment in global word productivity combined with normal clustering and switching strategies is due to an activation and initiation deficit, we observed an abnormal performance for the ASD group in the first time period only. We interpreted these results to be preliminary findings of deficits in initiation processes in ASD.

Semantic meaning can be extracted from pictures presented very briefly, in the order of tens of milliseconds. This ultra-rapid categorization processing appears to respect a coarse-to-fine path where lower level representations of concepts, or more detailed information, need additional time. We question whether variations in the levels of typicality of the target-item would implicate additional processing for correct classification, both in neurotypical (NT) individuals and with autism spectrum disorder (ASD). Previous research in ASD points out that atypical exemplars of a category might be abnormally processed (e.g., longer times in identifying a penguin as a bird), an observation that we further tested with a rapid serial visual presentation (RSVP) task. In this study, we applied a RSVP task, with four different presentation times (13, 27, 50, and 80 ms) and with typical and atypical exemplars to a group of NT individuals and a sample of individuals with ASD. We found, overall, a strong effect of typicality with a higher detection rate for typical items. In addition, we observed a group x typicality x duration interaction. We interpret these findings in the light of the competences of the feedforward sweep of information through our visual system. info:eu-repo/semantics/publishedVersion

Background According to the Global Diabetes Plan, a unified health system with preventive and educational strategies is essential to proper diabetes care and primary settings should be the main site of care. In Brazil, there is limited access to outpatient hospital diabetes services, while primary-care diabetes support is underutilized. Telemedicine can be a useful adjunct to support discharge of stable patients with type 2 diabetes to the primary care setting. In this paper, we present a randomized controlled trial (RCT) protocol designed to evaluate the effects of telehealth support for stable type 2 diabetes patients discharged from hospital outpatient diabetes clinics. Methods We designed a RCT. Patients with stable type 2 diabetes (glycated hemoglobin

CONTEXT AND OBJECTIVE: The prevalence and characteristics of gestational diabetes mellitus (GDM) have changed over time, reflecting the nutritional transition and changes in diagnostic criteria. We aimed to evaluate characteristics of women with GDM over a 20-year interval. DESIGN AND SETTING: Comparison of two pregnancy cohorts enrolled in different periods, in university hospitals in Porto Alegre, Brazil: 1991 to 1993 (n = 216); and 2009 to 2013 (n = 375). METHODS: We applied two diagnostic criteria to the cohorts: International Association of Diabetes and Pregnancy Study Groups (IADPSG)/World Health Organization (WHO); and National Institute for Health and Care Excellence (NICE). We compared maternal-fetal characteristics and outcomes between the cohorts and within each cohort. RESULTS: The women in the 2010s cohort were older (31 ± 7 versus 30 ± 6 years), more frequently obese (29.4% versus 15.2%), with more hypertensive disorders (14.1% versus 5.6%) and at increased risk of cesarean section (adjusted relative risk 1.8; 95% confidence interval: 1.4 - 2.3), compared with those in the 1990s cohort. Neonatal outcomes such as birth weight category and hypoglycemia were similar. In the 1990s cohort, women only fulfilling IADPSG/WHO or only fulfilling NICE criteria had similar characteristics and outcomes; in the 2010s cohort, women only diagnosed through IADPSG/WHO were more frequently obese than those diagnosed only through NICE (33 ± 8 kg/m2 versus 28 ± 6 kg/m2; P < 0.001). CONCLUSION: The epidemic of obesity seems to have modified the profile of women with GDM. Despite similar neonatal outcomes, there were differences in the intensity of treatment over time. The IADPSG/WHO criteria seemed to identify a profile more associated with obesity. RESUMO CONTEXTO E OBJETIVO: Prevalência e características do diabetes mellitus gestacional (DMG) modificaram-se com o tempo, refletindo transição nutricional e diferentes critérios diagnósticos. Nosso objetivo foi avaliar características de gestações com DMG em intervalo de 20 anos. TIPO DE ESTUDO E LOCAL: Comparação de duas coortes gestacionais arroladas em diferentes períodos, em hospitais universitários de Porto Alegre, Brasil: 1991 a 1993 (n = 216) e 2009 a 2013 (n = 375). MÉTODOS: Aplicamos dois critérios diagnósticos às coortes: International Association of Diabetes and Pregnancy Study Groups (IADPSG)/Organização Mundial de Saúde (OMS); e National Institute for Health and Care Excellence (NICE). Comparamos características e desfechos materno-fetais entre as coortes e dentro de cada uma. RESULTADOS: Na coorte dos anos 2010, as mulheres eram mais velhas (31 ± 7 versus 30 ± 6 anos), obesas (29,4% versus 15,2%), apresentaram mais distúrbios hipertensivos (14,1% versus 5,6%) e risco aumentado de cesariana (risco relativo ajustado 1,8; intervalo de confiança de 95% 1,4 - 2,3), comparadas às da coorte de 1990. Desfechos neonatais, como categoria do peso ao nascer e hipoglicemia, foram semelhantes. Na coorte de 1990, essas características e desfechos foram semelhantes nas mulheres que preenchiam apenas um dos critérios; na de 2010, mulheres diagnosticadas apenas pelo IADPSG/OMS eram mais obesas (33 ± 8 kg/m2 versus 28 ± 6 kg/m2, P < 0,001) do que as diagnosticadas apenas pelo NICE. CONCLUSÃO: A epidemia de obesidade parece ter modificado o perfil de mulheres com DMG. Embora desfechos neonatais sejam semelhantes, houve diferenças na intensidade de tratamento ao longo do tempo. O critério da IADPSG/OMS parece identificar um perfil mais associado à obesidade.

In the present study we aim at providing further evidences for the validity of an initiation processes impairment in autism spectrum disorder (ASD). We applied different verbal fluency tasks designed to decrease or enhance this limitation. A group of high-functioning individuals with ASD and a group of typically developed individuals matched for -age, -IQ and -education, were tested in three verbal fluency tasks. In task 1, we replicated previous findings of an initiation impairment. In tasks 2 and 3, with simple manipulations, we observed that the differences between the groups were respectively eliminated or enhanced. We have not only provided further evidence of impairments in the initiation of a response, but we remarkably show how to circumvent them.

Late-night salivary cortisol (LNSC) is one of the most reliable tests to screen for endogenous Cushing syndrome. This test is simple, inexpensive and noninvasive and has high sensitivity and specificity. The aim of our study was to analyze the putative influence of age, gender and body mass index (BMI) on LNSC levels in a healthy population.Cross-sectional study conducted in healthy adults. Midnight saliva samples were collected at home. Participants refrained from teeth brushing, eating or drinking for 2 h prior to collection. Salivary cortisol measured by electrochemiluminescence immunoassay (ECLIA). The study was approved by the Ethics Committee of the hospital (number 140073).We evaluated 122 nonsmoking healthy volunteers. Mean age was 35±14 years (range, 18-74 years); 63% were women. Mean BMI was 24±3 kg/m2, blood pressure 115/74 mmHg and fasting plasma glucose 4.8±0.5 mmol/L. LNSC presented a non-Gaussian distribution; the median was 3.58 (range, 0.55-8.55) nmol/L (0.13 [range, 0.02-0.31] μg/dL), and the 97.5th percentile (P97.5) was 8.3 nmol/L (0.3 μg/dL). Multiple linear regression disclosed a significant positive association between salivary cortisol levels and age (r2=0.21, p0.001), but no association with gender (p=0.105) or BMI (p=0.119). Accordingly, participants aged50 years had significantly higher salivary cortisol as compared to those aged50 years (5.24 nmol/L [0.19 μg/dL] vs. 3.31 nmol/L [0.12 μg/dL], respectively, p0.001).The maximum reference value (P97.5) of LNSC was set at 8.3 nmol/L (0.3 μg/dL) using ECLIA. Advanced age was associated with higher LNSC levels, with no evident influence of gender or BMI.

Objectives The aim of this study was to evaluate the rate of eGFR reporting in Southern Brazilian laboratories. Design and methods The eGFR automatic reporting, as assessed by Modification of Diet in Renal Disease (MDRD) and/or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equations, was evaluated in a representative cross-sectional sample. A standardized questionnaire to obtain this information was given out by mail or email. Results Five-hundred fifty laboratories, evenly distributed in the different state regions, completed the questionnaire. The eGFR was automatically reported by 54 (9.8%) laboratories, and the MDRD was the most commonly used equation (94.5%). The Jaffe methods were the most employed technique (94%) to measure serum creatinine. Conclusion The automatic eGFR reporting rate was unacceptably low, emphasizing the crucial role of educating medical teams and laboratories on the importance of having these tools available to optimize detection of renal disease and proper treatment.

Mesenchymal stem cells (MSCs) are self-renewing precursor cells that can differentiate into bone, fat, cartilage, and stromal cells of the bone marrow. Recent studies suggest that MSCs themselves are critical for forming a niche that maintains hematopoietic stem cells (HSCs). The ease by which human MSC-like and stromal progenitor cells can be isolated from the bone marrow and other tissues has led to the rapid development of clinical investigations exploring their anti-inflammatory properties, tissue preservation capabilities, and regenerative potential. However, the identity of genuine MSCs and their specific contributions to these various beneficial effects have remained enigmatic. In this article, we examine the definition of MSCs and discuss the importance of rigorously characterizing their stem cell activity. We review their role and that of other putative niche constituents in the regulation of bone marrow HSCs. Additionally, how MSCs and their stromal progeny alter immune function is discussed, as well as potential therapeutic implications.

Background Gestational diabetes mellitus (GDM) and vitamin D deficiency have been associated with increased risk of adverse perinatal outcomes but the consequences of both conditions simultaneously present in pregnancy have not yet been evaluated. Our objective was to study the influence of vitamin D deficiency in neonatal outcomes of pregnancies with GDM. Methods 184 pregnant women with GDM referred to specialized prenatal monitoring were included in this cohort and had blood sampled for 25-hydroxyvitamin D measurement. Vitamin D was measured by chemiluminescence and deficiency was defined as < 20 ng/mL. Participants were followed until puerperium and adverse neonatal outcomes were evaluated. Results Newborns of women with vitamin D deficiency had higher incidences of hospitalization in intensive care units (ICU) (32 vs 19%, P = 0.048), of hypoglycemia (any, 17.3 vs 7.1%, P = 0.039requiring ICU, 15.3 vs 3.6%, P = 0.008), and were more frequently small for gestational age (SGA) (17.3 vs 5.9%, P = 0.017). After adjustment, relative risk (RR) for hypoglycemia requiring ICU was 3.63 (95%CI 1.09–12.11) and for SGA was 4.32 (95%CI 1.75–10.66). The incidence of prematurity, jaundice and shoulder dystocia was no statistically different between groups. Conclusions In this cohort of pregnant women with GDM, vitamin D deficiency was associated with a major increase in the incidence of adverse neonatal outcomes such as SGA newborns and neonatal hypoglycemia.

The objective of this study was to evaluate the effect of metabolic syndrome (MetS) and its individual components on the renal function of patients with type 2 diabetes mellitus (DM). A cross-sectional study was performed in 842 type 2 DM patients. A clinical and laboratory evaluation, including estimated glomerular filtration rate (eGFR) calculated by the modification of diet in renal disease formula, was performed. MetS was defined according to National Cholesterol Education Program - Adult Treatment Panel III criteria. Mean patient age was 57.9 +/- 10.1 years and 313 (37.2%) patients were males. MetS was detected in 662 (78.6%) patients. A progressive reduction in eGFR was observed as the number of individual MetS components increased (one: 98.2 +/- 30.8; two: 92.9 +/- 28.1; three: 84.0 +/- 25.1; four: 83.8 +/- 28.5, and five: 79.0 +/- 23.0; P0.001). MetS increased the risk for low eGFR (60 mL x min(-1) x 1.73 (m2)(-1)) 2.82-fold (95%CI = 1.55-5.12, P0.001). Hypertension (OR = 2.2, 95%CI = 1.39-3.49, P = 0.001) and hypertriglyceridemia (OR = 1.62, 95%CI = 1.19-2.20, P = 0.002) were the individual components with the strongest associations with low eGFR. In conclusion, there is an association between MetS and the reduction of eGFR in patients with type 2 DM, with hypertension and hypertriglyceridemia being the most important contributors in this sample. Interventional studies should be conducted to determine if treatment of MetS can prevent renal failure in type 2 DM patients.

Background: Current data are conflicting about the influence of gender on cystatin C concentrations. The goal of this study was to determine the reference interval for serum cystatin C in normal Brazilian subjects, taking into account the influence of gender. Methods: Ninety-seven healthy volunteers, aged 18–70 years, 44% male, had glomerular filtration rate (GFR) measured using a 51Cr-EDTA method and estimated with the Modification of Diet in Renal Disease (MDRD) study equation. Serum cystatin C was measured using a turbidimetric method, and creatinine by the Jaffe method. Results: Mean serum cystatin C was not significantly different between males and females, 0.62±0.12 vs. 0.65±0.12 mg/L, respectively (p=0.26). However, median serum creatinine was significantly higher in men [97 (80–115) vs. 80 (53–88) μmol/L; p=0.0001]. There were also no significant differences between genders with respect to GFR measured using 51Cr-EDTA (103±14 for males and 106±19 mL/min/1.73 m2 for females, p=0.47), and estimated with the MDRD equation (86±12 vs. 83±16 mL/min/1.73 m2, respectively, p=0.24). Conclusions: There was no effect of gender on serum cystatin C, as well as on measured and estimated GFR. Clin Chem Lab Med 2010;48:405–8.

Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by overexpressing combinations of factors such as Oct4, Sox2, Klf4, and c-Myc. Reprogramming is slow and stochastic, suggesting the existence of barriers limiting its efficiency. Here we identify senescence as one such barrier. Expression of the four reprogramming factors triggers senescence by up-regulating p53, p16INK4a, and p21CIP1. Induction of DNA damage response and chromatin remodeling of the INK4a/ARF locus are two of the mechanisms behind senescence induction. Crucially, ablation of different senescence effectors improves the efficiency of reprogramming, suggesting novel strategies for maximizing the generation of iPS cells.

Pheochromocytoma resection is often complicated by intra-operative hypertension and post-resection hypotension. Factors associated with these hemodynamic alterations are not well defined. The aim of this study was to analyse the clinical-laboratory features associated with hemodynamic parameters during pheochromocytoma resection. Twenty-seven patients submitted to tumor resection - either open (no.=18) or video laparoscopic - between 1978-2007 were included. Nineteen received pre-operative alpha-blockers. Intra-operative hemodynamic data analysed were: maximum and minimum mean arterial blood pressure (MABP), no. of severe hypertensive (systolic BP200 mmHg) and hypotensive episodes (MABP60 mmHg), maximum and minimum heart rate (HR), no. of episodes of tachycardia and bradycardia, need to receive iv intra-operative treatment for hypertension and hypotension and the volume of fluids administered during surgery. Patients were 39.4+/-14.4-yr-old, 66% women. Intra-operative hemodynamic parameters were not different in patients submitted to open or video laparoscopic resection. Maximum intraoperative HR and the percentage of patients with HR100 beats/min were higher in patients without pre-operative alpha- blocker treatment (no.=8). Pre-operative urinary vanylmandelic acid was positively associated with intra-operative maximum MABP (r=0.535, p=0.047) and with maximum transoperative systolic BP (r=0.805, p=0.016). Pre-operative urinary catecholamine (Pearson correlation r=0.575, p=0.03) and vanylmandelic acid (Pearson correlation r=0.605, p=0.04) levels were associated with maximum intra- operative MABP, adjusted for the presence of pheochromocytoma symptoms, surgical approach and pre-operative alpha-blockers. In conclusion, the degree of pre-operative catecholamine secretion was the most important aspect of transoperative BP control.

BACKGROUND: The prevalence of chronic complications in type 2 diabetes mellitus (DM) is higher in black patients. The reason for this finding is still unknown. The objective of this study was to analyze the micro and macrovascular risk factor profile of type 2 DM patients without advanced diabetic nephropathy according to ethnicity. METHODS: A cross-sectional multicentric regional study was conducted evaluating 780 patients. All patients were submitted to clinical and laboratory evaluation. Ethnicity was self-reported as white (n = 585) or black (n = 195). RESULTS: Black patients had lower triglycerides [115 (35-892) vs. 152 (34-1236) mg/dl; P

In this study, we aimed to evaluate further the functioning and structuring of the semantic system in autism spectrum disorders (ASD). We analyzed the performance of 19 high-functioning young adults with ASD and a group of 20 age-, verbal IQ- and education-matched individuals with the Proactive Interference (PI) Paradigm to evaluate semantic functioning in ASD (Experiment 1). In Experiment 2, we analyzed the performances of both groups in a PI paradigm with manipulation of the level of typicality. In both experiments, we observed significant effects of trial and group but no trial by group interactions, which we interpreted as robust evidence of preserved PI (build up effect) that indicated the preservation of semantic mechanisms of encoding and retrieval.

How HSCs populate the fetal liver Hematopoietic stem cells (HSCs) undergo dramatic expansion in the fetal liver before migrating to their definitive site in the bone marrow. Khan et al. identify portal vessel–associated Nestin + NG2 + pericytes as critical HSC niche components (see the Perspective by Cabezas-Wallscheid and Trumpp). The portal vessel niche and HSCs expand according to fractal geometries, suggesting that niche cells—rather than factors expressed by the niche—drive HSC proliferation. After birth, arterial portal vessels transform into portal veins, and lose Nestin + NG2 + pericytes. When this happens, the niche is lost and HSCs migrate away from the neonatal liver. Science , this issue p. 176 ; see also p. 126

The role of glycated hemoglobin (A1C) in the screening and diagnosis of posttransplantation diabetes mellitus (PTDM) is still not entirely understood. We evaluated the use of A1C test in renal transplant recipients at four months after transplantation.A total of 122 out of 274 patients without previous diabetes that underwent kidney transplantation were enrolled. ROC curve was used to analyze the performance of A1C to diagnose PTDM considering OGTT as the reference standard.OGTT identified 32 (26.2%) patients with PTDM, whereas A1C≥6.5% (48 mmol/mol) identified only 16 patients. A1C showed moderate accuracy to detect PTDM in the ROC curve [AUC 0.832 (95% CI 0.740-0.924, p0.001)]. A1C of 5.8% (40 mmol/mol) was the equilibrium point (sensitivity 75% and specificity 72.2%) and A1C≥6.2% (44 mmol/mol) showed high specificity of 93.3%.A1C≥6.5% (48 mmol/mol) is not enough to be used alone in the diagnosis of PTDM. The combined use of A1C cut-off points of ≤5.8% (40 mmol/mol) and ≥6.2% (44 mmol/mol) would reduce the number of OGTT by 85%. The use of an algorithm with A1C test in combination with FPG and/or 2h-PG proved to be the most efficient strategy to diagnose or rule out PTDM.

Aims Gestational diabetes mellitus (GDM) is a prevalent and potentially serious condition which may put both mothers and neonates at risk. The current recommendation for diagnosis is the oral glucose tolerance test (OGTT). This study aimed to determine the usefulness of HbA1c test as a diagnostic tool for GDM as compared to the traditional criteria based on the OGTT. Methods This was a diagnostic test accuracy study. We performed OGTT and HbA1c test in women attending prenatal visits at a tertiary hospital. GDM was defined according to WHO1999 or ADA/WHO 2013 criteria. ROC curve was used to evaluate the diagnostic performance of HbA1c. Sensitivity, specificity and likelihood ratios for different HbA1c cut-off points were calculated. Results Of the 262 women in the third trimester of gestation enrolled in the study, 86 (33%) were diagnosed with GDM. Only five of these women presented HbA1c ≥48 mmol/mol (6.5%). This cut-off point presented 100% specificity but very low sensitivity (7%). Based on ROC curve, and considering OGTT as the reference criterion, HbA1c ≥40 mmol/mol (5.8%) showed adequate specificity in diagnosing GDM (94.9%) but low sensitivity (26.4%). Unlike, HbA1c values of 31 mmol/mol (5.0%) presented adequate sensitivity (89.7%) but low specificity (32.6%) to detect GDM. For women with HbA1c ≥40 mmol/mol (5.8%), the positive and negative likelihood ratios were 5.14 (95%CI 2.49–10.63) and 0.78 (0.68–0.88), respectively. The post-test probability of GDM was about 40%, representing a 4.0-fold increase in the mean pre-test probability. This cut-off point could eliminate the need for the unpleasant and laborious OGTT tests in almost one third of cases, as 38% of patients with GDM may be diagnosable by HbA1c test alone. Conclusions Our results show that combined HbA1c and OGTT measurements may be useful in diagnosing GDM.

Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects ∼40% of type 1 and type 2 diabetic patients. It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion (UAE) in the absence of other renal diseases. Diabetic nephropathy is categorized into stages: microalbuminuria (UAE >20 μg/min and ≤199 μg/min) and macroalbuminuria (UAE ≥200 μg/min). Hyperglycemia, increased blood pressure levels, and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Screening for microalbuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with micro- and macroalbuminuria should undergo an evaluation regarding the presence of comorbid associations, especially retinopathy and macrovascular disease. Achieving the best metabolic control (A1c 1.0 g/24 h and increased serum creatinine), using drugs with blockade effect on the renin-angiotensin-aldosterone system, and treating dyslipidemia (LDL cholesterol

OBJECTIVE To evaluate the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) in type 2 diabetic patients with GFR >60 mL/min/1.73 m2. RESEARCH DESIGN AND METHODS This was a cross-sectional study including 105 type 2 diabetic patients. GFR was measured by 51Cr-EDTA method and estimated by the MDRD and CKD-EPI equations. Serum creatinine was measured by the traceable Jaffe method. Bland-Altman plots were used. Bias, accuracy (P30), and precision were evaluated. RESULTS The mean age of patients was 57 ± 8 years; 53 (50%) were men and 90 (86%) were white. Forty-six (44%) patients had microalbuminuria, and 14 (13%) had macroalbuminuria. 51Cr-EDTA GFR was 103 ± 23, CKD-EPI GFR was 83 ± 15, and MDRD-GFR was 78 ± 17 mL/min/1.73 m2 (P < 0.001). Accuracy (95% CI) was 67% (58–74) for CKD-EPI and 64% (56–75) for MDRD. Precision was 21 and 22, respectively. CONCLUSIONS The CKD-EPI and MDRD equations pronouncedly underestimated GFR in type 2 diabetic patients.

Therefore, these contradictory evidences reinforce that a better understanding of calcium metabolism and its relation to blood pressure in pregnancy is needed.We did not measure parathyroid hor-mone (PTH) levels or other parameters related to calcium metabolism, like min-eral bone density. Some authors suggest an important association of high PTH levels to preeclampsia and secondary hyperparathyroidism was associated to a more than twice risk of preeclampsia in women with vitamin D deficiency in a large American cohort.

Thirty-two Brazilian families with MODY phenotype were screened for GCK and HNF1A mutations. GCK mutations were found in 8 families, all patients with mild asymptomatic hyperglycaemia; 3 of them are novel: p.Asp365Asn, p.Gly81Asp and p.Val253Leu. Previously described mutations in HNF1A were found in 2 families.

Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with "brittle T1DM", who have severe hypoglycemia without adrenergic symptoms (hypoglycemia unawareness), islet transplantation may be a therapeutic option to restore both insulin secretion and hypoglycemic perception. The Edmonton group demonstrated that most patients who received islet infusions from more than one donor and were treated with steroid-free immunosuppressive drugs displayed a considerable decline in the initial insulin independence rates at eight years following the transplantation, but showed permanent C-peptide secretion, which facilitated glycemic control and protected patients against hypoglycemic episodes. Recently, data published by the Collaborative Islet Transplant Registry (CITR) has revealed that approximately 50% of the patients who undergo islet transplantation are insulin independent after a 3-year follow-up. Therefore, islet transplantation is able to successfully decrease plasma glucose and HbA1c levels, the occurrence of severe hypoglycemia, and improve patient quality of life. The goal of this paper was to review the human islet isolation and transplantation processes, and to describe the establishment of a human islet isolation laboratory at the Endocrine Division of the Hospital de Clinicas de Porto Alegre - Rio Grande do Sul, Brazil.

Research into the extra-skeletal functions of vitamin D has been expanding in recent years. During pregnancy, maternal vitamin D status may be of concern because of the key role of this vitamin in fetal skeletal development and due to the association between hypovitaminosis D and adverse maternal-fetal outcomes. Therefore, the objective of this manuscript was to review the maternal-fetal impact of gestational vitamin D deficiency and the benefits of vitamin D supplementation during pregnancy. A literature search was performed in PubMed and Embase employing the following keywords: vitamin D deficiency, pregnancy, 25-hydroxyvitamin D, and hypovitaminosis D. All relevant articles in English language published since 1980 were analysed by the two authors. Neonatal complications derived from vitamin D deficiency include low birth weight, growth restriction, and respiratory tract infection. In the mother, vitamin D deficiency has been associated with altered glucose homeostasis and increased incidence of gestational diabetes mellitus, pre-eclampsia, and bacterial vaginosis. However, the current state of the evidence is controversial for some other endpoints and the actual benefit of vitamin D supplementation in pregnancy remains unclear. Additional longitudinal studies may clarify the actual impact of vitamin D deficiency during pregnancy, and randomised trials are required to define the benefits of vitamin D supplementation in reducing the incidence of adverse outcomes in the mother and infant.

background Vitamin D deficiency in pregnancy has been associated with an increased risk of preeclampsia. However, the association between serum vitamin D and blood pressure in pregnant women has been scarcely evaluated, particularly in women with a high risk of developing hypertensive disorders of pregnancy. We sought to evaluate the association between serum 25-hydroxyvitamin D and blood pressure in pregnant women with gestational diabetes mellitus (GDM). methods A cohort of 184 pregnant women with GDM was followed during the third trimester of pregnancy and early puerperium. Blood pressure was recorded in all prenatal visits, and serum vitamin D was measured by chemiluminescence immunoassay. Pearson’s coefficients and multiple linear regressions were used to study predictors of blood pressure levels. results Women with vitamin D insufficiency (

Objectives: The aims of this study were to estimate the local rate of postpartum diabetes screening after gestational diabetes mellitus (GDM) pregnancies, and to identify clinical variables associated with retesting rates and with the persistence of decreased glucose tolerance. Subjects and methods: Prospective cohort of GDM women with prenatal delivery at a specialized center, from November 2009 to May 2012. All women were advised to schedule a 6 weeks postpartum 75-g oral glucose tolerance test (OGTT). Results: Of the 209 women included, 108 (51.7%) returned to be tested with fasting plasma glucose (n = 14), OGTT (n = 93) or random glucose (n = 1). Return was associated with lower parity rate (2 vs. 3, p < 0.001) and higher pregnancy 2-h OGTT (165 vs. 155 mg/dL, p = 0.034), but not with socio-demographic characteristics. Four women (3.7%) had diabetes, 22 (20.4%) had impaired fasting glucose or impaired glucose tolerance. Persistent hyperglycemia was associated with a positive family history of diabetes (relative risk - RR 2.41, p = 0.050), diagnostic 2-h OGTT in pregnancy (RR 1.01, p = 0.045), insulin use during pregnancy (RR 2.37, p = 0.014), and cesarean section (RR 2.61, p = 0.015). Conclusions: Even though postpartum abnormalities were frequent in GDM, rates of postpartum diabetes screening were undesirably low. As no specific clinical profile defines who will adhere to postpartum testing, it is essential to encourage all women to reevaluate their glucose status, particularly those with a family history of diabetes and more severe hyperglycemia. Arq Bras Endocrinol Metab. 2014;58(2):197-204 Objetivos: Os objetivos foram estimar a taxa de reavaliação de diabetes pós-parto em mulheres com diabetes melito gestacional (DMG) e identificar fatores associados ao retorno e à persistência das alterações glicêmicas. Sujeitos e métodos: Coorte prospectiva de mulheres com DMG atendidas em ambulatório de pré-natal especializado, de novembro de 2009 a maio de 2012. Todas foram orientadas a agendar o teste oral de tolerância à glicose (TOTG) a partir da sexta semana pós-parto. Resultados: Das 209 mulheres arroladas na gestação, 108 (51,7%) foram avaliadas após o parto: 14 com glicemia de jejum, 93 com o TOTG e uma com glicemia ao acaso. O retorno para reavaliação foi associado com menor paridade (2 vs. 3, p < 0,001) e com glicemia de 2-h mais elevada no TOTG diagnóstico (165 vs. 155 mg/dL, p = 0,034). Diabetes foi diagnosticado em quatro mulheres (3,7%) e pré-diabetes em 22 (20,4%). Análise multivariada evidenciou que a história familiar de diabetes (risco relativo – RR 2,41, p = 0,050), a glicemia de 2 horas no TOTG da gestação (RR 1,01, p = 0,045), o uso de insulina na gestação (RR 2,37, p = 0,014) e a taxa de cesariana (RR 2,61, p = 0,015) foram os fatores associados à persistência da hiperglicemia. Conclusões: O retorno para reavaliação foi baixo, embora as alterações glicêmicas tenham sido frequentes. Como não houve fatores que indiquem quais mulheres retornarão, estratégias para aumentar a adesão são necessárias, especialmente quando há história familiar ou o DMG foi mais grave. Arq Bras Endocrinol Metab. 2014;58(2):197-204

Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation seems to correct the overdiagnosis of chronic kidney disease (CKD) provided by Modification of Diet in Renal Disease (MDRD) equation. However, this point has not been tested in some ethnic groups. This study investigated the performance of MDRD and CKD-EPI equations in South Brazilian individuals. Methods: This cross-sectional study included 354 individuals including healthy volunteers, diabetic and nondiabetic individuals with or without CKD. Glomerular filtration rate (GFR) was measured by the 51Cr-EDTA single- injection method (51Cr-GFR). Accuracy (P30), bias, and Bland-Altman agreement plots were evaluated. Results: In the group as a whole, 51Cr-GFR was 87 ± 37 (6-187), CKD-EPI eGFR, 82 ± 30 (6-152), and MDRD eGFR, 77 ± 28 (6-156) mL/min/1.73 m2 (p < 0.001 for all comparisons). Analyzing the subset of individuals with 51Cr-GFR < 60 mL/min/1.73 m2, P30 values were, respectively, 76% and 84% for MDRD and for CKD-EPI (p < 0.001) while for 51Cr-GFR ≥ 60 mL/min/1.73 m2, P30 values were 57.5% for both equations (p = 1.000). For MDRD and CKD-EPI, mean bias were negative for GFRs < 60 (–11 vs. –12, p = 0.221) and positive for values > 60 (16 vs. 9, p < 0.001). In multivariate analysis, absolute bias was unfavorably influenced by measured GFR > 60 (for MDRD) and being diabetic or younger (for CKD-EPI). Conclusions: CKD-EPI reduces GFR underestimation in individuals with GFRs > 60, but still presents a quite low accuracy at this GFR range. Moreover, it tends to overestimate GFR in subjects with GFRs < 60 mL/min/1.73 m2. CKD stages 1 and 2, diabetes and young age had a negative influence on the performance of the equations.

Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Endocrinol Unit, Postgrad Fellowship Program Endocrinol, Porto Alegre, RS, Brazil

OBJECTIVE To evaluate the urinary albumin excretion rate (UAER) and the glomerular filtration rate (GFR) of single-kidney type 2 diabetic patients (SKD) and of single-kidney non-diabetic patients (SKN). RESEARCH DESIGN AND METHODS Patients who had only one kidney for at least 5 years, with no renal disease or hypertension at the time of the nephrectomy and with no calculus or systemic disease at the time of the evaluation, were included in this controlled cross-sectional study A total of 20 SKD (8 men, age 62 ± 9 years; diabetes duration 8.5 ± 7 years), 17 SKN (2 men, age 57 ± 13 years), and 184 type 2 diabetic patients who were matched to the single-kidney diabetic group for age, sex, and BMI were studied. UAER was measured by immunoturbidimetry in timed 24-h sterile urine, and GFR was determined by the 51Cr-EDTA single-injection method. RESULTS SKD patients presented a higher proportion (8 of 20, 40%) of microalbuminuria (UAER 20-200 μg/min) than SKN patients (3 of 17, 17.6%) and type 2 diabetic patients (37 of 184, 20%). SKD patients presented a higher proportion of macroalbuminuria (UAER >200 μg/min; 6 of 20, 30%) than SKN patients (1 of 17, 6%) but were similar to type 2 diabetic patients (43 of 184, 23%). The GFRs of normoalbuminuric SKN (71.7 ± 21.4 ml · min−1 · 1.73 m−2) and SKD patients (73.0 ± 21.5 ml · min−1 · 1.73 m−2) were similar but higher than the one-kidney GFR (GFR ÷ 2) of the age-, sex-, and BMI-matched normal individuals (50.5 ± 9.0 ml · min−1 · 1.73 m−2) and normoalbuminuric type 2 diabetic patients (54.0 ± 11.6 ml · min−1 · 1.73 m−2). CONCLUSIONS Increased GFR related to single-kidney status confers an increased risk of developing renal disease in the presence of diabetes.

A 36 year old man with a large goiter was suspected of having iodide (I − ) transport defect based on low thyroidal and salivary gland radioiodide uptake. Thyroid surgery was performed, because thyroid cytology could not exclude a malignancy. Sequencing of the entire Na + /I − symporter (NIS) cDNA derived from thyroidal mRNA revealed a homozygous substitution of the normal cytosine in nucleotide (nt) 1163 with an adenine, resulting in a stop (TGA) at codon 272. This nonsense mutation produces a truncated NIS with undetectable I − transport activity when expressed into COS-7 cells. Genotyping confirmed that the propositus was homozygous for the mutation whereas his unaffected mother, son, and paternal aunt were heterozygous. This nt substitution was not detected in any of 50 normal individuals, ruling out a polymorphism. While the homozygous mutant NIS-272X causes congenital hypothyroidism, expression of one normal allele in the heterogygote (C272X) is sufficient to maintain active thyroidal I − uptake and function.

Aim To evaluate the influence of age of onset and duration of diabetes on the positivity of glutamic acid decarboxylase antibody (GADA) in South-Brazilian type 1 diabetes mellitus (DM) patients. Methods GADA was evaluated in 92 patients with type 1 diabetes, in 147 gestational DM patients, and in 59 subjects with normal glucose tolerance. Results Type 1 patients with positive GADA ( N = 44, 48%) were older at the onset of diabetes (22 ± 9 versus 18 ± 10 y, P = 0.043) and had a shorter DM duration (12 ± 8 versus 19 ± 9 y, P < 0.001), as compared with negative GADA patients. A logistic regression with antibody positivity as the dependent variable and diabetes duration as the independent variable, showed that the shorter diabetes duration was related to the presence of the antibody with an odds ratio (OR) = 5.6; (CI 95% = 2.1–14.6); P < 0.001. Another model, with age at diagnosis as the independent variable, did not show any association with antibody positivity. However, analysing only men, a shorter DM duration (OR = 6.5; CI = 1.7–24.0; P = 0.006), and also a higher age at diagnosis (OR = 5.5; CI = 1.5–21.0; P = 0.01) were significantly related to the antibody positivity. The performance of GADA was similar in up to 15 y of duration of DM ( P = 0.78), but significantly diminished with higher duration ( P = 0.001). Conclusion GADA testing is a helpful tool in the diagnosis of type 1 DM starting in young adults and older individuals. Even though the positivity rate declines along the course of disease, it still provides useful information up to 15 y after the diabetes diagnosis.

Over recent years, hair has become the ideal matrix for retrospective investigation of chronic abuse, including for tramadol. However, in order to exclude the possibility of external contamination, it is also important to quantify simultaneously its main metabolite, O-desmethyltramadol (M1), which presence in hair reflects systemic exposure. In the present study a methodology aimed at the simultaneous quantification of tramadol and M1 in human hair was developed and validated for the first time. After decontamination of hair samples (60 mg), tramadol and M1 were extracted with methanol in an ultrasonic bath (~5 h). Purification was performed by solid-phase extraction using mixed-mode extraction cartridges. Subsequently to derivatization, analysis was performed by gas chromatography-electron impact/mass spectrometry (GC-EI/MS). The method proved to be selective. The regression analysis for both analytes was shown to be linear in the range of 0.1-20.0 ng/mg with correlation coefficients of 0.9995 and 0.9997 for tramadol and M1, respectively. The coefficients of variation oscillated between 3.85 and 13.24%. The limits of detection were 0.03 and 0.02 ng/mg, and the lower limits of quantification were 0.08 and 0.06 ng/mg for tramadol and M1, respectively. The proof of applicability was performed in hair samples from six patients undergoing tramadol therapy. All samples were positive for tramadol and M1.

OBJECTIVE To evaluate the evolution of glomerular filtration rate (GFR) and albumin excretion rate (AER) of normofiltering (NF) and hyperfiltering (HF) normoalbuminuric NIDDM patients. RESEARCH DESIGN AND METHODS A longitudinal study of 32 normoalbuminuric (AER < 20 μg/min) NIDDM patients and 20 age-, sex-, and BMI-matched normal individuals was done. Subjects had their GFR (51Cr-labeled EDTA single-injection method) measured at entry and after 40 and 60 months. At entry, 13 NIDDM patients had GFR values above the upper limit of the normal range in our laboratory (> 137 ml · min−1 x 1.73 m−2) and were considered as HF. In NIDDM patients, the 24-h AER (radioimmunoassay), HbA1c, urinary urea, and mean arterial blood pressure (MBP) were analyzed at entry and after 40 and 60 months. RESULTS There was a significant decline of GFR in NIDDM patients and normal subjects at 60 months. The decline was significantly greater in HF patients (−0.61 ml · min−1.month−1; P = 0.001) than in NF (−0, 18) and control subjects (−0, 14); the rate of change in NF and control subjects was the same (P > 0.05). In stepwise multiple regression analysis, with GFR decline as the dependent variable and GFR and AER at baseline, age and change in MBP, change in urinary urea, change in HbA1c, and change in therapy as independent variables, only baseline GFR (R2 = 0.19, P = 0.002) and age (R2 = 0.31, P = 0.048) were significantly related to the outcome. At 60 months, AER raised > 20 μg/min in three HF and in four NF patients. In logistic regression analysis, only higher initial AER (although still in the normal range; P = 0.037) and an increase in urinary urea (P = 0.021) were significantly related to the later development of microalbuminuria. CONCLUSIONS The GFR of normoalbuminuric NIDDM patients declines significantly over 60 months. This decline is associated to baseline GFR and age. HF NIDDM patients show a faster decline in GFR than NF patients, whose GFR falls at a rate that is compatible with the age-related change observed in normal control subjects. The development of microalbuminuria is related to higher baseline AER and to increases in urinary urea and is similar in NF (4 of 19) and HF (3 of 13) NIDDM patients (P > 0.05).