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Background: Wearable sensors are rapidly evolving, particularly in health care, due to their ability to facilitate continuous or on-demand physiological monitoring., Objective: This study aimed to design and validate a wearable sensor prototype incorporating photoplethysmography (PPG) and long-range wide area network technology for heart rate (HR) measurement during a functional test., Methods: We conducted a transversal exploratory study involving 20 healthy participants aged between 20 and 30 years without contraindications for physical exercise. Initially, our laboratory developed a pulse wearable sensor prototype for HR monitoring. Following this, the participants were instructed to perform the Incremental Shuttle Walk Test while wearing the Polar H10 HR chest strap sensor (the reference for HR measurement) and the wearable sensor. This test allowed for real-time comparison of HR responses between the 2 devices. Agreement between these measurements was determined using the intraclass correlation coefficient (ICC 3.1 ) and Lin concordance correlation coefficient. The mean absolute percentage error was calculated to evaluate reliability or validity. Cohen d was used to calculate the agreement's effect size., Results: The mean differences between the Polar H10 and the wearable sensor during the test were -2.6 (95% CI -3.5 to -1.8) for rest HR, -4.1 (95% CI -5.3 to -3) for maximum HR, -2.4 (95% CI -3.5 to -1.4) for mean test HR, and -2.5 (95% CI -3.6 to -1.5) for mean recovery HR. The mean absolute percentage errors were -3% for rest HR, -2.2% for maximum HR, -1.8% for mean test HR, and -1.6% for recovery HR. Excellent agreement was observed between the Polar H10 and the wearable sensor for rest HR (ICC 3.1 =0.96), mean test HR (ICC 3.1 =0.92), and mean recovery HR (ICC 3.1 =0.96). The agreement for maximum HR (ICC 3.1 =0.78) was considered good. By the Lin concordance correlation coefficient, the agreement was found to be substantial for rest HR (r c =0.96) and recovery HR (r c =0.96), moderate for mean test HR (r c =0.92), and poor for maximum HR (r c =0.78). The power of agreement between the Polar H10 and the wearable sensor prototype was large for baseline HR (Cohen d=0.97), maximum HR (Cohen d=1.18), and mean recovery HR (Cohen d=0.8) and medium for mean test HR (Cohen d= 0.76)., Conclusions: The pulse-wearable sensor prototype tested in this study proves to be a valid tool for monitoring HR at rest, during functional tests, and during recovery compared with the Polar H10 reference device used in the laboratory setting., (©Fernanda Laís Loro, Riane Martins, Janaína Barcellos Ferreira, Cintia Laura Pereira de Araujo, Lucio Rene Prade, Cristiano Bonato Both, Jéferson Campos Nobre Nobre, Mariane Borba Monteiro, Pedro Dal Lago. Originally published in JMIR Biomedical Engineering (http://biomsedeng.jmir.org), 11.12.2024.)

We aimed to assess the prevalence, patient allocation adequacy, and mortality of adults with sepsis in Brazilian emergency departments (ED) in a point-prevalence 3-day investigation of patients with sepsis who presented to the ED and those who remained there due to inadequate allocation. Allocation was considered adequate if the patient was transferred to the intensive care unit (ICU), ward, or remained in the ED without ICU admission requests. Prevalence was estimated using the total ED visit number. Prognostic factors were assessed with logistic regression. Of 33,902 ED visits in 74 institutions, 183 were acute admissions (prevalence: 5.4 sepsis per 1000 visits [95% confidence interval (CI): 4.6-6.2)], and 148 were already in the ED; totaling 331 patients. Hospital mortality was 32% (103/322, 95% CI 23.0-51.0). Age (odds ratio (OR) 1.22 [95% CI 1.10-1.37]), Sequential Organ Failure Assessment (SOFA) score (OR 1.41 [95% CI 1.28-1.57]), healthcare-associated infections (OR 2.59 [95% CI 1.24-5.50]) and low-resource institution admission (OR 2.65 [95% CI 1.07-6.90]) were associated with higher mortality. Accredited institutions (OR 0.42 [95% CI 0.21-0.86]) had lower mortality rates. Allocation within 24 h was adequate in only 52.8% of patients (public hospitals: 42.4% (81/190) vs. private institutions: 67.4% (89/132, p < 0.001) with 39.2% (74/189) of public hospital patients remaining in the ED until discharge, of whom 55.4% (41/74) died. Sepsis exerts high burden and mortality in Brazilian EDs with frequent inadequate allocation. Modifiable factors, such as resources and quality of care, are associated with reduced mortality., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Objective: To determine, through a systematic review with meta-analysis, the prevalence of food addiction (FA) using the Yale Food Addiction Scale (YFAS) and its derivatives exploring possible factors associated with the prevalence of FA in several contexts., Methods: The following databases were searched: MEDLINE, ScienceDirect, LILACS, PsycArticles, CENTRAL, Greylit.org, and OpenGrey.eu. Studies that assessed FA using YFAS were included. Two independent reviewers assessed the eligibility of each report. Random-effects meta-analysis was performed to calculate the weighted prevalence of FA. Subgroup analyses and meta-regression were conducted to explore sources of heterogeneity., Results: Of the 6425 abstracts reviewed, 272 studies were included. The weighted mean prevalence of FA diagnosis was 20% (95% CI: 18%; 21%). The prevalence of FA was higher in individuals with clinical diagnosis of binge eating (55%; 95% CI 34%; 75%). The prevalence in clinical samples was higher compared to non-clinical samples. Two studies included children only and no studies included only elderly people., Conclusions: Food addiction is a topic in which there has been a significant growth in studies. The highest prevalence was found in the group of participants with eating disorders and weight disorders. More studies with children and the elderly are needed., (© 2021 Eating Disorders Association and John Wiley & Sons Ltd.)

CYP3A5 is the primary CYP3A subfamily enzyme expressed in the human kidney and its aberrant expression may contribute to a broad spectrum of renal disorders. Pharmacogenetic studies have reported inconsistent linkages between CYP3A5 expression and hypertension, however, most investigators have considered CYP3A5*1 as active and CYP3A5*3 as an inactive allele. Observations of gender specific differences in CYP3A5*3/*3 protein expression suggest additional complexity in gene regulation that may underpin an environmentally responsive role for CYP3A5 in renal function. Reconciliation of the molecular mechanism driving conditional restoration of functional CYP3A5*3 expression from alternatively spliced transcripts, and validation of a morpholino-based approach for selectively suppressing renal CYP3A5 expression, is the focus of this work. Morpholinos targeting a cryptic splice acceptor created by the CYP3A5*3 mutation in intron 3 rescued functional CYP3A5 expression in vitro, and salt-sensitive cellular mechanisms regulating splicing and conditional expression of CYP3A5*3 transcripts are reported. The potential for a G-quadruplex (G4) in intron 3 to mediate restored splicing to exon 4 in CYP3A5*3 transcripts was also investigated. Finally, a proximal tubule microphysiological system (PT-MPS) was used to evaluate the safety profile of morpholinos in proximal tubule epithelial cells, highlighting their potential as a therapeutic platform for the treatment of renal disease.

Background and Aim: 11β-Hydroxysteroid dehydrogenase 1 has been implicated in insulin resistance (IR) in the setting of metabolic disorders, and single nucleotide polymorphisms (SNPs) in its encoding gene (HSD11B1) have been associated with type 2 diabetes and metabolic syndrome. In type 1 diabetes (T1D), IR has been related to the development of chronic complications. We investigated the association of HSD11B1 SNPs with microvascular complications and with IR in a Brazilian cohort of T1D individuals., Materials and Methods: Five SNPs were genotyped in 466 T1D individuals (57% women; median of 37 years old, diabetes duration of 25 years and HbA1c of 8.4%)., Results: The minor allele T of rs11799643 was nominally associated with diabetic retinopathy (OR = 0.52; confidence interval [CI] 95% = 0.28-0.96; P = .036). The minor allele C of rs17389016 was nominally associated with overt diabetic kidney disease (DKD) (OR = 1.90; CI 95% = 1.07-3.37; P = .028). A follow-up study revealed that 29% of the individuals lost ≥5 mL min -1 × 1.73 m 2 per year of the estimated glomerular filtration rate (eGFR). In these individuals (eGFR decliners), C allele of rs17389016 was more frequent than in non-decliners (OR = 2.10; CI 95% = 1.14-3.89; P = .018). Finally, minor allele T of rs846906 associated with higher prevalence of arterial hypertension, higher body mass index and waist circumference, thus conferring risk to a lower estimated glucose disposal rate, a surrogate marker of insulin sensitivity (OR = 1.23; CI 95% = 1.06-1.42; P = .004)., Conclusion: SNPs in the HSD11B1 gene may confer susceptibility to DKD and to IR in T1D individuals., (© 2020 John Wiley & Sons Ltd.)

Rationale : Compliance with sepsis bundles is associated with better outcomes, but information to support structural actions that might improve compliance is scarce. Few studies have evaluated bundle compliance in different time periods, with conflicting results. Objectives : To evaluate the association of sepsis identification during the daytime versus during the nighttime and on weekdays versus weekends with 3-hour sepsis treatment bundle compliance. Methods : This was an observational, multicenter study including patients with sepsis admitted between 2010 and 2017 to 10 hospitals in Brazil. Our exposures of interest were daytime (7:00 a.m.-6:59 p.m.) versus nighttime (7:00 p.m.-6:59 a.m.) and weekdays (Monday 7:00 a.m.-Friday 6:59 p.m.) versus weekends (Friday 7:00 p.m.-Monday 6:59 a.m.). Our primary outcome was full compliance with the 3-hour sepsis treatment bundles. We adjusted by potential confounding factors with multivariable logistic regression models. Results : Of 11,737 patients (8,733 sepsis and 3,004 septic shock), 3-hour bundle compliance was 79.1% and hospital mortality was 24.7%. The adjusted odds ratio (adjOR) for 3-hour full bundle compliance for patients diagnosed during the daytime versus during the nighttime was 1.35 (95% confidence interval [CI], 1.23-1.49; P  < 0.001) and was more pronounced in the emergency department (adjOR, 1.55; 95% CI, 1.35-1.77; P  < 0.001) than in nonemergency areas (adjOR, 1.19; 95% CI, 1.04-1.37; P  = 0.014). Overall, there was no association between diagnosis on the weekends versus on weekdays and 3-hour full bundle compliance (adjOR, 1.08; 95% CI, 0.98-1.19; P  = 0.115), although there was an association among those diagnosed in nonemergency areas (adjOR, 1.15; 95% CI, 1.00-1.32; P  = 0.047). The lower compliance observed for sepsis diagnosed during the nighttime was more evident 2 years after implementation of the quality improvement initiative. Conclusions : Compliance with sepsis bundles was associated with the moment of sepsis diagnosis. The place of diagnosis and the time from campaign implementation were factors modifying this association. Our results support areas for better design of quality improvement initiatives to mitigate the influence of the period of sepsis diagnosis on treatment compliance.

Introduction: Using a discovery/validation approach we investigated associations between a panel of genes selected from a transcriptomic study and the estimated glomerular filtration rate (eGFR) decline across time in a cohort of type 1 diabetes (T1D) patients. Experimental: Urinary sediment transcriptomic was performed to select highly modulated genes in T1D patients with rapid eGFR decline (decliners) vs. patients with stable eGFR (non-decliners). The selected genes were validated in samples from a T1D cohort ( n = 54, mean diabetes duration of 21 years, 61% women) followed longitudinally for a median of 12 years in a Diabetes Outpatient Clinic. Results: In the discovery phase, the transcriptomic study revealed 158 genes significantly different between decliners and non-decliners. Ten genes increasingly up or down-regulated according to renal function worsening were selected for validation by qRT-PCR; the genes CYP4F22 , and PMP22 were confirmed as differentially expressed comparing decliners vs. non-decliners after adjustment for potential confounders. CYP4F22, LYPD3, PMP22, MAP1LC3C, HS3ST2, GPNMB, CDH6 , and PKD2L1 significantly modified the slope of eGFR in T1D patients across time. Conclusions: Eight genes identified as differentially expressed in the urinary sediment of T1D patients presenting different eGFR decline rates significantly increased the accuracy of predicted renal function across time in the studied cohort. These genes may be a promising way of unveiling novel mechanisms associated with diabetic kidney disease progression., (Copyright © 2020 Monteiro, Pelaes, Santos-Bezerra, Thieme, Lerario, Oba-Shinjo, Machado, Passarelli, Marie and Corrêa-Giannella.)

Rationale: Although proposed as a clinical prompt to sepsis based on predictive validity for mortality, the Quick Sepsis-related Organ Failure Assessment (qSOFA) score is often used as a screening tool, which requires high sensitivity. Objectives: To assess the predictive accuracy of qSOFA for mortality in Brazil, focusing on sensitivity. Methods: We prospectively collected data from two cohorts of emergency department and ward patients. Cohort 1 included patients with suspected infection but without organ dysfunction or sepsis (22 hospitals: 3 public and 19 private). Cohort 2 included patients with sepsis (54 hospitals: 24 public and 28 private). The primary outcome was in-hospital mortality. The predictive accuracy of qSOFA was examined considering only the worst values before the suspicion of infection or sepsis. Measurements and Main Results: Cohort 1 contained 5,460 patients (mortality rate, 14.0%; 95% confidence interval [CI], 13.1-15.0), among whom 78.3% had a qSOFA score less than or equal to 1 (mortality rate, 8.3%; 95% CI, 7.5-9.1). The sensitivity of a qSOFA score greater than or equal to 2 for predicting mortality was 53.9% and the 95% CI was 50.3 to 57.5. The sensitivity was higher for a qSOFA greater than or equal to 1 (84.9%; 95% CI, 82.1-87.3), a qSOFA score greater than or equal to 1 or lactate greater than 2 mmol/L (91.3%; 95% CI, 89.0-93.2), and systemic inflammatory response syndrome plus organ dysfunction (68.7%; 95% CI, 65.2-71.9). Cohort 2 contained 4,711 patients, among whom 62.3% had a qSOFA score less than or equal to 1 (mortality rate, 17.3%; 95% CI, 15.9-18.7), whereas in public hospitals the mortality rate was 39.3% (95% CI, 35.5-43.3). Conclusions: A qSOFA score greater than or equal to 2 has low sensitivity for predicting death in patients with suspected infection in a developing country. Using a qSOFA score greater than or equal to 2 as a screening tool for sepsis may miss patients who ultimately die. Using a qSOFA score greater than or equal to 1 or adding lactate to a qSOFA score greater than or equal to 1 may improve sensitivity.Clinical trial registered with www.clinicaltrials.gov (NCT03158493).

Background and Aims: Since hyperglycemia promotes inflammation by different pathways and inflammation participates in the development of chronic diabetes complications, we investigated the association between the leukotriene (LT) pathway and microvascular diabetes complications., Methods and Results: Quantitative polymerase chain reaction was employed to quantify the expression of ALOX5 (encodes 5-lipoxygenase), LTB4R (encodes one of the LTB4 receptors), and MYD88 in peripheral blood mononuclear cells from 164 type 1 diabetes (T1D) individuals presenting or not diabetes kidney disease, retinopathy, peripheral neuropathy, and cardiovascular autonomic neuropathy (CAN); 26 nondiabetic subjects were included as controls. LTB4 plasmatic concentrations were also evaluated. The expression of LTB4R was significantly higher in T1D individuals than in controls. T1D individuals with microvascular complications presented lower MYD88 mRNA expression when compared to those without microvascular complications. Higher LTB4 concentrations were found in individuals with CAN versus without CAN. The observation of two distinct subgroups of T1D individuals in the correlation analyses motivated us to evaluate the characteristics of each one of these groups separately. The group presenting higher expression of ALOX5 and of LTB4R also presented higher values of HbA 1 C, of fructosamine, and of plasmatic LTB4., Conclusion: In the diabetes setting, the LT pathway is not only activated by hyperglycemia but is also modulated by the status of the autonomic nervous system., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Daniele P. Santos-Bezerra et al.)

Aims/introduction: Epigenetics participate in the pathogenesis of metabolic memory, a situation in which hyperglycemia exerts prolonged deleterious effects even after its normalization. We tested the hypothesis that genetic variants in an epigenetic gene could predispose to diabetes complications., Material and Methods: We assessed the frequency of five single-nucleotide polymorphisms in the gene encoding deoxyribonucleic acid methytransferase 1 (DNMT1; rs8112895, rs7254567, rs11085721, rs17291414 and rs10854076), and their associations with diabetic kidney disease, retinopathy, distal polyneuropathy and autonomic cardiovascular neuropathy in 359 individuals with long-term type 1 diabetes., Results: None of the single-nucleotide polymorphisms studied was significantly associated with the presence of chronic complications in the overall population. However, after sex stratification, the minor allele C of rs11085721 conferred risk for cardiovascular neuropathy in women after adjustment for confounding variables (odds ratio 2.32; 95% confidence interval 1.26-4.33; P = 0.006)., Conclusions: The fact that heterozygous mutations in DNMT1 are associated with hereditary sensory autonomic neuropathy provides plausibility to the present finding. If confirmed in independent samples, it suggests that genetic variants in epigenetic genes might predispose to more or fewer epigenetic changes in the face of similar metabolic derangements triggered by hyperglycemia, constituting the "genetics of epigenetics" for microvascular diabetes complications., (© 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aims: Given the participation of oxidative stress in the pathogenesis of diabetic complications, we evaluated, in type 1 diabetes (T1D) individuals, the association between diabetic retinopathy (DR) and functional single nucleotide polymorphisms (SNPs) in regulatory regions of two genes belonging to the antioxidant glutathione (GSH) system: rs17883901 in GCLC and rs713041 in GPX4., Methods: A cross-sectional case-control study included 288 individuals (61% women, 34[±11] years old, diabetes duration of 22[±9] years, mean [±SD]) sorted according to DR stages: absence of DR (ADR), non-proliferative DR (NPDR) and proliferative DR (PDR). SNPs were genotyped by real-time PCR using fluorescent labelled probes. Logistic regression models with adjustment for confounding covariates were employed., Results: The presence of at least one T-allele of rs17883901 in GCLC was an independent risk factor for PDR (OR 4.13, 95% CI 1.38-13.66, p = 0.014) in a polytomous regression model (PDR versus ADR). The presence of at least one T-allele of rs713041 in GPX4 conferred protection against PDR (OR 0.30, 95% CI 0.11-0.80, p = 0.017) in female T1D individuals., Conclusion: The functional SNPs rs17883901 and rs713041 modulate the risk for PDR in the studied population of T1D individuals, widening the spectrum of candidate genes for this complication., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The failure to predict kidney toxicity of new chemical entities early in the development process before they reach humans remains a critical issue. Here, we used primary human kidney cells and applied a systems biology approach that combines multidimensional datasets and machine learning to identify biomarkers that not only predict nephrotoxic compounds but also provide hints toward their mechanism of toxicity. Gene expression and high-content imaging-derived phenotypical data from 46 diverse kidney toxicants were analyzed using Random Forest machine learning. Imaging features capturing changes in cell morphology and nucleus texture along with mRNA levels of HMOX1 and SQSTM1 were identified as the most powerful predictors of toxicity. These biomarkers were validated by their ability to accurately predict kidney toxicity of four out of six candidate therapeutics that exhibited toxicity only in late stage preclinical/clinical studies. Network analysis of similarities in toxic phenotypes was performed based on live-cell high-content image analysis at seven time points. Using compounds with known mechanism as reference, we could infer potential mechanisms of toxicity of candidate therapeutics. In summary, we report an approach to generate a multidimensional biomarker panel for mechanistic de-risking and prediction of kidney toxicity in in vitro for new therapeutic candidates and chemical entities., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Drug-induced kidney injury, largely caused by proximal tubular intoxicants, limits development and clinical use of new and approved drugs. Assessing preclinical nephrotoxicity relies on animal models that are frequently insensitive; thus, potentially novel techniques - including human microphysiological systems, or "organs on chips" - are proposed to accelerate drug development and predict safety. Polymyxins are potent antibiotics against multidrug-resistant microorganisms; however, clinical use remains restricted because of high risk of nephrotoxicity and limited understanding of toxicological mechanisms. To mitigate risks, structural analogs of polymyxins (NAB739 and NAB741) are currently in clinical development. Using a microphysiological system to model human kidney proximal tubule, we exposed cells to polymyxin B (PMB) and observed significant increases of injury signals, including kidney injury molecule-1 KIM-1and a panel of injury-associated miRNAs (each P < 0.001). Surprisingly, transcriptional profiling identified cholesterol biosynthesis as the primary cellular pathway induced by PMB (P = 1.22 ×10-16), and effluent cholesterol concentrations were significantly increased after exposure (P < 0.01). Additionally, we observed no upregulation of the nuclear factor (erythroid derived-2)-like 2 pathway, despite this being a common pathway upregulated in response to proximal tubule toxicants. In contrast with PMB exposure, minimal changes in gene expression, injury biomarkers, and cholesterol concentrations were observed in response to NAB739 and NAB741. Our findings demonstrate the preclinical safety of NAB739 and NAB741 and reveal cholesterol biosynthesis as a potentially novel pathway for PMB-induced injury. To our knowledge, this is the first demonstration of a human-on-chip platform used for simultaneous safety testing of new chemical entities and defining unique toxicological pathway responses of an FDA-approved molecule.

Background: The death of epithelial cells in the proximal tubules is thought to be the primary cause of AKI, but epithelial cells that survive kidney injury have a remarkable ability to proliferate. Because proximal tubular epithelial cells play a predominant role in kidney regeneration after damage, a potential approach to treat AKI is to discover regenerative therapeutics capable of stimulating proliferation of these cells., Methods: We conducted a high-throughput phenotypic screen using 1902 biologically active compounds to identify new molecules that promote proliferation of primary human proximal tubular epithelial cells in vitro ., Results: The primary screen identified 129 compounds that stimulated tubular epithelial cell proliferation. A secondary screen against these compounds over a range of four doses confirmed that eight resulted in a significant increase in cell number and incorporation of the modified thymidine analog EdU (indicating actively proliferating cells), compared with control conditions. These eight compounds also stimulated tubular cell proliferation in vitro after damage induced by hypoxia, cadmium chloride, cyclosporin A, or polymyxin B. ID-8, an inhibitor of dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), was the top candidate identified as having a robust proproliferative effect in two-dimensional culture models as well as a microphysiologic, three-dimensional cell culture system. Target engagement and genetic knockdown studies and RNA sequencing confirmed binding of ID-8 to DYRK1A and upregulation of cyclins and other cell cycle regulators, leading to epithelial cell proliferation., Conclusions: We have identified a potential first-in-class compound that stimulates human kidney tubular epithelial cell proliferation after acute damage in vitro ., (Copyright © 2018 by the American Society of Nephrology.)

Purpose: To evaluate the acute response of natural killer (NK) cell subsets of chronic kidney disease patients submitted to intradialytic exercise in a randomized crossover study., Methods: Nine patients were submitted to a single bout of 20-min intradialytic exercise and a control hemodialysis (HD) session with an interval of 7 days between them. Peripheral blood sample was collected at baseline, during HD and immediately after HD in each trial to evaluate the peripheral frequency of NK cells and their subsets (CD3-CD56 bright and CD3-CD56 dim ), systemic cortisol concentrations, C-reactive protein (CRP), creatine kinase activity (CK), and urea and creatinine levels., Results: HD therapy induced a significant decrease in NK cells frequency (p = 0.039), NK CD3-CD56 bright cells (p = 0.04), and CD3-CD56 dim cells (p = 0.036). On the other hand, no significant alterations were observed in NK cells and NK subsets during and after intradialytic exercise trial (p > 0.05). Neither trial altered CRP levels or serum CK activity during and after HD therapy (p > 0.05). However, HD therapy increased cortisol concentrations after HD therapy (p = 0.034)., Conclusions: This study suggests the potential role of intradialytic exercise to prevent the decrease in peripheral frequency of NK cell subsets during HD therapy. Moreover, moderate intensity intradialytic exercise did not exacerbate the systemic inflammation or induce muscle damage during HD therapy.

Although inflammasome plays a well-known role in animal models of renal injury, limited studies in humans are available, and its participation in diabetic kidney disease (DKD) remains unknown. Aim of this study was to elucidate the contribution of inflammasome genetics in the development of DKD in type-1 diabetes (T1D). The association of functional variants in inflammasome genes with DKD was assessed by multivariate analysis in a retrospective and in a prospective cohort. NLRP1 rs2670660 and rs11651270 polymorphisms were significantly associated with a decrease risk to develop DKD (p adj <0.01), and rs11651270 also with a lower risk of new renal events during follow-up (p adj =0.01). Supporting these findings, diabetes metabolites (glycated albumin and high glucose) were able to modulate NLRP1 expression. This study is the first to suggest a protective role of NLRP1 in DKD, highlighting an emerging role of NLRP1 as a homeostatic factor against metabolic stress., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Quantitative polymerase chain reaction was employed to quantify expression of two genes coding for advanced glycation end-product receptors [RAGE ( AGER) and AGER1 ( DDOST)] and of the gene coding the deacetylase SIRT1 ( SIRT1) in peripheral blood mononuclear cells from type 1 diabetes patients without [Group A, n = 35; 28.5 (24-39) years old; median (interquartile interval)] or with at least one microvascular complication [Group B, n = 117; 34.5 (30-42) years old]; 31 healthy controls were also included. In a subgroup of 48 patients, daily advanced glycation end-products intake before blood collection was assessed. Lower expression of DDOST was found in patients than in controls after adjustment for sex, age, use of statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Higher expressions of AGER, DDOST and SIRT1 were observed in Group A. Stratifying by complications, AGER and DDOST expressions were higher in those without retinopathy and without diabetic kidney disease, respectively, compared to patients with these complications. Patients using statins or angiotensin receptor blockers presented higher expression of DDOST. Expression of SIRT1 was higher in patients consuming ≥12,872 KU daily of advanced glycation end-products. Although AGER, DDOST and SIRT1 are differently expressed in peripheral blood mononuclear cells from type 1 diabetes patients with and without microvascular complications, they are also influenced by dietary advanced glycation end-products and by statins and angiotensin receptor blockers.

This study aimed to evaluate the immune profile of lean and overweight-obese COPD patients. Forty patients with moderate to very severe COPD were divided into lean group (n=20; aged 62.00±8.91years; BMI 22.26±1.65kg/m 2 ) or overweight-obese group (n=20; aged 65.40±6.69years; BMI 29.19±3.55kg/m 2 ). The cytokine profile (IL-2, IL-4, IL-6, IL-10, INF-γ, and TNF-α) was evaluated through the Cytometric Bead Array technique, and the expression of CD4, CD8, CD25, CD45ra, CD45ro, CD69, CD195(CCr5) and HLA-DR were evaluated in CD3+ T-cells. Overweight-obese COPD group had lower levels of IL-2 (p=0.01) and higher INF-γ levels (p=0.02) and IL-6 (p=0.003) than lean COPD. Lean COPD patients had higher CD25+ (p=0.01), CCr5 (p=0.04) and HLA-DR (p=0.007) expression on T cell surface compared to overweight-obese COPD participants. These changes are related to immune dysfunction of obesity, and excess of fat mass in COPD can be a key factor to low T-cells activation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Nutrition is one of the most important factors that affect animal performance, and it therefore also impacts on financial results in beef systems. In this way, finding the best strategy for feeding supplements is of paramount importance. Aiming to evaluate the effect of supplement feeding strategies for beef cows in the last third of gestation, two experiments were conducted. In Experiment 1, 35 pregnant Nellore cows were assigned to a completely randomized design with four treatments: control, which received no supplement; supplementation for the last 30 d of gestation (30-d; 3.0 kg/d); supplementation for the last 60 d of gestation (60-d; 1.5 kg/d); or supplementation for the last 90 d of gestation (90-d; 1.0 kg/d). All supplemented treatments received the same total amount of supplement throughout the experiment: 90 kg (20% of crude protein). A second experiment (Experiment 2) was delineated to evaluate the effects of the amounts offered in Experiment 1 on intake and metabolism. Four multiparous pregnant Nellore cows were assigned to a 4 × 4 Latin square design, with periods of 15 d each., Results: There was a linear effect of the number of days of supplementation on calving body weight (BW; P  < 0.05) and a quadratic effect on BW change from parturition to d 31 post-calving ( P  < 0.05), with cows on the 60-d strategy losing less BW post-calving. No difference was found in offspring birth BW ( P  > 0.10). A significant linear effect on interval from parturition to conception ( P  < 0.05) was observed, with the highest calving to conception interval being observed in the 90-d strategy. The level of supplementation did not affect forage intake or neutral detergent fiber digestibility ( P  > 0.10). Nitrogen excreted through urine tended to increase linearly with the level of supplementation ( P  < 0.10)., Conclusion: Providing 1.5 kg of supplement during the last 60 d of gestation improves cow performance after calving, reducing the magnitude of BW lost, and reduces the number of days from calving to re-conception in the following breeding season compared to the usually recommended period of supplementation of 90 d pre-partum.

Introduction: The application of expiratory positive airway pressure (EPAP) in patients with COPD during exercise may reduce dynamic hyperinflation, while, on the other hand, it can increase the resistive work of breathing. Therefore, we evaluated the effects of 2 intensities of EPAP during exercise on tolerance, dynamic hyperinflation, and dyspnea in subjects with moderate to very severe COPD., Methods: We performed a cross-sectional, experimental, 4-visit study. In visit 1, subjects performed symptom-limited cycling incremental cardiopulmonary exercise test (CPET). In visits 2-4, at least 48 h apart, in a randomized order, subjects performed constant CPET without EPAP, EPAP with 5 cm H 2 O (EPAP5), or EPAP with 10 cm H 2 O (EPAP10)., Results: The study included 15 non-hypoxemic subjects ranging from moderate to very severe COPD (mean FEV 1 = 35 ± 11% predicted). Increasing intensities of EPAP during constant CPET tended to cause progressive reduction in exercise tolerance ( P = .11). Of note, 10 of 15 subjects demonstrated significantly shorter average exercise duration with EPAP10 compared to the test without EPAP (-151 ± 105 s, P = .03 or -41 ± 26%). Minute ventilation increment was constrained by EPAP, secondary to a limited increase in tidal volume ( P = .01). Finally, dyspnea sensation and serial measurements of inspiratory capacity during exercise were similar when comparing the three interventions at isotime and at end-constant CPETs., Conclusions: The application of EPAP5 or EPAP10 during exercise tended to cause a progressive reduction in exercise tolerance in subjects with COPD without improvement in dyspnea or dynamic hyperinflation at equivalent exercise duration., (Copyright © 2017 by Daedalus Enterprises.)

Objective: We aimed to assess the results of a quality improvement initiative in sepsis in an emerging setting and to analyze it according to the institutions' main source of income (public or private)., Design: Retrospective analysis of the Latin American Sepsis Institute database from 2005 to 2014., Settings: Brazilian public and private institutions., Patients: Patients with sepsis admitted in the participant institutions., Interventions: The quality improvement initiative was based on a multifaceted intervention. The institutions were instructed to collect data on 6-hour bundle compliance and outcomes in patients with sepsis in all hospital settings. Outcomes and compliance was measured for eight periods of 6 months each, starting at the time of the enrollment in the intervention. The primary outcomes were hospital mortality and compliance with 6-hour bundle., Measurements and Main Results: We included 21,103 patients; 9,032 from public institutions and 12,071 from private institutions. Comparing the first period with the eigth period, compliance with the 6-hour bundle increased from 13.5% to 58.2% in the private institutions (p < 0.0001) and from 7.4% to 15.7% in the public institutions (p < 0.0001). Mortality rates significantly decreased throughout the program in private institutions, from 47.6% to 27.2% in the eighth period (adjusted odds ratio, 0.45; 95% CI, 0.32-0.64). However, in the public hospitals, mortality diminished significantly only in the first two periods., Conclusion: This quality improvement initiative in sepsis in an emerging country was associated with a reduction in mortality and with improved compliance with quality indicators. However, this reduction was sustained only in private institutions.

Introduction: Hemodialysis contributes to increased oxidative stress and induces transitory hypoxemia. Compartmentalization decreases the supply of solutes to the dialyzer during treatment. The aim of this study was to investigate the acute effects of intradialytic aerobic exercise on solute removal, blood gases and oxidative stress in patients with chronic kidney disease during a single hemodialysis session., Methods: Thirty patients were randomized to perform aerobic exercise with cycle ergometer for lower limbs during 30 minutes with intensity between 60-70% of maximal heart rate, or control group (CG). Blood samples were collected prior to and immediately after exercise or the equivalent time in CG. Analysis of blood and dialysate biochemistry as well as blood gases were performed. Mass removal and solute clearance were calculated. Oxidative stress was determined by lipid peroxidation and by the total antioxidant capacity., Results: Serum concentrations of solutes increased with exercise, but only phosphorus showed a significant elevation (p = 0.035). There were no significant changes in solute removal and in the acid-base balance. Both oxygen partial pressure and saturation increased with exercise (p = 0.035 and p = 0.024, respectivelly), which did not occur in the CG. The total antioxidant capacity decreased significantly (p = 0.027)., Conclusion: The acute intradialytic aerobic exercise increased phosphorus serum concentration and decreased total antioxidant capacity, reversing hypoxemia resulting from hemodialysis. The intradialytic exercise did not change the blood acid-base balance and the removal of solutes.

Extracting RNA from human urinary sediment is notoriously challenging because of cell paucity and hostile environment and column-based commercial kits using silica technology are commonly used. Nonetheless, in our experience, this methodology yields low amounts of total RNA and has low rates of success. We replaced the column-based commercial kit by a protocol using guanidine isothiocyanate-phenol-chloroform buffer (Trizol reagent) followed by addition of glycogen as a carrier and precipitation with isopropanol plus sodium acetate. This methodology was more affordable and efficient for urinary sediment total RNA isolation than silica technology, resulting in higher concentrations of total RNA of better quality., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: After observing variation in the expression of the housekeeping gene B2M in cells of the urinary sediment during a study of candidate genes potentially involved in diabetic kidney disease (DKD), we hypothesized that B2M mRNA expression in the urinary sediment could reflect the presence of DKD., Methods: qPCR was used to quantify B2M mRNA expression in cells of the urinary sediment of 51 type 1 diabetes (T1D) patients (61% women, 33.5 [27.0-39.7] years old, with diabetes duration of 21.0 [15.0-28.0] years and HbA1c of 8.2% [7.3-8.9]; median [interquartile interval]) sorted according to the diabetic nephropathy (DN) stages; 8 focal segmental glomerulosclerosis (FSGS) patients and 10 healthy controls. B2M mRNA expression was also evaluated in human embryonic kidney epithelium-like (HEK-293) cells exposed to 25mM glucose and to albumin in order to mimic, respectively, a diabetic and a proteinuric milieu., Results: No differences were found in B2M mRNA expression among healthy controls, FSGS and T1D patients. Nonetheless B2M mRNA expression was higher in the group composed by T1D patients with incipient or overt DN combined with FSGS patients versus T1D patients without DN combined with healthy controls (P=0.0007). B2M mRNA expression was higher in T1D patients with incipient or overt DN versus without DN (P=0.03). B2M mRNA expression positively correlated with albuminuria in the overall T1D population (r=0.43; P=0.01) and negatively correlated with estimated glomerular filtration rate in male T1D patients (r=- 0.57; P=0.01). Increased B2M expression was observed in HEK-293 cells exposed to 25mM glucose and to albumin., Conclusions: Β2M mRNA expression in cells of the urinary sediment is higher in T1D patients with DKD and in patients with FSGS in comparison to healthy subjects, maybe reflecting a tubulointerstitial injury promoted by albumin. Given the proinflammatory nature of B2M, we suggest that this protein contributes to diabetic (and possibly, to non-diabetic) tubulopathy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Aim: Physical exercise is a key part of rehabilitation programs in chronic obstructive pulmonary disease (COPD) patients, although it could modulates immune system responses by altering the cytokine profile of such individuals. Furthermore, the degree of severity of COPD could influence the inflammatory response induced by exercise. To evaluate the cytokine profile of individuals with different degrees of COPD in response to a 6-min walk test (6MWT)., Methods: Forty-one patients with COPD were classified according to the severity of the disease by Global Initiative for Chronic Obstructive Lung Disease method: moderate = 14 individuals; severe = 14 individuals; very severe = 13 individuals. Blood sample collection was performed in the subjects pre and post a 6MWT. Cytokine plasma levels were analyzed to determine the cytokine profile using a Cytometric Bead Array technique (Becton Dickinson, San Jose, CA, USA) assay in flow cytometry., Results: A significant difference was observed in the interleukin (IL)-6 levels after test between very severe and severe groups (P = 0.036). Also, lower levels of IL-4 were observed in the severe group compared with the very severe and the moderate groups in the pretest (P = 0.029; P = 0.003, respectively), and different values between the moderate and severe groups in the post-test (P = 0.044). A significant time pre-post effect was found in the IL-4 levels on the very severe group (P = 0.046)., Conclusion: After the 6MWT, a discrete inflammatory response was observed in COPD patients, independent of the degree of severity. The results concerning IL-4 and IL-6 levels can be indicative of an attempt to control inflammation after the 6MWT in COPD patients., (© 2014 John Wiley & Sons Ltd.)

The aim of this study was to verify the effects of the Pilates Method (PM) training program on the thickness of the abdominal wall muscles, respiratory muscle strength and performance, and lung function. This uncontrolled clinical trial involved 16 sedentary women who were assessed before and after eight weeks of PM training. The thickness of the transversus abdominis (TrA), internal oblique (IO) and external oblique (EO) muscles was assessed. The respiratory muscle strength was assessed by measuring the maximum inspiratory (MIP) and expiratory (MEP) pressure. The lung function and respiratory muscle performance were assessed by spirometry. An increase was found in MIP (p = 0.001), MEP (p = 0.031), maximum voluntary ventilation (p = 0.020) and the TrA (p < 0.001), IO (p = 0.002) and EO (p < 0.001) thickness after the PM program. No alterations in lung function were found. These findings suggest that the PM program promotes abdominal wall muscle hypertrophy and an increase in respiratory muscle strength and performance, preventing weakness in abdominal muscles and dysfunction in ventilatory mechanics, which could favor the appearance of illnesses., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims: Thioredoxin interacting protein (TXNIP), an inhibitor of antioxidant thioredoxin (Trx), is upregulated by hyperglycemia and implicated in pathogenesis of diabetes complications. We evaluated mRNA expressions of genes encoding TXNIP and Trx (TXN) in urinary sediment and peripheral blood mononuclear cells (PBMC) of type 1 diabetes (T1D) patients with different degrees of chronic complications., Methods: qPCR was employed to quantify target genes in urinary sediment (n = 55) and PBMC (n = 161) from patients sorted by presence or absence of diabetic nephropathy (DN), retinopathy, peripheral and cardiovascular neuropathy; 26 healthy controls and 13 patients presenting non-diabetic nephropathy (focal and segmental glomerulosclerosis, FSGS) were also included., Results: Regarding the urinary sediment, TXNIP (but not TXN) expression was higher in T1D (p = 0.0023) and FSGS (p = 0.0027) patients versus controls. Expressions of TXNIP and TXN were higher, respectively, in T1D patients with versus without DN (p = 0.032) and in those with estimated glomerular filtration rate (eGFR) < 60 versus ≥60 mL/min/1.73 m(2) (p = 0.008). eGFR negatively correlated with TXNIP (p = 0.04, r = -0.28) and TXN (p = 0.04, r = -0.30) expressions. T1D patients who lost ≥5 mL/min/1.73 m(2) yearly of eGFR presented higher basal TXNIP expression than those who lost <5 mL/min/1.73 m(2) yearly after median follow-up of 24 months. TXNIP (p < 0.0001) and TXN (p = 0.002) expressions in PBMC of T1D patients were significantly higher than in controls but no differences were observed between patients with or without chronic complications., Conclusions: TXNIP and TXN are upregulated in urinary sediment of T1D patients with diabetic kidney disease (DKD), but only TXNIP expression is associated with magnitude of eGFR decline.

Aim: To assess the renal effects of chronic exposure to advanced glycation end-products (AGEs) in the absence of diabetes and the potential impact of concomitant treatment with the antioxidant N-acetyl cysteine (NAC)., Methods: Wistar rats received intraperitoneally 20 mg/kg/day of albumin modified (AlbAGE) or not (AlbC) by advanced glycation for 12 weeks and oral NAC (600mg/L; AlbAGE+NAC and AlbC+NAC, respectively). Biochemical, urinary and renal morphological analyses; carboxymethyl-lysine (CML, an AGE), CD68 (macrophage infiltration), and 4-hydroxynonenal (4-HNE, marker of oxidative stress) immunostaining; intrarenal mRNA expression of genes belonging to pathways related to AGEs (Ager, Ddost, Nfkb1), renin-angiotensin system (Agt, Ren, Ace), fibrosis (Tgfb1, Col4a1), oxidative stress (Nox4, Txnip), and apoptosis (Bax, Bcl2); and reactive oxidative species (ROS) content were performed., Results: AlbAGE significantly increased urine protein-to-creatinine ratio; glomerular area; renal CML content and macrophage infiltration; expression of Ager, Nfkb1, Agt, Ren, Tgfb1, Col4a1, Txnip, Bax/Bcl2 ratio; and 4-HNE and ROS contents. Some of these effects were attenuated by NAC concomitant treatment., Conclusion: Because AGEs are highly consumed in modern diets and implicated in the progression of different kidney diseases, NAC could be a therapeutic intervention to decrease renal damage, considering that long-term restriction of dietary AGEs is difficult to achieve in practice., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Two studies addressed the role of Black meta-perception of acculturation attitudes on the relation between minority acculturation attitudes and their social adjustment (school achievement and perceived quality of intergroup relations). Participants in both studies were Black Lusophone adolescents living in Portugal. Study 1 (N = 140) indicated that participants' attitude regarding the host culture was positively correlated with their school achievement and to their evaluation of intergroup relations. It also indicated that participants' meta-perception of majority attitude add to the explained variance of participants' social adjustment. Study 2 (N = 62) manipulated the perceived majority high/low support of immigrants' learning the host culture. The dependent variable (DV) was perceived quality of intergroup relations. Only in the low support condition were participants' attitudes towards the host culture positively related to perceived quality of Black-White relationships. These results suggest that perceived social context is central to understand the relationship between minority adolescents' acculturation attitudes and key dimensions of their adjustment to host societies., (© 2015 International Union of Psychological Science.)

Background: A functional variant in the promoter region of the gene encoding tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility to T1D. However, TNF rs1800629 was found, in several populations, to be in linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and assessed the impact of HLA susceptibility haplotypes in this association., Methods: 659 subjects with T1D and 539 control subjects were genotyped for TNF-308G>A variant. HLA-DRB1 and HLA-DQB1 genes were genotyped in a subset of 313 subjects with T1D and 139 control subjects., Results: Associations with T1D were observed for the A-allele of rs1800629 (OR 1.69, 95% CI 1.33-2.15, p<0.0001, in a codominant model) and for 3 HLA haplotypes: DRB1*03:01-DQB1*02:01 (OR 5.37, 95% CI 3.23-8.59, p<0.0001), DRB1*04:01-DQB1*03:02 (OR 2.95, 95% CI 1.21-7.21, p=0.01) and DRB1*04:02-DQB1*03:02 (OR 2.14, 95% CI 1.02-4.50, p=0.04). Linkage disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1 alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629, remained independently associated with T1D., Conclusion: Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Immunological dysfunctions and a pro-inflammatory environment are associated with higher risk of cardiovascular diseases in chronic kidney disease (CKD). Physical exercise can be an important anti-inflammatory strategy, but the effects in CKD remain poorly investigated., Objective: Evaluate the acute inflammatory response to intradialytic exercise in the peripheral blood of individuals with CKD., Methods: Nine patients, of both genders, with CKD and allocated in the ambulatory of hemodialysis of Hospital Ernesto Dornelles (Brazil), performed two sessions of hemodialysis (HD) in random form: aerobic intradialytic exercise sessions (EX, 20 min of moderate exercise in cycle-ergometer) and a control hemodialysis session (CON). Peripheral blood collection was made at the baseline, during and immediately after HD to evaluate the cytokine profile: interleukin-6, interleukin-10 (IL-10), interleukin-17a (IL-17a), interferon-gamma (INF-γ) and tumoral necrosis factor-alpha (TNF-α)., Results: INF-γ decreased during HD when compared with the pre moment in both sessions, while an increase in post HD was only found in the CON session. IL-17 was higher in post when compared with during HD in both sessions. In addition to the time effect, IL-10 presented a time × group interaction and the relative changes were significantly higher in EX when compared with the CON session. The relative changes in TNF-α tended to be higher in CON when compared with EX immediately post HD session., Conclusions: These data indicate that 20 min of intradialytic exercise have modest effect in systemic inflammation. However, the significant increase in IL-10 may indicate an immunoregulatory effect of physical exercise.

Mesangial cells subject to high extracellular glucose concentrations, as occur in hyperglycaemic states, are unable to down regulate glucose influx, resulting in intracellular activation of deleterious biochemical pathways. A high expression of GLUT1 participates in the development of diabetic glomerulopathy. Variants in the gene encoding GLUT1 (SLC2A1) have been associated to this diabetic complication. The aim of this study was to test whether polymorphisms in SLC2A1 confer susceptibility to diabetic nephropathy (DN) in Brazilian type 1 diabetes patients. Four polymorphisms (rs3820589, rs1385129, rs841847 and rs841848) were genotyped in a Brazilian cohort comprised of 452 patients. A prospective analysis was performed in 155 patients. Mean duration of follow-up was 5.6 ± 2.4 years and the incidence of renal events was 18.0%. The rs3820589 presented an inverse association with the prevalence of incipient DN (OR: 0.36, 95% CI: 0.16 - 0.80, p=0.01) and with progression to renal events (HR: 0.20; 95% CI: 0.03 - 0.70; p=0.009). AGGT and AGAC haplotypes were associated with the prevalence of incipient DN and the AGAC haplotype was also associated with the prevalence of established/advanced DN. In conclusion, rs3820589 in the SLC2A1 gene modulates the risk to DN in Brazilian patients with inadequate type 1 diabetes control., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A measure of subjective social status (SSS) was examined among high (White), and low (Black and Roma) ethnic status children in Portugal within a developmental design including 6-8-year-old and 9-12-year-old children. White children favoured their in-group over the Black and Roma out-groups on the SSS measure, social preferences and positive as well as negative trait attributions. Generally, the Black and Roma showed equal SSS, preferences and trait attribution for their in-group and the high status White out-group, but not the other low-status out-group. With age White children generally demonstrated higher SSS for Black and Roma, preferred them more and attributed more positive traits. For low-status groups, an age effect was found only for Black children who preferred the Roma more with age and attributed more positive traits. Changes on preferences and trait attribution depending on age-group were mediated by SSS. It is concluded that minority group's SSS does not parallel the objective status hierarchy but, rather, is a dynamic reorganisation of group's relative positions serving strategies to cope with their minority condition., (© 2013 The British Psychological Society.)

Purpose: To evaluate whether a multifaceted, centrally coordinated quality improvement program in a network of hospitals can increase compliance with the resuscitation bundle and improve clinical and economic outcomes in an emerging country setting., Methods: This was a pre- and post-intervention study in ten private hospitals (1,650 beds) in Brazil (from May 2010 to January 2012), enrolling 2,120 patients with severe sepsis or septic shock. The program used a multifaceted approach: screening strategies, multidisciplinary educational sessions, case management, and continuous performance assessment. The network administration and an external consultant provided performance feedback and benchmarking within the network. The primary outcome was compliance with the resuscitation bundle. The secondary outcomes were hospital mortality, hospital and ICU length of stay, quality-adjusted life year (QALY) gain, and cost-effectiveness., Results: The proportion of patients who received all the required items for the resuscitation bundle improved from 13% [95% confidence interval (CI) 8-18%] at baseline to 62% (95% CI 54-69%) in the last trimester (p < 0.001). Hospital mortality decreased from 55% (95% CI 48-62%) to 26% (95% CI 19-32%, p < 0.001). Full compliance with the resuscitation bundle was associated with lower risk of hospital mortality (propensity weighted corrected risk ratio 0.74; 95% CI 0.56-0.94, p = 0.02). There was a reduction in the total cost per patient from 29.3 (95% CI 23.9-35.4) to 17.5 (95% CI 14.3-21.1) thousand US dollars from baseline to the last 3 months (mean difference -11,815; 95% CI -18,604 to -5,338). The mean QALY increased from 2.63 (95% CI 2.15-3.14) to 4.06 (95% CI 3.58-4.57). For each QALY, the full compliance saves US$5,383., Conclusions: A multifaceted approach to severe sepsis and septic shock patients in an emerging country setting led to high compliance with the resuscitation bundle. The intervention was cost-effective and associated with a reduction in mortality.

The Spanish team of the Human Proteome Project (SpHPP) marked the annotation of Chr16 and data analysis as one of its priorities. Precise annotation of Chromosome 16 proteins according to C-HPP criteria is presented. Moreover, Human Body Map 2.0 RNA-Seq and Encyclopedia of DNA Elements (ENCODE) data sets were used to obtain further information relative to cell/tissue specific chromosome 16 coding gene expression patterns and to infer the presence of missing proteins. Twenty-four shotgun 2D-LC-MS/MS and gel/LC-MS/MS MIAPE compliant experiments, representing 41% coverage of chromosome 16 proteins, were performed. Furthermore, mapping of large-scale multicenter mass spectrometry data sets from CCD18, MCF7, Jurkat, and Ramos cell lines into RNA-Seq data allowed further insights relative to correlation of chromosome 16 transcripts and proteins. Detection and quantification of chromosome 16 proteins in biological matrices by SRM procedures are also primary goals of the SpHPP. Two strategies were undertaken: one focused on known proteins, taking advantage of MS data already available, and the second, aimed at the detection of the missing proteins, is based on the expression of recombinant proteins to gather MS information and optimize SRM methods that will be used in real biological samples. SRM methods for 49 known proteins and for recombinant forms of 24 missing proteins are reported in this study.

Aims/hypothesis: Oxidative stress is involved in the pathogenesis of diabetic nephropathy. The antioxidant enzyme catalase plays a key role in redox regulation in the kidney. We investigated associations of catalase gene (CAT) polymorphisms and plasma catalase activity with diabetic nephropathy in type 1 diabetic patients., Methods: We genotyped nine single nucleotide polymorphisms (SNPs) in the CAT region in participants from the Survival Genetic Nephropathy (SURGENE) (340 French participants, 10 year follow-up) and the Génétique de la Néphropathie Diabétique (GENEDIAB) (444 Belgian and French participants, 8 year follow-up) study cohorts. Replication was performed in a Brazilian cross-sectional cohort (n = 451). Baseline plasma catalase activity was measured in SURGENE (n = 120) and GENEDIAB (n = 391) participants., Results: The A allele of rs7947841 was associated with the prevalence of incipient (OR 2.79, 95% CI 1.21, 6.24, p = 0.01) and established or advanced nephropathy (OR 5.72, 95% CI 1.62, 22.03, p = 0.007), and with the incidence of renal events, which were defined as new cases of microalbuminuria or progression to a more severe stage of nephropathy during follow-up (HR 1.82, 95% CI 1.13, 2.81, p = 0.01) in SURGENE participants. The same risk allele was associated with incipient nephropathy (OR 3.13, 95% CI 1.42, 7.24, p = 0.004) and with the incidence of end-stage renal disease (ESRD) (HR 2.11, 95% CI 1.23, 3.60, p = 0.008) in GENEDIAB participants. In both cohorts, the risk allele was associated with lower catalase activity. Associations with incipient and established or advanced nephropathy were confirmed in the replication cohort., Conclusions/interpretation: CAT variants were associated with the prevalence and incidence of diabetic nephropathy and ESRD in type 1 diabetic patients. Our results confirm the protective role of catalase against oxidative stress in the kidney.

Oxidative stress is involved in the pathophysiology of diabetic nephropathy. The superoxide-generating nicotinamide adenine dinucleotide phosphate-oxidase 2 (NOX2, encoded by the CYBB gene) and the antioxidant enzyme glutathione peroxidase 4 (GPX4) play opposing roles in the balance of cellular redox status. In the present study, we investigated associations of single nucleotide polymorphisms (SNPs) in the regulatory regions of CYBB and GPX4 with kidney disease in patients with type 1 diabetes. Two functional SNPs, rs6610650 (CYBB promoter region, chromosome X) and rs713041 (GPX4 3'untranslated region, chromosome 19), were genotyped in 451 patients with type 1 diabetes from a Brazilian cohort (diabetic nephropathy: 44.6%) and in 945 French/Belgian patients with type 1 diabetes from Genesis and GENEDIAB cohorts (diabetic nephropathy: 62.3%). The minor A-allele of CYBB rs6610650 was associated with lower estimated glomerular filtration rate (eGFR) in Brazilian women, and with the prevalence of established/advanced nephropathy in French/Belgian women (odds ratio 1.75, 95% CI 1.11-2.78, p = 0.016). The minor T-allele of GPX4 rs713041 was inversely associated with the prevalence of established/advanced nephropathy in Brazilian men (odds ratio 0.30, 95% CI 0.13-0.68, p = 0.004), and associated with higher eGFR in French/Belgian men. In conclusion, these heterogeneous results suggest that neither CYBB nor GPX4 are major genetic determinants of diabetic nephropathy, but nevertheless, they could modulate in a gender-specific manner the risk for renal disease in patients with type 1 diabetes.

Objective: The current definition of severe sepsis and septic shock includes a heterogeneous profile of patients. Although the prognostic value of hyperlactatemia is well established, hyperlactatemia is observed in patients with and without shock. The present study aimed to compare the prognosis of septic patients by stratifying them according to two factors: hyperlactatemia and persistent hypotension., Methods: The present study is a secondary analysis of an observational study conducted in ten hospitals in Brazil (Rede Amil - SP). Septic patients with initial lactate measurements in the first 6 hours of diagnosis were included and divided into 4 groups according to hyperlactatemia (lactate >4mmol/L) and persistent hypotension: (1) severe sepsis (without both criteria); (2) cryptic shock (hyperlactatemia without persistent hypotension); (3) vasoplegic shock (persistent hypotension without hyperlactatemia); and (4) dysoxic shock (both criteria)., Results: In total, 1,948 patients were analyzed, and the sepsis group represented 52% of the patients, followed by 28% with vasoplegic shock, 12% with dysoxic shock and 8% with cryptic shock. Survival at 28 days differed among the groups (p<0.001). Survival was highest among the severe sepsis group (69%, p<0.001 versus others), similar in the cryptic and vasoplegic shock groups (53%, p=0.39), and lowest in the dysoxic shock group (38%, p<0.001 versus others). In the adjusted analysis, the survival at 28 days remained different among the groups (p<0.001) and the dysoxic shock group exhibited the highest hazard ratio (HR=2.99, 95%CI 2.21-4.05)., Conclusion: The definition of sepsis includes four different profiles if we consider the presence of hyperlactatemia. Further studies are needed to better characterize septic patients, to understand the etiology and to design adequate targeted treatments.

Introduction: Pediatric patients undergoing kidney transplantation can present changes in pulmonary function and functional capacity for exercise., Objective: To evaluate the functional capacity and pulmonary function in children and adolescents undergoing kidney transplantation., Method: Children and adolescents aged six to 18 years of age were evaluated in Outpatient Clinic of Nephrology, Hospital da Criança Santo Antônio, Santa Casa de Porto Alegre, RS, Brazil in period the june of 2010 the march of 2011. Pulmonary capacity was assessed by spirometry and maximal respiratory pressures and functional capacity through 6-minute walk test (6MWT)., Results: The sample comprised 25 patients, 14 (56%) males with a mean age of 13.5 ± 3.3 years. From, 19 (76%) underwent dialysis before transplantation. Mean forced vital capacity (FVC) was 97.91 + 24.32% and forced expiratory volume in one second (FEV1) 100.53 + 17.66% from predicted value. In the 6MWT, the patients walked 229.14 meters less than predicted (p < 0.001). The maximum inspiratory pressure (MIP) was significantly lower than predicted, and the difference in cmH₂O -24.63 (p = 0.03), as the maximum expiratory pressure (MEP), with a difference of 49.27 cmH₂O (p < 0.001). By correlating, functional capacity, spirometry and maximal respiratory pressures, find an association between FVC and 6MWT (r = 0.52, p = 0.01) and FVC and MIP (r = 0.54, p = 0.01)., Conclusion: Reduced functional capacity and maximum respiratory pressures were diagnosed in a small cohort of pediatric patients after kidney transplantation. Better the functional capacity and PiMáx better the FVC.

Rational: Patients under regular dialysis can also present alterations in the cardiovascular, musculoskeletal, and metabolic systems., Objectives: The aim of this study is to compare the effects of strength and aerobic exercises performed during hemodialysis (HD) in individuals with chronic renal disease., Materials and Methods: Randomized clinical trial. It was developed as a program of exercises three times a week, in the first 2 h of HD for 8 weeks. The patients were divided into three groups: control (Group 1, n: 11), strength (Group 2, n: 11), and aerobic (Group 3, n: 10). G1 has not developed any type of physical training; G2 utilized a training load of 40% of one repetition maximum (1RM) with anklets, and developed three series of 15 repetitions. G3 pedaled seated in the dialysis seat, during 20 min, in an ergometric bicycle, with intensity regulated by the perceived effort scale. Before and after 8 weeks, the following variables were evaluated: respiratory muscular strength, pulmonary function, functional capacity, blood biochemistry, and quality of life., Main Findings: In the pre- and post-training comparison, there was statistically significant improvement (p < 0.05) in the maximal inspiratory pressure (MIP), number of steps achieved (NSA), and quality of life (QoL) in the trained groups, as compared to the non-exercised group (G1)., Conclusions: The strength and aerobic exercises developed during HD can improve the respiratory muscular strength, functional performance, and quality of life, when compared to individuals presenting the disease who have not developed any type of physical training.

Background: Expiratory positive airway pressure (EPAP) is a form of noninvasive positive-pressure ventilatory support that, in spite of not unloading respiratory muscles during inspiration, may reduce the inspiratory threshold load and attenuate expiratory dynamic airway compression, contributing to reduced expiratory air-flow limitation in patients with COPD. We sought to determine the effects of EPAP on operational lung volumes during exercise in COPD patients., Methods: This was a nonrandomized, experimental comparison of 2 exercise conditions (with and without EPAP); subjects completed a treadmill exercise test and performed, before and immediately after exercise, lung volume measurements. Those who overtly developed dynamic hyperinflation (DH), as defined by at least a 15% reduction from pre-exercise inspiratory capacity (IC), were invited for an additional research visit to repeat the same exercise protocol while receiving EPAP through a spring loaded resistor face mask. The primary outcome was IC variance (pre-post exercise) comparison under the 2 exercise conditions., Results: Forty-six subjects (32 males), a mean 65.0 ± 8.2 years of age, and with moderate to severe COPD (FEV(1) = 38 ± 16% predicted) were initially enrolled. From this initial sample, 17 (37%) presented overt DH, as previously defined. No significant difference was found between these subjects and the rest of the initial sample. Comparing before and after exercise, there was significantly less reduction in IC observed when EPAP was used (-0.18 ± 0.35 L vs -0.57 ± 0.45 L, P = .02), allowing greater IC final values (1.45 ± 0.50 L vs 1.13 ± 0.52 L, P = .02)., Conclusions: The application of EPAP reduced DH, as shown by lower operational lung volumes after submaximal exercise in COPD patients who previously manifested exercise DH., (Copyright 2012 Daedalus Enterprises)

Introduction: Patients with chronic kidney disease (CKD) have reduced physical and functional capacity when compared with the general population. Hemodialysis (HD) restricts patients activities, favoring a sedentary lifestyle and leading to functional limitations. HD patients are less active, present low exercise tolerance and have high physical deconditioning. Physical exercise programs have been proposed as a strategy not only to treat clinical symptoms, but also to reduce physical limitations and improve the quality of life of these patients., Objectives: The purpose of this study was to review the literature on the effects of physical exercise (aerobic exercise on a cycle ergometer for the lower limbs) on CKD undergoing HD., Methods: The Medline, PubMed, Scielo, Embase and DirectScience databases were searched., Results: Fourteen randomized controlled clinical trials were analyzed as regards the timing of the intervention during the HD session, exercise intensity and frequency, the duration of the intervention and the main results., Conclusion: The studies demonstrated that aerobic exercises performed during HD improve the aerobic capacity and physical conditioning, reduce fatigue and anxiety, improve muscle capillarization and resting blood pressure, increase exercise duration and improve urea clearance.

Background: Oxidative stress is recognized as a major pathogenic factor of cellular damage caused by hyperglycemia. NOX/NADPH oxidases generate reactive oxygen species and NOX1, NOX2 and NOX4 isoforms are expressed in kidney and require association with subunit p22phox (encoded by the CYBA gene). Increased expression of p22phox was described in animal models of diabetic nephropathy. In the opposite direction, glutathione is one of the main endogenous antioxidants whose plasmatic concentrations were reported to be reduced in diabetes patients. The aim of the present investigation was to test whether functional single nucleotide polymorphisms (SNPs) in genes involved in the generation of NADPH-dependent O₂•⁻ (-675 T → A in CYBA, unregistered) and in glutathione metabolism (-129 C → T in GCLC [rs17883901] and -65 T → C in GPX3 [rs8177412]) confer susceptibility to renal disease in type 1 diabetes patients., Methods: 401 patients were sorted into two groups according to the presence (n = 104) or absence (n = 196) of overt diabetic nephropathy or according to glomerular filtration rate (GFR) estimated by Modification of Diet in Renal Disease (MDRD) equation: ≥ 60 mL (n = 265) or < 60 mL/min/1.73 m² (n = 136) and were genotyped., Results: No differences were found in the frequency of genotypes between diabetic and non-diabetic subjects. The frequency of GFR < 60 mL/min was significantly lower in the group of patients carrying CYBA genotypes T/A+A/A (18.7%) than in the group carrying the T/T genotype (35.3%) (P = 0.0143) and the frequency of GFR < 60 mL/min was significantly higher in the group of patients carrying GCLC genotypes C/T+T/T (47.1%) than in the group carrying the C/C genotype (31.1%) (p = 0.0082). Logistic regression analysis identified the presence of at least one A allele of the CYBA SNP as an independent protection factor against decreased GFR (OR = 0.38, CI95% 0.14-0.88, p = 0.0354) and the presence of at least one T allele of the GCLC rs17883901 SNP as an independent risk factor for decreased GFR (OR = 2.40, CI95% 1.27-4.56, p = 0.0068)., Conclusions: The functional SNPs CYBA -675 T → A and GCLC rs17883901, probably associated with cellular redox imbalances, modulate the risk for renal disease in the studied population of type 1 diabetes patients and require validation in additional cohorts.

Introduction: The aim of this study was to evaluate the frequency of anti-Toxocara antibodies in serum from 7-year-old children attending elementary school in Vitória-ES, Brazil and to correlate these antibodies with socio-demographic factors, the presence of intestinal helminths, blood eosinophil numbers, past history of allergy or asthma, and clinical manifestations of helminth infections., Methods: The detection of anti-Toxocara antibodies was performed using an ELISA (Cellabs Pty Ltd)on serum from 391 children who had already been examined by fecal examination and blood cell counts. Data from clinical and physical examinations were obtained for all children., Results: The prevalence of anti-Toxocara antibodies was 51.6%, with no gender differences. No significant differences were observed between positive serology and the presence or absence of intestinal worms (60.3 and 51.7%, respectively; p = 0.286). The only variables significantly related to positive serology were onycophagy and the use of unfiltered water. Although eosinophilia (blood eosinophil count higher than 600/mm³) was significantly related to the presence of a positive ELISA result, this significance disappeared when we considered only children without worms or without a past history of allergy or asthma. No clinical symptoms related to Toxocara infection were observed., Conclusions: There is a high prevalence of anti-Toxocara antibodies in children attending elementary schools in Vitória, which may be partially related to cross-reactivity with intestinal helminths or to a high frequency of infection with a small number of Toxocara eggs.

Introduction: Chronic kidney disease associated with hemodialysis can have a variety of musculoskeletal complications, in addition to repercussions in pulmonary function., Objective: To evaluate the effects of inspiratory muscle training on inspiratory muscle strength, pulmonary function, and functional capacity in patients with chronic kidney failure undergoing hemodialysis., Method: Non-controlled clinical trial, comprising 15 individuals diagnosed with chronic kidney failure and undergoing hemodialysis. Maximum inspiratory (PImax) and expiratory (PEmax) pressures were assessed by use of pressure vacuum meter reading. Pulmonary function was assessed by use of spirometry. Functional capacity was assessed by use of walked distance and oxygen consumption obtained in the six-minute walk test (6MWT). For eight weeks, the inspiratory muscle training (IMT) protocol was applied during hemodialysis sessions, with load set to 40% of PImax and weekly frequency of three alternate days., Results: A significant increase in the walked distance was observed after training (455.5 ± 98 versus 557.8 ± 121.0; p = 0.003). No statistically significant difference was observed in the other variables when comparing their pre- and posttraining values., Conclusion: The study showed no statistically significant difference in respiratory muscle strength, pulmonary function, and oxygen consumption. An increase in the walked distance was observed in the 6MWT.