Hormona Paratiróideia Como Factor Predictivo de Hipocalcemia Após Tiroidectomia: Estudo Prospectivo em 100 Doentes

INTRODUCTION: Hypocalcemia is a frequent complication after total thyroidectomy and the main reason for prolonged hospitalization of these patients. MATERIAL AND METHODS: We studied prospectively 112 patients who underwent total or completation thyroidectomy between June 2012 and November 2013. Twelve patients with preoperative changes in parathyroid function were excluded. Parathyroid hormone and calcium levels were determined pre-operatively, immediately after surgery, on 1st day and on 14th day after surgery. RESULTS: Of the 100 patients enrolled, 60 have developed hypocalcaemia (60%) but only 14 patients had symptomatic hypocalcaemia. It mostly occurs 24 hours after surgery (76.7%). It was permanent in 3 patients and temporary in the others. In the 60 patients with hypocalcaemia, it has been found hypoparathyroidism in 19 patients immediately after surgery, in 14 patients on 1st day but only 3 had hypoparathyroidism (patients with permanent hypocalcaemia). Comparing the group of patients with and without hypocalcaemia we found a decrease of parathyroid hormone in both (immediately after surgery and on 1st day) but was more important in the hypocalcaemia group (p = 0.004 and p 19.4% determined on the 1st day (sensitivity = 82%; specificity = 63%). DISCUSSION: In our study there was a high incidence of hypocalcemia (60%), expressed predominantly 24 hours after surgery and conditioned, in these patients, a longer hospital stay. However, only 3 patients (3%) had permanent hypocalcemia. We still found a match in the oscillation of serum calcium levels and parathyroid hormone which identified the decrease in parathyroid hormone on the first day after surgery as a reliable predictor of hypocalcemia. CONCLUSION: Decrease of parathyroid hormone levels > 19.4% determined on 1st day is a good predictor of hypocalcemia after total / completation thyroidectomy, allowing to identify patients at higher risk of hypocalcemia, medicate them prophylactically and get early and safe discharges.info:eu-repo/semantics/publishedVersio

Designing bioactive porous titanium interfaces to balance mechanical properties and in vitro cells behavior towards increased osseointegration

Titanium implant failures are mainly related to stress shielding phenomenon and the poor cell interaction with host bone tissue. The development of bioactive and biomimetic Ti scaffolds for bone regeneration remains a challenge which needs the design of Ti implants with enhanced osseointegration. In this context, 4 types of titanium samples were fabricated using conventional powder metallurgy, fully dense, dense etched, porous Ti, and porous etched Ti. Porous samples were manufactured by space holder technique, using ammonium bicarbonate particles as spacer in three different ranges of particle size (100–200 μm, 250–355 μm and 355–500 μm). Substrates were chemically etched by immersion in fluorhydric acid at different times (125 and 625 s) and subsequently, were characterized from a micro-structural, topographical and mechanical point of view. Etched surfaces showed an additional roughness preferentially located inside pores. In vitro tests showed that all substrates were biocompatible (80% of cell viability), confirming cell adhesion of premioblastic cells. Similarly, osteoblast showed similar cell proliferation rates at 4 days, however, higher cell metabolic activity was observed in fully dense and dense etched surfaces at 7 days. In contrast, a significant increase of alkaline phosphatase enzyme expression was observed in porous and porous etched samples compared to control surfaces (dense and dense etched), noticing the suitable surface modification parameters (porosity and roughness) to improve cell differentiation. Furthermore, the presence of pores and rough surfaces of porous Ti substrates remarkably decreased macrophage activation reducing the M1 phenotype polarization as well M1 cell marker expression. Thus, a successful surface modification of porous Ti scaffolds has been performed towards a reduction on stress shielding phenomenon and enhancement of bone osseointegration, achieving a biomechanical and biofunctional equilibrium.Ministry of Economy and Competitiveness of Spain grant MAT2015-71284-PJunta de Andalucía – FEDER (Spain) Project Ref. P12-TEP-140

Evaluation of the Predictive Ability, Environmental Regulation and Pharmacogenetics Utility of a BMI-Predisposing Genetic Risk Score during Childhood and Puberty

The authors would like to thank the Spanish children and parents who participated in the study.Polygenetic risk scores (pGRSs) consisting of adult body mass index (BMI) genetic variants have been widely associated with obesity in children populations. The implication of such obesity pGRSs in the development of cardio-metabolic alterations during childhood as well as their utility for the clinical prediction of pubertal obesity outcomes has been barely investigated otherwise. In the present study, we evaluated the utility of an adult BMI predisposing pGRS for the prediction and pharmacological management of obesity in Spanish children, further investigating its implication in the appearance of cardio-metabolic alterations. For that purpose, we counted on genetics data from three well-characterized children populations (composed of 574, 96 and 124 individuals), following both cross-sectional and longitudinal designs, expanding childhood and puberty. As a result, we demonstrated that the pGRS is strongly associated with childhood BMI Z-Score (B = 1.56, SE = 0.27 and p-value = 1.90 × 10−8 ), and that could be used as a good predictor of obesity longitudinal trajectories during puberty. On the other hand, we showed that the pGRS is not associated with cardio-metabolic comorbidities in children and that certain environmental factors interact with the genetic predisposition to the disease. Finally, according to the results derived from a weight-reduction metformin intervention in children with obesity, we discarded the utility of the pGRS as a pharmacogenetics marker of metformin response.Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) PI1102042 PI1102059 PI1601301 PI1600871Spanish Ministry of Health, Social and Equality, General Department for Pharmacy and Health Products EC10-243 EC10-056 EC10-281 EC10-227Regional Government of Andalusia ("Plan Andaluz de investigacion, desarrollo e innovacion (2018)") P18-RT-2248Mapfre Foundation ("Research grants by Ignacio H. de Larramendi 2017")Instituto de Salud Carlos III IFI17/0004

Construction of an In Silico Structural Profiling Tool Facilitating Mechanistically Grounded Classification of Aquatic Toxicants.

The performance of chemical safety assessment within the domain of environmental toxicology is often impeded by a shortfall of appropriate experimental data describing potential hazards across the many compounds in regular industrial use. In silico schemes for assigning aquatic-relevant modes or mechanisms of toxic action to substances, based solely on consideration of chemical structure, have seen widespread employment─including those of Verhaar, Russom, and later Bauer (MechoA). Recently, development of a further system was reported by Sapounidou, which, in common with MechoA, seeks to ground its classifications in understanding and appreciation of molecular initiating events. Until now, this Sapounidou scheme has not seen implementation as a tool for practical screening use. Accordingly, the primary purpose of this study was to create such a resource─in the form of a computational workflow. This exercise was facilitated through the formulation of 183 structural alerts/rules describing molecular features associated with narcosis, chemical reactivity, and specific mechanisms of action. Output was subsequently compared relative to that of the three aforementioned alternative systems to identify strengths and shortcomings as regards coverage of chemical space

Esophageal cooling for protection during left atrial ablation: a systematic review and meta-analysis.

PURPOSE: Thermal damage to the esophagus is a risk from radiofrequency (RF) ablation of the left atrium for the treatment of atrial fibrillation (AF). The most extreme type of thermal injury results in atrio-esophageal fistula (AEF) and a correspondingly high mortality rate. Various strategies for reducing esophageal injury have been developed, including power reduction, esophageal deviation, and esophageal cooling. One method of esophageal cooling involves the direct instillation of cold water or saline into the esophagus during RF ablation. Although this method provides limited heat-extraction capacity, studies of it have suggested potential benefit. We sought to perform a meta-analysis of published studies evaluating the use of esophageal cooling via direct liquid instillation for the reduction of thermal injury during RF ablation. METHODS: We searched PubMed for studies that used esophageal cooling to protect the esophagus from thermal injury during RF ablation. We then performed a meta-analysis using a random effects model to calculate estimated effect size with 95% confidence intervals, with an outcome of esophageal lesions stratified by severity, as determined by post-procedure endoscopy. RESULTS: A total of 9 studies were identified and reviewed. After excluding preclinical and mathematical model studies, 3 were included in the meta-analysis, totaling 494 patients. Esophageal cooling showed a tendency to shift lesion severity downward, such that total lesions did not show a statistically significant change (OR 0.6, 95% CI 0.15 to 2.38). For high-grade lesions, a significant OR of 0.39 (95% CI 0.17 to 0.89) in favor of esophageal cooling was found, suggesting that esophageal cooling, even with a low-capacity thermal extraction technique, reduces the severity of lesions resulting from RF ablation. CONCLUSIONS: Esophageal cooling reduces the severity of the lesions that may result from RF ablation, even when relatively low heat extraction methods are used, such as the direct instillation of small volumes of cold liquid. Further investigation of this approach is warranted, particularly with higher heat extraction capacity techniques

Variation and genetic structure of Melipona quadrifasciata Lepeletier (Hymenoptera, Apidae) populations based on ISSR pattern

For a study of diversity and genetic structuring in Melipona quadrifasciata, 61 colonies were collected in eight locations in the state of Minas Gerais, Brazil. By means of PCR analysis, 119 ISSR bands were obtained, 80 (68%) being polymorphic. He and H B were 0.20 and 0.16, respectively. Two large groups were obtained by the UPGMA method, one formed by individuals from Januária, Urucuia, Rio Vermelho and Caeté and the other by individuals from São João Del Rei, Barbacena, Ressaquinha and Cristiano Otoni. The Φst and θB values were 0.65 and 0.58, respectively, thereby indicating high population structuring. UPGMA grouping did not reveal genetic structuring of M. quadrifasciata in function of the tergite stripe pattern. The significant correlation between dissimilarity values and geographic distances (r = 0.3998; p < 0.05) implies possible geographic isolation. The genetic differentiation in population grouping was probably the result of an interruption in gene flow, brought about by geographic barriers between mutually close geographical locations. Our results also demonstrate the potential of ISSR markers in the study of Melipona quadrifasciata population structuring, possibly applicable to the studies of other bee species

A scheme to evaluate structural alerts to predict toxicity – Assessing confidence by characterising uncertainties

Structure-activity relationships (SARs) in toxicology have enabled the formation of structural rules which, when coded as structural alerts, are an essential tool in in silico toxicology. Whilst other in silico methods have approaches for their evaluation, there is no formal process to assess the confidence that may be associated with a structural alert. This investigation proposes twelve criteria to assess the uncertainty associated with structural alerts, allowing for an assessment of confidence. The criteria are based around the stated purpose, description of the chemistry, toxicology and mechanism, performance and coverage, as well as corroborating and supporting evidence of the alert. Alerts can be given a confidence assessment and score, enabling the identification of areas where more information may be beneficial. The scheme to evaluate structural alerts was placed in the context of various use cases for industrial and regulatory applications. The analysis of alerts, and consideration of the evaluation scheme, identifies the different characteristics an alert may have, such as being highly specific or generic. These characteristics may determine when an alert can be used for specific uses such as identification of analogues for read-across or hazard identification

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation