Multivariate Analysis of Solubility Parameters for Drug-Polymer Miscibility Assessment in Preparing Raloxifene Hydrochloride Amorphous Solid Dispersions.

The success of obtaining solid dispersions for solubility improvement invariably depends on the miscibility of the drug and polymeric carriers. This study aimed to categorize and select polymeric carriers via the classical group contribution method using the multivariate analysis of the calculated solubility parameter of RX-HCl. The total, partial, and derivate parameters for RX-HCl were calculated. The data were compared with the results of excipients (N = 36), and a hierarchical clustering analysis was further performed. Solid dispersions of selected polymers in different drug loads were produced using solvent casting and characterized via X-ray diffraction, infrared spectroscopy and scanning electron microscopy. RX-HCl presented a Hansen solubility parameter (HSP) of 23.52 MPa1/2. The exploratory analysis of HSP and relative energy difference (RED) elicited a classification for miscible (n = 11), partially miscible (n = 15), and immiscible (n = 10) combinations. The experimental validation followed by a principal component regression exhibited a significant correlation between the crystallinity reduction and calculated parameters, whereas the spectroscopic evaluation highlighted the hydrogen-bonding contribution towards amorphization. The systematic approach presented a high discrimination ability, contributing to optimal excipient selection for the obtention of solid solutions of RX-HCl.

Postoperative pain after single-visit root canal treatments in necrotic teeth comparing instruments' kinematics and apical instrumentation limits - a prospective randomized multicenter clinical trial.

OBJECTIVES: This prospective randomized multicenter clinical trial (PRMCT) investigated postoperative pain after single-visit root canal treatments in teeth affected by pulp necrosis (PN), and asymptomatic apical periodontitis (AAP) (with apical radiolucent areas) or normal periradicular tissues (without apical radiolucent areas) comparing different instruments' kinematics and apical instrumentation limits. METHODS: Before chemomechanical preparation, 240 patients/teeth were randomly distributed into four groups (n = 60) according to the instruments' kinematics (rotary or reciprocating) and apical instrumentation limits (with or without intentional foraminal enlargement [IFE]). After that, specimens were submitted to the same irrigation and obturation techniques, and the patients were referred to undergo the definitive restorations. No medication was prescribed, but the patients were instructed to take either paracetamol (750 mg every 6 h for three days) or ibuprofen (600 mg every 6 h for three days) in pain cases. Postoperative pain incidence and levels were assessed at 24-, 48-, and 72 h following treatment completion according to a verbal rating scale (VRS) following a score. The Kolmogorov-Smirnov test was applied to assess the normality of the data. Mann-Whitney U, Chi-square, Friedman's ANOVA, and Friedman's multiple 2 to 2 comparison tests were employed to identify potential significant statistical differences among the variables in the study groups (P < .05). RESULTS: Significant statistical differences were only observed among the groups considering tooth, periradicular status, and the occurrence of overfilling (sealer extrusion) (P < 0.00). Patients with teeth instrumented through rotary kinematics and without IFE experienced lower rates of postoperative pain; however, this difference was relevant only at 24 h (P < 0.05). CONCLUSIONS: Postoperative pain was lower after using a rotary file system (Profile 04) inserted up to the apical constriction (AC). However, this finding was just statistically meaningful at 24 h. TRIAL REGISTRATION: This PRMCT was approved by the Human Research Ethics Committee of the Paranaense University - UNIPAR, Francisco Beltrão, PR, Brazil (CAAE. 46,774,621.6.0000.0109) on 02/09/2021. It was registered at The Brazilian Registry of Clinical Trials - ReBEC (RBR-3r967t) on 01/06/2023, was performed according to the Principles of the Helsinki Declaration and is reported following the Consolidated Standards of Reporting Trials Statement.

Kinematic and dynamic data from a robotic assembly of aeronautical threaded fasteners.

Industrial screwing is one of several industry branches' most common manufacturing processes. Good quality and structured data from these operations have increased demand with the popularization of data-driven techniques for manufacturing automation. The dataset presented in this paper comprises screwing experiments with aeronautical nuts performed by an industrial robot Kuka KR-16 in a lab setting. The data comprises force, torque, linear and angular displacements, and velocities in time-series format. The dataset contains three different experiment results: mounted, jammed, and not mounted, which can be used as labels for classification techniques.

Neurosurgical Emergencies in the Amazon: An Epidemiologic Study of Patients Referred by Air Transport for Neurosurgical Evaluation at a Referral Center in Amazonas.

BACKGROUND: Amazonas is the largest state in Brazil, covering an area of 1,559,159.148 km2 and primarily occupied by the Amazon rainforest. Fluvial and aerial transport are the primary means of transportation. Studying the epidemiologic profile of patients transported by neurologic emergencies is essential because there is only 1 referral center hospital serving approximately 4 million inhabitants in Amazonas. METHODS: This work studies the epidemiologic profile of patients referred by air transport for evaluation by the neurosurgery team at a referral center in the Amazon. RESULTS: Of the 68 patients transferred, 50 (75.53%) were men. The study covered 15 municipalities in Amazonas. Of the patients, 67.64% had a traumatic brain injury due to various causes, and 22.05% had had a stroke. Of all patients, 67.65% did not undergo surgery and 43.9% evolved with good evolution and without complications. CONCLUSIONS: Air transportation for neurologic evaluation is essential in Amazonas. However, most patients did not require neurosurgical intervention, indicating that investments in medical infrastructures, such as computed tomography scanners and telemedicine, may optimize health costs.

Contracepção pós-parto e pós-abortamento: um compilado das evidências atuais / Postpartum and post-abortion contraception: a compilation of current evidences

Idealmente, a contracepção deve ser iniciada o mais precocemente possível após o parto ou após o abortamento, permitindo que as mulheres sejam protegidas contra uma gravidez não programada subsequente. O objetivo desta revisão é discutir a contracepção no pós-parto e pós-aborto, por meio da análise de ensaios clínicos e metanálises, além das principais diretrizes internacionais, com ênfase nas indicações e contraindicações, tempo de início do uso dos métodos contraceptivos e possíveis complicações. Nesta revisão não sistemática, são discutidos os principais métodos contraceptivos: dispositivos intrauterinos, métodos somente de progestagênios, métodos hormonais combinados, métodos de barreira, método de amenorreia lactacional e esterilização. O aconselhamento contraceptivo pós-parto deve começar durante o pré-natal e, em pacientes após abortamento, durante a internação hospitalar. Todas as mulheres devem ter acesso a informações claras sobre cada método contraceptivo, e o processo de tomada de decisão deve ser compartilhado com o médico assistente. Idealmente, métodos de contracepção reversíveis de longa duração devem ser priorizados em relação aos outros. Em conjunto, todas as evidências demonstram que o melhor método para cada paciente é aquele que combine altas taxas de segurança com o desejo da paciente de iniciá-lo e mantê-lo pelo tempo que desejar.

Contraception should ideally be started as early as possible after childbirth or abortion to allow women to be protected against a subsequent unplanned pregnancy. The aim of this review is to discuss postpartum and postabortion contraception, through the analysis of clinical trials and meta-analyses, in addition to the main international guidelines, with emphasis on indications and contraindications, time to start contraceptive method and possible complications. In this review, the main contraceptive methods are discussed: intrauterine devices, progestin-only methods, combined hormonal methods, barrier methods, lactational amenorrhea method and sterilization. Postpartum contraceptive counseling should start during prenatal care and during hospital stay in post-abortion patients. All women should have access to clear information about each contraceptive method and the decision-making process must be shared. Ideally, long acting reversible contraception methods should be prioritized over others. Taken together, all the evidence shows that the best method for each patient is the one that combines high safety rates with the patient's desire to start and maintain it for as long as she wants.

Tau liquid-liquid phase separation is modulated by the Ca2+ -switched chaperone activity of the S100B protein.

Aggregation of the microtubule-associated protein tau is implicated in several neurodegenerative tauopathies including Alzheimer's disease (AD). Recent studies evidenced tau liquid-liquid phase separation (LLPS) into droplets as an early event in tau pathogenesis with the potential to enhance aggregation. Tauopathies like AD are accompanied by sustained neuroinflammation and the release of alarmins at early stages of inflammatory responses encompass protective functions. The Ca2+ -binding S100B protein is an alarmin augmented in AD that was recently implicated as a proteostasis regulator acting as a chaperone-type protein, inhibiting aggregation and toxicity through interactions of amyloidogenic clients with a regulatory surface exposed upon Ca2+ -binding. Here we expand the regulatory functions of S100B over protein condensation phenomena by reporting its Ca2+ -dependent activity as a modulator of tau LLPS induced by crowding agents (PEG) and metal ions (Zn2+ ). We observe that apo S100B has a negligible effect on PEG-induced tau demixing but that Ca2+ -bound S100B prevents demixing, resulting in a shift of the phase diagram boundary to higher crowding concentrations. Also, while incubation with apo S100B does not compromise tau LLPS, addition of Ca2+ results in a sharp decrease in turbidity, indicating that interactions with S100B-Ca2+ promote transition of tau to the mixed phase. Further, electrophoretic analysis and FLIM-FRET studies revealed that S100B incorporates into tau liquid droplets, suggesting an important stabilizing and chaperoning role contributing to minimize toxic tau aggregates. Resorting to Alexa488-labeled tau we observed that S100B-Ca2+ reduces the formation of tau fluorescent droplets, without compromising liquid-like behavior and droplet fusion events. The Zn2+ -binding properties of S100B also contribute to regulate Zn2+ -promoted tau LLPS as droplets are decreased by Zn2+ buffering by S100B, in addition to the Ca2+ -triggered interactions with tau. Altogether this work uncovers the versatility of S100B as a proteostasis regulator acting on protein condensation phenomena of relevance across the neurodegeneration continuum.

Process optimization of physicochemical properties of spray-dried Hydrocotyle umbellata L. extract

Abstract Hydrocotyle umbellata L., Araliaceae, is a species that is recommended in Ayurvedic medicine for its effects on the central nervous system, such as anxiolytic and memory-stimulant effects. Despite the medicinal potential of this species, its phytopharmaceutical and technological potential to produce standardized extracts has not been investigated. This study analyzes the influence of spray drying parameters on the contents of the chemical markers (total phenolic, total flavonoid, and hibalactone) and the functional properties of H. umbellata extract. The optimization of drying conditions was performed using a central composite design combined with response surface methodology and desirability function approach. The mathematical models fitted to experimental data indicated that all the evaluated drying parameters significantly influenced the chemical contents. The optimal conditions were: inlet temperature of 120 °C, feed flow rate of 4 mL min-1, and colloidal silicon dioxide:maltodextrin ratio of 16%:4%. Under these conditions, the powder samples had spherical particles and desirable physicochemical and functional properties, such as low water activity and moisture content, good product recovery, reconstitution, and flowability. Thus, spray drying might be a promising technique for processing standardized H. umbellata extracts.

New bicompartmental model: an application for the production of gases using the in vitro technique / Novo modelo bicompartimental: uma aplicação para a produção de gases pela técnica in vitro

The purpose of this study was to propose a bicompartmental nonlinear model and to identify the best-performing model between the proposed model and the bicompartmental logistic (BL) mode regarding the quality of fit to the curve of cumulative gas production (CGP) using corn silage, sunflower, and their mixtures. Gas production was measured 2, 3, 4, 6, 8, 9, 10, 12, 15, 19, 24, 30, 36, 48, 72, and 96 h after beginning the in vitro fermentation process. The generated data were used to generate the parameters of each model tested using the stats package of the R computational tool version 4.0.4. The mathematical models were subjected to the following selection criteria: the adjusted coefficient of determination (Raj.), residual mean square (RMS), mean absolute deviation (MAD), and Akaike information criterion (AIC). It was demonstrated that the proposed model had better performance with a high Raj., and lower values of RMS, AIC, and MAD than the bicompartmental logistic model for the prediction of the parameters of cumulative gas production (CGP), per to present a superior fit in the set of criteria according to the methodology and conditions in which the present study was developed.(AU)

No presente trabalho, com silagem de milho, girassol e suas misturas, objetivou-se propor um modelo não linear bicompartimental e identificar entre o modelo proposto e Logístico Bicompartimental (LB), aquele que apresenta maior qualidade de ajuste à curva de cinética de produção cumulativa de gases (PCG). A leitura da produção de gás foi realizada nos tempos 2, 3, 4, 6, 8, 9, 10, 12, 15, 19, 24, 30, 36, 48, 72 e 96 horas, após o início do processo de fermentação in vitro. Os dados gerados foram utilizados para geração dos parâmetros de cada modelo testado com auxílio do pacote stats da ferramenta computacional R versão 4.0.4. Os modelos matemáticos foram submetidos aos seguintes critérios de seleção o coeficiente de determinação ajustado (Raj.), quadrado médio do resíduo (QMR), desvio médio absoluto (DMA) e o critério de informação de Akaike (AIC). Foi demonstrado que o modelo proposto teve melhor desempenho com altos Raj., e menores valores de QMR, AIC e DMA, por apresentar um ajustamento superior no conjunto dos critérios em comparação com o modelo logístico bicompartimental para a predição dos parâmetros de produção cumulativa de gases (PCG) de acordo com a metodologia e condições em que foi desenvolvido o presente estudo.(AU)

Proposal of a non-linear model to adjust in vitro gas production at different incubation times

This work aims to propose a new model named Gompertz-Von Bertalanffy bicompartmental (GVB), a combination of the models Gompertz and Von Bertalanffy. The GVB models is applied to fit the kinetic curve of cumulative gas production (CGP) of four foods (SS ­ sunflower silage; CS ­ corn silage; and the mixtures 340SS ­ 660 gkg-1 of corn silage and 340 gkg-1 of sunflower silage; and 660SS ­ 340 gkg-1 of corn silage and 660 gkg-1 of sunflower silage). The GVB fit is compared to models Logistic-Von Bertalanffy bicompartmental (LVB) and bicompartmental logistic (BL). All the process studied employed the semi-automatic "in vitro" technique of producing gases used in ruminant nutrition. The gas production readout was performed at times 2, 4, 6, 8, 10, 12, 15, 19, 24, 30, 48, 72, and 96 h. The data generated were used to estimate the models' parameters by the least squared method with the iterative Gauss-Newton process. The data fit quality of the models was verified using the adjusted coefficient of determination criterion (), mean residual square (MRS), Akaike information criterion (AIC), and mean absolute deviation (MAD). Among the analyzed models, the LVB model presented the best quality of fit evaluators for CS. In contrast, the GVB model showed better quality of fit to describe CGP over time for 340SS, 660SS, and SS, presenting the highest values of () and the lowest values of MSR, AIC, and MAD.

Tetramerization of the S100B Chaperone Spawns a Ca2+ Independent Regulatory Surface that Enhances Anti-aggregation Activity and Client Specificity.

Alzheimer's disease (AD) hallmarks include the aggregation of amyloid-ß (Aß), tau and neuroinflammation promoted by several alarmins. Among these is S100B, a small astrocytic homodimeric protein, upregulated in AD, whose multiple biological activities depend on localization, concentration, and assembly state. S100B was reported to inhibit the aggregation and toxicity of Aß42 and tau similarly to a holdase-type chaperone. This activity is dependent of Ca2+-binding, which triggers the exposure of a regulatory binding cleft at the S100B dimer interface with which amyloidogenic clients dynamically interact. Although the dimer prevails, a significant portion of secreted S100B in the human brain occurs as higher order multimers, whose protective functions remain uncharacterized and which we here investigate. Resorting to ThT-monitored aggregation kinetics, we determined that unlike the dimer, tetrameric S100B inhibits Aß42 aggregation at sub/equimolar ratios, an effect that persists in the absence of Ca2+ binding. Structural analysis revealed that S100B tetramerization spawns a novel extended cleft accommodating an aggregation-prone surface that mediates interactions with monomeric Aß client via hydrophobic interactions, as corroborated by Bis-ANS fluorescence and docking analysis. Correspondingly, at high ionic strength that reduces solvation and favours hydrophobic contacts, the inhibition of Aß42 aggregation by tetrameric S100B is 3-fold increased. Interestingly, this extended Ca2+-independent surface favours Aß42 as substrate, as tau K18 aggregation is not inhibited by the apo tetramer. Overall, results illustrate a mechanism through which oligomerization of the S100B chaperone fine-tunes anti-aggregation activity and client specificity, highlighting the potential functional relevance of S100B multimers in the regulation of AD proteotoxicity.

Correlation between short-term blood pressure variability parameters with mobil-O-graph pulse wave velocity.

BACKGROUND: Blood pressure variability (BPV) and arterial stiffness show an association with increased cardiovascular events. Evidences demonstrated an association between higher short-term systolic BPV and stiffer arteries. There is no previous study assessed the correlation between BPV and arterial stiffness measured by a Mobil-O-Graph device. We issued to evaluate the correlation between short-term BPV parameters and Mobil-O-Graph pulse wave velocity (PWV) among suspected hypertensive individuals under treatment. METHODS: Mobil-O-Graph device estimated arterial stiffness (oscillometric PWV [oPWV]) in 649 individuals, and they recorded 24-h ambulatory BP; 428 had suspected hypertension and 221 under treatment. We analyzed the correlation between oPWV and measures of BPV: SD of 24 h BP (24-h SD), SD of daytime BP (daytime-SD), and SD of nighttime BP (nighttime-SD), weighted SD of 24-h BP (wSD), coefficient of variation of 24-h BP (CV 24-h) and average real variability (ARV). RESULTS: Oscillometric PWV showed a positive correlation with all systolic BPV measures, in both groups. Among suspected hypertensives: 24-h SD, r = 0.30; SD daytime-SD, r = 0.34; nighttime-SD, r = 0.16; wSD, r = 0.30; CV 24-h, r = 0.24; ARV, r = 0.22. In the treated individuals: 24-h SD, r = 0.46; daytime-SD, r = 0.47; nighttime-SD, r = 0.35; wSD, r = 0.50; CV 24-h, r = 0.43; ARV, r = 0.37, all P < 0.001. Diastolic BPV demonstrated association with some measures of BPV. In suspected hypertensive group: nighttime-SD, r = 0.13; wSD, r = 0.10, both P < 0.001. And in treated individuals: daytime-SD, r = 0.23; wSD, r = 0.22; CV 24-h, r = 0.19 (all P < 0.001), ARV, r = 0.15 (P < 0.05). Systolic daytime-SD in suspected and diastolic CV 24-h in treated group independently predicted oPWV. CONCLUSION: We observed a positive and independent correlation between Mobil-O-Graph pulse wave velocity and BPV measures, strong to systolic BPV and weak to diastolic BP.

Dynamic interactions and Ca2+-binding modulate the holdase-type chaperone activity of S100B preventing tau aggregation and seeding.

The microtubule-associated protein tau is implicated in the formation of oligomers and fibrillar aggregates that evade proteostasis control and spread from cell-to-cell. Tau pathology is accompanied by sustained neuroinflammation and, while the release of alarmin mediators aggravates disease at late stages, early inflammatory responses encompass protective functions. This is the case of the Ca2+-binding S100B protein, an astrocytic alarmin which is augmented in AD and which has been recently implicated as a proteostasis regulator, acting over amyloid ß aggregation. Here we report the activity of S100B as a suppressor of tau aggregation and seeding, operating at sub-stoichiometric conditions. We show that S100B interacts with tau in living cells even in microtubule-destabilizing conditions. Structural analysis revealed that tau undergoes dynamic interactions with S100B, in a Ca2+-dependent manner, notably with the aggregation prone repeat segments at the microtubule binding regions. This interaction involves contacts of tau with a cleft formed at the interface of the S100B dimer. Kinetic and mechanistic analysis revealed that S100B inhibits the aggregation of both full-length tau and of the microtubule binding domain, and that this proceeds through effects over primary and secondary nucleation, as confirmed by seeding assays and direct observation of S100B binding to tau oligomers and fibrils. In agreement with a role as an extracellular chaperone and its accumulation near tau positive inclusions, we show that S100B blocks proteopathic tau seeding. Together, our findings establish tau as a client of the S100B chaperone, providing evidence for neuro-protective functions of this inflammatory mediator across different tauopathies.

Evaluation of three methods of suture for skin closure in total knee arthroplasty: a randomized trial.

BACKGROUND: There are several studies comparing techniques and different materials, yet the results are not unanimous. We compared three methods of skin closure in total knee arthroplasty (TKA), including suture with single stitches and unabsorbable MonoNylon®, as well as continuous subcuticular suture with Monocryl® or barbed Stratafix® absorbable suture. METHODS: A prospective, randomized study was conducted with 63 patients undergoing TKA between March 2016 and December 2016. Patients were divided into three groups: traditional suture MonoNylon® (n 22), subcuticular continuous suture with Monocryl® (n 20), and another barbed with Stratafix® (n 21). The closure time, length of wire used, pain intensity, possible complications, and cosmeses were evaluated. RESULTS: Subcuticular continuous suture using Monocryl® was superior to traditional suture using MonoNylon® as less thread was used (p 0.01) and a better cosmetic effect was achieved (p < 0.01), which was equal to Stratafix® aspects analyzed (p > 0.05). Complications were observed mostly in patients who used Stratafix®. CONCLUSIONS: This study concluded that the subcuticular suture with absorbable monofilament Monocryl® proved to be advantageous compared to the others because it presented results equal to the barbed Stratafix®, however with fewer complications. Furthermore, Monocryl® was shown to be equal or superior to traditional MonoNylon® suture regarding in relation pain intensity, aesthetic result, and effective cost. TRIAL REGISTRATION: WHO ICTRP identifier RBR78dh5d. Retrospectively registered: 07/29/2020.

Genetic divergence for adaptability and stability in sugarcane: Proposal for a more accurate evaluation.

The best agro-industrial performance presented by a crop genotype in one environment may not be reproduced in another owing to complex edaphoclimatic variations. Therefore, breeding programs are constantly attempting to obtain, through artificial hybridization, novel genotypes with high adaptability and stability potential. The objective of this study was to analyze genetic divergence in sugarcane based on the genotypic values of adaptability and stability. A total of 11 sugarcane genotypes were analyzed for eight agro-industrial traits. The genotypic values of the traits were determined using mixed model methodology, and the genetic divergence based on phenotypic and genotypic values was measured using the Mahalanobis distance. The distance matrices were correlated using the Mantel test, and the genotypes were grouped using the Tocher method. Genetic divergence is more accurate when based on genotypic values free of genotype-environment interactions and will differ from genetic divergence based on phenotypic data, changing the genotype allocations in the groups. The above methodology can be applied to assess genetic divergence to obtain novel sugarcane genotypes with higher productivity that are adapted to intensive agricultural systems using diverse technologies. This methodology can also be tested in other crops to increase accuracy in selecting the parents to be crossed.

Cu2+-binding to S100B triggers polymerization of disulfide cross-linked tetramers with enhanced chaperone activity against amyloid-ß aggregation.

S100B is an extracellular protein implicated in Alzheimer's Disease and a suppressor of amyloid-ß aggregation. Herein we report a mechanism tying Cu2+ binding to a change in assembly state yielding disulfide cross-linked oligomers with higher anti-aggregation activity. This chemical control of chaperone function illustrates a regulatory process relevant under metal and proteostasis dysfunction as in neurodegeneration.

Generation of models from existing models composition: An application to agrarian sciences.

Mathematical models that describe gas production are widely used to estimate the rumen degradation digestibility and kinetics. The present study presents a method to generate models by combining existing models and to propose the von Bertalanffy-Gompertz two-compartment model based on this method. The proposed model was compared with the logistic two-compartment one to indicate which best describes the kinetic curve of gas production through the semi-automated in vitro technique from different pinto peanut cultivars. The data came from an experiment grown and harvested at the Far South Animal Sciences station (Essul) in Itabela, BA, Brazil and gas production was read at 2, 4, 6, 8, 10, 12, 14, 17, 20, 24, 28, 32, 48, 72, and 96 h after the start of the in vitro fermentation process. The parameters were estimated by the least squares method using the iterative Gauss-Newton process in the software R version 3.4.1. The best model to describe gas accumulation was based on the adjusted coefficient of determination, residual mean squares, mean absolute deviation, Akaike information criterion, and Bayesian information criterion. The von Bertalanffy-Gompertz two-compartment model had the best fit to describe the cumulative gas production over time according to the methodology and conditions of the present study.

Zinc Binding to Tau Influences Aggregation Kinetics and Oligomer Distribution.

Metal ions are well known modulators of protein aggregation and are key players in Alzheimer's Disease, being found to be associated to pathologic protein deposits in diseased brains. Therefore, understanding how metals influence amyloid aggregation is critical in establishing molecular mechanisms that underlie disease onset and progression. Here, we report data on the interaction of full-length human Tau protein with calcium and zinc ions, evidencing that Tau self-assembly is differently regulated, depending on the type of bound metal ion. We established that Tau binds 4 Zn2+ and 1 Ca2+ per monomer while using native mass spectrometry analysis, without inducing order or substantial conformational changes in the intrinsically disordered Tau, as determined by structural analysis using circular dichroism and Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopies. However, Tau aggregation is found to proceed differently in the calcium- and -zinc bound forms. While the rate of aggregation, as determined from thioflavin-T (ThT) fluorescence kinetics, is highly increased in both cases, the reaction proceeds via different mechanisms, as evidenced by the absence of the lag phase in the reaction of zinc-bound Tau. Monitoring Tau aggregation using native mass spectrometry indeed evidenced a distinct distribution of Tau conformers along the reaction, as confirmed by dynamic light scattering analysis. We propose that such differences arise from zinc binding at distinct locations within the Tau sequence that prompt both the rapid formation of seeding oligomers through interactions at high affinity sites within the repeat domains, as well as amorphous aggregation, through low affinity interactions with residues elsewhere in the sequence, including at the fuzzy coat domain.

Effect of Low-Level Laser on the Healing of Bone Defects Filled with Autogenous Bone or Bioactive Glass: In Vivo Study.

PURPOSE: This study evaluated the effect of low-level laser therapy (LLLT) on the healing of bone defects filled with autogenous bone or bioactive glass. MATERIALS AND METHODS: A critical size defect with 5-mm diameter was created on the calvaria of 60 adult male rats divided into 6 groups (n = 10): group C (control), group LLLT (LLLT - GaAlAs, wavelength of 780 nm, power of 100 mW, energy density of 210 J/cm2 per point during 60 seconds/point, in five points, only once, after creation of the surgical defect), group AB (autogenous bone), group AB+LLLT (autogenous bone + LLLT), group BG (bioactive glass), group BG+LLLT (bioactive glass + LLLT). All animals were sacrificed at 30 days after surgery. The areas of newly formed bone (ANFB) and areas of remaining particles (ARP) were calculated in relation to the total area (TA). RESULTS: The highest mean ± SD ANFB was observed for group LLLT (47.67% ± 8.66%), followed by groups AB+LLLT (30.98% ± 16.59%) and BG+LLLT (31.13% ± 16.98%). There was a statistically significant difference in relation to ANFB between group C and the other groups, except for comparison with group BG (Tukey test, P > .05). There was no statistically significant difference in ANFB values between group AB and the other study groups (Tukey test, P > .05), group AB+LLLT and groups BG and BG+LLLT (Tukey test, P > .05), and between groups BG and BG+LLLT (Tukey test, P > .05). The highest mean ± SD ARP was found for group BG (25.15% ± 4.82%), followed by group BG+LLLT (17.06% ± 9.01%), and there was no significant difference between groups (t test, P > .05). CONCLUSION: The LLLT, in the present application protocol, did not increase the area of new bone formation when associated with autogenous bone or bioactive glass.

Doenças e agravos do trabalho em Minas Gerais de 2008 a 2012 / Work diseases and injuries in Minas Gerais from 2008 to 2012

A notificação dos acidentes de trabalho é de fundamental importância na gestão da saúde pública, tendo grande impacto no atendimento dos serviços de emergência e nos benefícios acidentários da Previdência Social. O objetivo deste estudo foi realizar uma análise descritiva dos dados de doenças ou agravos relacionados ao trabalho notificados em Minas Gerais, Brasil por meio de sistemas de informação do SUS, disponíveis no DATASUS. Tratou-se de estudo ecológico, exploratório descritivo, quantitativo, retrospectivo, apoiado em análise de base de dados secundários, no período de janeiro de 2008 a dezembro de 2012. Os resultados apontaram um aumento de 101,1% na proporção de municípios com casos de doenças ou agravos notificados relacionados ao trabalho e de 39,1% na taxa de acidentes de trabalho em Minas Gerais por 100 mil habitantes, taxa não proporcional ao crescimento populacional do estado no mesmo período. Concluiu-se que havia ainda um grande sub-registro nos sistemas de informação, principalmente no Sistema de Informação de Agravos de Notificação, apesar do crescimento das variáveis analisadas

The notification of occupational accidents has fundamental importance to the management of public health, with great impact on the attendance of emergency services and accidental benefits of Social Security. The objective of this study was to conduct a descriptive analysis of work diseases and injuries data reported in Minas Gerais, Brazil by means of SUS information systems available in DATASUS. This was an ecological, exploratory, descriptive, quantitative, retrospective study, based on secondary data analysis, from january 2008 to december 2012. The results indicated a 101.1% increase to the proportion of municipalities with reported cases of work related diseases or injuries and 39.1% to the rate of work accidents in Minas Gerais per 100,000 habitants, a not proportional rate to the state's population growth in the same period. In conclusion, there was still a great underreporting to the information systems, especially in the Notification of Injury Information System, despite the growth of the analyzed variables