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Diamond-Blackfan anaemia (DBA), first described over 80 years ago, is a congenital disorder of erythropoiesis with a predilection for birth defects and cancer. Despite scientific advances, this chronic, debilitating, and life-limiting disorder continues to cause a substantial physical, psychological, and financial toll on patients and their families. The highly complex medical needs of affected patients require specialised expertise and multidisciplinary care. However, gaps remain in effectively bridging scientific discoveries to clinical practice and disseminating the latest knowledge and best practices to providers. Following the publication of the first international consensus in 2008, advances in our understanding of the genetics, natural history, and clinical management of DBA have strongly supported the need for new consensus recommendations. In 2014 in Freiburg, Germany, a panel of 53 experts including clinicians, diagnosticians, and researchers from 27 countries convened. With support from patient advocates, the panel met repeatedly over subsequent years, engaging in ongoing discussions. These meetings led to the development of new consensus recommendations in 2024, replacing the previous guidelines. To account for the diverse phenotypes including presentation without anaemia, the panel agreed to adopt the term DBA syndrome. We propose new simplified diagnostic criteria, describe the genetics of DBA syndrome and its phenocopies, and introduce major changes in therapeutic standards. These changes include lowering the prednisone maintenance dose to maximum 0·3 mg/kg per day, raising the pre-transfusion haemoglobin to 9-10 g/dL independent of age, recommending early aggressive chelation, broadening indications for haematopoietic stem-cell transplantation, and recommending systematic clinical surveillance including early colorectal cancer screening. In summary, the current practice guidelines standardise the diagnostics, treatment, and long-term surveillance of patients with DBA syndrome of all ages worldwide., Competing Interests: Declaration of interests AK declares honoraria from chiesi and Novartis and a research grant from Novaris. AK is on the advisory board of Chiesi and Novartis. FML declares honoraria from Chiesi and is on the advisory board of Chiesi. LK is on the advisory board of Agios, Amgen, Bayer, and Novartis. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Context: A complex supramolecular process involving electrostatic and dispersion interactions and asphaltene aggregation is associated with detrimental petroleum deposition and scaling that pose challenges to petroleum recovery, transportation, and upgrading. The homodimers of seven heterocyclic model compounds, representative of moieties commonly found in asphaltene structures, were studied: pyridine, thiophene, furan, isoquinoline, pyrazine, thiazole, and 1,3-oxazole. The contributions of hydrogen bonding involving water bridges spanning between dimers and π-π stacking to the total interaction energy were calculated and analyzed. The distance between the planes of the aromatic rings is correlated with the π-π stacking interaction strength. All the dimerization reactions were exothermic, although not spontaneous. This was mostly modulated by the strength of the hydrogen bond of the water bridge and the π-π stacking interaction. Dimers bridged by two water molecules were more stable than those with additional water molecules or without any water molecule in the bridge. Energy decomposition analysis showed that the electrostatic and polarization components were the main stabilizing terms for the hydrogen bond interaction in the bridge, contributing at least 80% of the interaction energy in all dimers. The non-covalent interaction analysis confirmed the molecular sites that had the strongest (hydrogen bond) and weak (π-π stacking) attractive interactions. They were concentrated in the water bridge and in the plane between the aromatic rings, respectively., Methods: The density functional ωB97X-D with a dispersion correction and the Def2-SVP basis set were employed to investigate supramolecular aggregates incorporating heterocycles dimers with 0, 1, 2, and 3 water molecules forming a stabilizing bridge connecting the monomers. The non-covalent interactions were analyzed using the NCIplot software and plotted as isosurface maps using Visual Molecular Dynamics., (© 2024. Crown.)

Background: Oral squamous cell carcinoma is characterized by high rates of morbidity and mortality. Evidence obtained for different types of cancer shows that tumor initiation, progression, and therapeutic resistance are regulated by heat shock factor 1. This research aimed to analyze the effects of heat shock factor 1 on the biological behavior of oral squamous cell carcinoma., Methods: Clinicopathological and immunoexpression study of heat shock factor 1 in 70 cases of oral tongue SCC and functional assays by gene silencing of this factor in an oral tongue SCC cell line., Results: Heat shock factor 1 was overexpressed in oral tongue SCC specimens compared to normal oral mucosa (p < 0.0001) and in the SCC15 line compared to immortalized keratinocytes (p < 0.005). No significant associations were observed between overexpression of heat shock factor 1 and clinicopathological parameters or survival rates of the oral tongue SCC cases in the present sample. In vitro experiments showed that heat shock factor 1 silencing inhibited cell proliferation (p < 0.005) and cell cycle progression, with the accumulation of cells in the G0/G1 phase (p < 0.01). In addition, heat shock factor 1 silencing reduced cell invasion capacity (p < 0.05) and epithelial-mesenchymal transition, characterized by a decrease in vimentin expression (p < 0.05) and an increase in E-cadherin expression (p < 0.001)., Conclusion: Heat shock factor 1 may exert several functions that help maintain cell stability under the stressful conditions of the tumor microenvironment. Thus, strategies targeting the regulation of this protein may in the future be a useful therapeutic tool to control the progression of oral squamous cell carcinoma., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Patients undergoing transcatheter aortic valve implantation (TAVI) due to severe aortic stenosis have a high prevalence of coronary artery disease (CAD). As many of them have high surgical risk, CAD treatment in this group has typically been carried out with optimal medical treatment or paired with percutaneous coronary intervention (PCI). However, the best approach in this scenario is not well established. We aimed to evaluate 5-year cardiovascular outcomes in patients with aortic stenosis and chronic CAD treated with medical treatment alone compared to PCI coupled with medical therapy before or during TAVI. We used data from a large multinational electronic health record network (TriNetX). Patients aged 18 years or older with severe aortic stenosis and CAD who underwent TAVI in the last 10 years before the analysis were considered eligible. Five-year Kaplan-Meier curves and hazard ratios were calculated. We identified 19 058 patients undergoing isolated TAVI and 2277 patients undergoing TAVI and PCI. Using propensity matching scores, 2277 patients in each group were compared. The 5-year cumulative incidence of MACE was 22.92% in the isolated TAVI group, vs. 25.91% in the PCI-TAVI group. The probability of the composite primary outcome was not significantly different between the isolated TAVI group vs. the PCI-TAVI group [53.1 vs. 47.6%, adjusted hazard ratio (HR) 0.92, 95% confidence interval (CI), 0.80-1.05]. In a real-world study of patients with CAD and severe aortic stenosis, the 5-year probability of death, acute coronary syndrome and ischemic stroke did not differ between patients undergoing isolated TAVI compared to patients undergoing PCI before or during TAVI., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Reconciling the restoration of ecosystem services within agricultural landscapes is an effort that has been advancing within degraded areas restoration through agroforestry systems. However, to contribute to the effectiveness of these initiatives, it is essential to integrate landscape vulnerability and local demands to better highlight in which areas the implementation of agroforestry systems should be prioritized. Thus, we developed a spatial hierarchization methodology as a decision support tool as an active strategy for agroecosystem restoration. The proposed method constitutes a spatial indicator of priority areas to guide agroforestry interventions, including resource allocation and public policies for payment for environmental services. The methodology consists of Multicriteria Decision Analysis implemented in GIS software by combining input datasets based on biophysical conditions, environmental and socioeconomic aspects, that integrated promotes an assessment of the environment fragility, the pressures and responses to land use dynamic; a strategy for landscape restoration and conservation of the natural habitats, and multiple specific scenarios for decision making regarding the agricultural and the local actors demands. The output of the model provides the spatial distribution of areas suitable for the implementation of agroforestry systems, sorted into four priority levels (Low, Medium, High, and Extreme priority). The method is a promising tool proposal for territorial management and governance and subsidizes future research on the flows of ecosystem services.•Assessment of the environment fragility and the pressures and responses to land use dynamic.•Strategy for landscape restoration and conservation of remaining natural habitats.•Multiple specific scenarios for decision making regarding the agricultural and the local actors demands., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Buccal drug administration may be chosen as a medication route to treat various diseases for local or systemic effects. This study proposes the development of a thermosensitive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan to increase mucoadhesion, circumventing several limitations of this route of administration. Hydroxypropylmethylcellulose and Poloxamer ® 407 were incorporated for hydrogel production. Physicochemical characterization parameters, such as particle size distribution, mean diameter, polydispersity index, zeta potential, and morphology, were analyzed. Spherical homogeneous particles were obtained with average diameter, of 173 ± 22 nm for LNCc (curcumin lipid-core nanocapsules) and 179 ± 48 nm for CLNCc (chitosan-curcumin lipid-core nanocapsules). A PDI equal to 0.09 ± 0.02 for LNCc and 0.26 ± 0.01 for CLNCc confirmed homogeneity. Tensile analysis and washability test on porcine buccal mucosa indicated higher mucoadhesion for hydrogels in comparison to the nanocapsules in suspension, remaining on the mucous membrane up to 8 h (10.92 ± 3.95 µg of curcumin washed for H-LNCc and 28.41 ± 24.47 µg for H-CLNCc) versus the latter, which remained washed on the membrane for 90 min only (62.60 ± 4.72 µg for LNCc and 52.08 ± 1.63 µg for CLNCc). The irritant potential (IR) of the formulations was evaluated by the hen's egg chorioallantoic membrane test (HET-CAM), with no irritation phenomena observed. Formulations were tested for their efficacy in an in vitro model against oral squamous cancer cell line, showing a significant reduction in cell viability on all tested groups. These findings demonstrated that the proposed nanosystem is mucoadhesive and has potential to deliver buccal treatments., (© 2022. Controlled Release Society.)

The detection of Solar-Induced chlorophyll Fluorescence (SIF) by remote sensing has opened new perspectives on ecosystem studies and other related aspects such as photosynthesis. In general, fluorescence high-resolution studies were limited to proximal sensors, but new approaches were developed to improve SIF resolution by combining OCO-2 with MODIS orbital observations, improving its resolution from 0.5° to 0.05 on a global scale. Using a high-resolution dataset and rainfall data some SIF characteristics of the satellite were studied based across 06 contrasting ecosystems in Brazil: Amazonia, Caatinga, Cerrado, Atlantic Forest, Pampa, and Pantanal, from years 2015-2018. SIF spatial variability in each biome presented significant spatial variability structures with high R 2 values (>0.6, Gaussian models) in all studied years. The rainfall maps were positively and similar related to SIF spatial distribution and were able to explain more than 40% of SIF's spatial variability. The Amazon biome presented the higher SIF values (>0.4 W m -2 sr -1 μm -1 ) and also the higher annual rainfall precipitation (around 2000 mm), while Caatinga had the lowest SIF values and precipitations (<0.1 W m -2 sr -1 μm -1 , precipitation around 500 mm). The linear relationship of SIF to rainfall across biomes was mostly significant (except in Pantanal) and presented contrasting sensitivities as in Caatinga SIF was mostly affected while in the Amazon, SIF was lesser affected by precipitation events. We believe that the features presented here indicate that SIF could be highly affected by rainfall precipitation changes in some Brazilian biomes. Combining rainfall with SIF allowed us to detect the differences and similarities across Brazil's biomes improving our understanding on how these ecosystems could be affected by climate change and severe weather conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The recent studies of the variations in the atmospheric column-averaged CO 2 concentration ([Formula: see text]) above croplands and forests show a negative correlation between [Formula: see text]and Sun Induced Chlorophyll Fluorescence (SIF) and confirmed that photosynthesis is the main regulator of the terrestrial uptake for atmospheric CO 2 . The remote sensing techniques in this context are very important to observe this relation, however, there is still a time gap in orbital data, since the observation is not daily. Here we analyzed the effects of several variables related to the photosynthetic capacity of vegetation on [Formula: see text] above São Paulo state during the period from 2015 to 2019 and propose a daily model to estimate the natural changes in atmospheric CO 2 ., Results: The data retrieved from the Orbiting Carbon Observatory-2 (OCO-2), NASA-POWER and Application for Extracting and Exploring Analysis Ready Samples (AppEEARS) show that Global Radiation (Qg), Sun Induced Chlorophyll Fluorescence (SIF) and, Relative Humidity (RH) are the most significant factors for predicting the annual [Formula: see text] cycle. The daily model of [Formula: see text] estimated from Qg and RH predicts daily [Formula: see text] with root mean squared error of 0.47 ppm (the coefficient of determination is equal to 0.44, p < 0.01)., Conclusion: The obtained results imply that a significant part of daily [Formula: see text] variations could be explained by meteorological factors and that further research should be done to quantify the effects of the atmospheric transport and anthropogenic emissions., (© 2022. The Author(s).)

Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome, characterized as a rare congenital bone marrow erythroid hypoplasia (OMIM#105650). Erythroid defect in DBA results in erythroblastopenia in bone marrow as a consequence of maturation blockade between the burst forming unit-erythroid and colony forming unit-erythroid developmental stages, leading to moderate to severe usually macrocytic aregenerative (<20 × 109/L of reticulocytes) anemia. Congenital malformations localized mostly in the cephalic area and in the extremities (thumbs), as well as short stature and cardiac and urogenital tract abnormalities, are a feature of 50% of the DBA-affected patients. A significant increased risk for malignancy has been reported. DBA is due to a defect in the ribosomal RNA (rRNA) maturation as a consequence of a heterozygous mutation in 1 of the 20 ribosomal protein genes. Besides classical DBA, some DBA-like diseases have been identified. The relation between the defect in rRNA maturation and the erythroid defect in DBA has yet to be fully defined. However, recent studies have identified a role for GATA1 either due to a specific defect in its translation or due to its defective regulation by its chaperone HSP70. In addition, excess free heme-induced reactive oxygen species and apoptosis have been implicated in the DBA erythroid phenotype. Current treatment options are either regular transfusions with appropriate iron chelation or treatment with corticosteroids starting at 1 year of age. The only curative treatment for the anemia of DBA to date is bone marrow transplantation. Use of gene therapy as a therapeutic strategy is currently being explored., (Copyright © 2021 by The American Society of Hematology.)

The present study investigated the possibility of apoptosis-inducing activity in human leukemia U-937 and THP-1 cells by the flavonoid morin. The treatments were evaluated by using the MTT and LDH assays; analysis of mitochondrial membrane potential (ΔΨm) was evaluated by flow cytometry, cell death by apoptosis was confirmed by fluorescence microscopy and by assessing the activity of caspases-3 and -6. The data indicated that the flavonoid morin has promoted a decrease in cell viability in a concentration-dependent way for both of the cancerous cell lines. An increase in the percentage of cell death caused by apoptosis was associated to a potential alteration in the mitochondrial membrane (ΔΨm) suggesting the involvement of cell death in intrinsic apoptotic pathways. Activation of caspases-3 and -6 confirmed the presence of apoptotic activity from morin. The results reinforce the antileukemic potential of flavonol morin.

Background: The transition in the population pyramid is a reality in several locations around the world and projections of an increase in the older population in Brazil demonstrate the relevance of studies on factors that may interfere in the functionality and quality of life in this age group. Thus, the present study aims to assess depression levels and their relationship with sleep quality in institutionalized and community older adults., Methods: This cross-sectional study included 220 older people of both sexes, divided into two groups, institutionalized older adults, and community older adults. The older adults were monitored by Community Health Agents (CHA), through identification of everyone in their micro area using a method of random name generation, based on geographic location. Due to the small number of institutionalized older adults, all residents in the institutions were recruited, according to the inclusion and exclusion criteria. The Geriatric Depression Scale (GDS-15) and Pittsburgh Sleep Quality Index (PSQI) were used to assess depression and sleep quality., Results: Among the 220 older adults, 175 were community members and 45 were institutionalized. The survey revealed that institutionalized older adults had a higher percentage of severe depression compared to community dwelling older adults (p <  0.039)., Conclusion: Older adults in the community present greater symptoms of depression and better sleep than institutionalized older adults. There was a direct association between sleep quality and depression. In our sample, being institutionalized and female positively influenced and feeling alone negatively influenced depressive symptoms., (© 2021. The Author(s).)

The conversion of CO 2 into dimethyl carbonate (DMC) is an environmental and industrial appealing topic because it contributes to reduce the emissions of CO 2 and to increase its use as raw material. In the present study we employed the CAM-B3LYP/def2-SVP DFT approach to evaluate the thermodynamic and kinetic parameters for the catalytic conversion of CO 2 and methanol into DMC. Starting with the activation of four methanol molecules by the [Me 2 SnO] 2 dimer, we computed all the stationary points along the pathway to convert CO 2 and methanol into the DMC. The capture of two CO 2 molecules is promoted by an alkoxitin intermediate, in an exothermic process, with low activation energy. Formation of a first DMC occurs after an intramolecular rerrangement involving a tetrahedral intermediate. The formation of a second DMC may occur either in a process similar to the first one or by dimerization of the hemicarbonate formed after releasing the first DMC. In this pathway, the [Me 2 (OH)SnO(OMe)SnMe 2 ] 2 complex is formed. This complex is less reactive than [Me 2 Sn(OMe) 2 ] 2 but still conserves the catalytic activity. Identification of this mechanism suggests that the catalytic action of Me 2 SnO can be improved by modulating the formation of the final [Me 2 (OH)SnO(OMe)SnMe 2 ] 2 complex.

We report thermodynamic, geometric, and electronic parameters for the interaction between neutral ligands and the [Hg(H 2 O)] 2+ dication, using the B3LYP/6-311 + G(d,p) approach. Gibbs free energies for the interaction were employed to rank the affinity order of the several neutral ligands. To identify the parameters that characterize the affinity between the two fragments, the metal-ligand interaction was analyzed according to the EDA, NBO, and QTAIM decomposition schemes. The phosphine oxide showed the highest affinity for the Hg(H 2 O) 2+ dication, mainly due to the P=O bond polarization. Ligands containing the sulfur atom, characterized by a high covalent component for the metal-ligand interaction, are the following in the interaction order. According to the Gibbs free energy for substitution of one water molecule in the [Hg(H 2 O) 2 ] 2+ complex, the sequence for the affinity order is: phosphine oxide > thioketone > thioesther > lactam > amide > amine > carboxylic acid > thiophene > ketone > esther > thiol > thiocyanate > ammonia > disulfide > aldehyde > ether > haloydrin > alcohol > enol > azide. Graphical abstract Synopsis The interaction between the Hg 2+ cation and monodentate ligands containing S, O, or N atoms was evaluated in terms of energetic (bond strength, electrostatic and covalent interactions, donation energy), geometric (metal-ligand distance), electronic (atomic charges, orbital overlap, orbital hybridization) and topologic parameters.

Diamond-Blackfan anemia (DBA) is a congenital pure red cell aplasia associated with congenital abnormalities and cancer predisposition. Allogeneic hematopoietic stem cell transplantation (HSCT) can correct the hematological phenotype and is indicated in transfusion-dependent patients. In 70 children reported to the German DBA and French HSCT registries, HSCT was performed from 1985 to 2017. Median age at HSCT was 5.5 years (range, 0.9-17.3 years). Two-thirds of patients (64%) were transplanted from a matched sibling donor (MSD), and most procedures were performed after the year 1999 (73%). Primary engraftment was achieved in all patients. One patient developed secondary graft failure. Cumulative incidence of acute graft-versus-host disease (GVHD) was 24% for °II-IV (95% confidence interval [CI], 16% to 37%) and 7% for °III-IV (95% CI, 3% to 17%); cumulative incidence of chronic GVHD was 11% (95% CI, 5% to 22%). The probability of chronic GVHD-free survival (cGFS) was 87% (95% CI, 79% to 95%) and significantly improved over time (<2000: 68% [95% CI, 47% to 89%] vs ≥2000: 94% [95% CI, 87% to 100%], P < .01). cGFS was comparable following HSCT from a MSD and an unrelated donor (UD). Of note, no severe chronic GVHD or deaths were reported following MSD-HSCT after 1999. The difference of cGFS in children transplanted <10 years of age compared with older patients did not reach statistical significance (<10 years: 90% [95% CI, 81% to 99%] vs 10-18 years 78% [95% CI, 58% to 98%]). In summary, these data indicate that HSCT is efficient and safe in young DBA patients and should be considered if a MSD or matched UD is available. HSCT for transfusion dependency only must be critically discussed in older patients., (© 2020 by The American Society of Hematology.)

The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases (RTKs) are among the first layer of molecules that receive, interpret, and transduce signals leading to distinct cancer cell phenotypes. Since the discovery of the tooth-lid factor-later characterized as the epidermal growth factor (EGF)-and its high-affinity binding EGF receptor, HER kinases have emerged as one of the commonly upregulated or hyperactivated or mutated kinases in epithelial tumors, thus allowing HER1-3 family members to regulate several hallmarks of cancer development and progression. Each member of the HER family exhibits shared and unique structural features to engage multiple receptor activation modes, leading to a range of overlapping and distinct phenotypes. EGFR, the founding HER family member, provided the roadmap for the development of the cell surface RTK-directed targeted cancer therapy by serving as a prototype/precursor for the currently used HER-directed cancer drugs. We herein provide a brief account of the discoveries, defining moments, and historical context of the HER family and guidepost advances in basic, translational, and clinical research that solidified a prominent position of the HER family in cancer research and treatment. We also discuss the significance of HER3 pseudokinase in cancer biology; its unique structural features that drive transregulation among HER1-3, leading to a superior proximal signaling response; and potential role of HER3 as a shared effector of acquired therapeutic resistance against diverse oncology drugs. Finally, we also narrate some of the current drawbacks of HER-directed therapies and provide insights into postulated advances in HER biology with extensive implications of these therapies in cancer research and treatment., (© 2020 Elsevier Inc. All rights reserved.)

Background: Previous studies found a high prevalence of pathogens among female sex workers (FSWs) in the Amazon region, and established their parenteral and sexual transmission. This study estimated the prevalence of hepatitis C virus (HCV) infection and associated risk factors, and the frequency of HCV genotypes and resistance-associated substitutions (RASs) in this vulnerable group., Methods: Distinct sampling methods were used to access 412 FSWs in cities and riverside communities in the Amazon region from 2015 to 2018. Three methods for HCV diagnosis were used to determine infection status. HCV genotypes and RASs were identified by sequencing and nucleotide fragment analysis. An association between HCV infection and exposure factors was determined by bivariate and multivariate analysis., Results: In total, 44 (10.7%) FSWs were exposed to HCV, and 32 (7.8%) of them had active infection. Nine socioeconomic characteristics and risky sexual behaviors were associated with HCV exposure, particularly unprotected sex and condom exemption for the clients who paid extra money. Genotype 1 (81.3%) and 3 (18.7%) were detected. The frequency of FSWs with RASs was 23.1% (6/26) for grazoprevir related to the occurrence of substitutions Y56F and S122G., Conclusions: HCV infection among FSWs is highly prevalent and dominated by genotype I. Urgent preventive and treatment measures are required to reduce HCV infection in FSWs and the general population., Competing Interests: The authors declare no conflict of interest.

Background: Appropriate dietary recommendations represent a key part of secondary prevention in cardiovascular disease (CVD). We evaluated the effectiveness of the implementation of a nutritional program on quality of diet, cardiovascular events, and death in patients with established CVD., Methods: In this open-label, multicenter trial conducted in 35 sites in Brazil, we randomly assigned (1:1) patients aged 45 years or older to receive either the BALANCE Program (experimental group) or conventional nutrition advice (control group). The BALANCE Program included a unique nutritional education strategy to implement recommendations from guidelines, adapted to the use of affordable and regional foods. Adherence to diet was evaluated by the modified Alternative Healthy Eating Index. The primary end point was a composite of all-cause mortality, cardiovascular death, cardiac arrest, myocardial infarction, stroke, myocardial revascularization, amputation, or hospitalization for unstable angina. Secondary end points included biochemical and anthropometric data, and blood pressure levels., Results: From March 5, 2013, to Abril 7, 2015, a total of 2534 eligible patients were randomly assigned to either the BALANCE Program group (n = 1,266) or the control group (n = 1,268) and were followed up for a median of 3.5 years. In total, 235 (9.3%) participants had been lost to follow-up. After 3 years of follow-up, mean modified Alternative Healthy Eating Index (scale 0-70) was only slightly higher in the BALANCE group versus the control group (26.2 ± 8.4 vs 24.7 ± 8.6, P < .01), mainly due to a 0.5-serving/d greater intake of fruits and of vegetables in the BALANCE group. Primary end point events occurred in 236 participants (18.8%) in the BALANCE group and in 207 participants (16.4%) in the control group (hazard ratio, 1.15; 95% CI 0.95-1.38; P = .15). Secondary end points did not differ between groups after follow-up., Conclusions: The BALANCE Program only slightly improved adherence to a healthy diet in patients with established CVD and had no significant effect on the incidence of cardiovascular events or death., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

This study determined the prevalence of human immunodeficiency virus (HIV) infection and its associated factors in female sex workers (FSWs) from the municipality of Bragança in the state of Pará, Brazil. A cross-sectional study using a respondent-driven sampling method was used to investigate 137 FSWs. They were interviewed using a questionnaire for the collection of data on their characteristics and risk behavior. Blood samples were collected for serological and molecular testing for HIV. Poisson regression models were used to estimate the reasons of prevalence (RP). The majority was single, young, poorly educated, had a low monthly income, and had worked in the sex trade for more than 7 years. Sexual services were offered either directly (easy identification of FSWs in street markets, town squares, street corners, bars, and gas stations) or indirectly/discretely (more complex identification of FSWs, offering services through a cryptic approach or an intermediary). Overall, 22 (16.06%) FSWs had anti-HIV-1/2 antibodies, and 21 (15.33%) also had complementary DNA-HIV. The use of illicit drugs [adjusted RP (aRP) = 3.13; 95% confidence interval (CI) = 1.27-8.41], unprotected sex (aRP = 4.09; 95% CI = 1.34-11.62), anal sex (aRP = 4.01; 95% CI = 1.37-10.15), the exemption of condoms for clients paying extra (aRP = 4.71; 95% CI = 1.52-10.89), more than 7 years working as a sex worker (aRP = 6.04; 95% CI = 1.20-16.33), low levels of education (aRP = 3.55; 95% CI = 1.15-11.02), and a lack of regular medical or gynecological examinations were all associated with HIV infection (aRP = 5.87; 95% CI = 1.26-15.71). The FSWs who offered their services indirectly suffered significantly less physical and sexual aggression, charged more for encounters, had a significantly higher monthly income, and were more likely to have undergone a medical or gynecological examination within the preceding 12 months. This study identified information relevant to the control and prevention of HIV in FSWs.

The recovery of walking function following spinal cord injury (SCI) is of major importance to patients and clinicians. In experimental SCI studies, a rat model is widely used to assess walking function, following thoracic spinal cord lesion. In an effort to provide a resource which investigators can refer to when seeking the most appropriate functional assay, the authors have compiled and categorized the behavioral assessments used to measure the deficits and recovery of the gait in thoracic SCI rats. These categories include kinematic and kinetic measurements. Within this categorization, we discuss the advantages and disadvantages of each type of measurement. The present review includes the type of outcome data that they produce, the technical difficulty and the time required to potentially train the animals to perform them, and the need for expensive or highly specialized equipment. The use of multiple kinematic and kinetic parameters is recommended to identify subtle deficits and processes involved in the compensatory mechanisms of walking function after experimental thoracic SCI in rats., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Antihistamines are widely used to alleviate the symptoms caused by allergic reactions. Most of these drugs have zwitteriónicas and/or amphoteric characteristics, which confer additional analytical challenges. This work aimed to develop a single eco-friendly and efficient chromatographic methods for analysis of seven antihistamines, namely, azelastine HCl, desloratadine, ebastine, fexofenadine HCl, ketotifen, loratadine, and olopatadine HCl. The separations were obtained using RP C-18 LUNA (150x4.6mm, 5  μ m) column. The mobile phase consisted of acetonitrile and acidified water (pH 2.1) in the following proportion: 15:85, v/v for desloratadine, 25:75, v/v for ketotifen and olopatadine, 32:68, v/v for fexofenadine, 35:65, v/v for azelastine and loratadine, and 45:55, v/v for ebastine. All separations were obtained in less than 7.0 min. A prototype method was fully validated and applied in the assay of azelastine HCl in nasal solutions. The proposed methods for analysis of seven antihistamines are highly efficient, selective, and sensitive. Moreover, all methods can be considered excellent in terms of greenness, with total organic residue < 2.5 mL/analysis. An improved gradient method is also described for separation of azelastine HCl and its related impurities.

A series of B3LYP/6-311+G(d,p) calculations of the affinity of monodentate ligands for [Cd(H 2 O) 3 ] 2+ are performed. Three types of ligands containing O (phosphine oxide, lactam, amide, carboxylic acid, ester, ketone, aldehyde, ether, halohydrin, enol, furan), N (thiocyanate, amine, ammonia, azide), and S (thioester, thioketone, thiol, thiophene, disulfide) interacting atoms are investigated. The results show that phosphine oxide has the largest affinity for the cadmium cation due to the polarization of the P=O bond. As the P atom has a large atomic radius, the O atom can polarize the electronic cloud enhancing its amount of electronic charge and favoring the interaction with Cd 2+ . The affinity order found is phosphine oxide > thioester > lactam > amide > carboxylic acid > ester > thioketone > ketone > thiocyanate > amine > ammonia > aldehyde > ether > thiol > thiophene > enol > halohydrin > disulfide > azide > furan ligands. These results were also corroborated by the functional M06-2X. The electronic effects (resonance and induction) of neighboring groups of the interacting atom modulate the strength of metal-ligand binding. For almost all the O-donor ligands the electrostatic component has the same magnitude as the covalent term, while for the N- and S-donor ligands the covalent term is predominant. The polarization term accounts for twice the exchange term as part of the covalent component. The dispersion term varies less than 2 kcal mol -1 for the complexes analyzed. The Pauli repulsion term is correlated with the metal ligand distance, increasing in the compounds with decreased metal-ligand bond length. The charge between the interacting atoms is also strongly correlated with both the interacting strength and the electrostatic interaction component. The natural bond orbital analysis highlights correlations of the bond order, and S and P contributions of the interacting metal-ligand orbital with the coordination strength. Graphical abstract The affinity of 20 monodentate ligands with different functional groups for the [Cd(H 2 O) 3 ] 2+ cation is calculated based on the interaction enthalpy and Gibbs free energy for the substitution of one water molecule from the fully hydrated cation. The affinity is correlated with geometric, electronic, and energetic parameters of the ligands and the complexes as well as with energy decomposition and natural bond order analyses results.

Calcium complexes with bidentate carbonyl ligands are important in biological systems, medicine and industry, where the concentration of Ca 2+ is controlled using chelating ligands. The exchange of two water molecules of [Ca(H 2 O) 6 ] 2+ for one bidentate monosubstituted and homo disubstituted dicarbonyl ligand was investigated using the B3LYP/6-311++G(d,p) method. The ligand substituents NH 2 , OCH 3 , OH, CH 3 , H, F, Cl, CN and NO 2 are functional groups with distinct electron-donating and -withdrawing effects that bond directly to the sp 2 C atom of the carbonyl group. The geometry, charge and energy characteristics of the complexes were analyzed to help understand the effects of substituents, spacer length and chelation. Coordination strength was quantified in terms of the enthalpy and free energy of the exchange reaction. The most negative enthalpies were calculated for the coordination of bidentate ligands containing three to five methylene group spacers between carbonyls. The chelate effect contribution was analyzed based on the thermochemistry. The electronic character of the substituent modulates the strength of binding to the metal cation, as ligands containing electron-donor substituents coordinate stronger than those with electron-acceptor substituents. This is reflected in the geometric (bond length and chelating angle), electronic (atomic charges) and energetic (components of the total interacting energy) characteristics of the complexes. Energy decomposition analysis (EDA)-an approach for partitioning of the energy into its chemical origins-shows that the electrostatic component of the coordination is predominant, and yields relevant contribution of the covalent term, especially for the electron-withdrawing substituted ligands. The chelate effect of the bidentate ligands was noticeable when compared with substitution by two monodentate ligands. Graphical abstract The affinity of 18 bidentate carbonyl ligands toward the [Ca(H 2 O) 4 ] 2+ cation is evaluated in terms of energetic, geometric and electronic parameters of the isolated ligands and the substituted aqua complexes. The electronic effects-inductive and mesomeric-intrinsic to the molecular structure of each ligand are found to modulate the strength of the metal-ligand interaction. The effects of polysubstitution, chelation and the length of the alkyl spacers between the anchor points of the ligand are also analyzed.

Background: The lack of a correlation between myocardial necrosis biomarkers and electrocardiographic abnormalities after revascularization procedures has resulted in a change in the myocardial infarction (MI) definition., Methods: Patients with stable multivessel disease who underwent percutaneous or surgical revascularization were included. Electrocardiograms and concentrations of high-sensitive cardiac troponin I (cTnI) and creatine kinase (CK)-MB were assessed before and after procedures. Cardiac magnetic resonance and late gadolinium enhancement were performed before and after procedures. MI was defined as more than five times the 99th percentile upper reference limit for cTnI and 10 times for CK-MB in percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), respectively, and new late gadolinium enhancement for cardiac magnetic resonance., Results: Of the 202 patients studied, 69 (34.1%) underwent on-pump CABG, 67 (33.2%) off-pump CABG, and 66 (32.7%) PCI. The receiver operating characteristic curve showed the accuracy of cTnI for on-pump CABG, off-pump CABG, and PCI patients was 21.7%, 28.3%, and 52.4% and for CK-MB was 72.5%, 81.2%, and 90.5%, respectively. The specificity of cTnI was 3.6%, 9.4%, and 42.1% and of CK-MB was 73.2%, 86.8%, and 96.4%, respectively. Sensitivity of cTnI was 100%, 100%, and 100% and of CK-MB was 69.2%, 64.3%, and 44.4%, respectively. The best cutoff of cTnI for on-pump CABG, off-pump CABG, and PCI was 6.5 ng/mL, 4.5 ng/mL, and 4.5 ng/mL (162.5, 112.5, and 112.5 times the 99th percentile upper reference limit) and of CK-MB was 37.5 ng/mL, 22.5 ng/mL, and 11.5 ng/mL (8.5, 5.1, and 2.6 times the 99th percentile upper reference limit), respectively., Conclusions: Compared with cardiac magnetic resonance, CK-MB was more accurate than cTnI for diagnosing MI. These data suggest a higher troponin cutoff for the diagnosis of procedure-related MI., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The influence of diabetes mellitus on myocardial ischemic preconditioning is not clearly defined. Experimental studies are conflicting and human studies are scarce and inconclusive., Objectives: Identify whether diabetes mellitus intervenes on ischemic preconditioning in symptomatic coronary artery disease patients., Methods: Symptomatic multivessel coronary artery disease patients with preserved systolic ventricular function and a positive exercise test underwent two sequential exercise tests to demonstrate ischemic preconditioning. Ischemic parameters were compared among patients with and without type 2 diabetes mellitus. Ischemic preconditioning was considered present when the time to 1.0 mm ST deviation and rate pressure-product were greater in the second of 2 exercise tests. Sequential exercise tests were analyzed by 2 independent cardiologists., Results: Of the 2,140 consecutive coronary artery disease patients screened, 361 met inclusion criteria, and 174 patients (64.2 ± 7.6 years) completed the study protocol. Of these, 86 had the diagnosis of type 2 diabetes. Among diabetic patients, 62 (72 %) manifested an improvement in ischemic parameters consistent with ischemic preconditioning, whereas among nondiabetic patients, 60 (68 %) manifested ischemic preconditioning (p = 0.62). The analysis of patients who demonstrated ischemic preconditioning showed similar improvement in the time to 1.0 mm ST deviation between diabetic and nondiabetic groups (79.4 ± 47.6 vs 65.5 ± 36.4 s, respectively, p = 0.12). Regarding rate pressure-product, the improvement was greater in diabetic compared to nondiabetic patients (3011 ± 2430 vs 2081 ± 2139 bpm x mmHg, respectively, p = 0.01)., Conclusions: In this study, diabetes mellitus was not associated with impairment in ischemic preconditioning in symptomatic coronary artery disease patients. Furthermore, diabetic patients experienced an improvement in this significant mechanism of myocardial protection.

Objectives: The technical difficulty in the revascularization of the circumflex artery territory with off-pump surgery may compromise the outcome of this method in clinical follow-up. We aimed to evaluate cardiac events in patients with stable coronary artery disease and severe obstruction of the circumflex system, undergoing coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass., Methods: MASS III was a single-centre study that evaluated 308 patients with multivessel coronary artery disease randomized to on-pump (153) or off-pump (155) CABG. Of this total, 260 (84.4%) patients had, on coronary angiography, at least one 70% obstruction in the circumflex territory (141 on-pump and 119 off-pump). The combined outcome was death, myocardial infarction, target vessel revascularization (angioplasty or surgery) or hospitalization for cardiac causes. Variables with possible associations (P < 0.1) were included in the multivariate analysis., Results: The two groups were well matched for demographics and clinical and angiographic characteristics. After 5 years of follow-up, off-pump CABG had higher combined events than on-pump had: 25 (21%) vs 17 (12%), hazard ratio 1.88, 95% confidence interval 1.02-3.48, P = 0.041. In the multivariate model with the inclusion of the following variables: age (P = 0.09) and complete revascularization (P = 0.68), off-pump surgery remained as a predictor of combined events in 5 years, P = 0.03., Conclusions: In patients with multivessel coronary artery disease and severe lesions in the circumflex territory, off-pump coronary artery bypass surgery resulted in a higher incidence of cardiac events at 5-year follow-up., Clinical Trial Registration Number: ISRCTN59539154 (http://www.controlled-trials.com)., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Patients with coronary artery disease vary widely in terms of prognosis, which is mainly dependent on ventricular function. In relation to the major outcomes of death and myocardial infarction, it is not clear in the literature if an invasive strategy of myocardial revascularization is superior to a conservative strategy of optimized medical therapy. Moreover, with the exception of patients with left main coronary disease, this similarity in prognosis also occurs in different subgroups of patients.

Since 2009 a policy has been implemented in Brazil to establish the natural concentrations of potentially toxic substances in soil for each state. Historically a 'mining state', Minas Gerais established a Quality Reference Value for metal(loid)s for all of the soils in the state. To successfully establish these values it is important to study the spatial geochemical diversity for the state. In this context, the objectives of this work are: (1) to evaluate the natural concentrations of metal(loid)s in pristine Minas Gerais soils and (2) to interpret the spatial variability in concentration of these elements. The 0-20 cm layer of soils was sampled for 697 georeferenced sites including the main geological materials and soil groups. Soil properties were analyzed according to methodologies suitable for Brazilian soils. The concentration of metal(loid)s was determined by acid extraction according to EPA 3051A. Descriptive statistics, Pearson correlation and spatial variability analyses were performed. The dominance of acidic pH and low CEC values reflects the pervasive deep acid weathering. The variability of metal(loid) concentrations for soils of the state may be attributed to geological diversity and different pedogenesis. Correlation and spatial analysis indicated that the Fe concentration is strongly associated with metal(loid) concentrations in topsoil. According to the spatial geochemical diversity of the state, a k-means cluster analysis was performed which identified four clusters. A significant difference in the mean values of metal(loid) concentrations between the clusters confirmed that the single Quality Reference Value established does not represent the geochemical diversity of soils in Minas Gerais., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction. Bipolar disorder (BD) implies risk of suicide. The age at onset (AAO) of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words "bipolar disorder," "suicide attempts," "cannabis," "marijuana," "early age at onset," and "early onset." Results. The following percentages in bipolar patients were found: suicide attempts 3.6-42%; suicide attempts and substance use 5-60%; suicide attempts and cannabis use 15-42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD) was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear.

Coronary subclavian steal syndrome is a rare cause of recurrent angina after coronary artery bypass grafting. Identification of the myocardial ischemic region is crucial because it guides revascularization interventions to improve symptoms and myocardial ischemia. Positron emission computed tomography (PET) with rubidium might be a helpful tool because it identifies ischemia, localizes more precisely the ischemic region, and evaluates coronary flow reserve. Here, we report a case of recurrence of angina after coronary artery bypass grafting caused by an obstruction in the left subclavian artery and consequently by coronary steal syndrome confirmed by PET., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Hypertrophic cardiomyopathy is a genetic cardiac disease characterized by marked variability in morphological expression and natural history. The hypertrophic myocardium is often confined to the septum or lateral wall of the left ventricle, but it can also be encountered in the middle or apical segments of the myocardium. Treatment is based on medical therapy. Others therapies, such as embolization of the septal artery or ventriculomyectomy, are indicated in special situations. Surgery is the standard treatment, and it is classically done via a transaortic approach; however, in cases in which the hypertrophic myocardium is confined to mid-apical segments, a transapical approach is an option. Only a few cases of mid-apical obstructive hypertrophic cardiomyopathy treated with a myectomy using a transapical approach have been reported in the English-language literature. In this report, we present a case of a patient with mid-apical obstructive hypertrophic cardiomyopathy treated using this new approach., Case Presentation: A 63-year-old Caucasian woman presented with a history of chest pain and shortness of breath causing significant limitations on her daily life activities. She had a history of coronary artery disease. Her physical examination was unremarkable. Transthoracic echocardiography revealed normal systolic function and significant concentric left ventricular hypertrophy that was greater in the mid-apical region. Nuclear magnetic resonance imaging confirmed significant hypertrophy of the median segments of the left ventricle. The patient had persistent symptoms despite receiving optimized medical treatment, and a surgical approach was indicated. As a myectomy using transaortic technique was thought to be difficult to perform in her case, a transapical approach was used. No complications occurred, and her symptoms resolved., Conclusion: A transapical myectomy should be taken into consideration for patients with mid-apical obstructive hypertrophic cardiomyopathy that is refractory to medical treatment.

Objective: To evaluate whether flexibility and gender influence students' posture., Method: Evaluation of 60 female and male students, aged 5 to 14 years, divided into two groups: normal flexibility (n=21) and reduced flexibility (n=39). Flexibility and posture were assessed by photogrammetry and by the elevation of the lower limbs in extension, considering the leg angle and the postural evaluation. Descriptive statistics (mean and standard deviation) were used for data analysis. Analysis of variance (ANOVA) was applied to assess the joint influence of flexibility and gender on the posture-dependent variables. After verifying an interactive effect between the variables of gender and flexibility, multiple comparisons using the t test were applied., Results: Flexibility influenced the symmetry angle of the knee (p<0.05) and anteroposterior body tilt (p<0.05). Gender did not influence postural angles (p>0.05). There was an interactive effect between the variables of gender and flexibility on the knee symmetry angle (p<0.02). Male students with reduced flexibility had greater asymmetry of the knee when compared to the other subgroups., Conclusion: Posture was influenced by an isolated effect of the variable of flexibility and by an interactive effect between gender and flexibility., (Copyright © 2014 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.)

Objective: To describe a clinical report pre- and post-neurofunctional intervention in a case of agenesis of the corpus callosum., Case Description: Preterm infant with corpus callosum agenesis and hypoplasia of the cerebellum vermis and lateral ventricles, who, at the age of two years, started the proposed intervention. Functional performance tests were used such as the neurofunctional evaluation, the Gross Motor Function Measure and the Gross Motor Function Classification System. In the initial evaluation, absence of equilibrium reactions, postural transfers, deficits in manual and trunk control were observed. The intervention was conducted with a focus on function, prioritizing postural control and guidance of the family to continue care in the home environment. After the intervention, there was an improvement of body reactions, postural control and movement acquisition of hands and limbs. The intervention also showed improvement in functional performance., Comments: Postural control and transfers of positions were benefited by the neurofunction intervention in this case of agenesis of the corpus callosum. The approach based on function with activities that involve muscle strengthening and balance training reactions, influenced the acquisition of a more selective motor behavior., (Copyright © 2014 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.)

Leprosy remains a public health problem in Brazil with new case incidence exceeding World Health Organization (WHO) goals in endemic clusters throughout the country. Migration can facilitate movement of disease between endemic and non-endemic areas, and has been considered a possible factor in continued leprosy incidence in Brazil. A study was conducted to investigate migration as a risk factor for leprosy. The study had three aims: (1) examine past five year migration as a risk factor for leprosy, (2) describe and compare geographic and temporal patterns of migration among past 5-year migrants with leprosy and a control group, and (3) examine social determinants of health associated with leprosy among past 5-year migrants. The study implemented a matched case-control design and analysis comparing individuals newly diagnosed with leprosy (n = 340) and a clinically unapparent control group (n = 340) without clinical signs of leprosy, matched for age, sex and location in four endemic municipalities in the state of Maranhão, northeastern Brazil. Fishers exact test was used to conduct bivariate analyses. A multivariate logistic regression analysis was employed to control for possible confounding variables. Eighty cases (23.5%) migrated 5-years prior to diagnosis, and 55 controls (16.2%) migrated 5-years prior to the corresponding case diagnosis. Past 5 year migration was found to be associated with leprosy (OR: 1.59; 95% CI 1.07-2.38; p = 0.02), and remained significantly associated with leprosy after controlling for leprosy contact in the family, household, and family/household contact. Poverty, as well as leprosy contact in the family, household and other leprosy contact, was associated with leprosy among past 5-year migrants in the bivariate analysis. Alcohol consumption was also associated with leprosy, a relevant risk factor in susceptibility to infection that should be explored in future research. Our findings provide insight into patterns of migration to localize focused control efforts in endemic areas with high population mobility.

The affinity of the pentaaqua Mg(2+) cation for a set of para-substituted imino [HN = CHC₆H₄(R)] and thiocarbonyl [S = CHC₆H₄(R)] ligands (R = H, F, Cl, Br, OH, OCH₃, CH₃, CN, NH₂ and NO₂) was analyzed with DFT (B3LYP/6-31+G(d)) and semi-empirical (PM6-DH2) methods. The interaction enthalpy was calculated to quantify the affinity of the Mg(2+) cation for the ligands. Additionally, geometric and electronic parameters were correlated with the intensity of the metal-ligand interaction. The imino ligands have stronger interaction with the pentaaqua Mg(2+) cation than the thiocarbonyl derivatives. The electronic nature of the substituent is the main parameter that determines the interaction enthalpy. Ligands with electron donor substituents have more exothermic interaction enthalpies than those with electron withdrawing groups. The HSBA analysis showed that the interaction between the Mg(2+) cation and hard bases (imino ligands) is stronger than with soft bases (thiocarbonyl derivatives). The EDA analysis showed that the electrostatic, covalent and repulsion components of the interaction are the most affected by the substituent, whereas the dispersion and exchange components are almost constant.

In Brazil, leprosy is endemic and concentrated in high-risk clusters. Internal migration is common in the country and may influence leprosy transmission and hamper control efforts. We performed a cross-sectional study with two separate analyses evaluating factors associated with migration in Brazil's Northeast: one among individuals newly diagnosed with leprosy and the other among a clinically unapparent population with no symptoms of leprosy for comparison. We included 394 individuals newly diagnosed with leprosy and 391 from the clinically unapparent population. Of those with leprosy, 258 (65.5%) were birth migrants, 105 (26.6%) were past five-year migrants, and 43 (10.9%) were circular migrants. In multivariate logistic regression, three independent factors were found to be significantly associated with migration among those with leprosy: (1) alcohol consumption, (2) separation from family/friends, and (3) difficulty reaching the healthcare facility. Separation from family/friends was also associated with migration in the clinically unapparent population. The health sector may consider adapting services to meet the needs of migrating populations. Future research is needed to explore risks associated with leprosy susceptibility from life stressors, such as separation from family and friends, access to healthcare facilities, and alcohol consumption to establish causal relationships.

Background: Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis., Methods/design: The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR., Discussion: The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.

We applied a multiscale modeling approach that involves the statistical-mechanical three-dimensional reference interaction site model with the Kovalenko-Hirata closure approximation (3D-RISM-KH molecular theory of solvation) as well as density functional theory (DFT) of electronic structure to study the role of water in aggregation of the asphaltene model compound 4,4'-bis(2-pyren-1-yl-ethyl)-2,2'-bipyridine (PBP) [X. Tan, H. Fenniri and M. R. Gray, Energy Fuels, 2008, 22, 715]. The solvation free energy and potential of mean force predicted by 3D-RISM-KH reveal favorable pathways for disaggregation of PBP dimers in pure versus water-saturated chloroform solvent. The water density distribution functions elucidate hydrogen bonding preferences and water bridge formation between PBP monomers. The ΔG(298) values of -5 to -7 kcal mol(-1) for transfer of water molecules in chloroform to a state interacting with PBP molecules are in agreement with experimental results. Geometry optimization and thermochemistry analysis of PBP dimers with and without water bridges using WB97Xd/6-31G(d,p) predict that both PBP dimerization and dimer stabilization by water bridges are spontaneous (ΔG(298) < 0). The (1)H NMR chemical shifts of PBP monomers and dimers predicted using the gauge-independent atomic orbital method and polarizable continuum model for solvation in chloroform are in an excellent agreement with the experimental results for dilute and concentrated PBP solutions in chloroform, respectively [X. Tan, H. Fenniri and M. R. Gray, Energy Fuels, 2009, 23, 3687]. The DFT calculations of PBP dimers with explicit water show that bridges containing 1-3 water molecules lead to stabilization of PBP dimers. Additional water molecules form hydrogen bonds with these bridges and de-shield the PBP protons, negating the effect of water on the (1)H(C3) NMR chemical shift of PBP, in agreement with experiment. The ΔG(298) results show that hydrogen bonding to water and water-promoted polynuclear assembly bridging is as important as π-π interactions for asphaltene aggregation.

DFT (B3LYP/6-31+G(d)) calculations of Mg(2+) affinities for a set of phosphoryl ligands were performed. Two types of ligands were studied: a set of trivalent [O = P(R)] and a set of pentavalent phosphoryl ligands [O = P(R)(3)] (R = H, F, Cl, Br, OH, OCH(3), CH(3), CN, NH(2) and NO(2)), with R either bound directly to the phosphorus atom or to the para position of a phenyl ring. The affinity of the Mg(2+) cation for the ligands was quantified by means of the enthalpy for the substitution of one water molecule in the [Mg(H(2)O)(6)](2+) complex for a ligand. The enthalpy of substitution was correlated with electronic and geometric parameters. Electron-donor groups increase the interaction between the cation and the ligand, while electron-acceptor groups decrease the interaction enthalpy.

Background: West syndrome (WS), an age-specific epilepsy of infancy and early childhood, considered of poor prognosis, may have remission. With the objective of describing the clinical features, treatment and outcome of the children with WS followed in a Latin American country, we devised a retrospective study., Methods: Infants with recurrent spasms, and typical or atypical hypsarrhythmia on electroencephalography (EEG) were included, and their medical report reviewed with particular interest on therapy (anti-epileptic drug, steroids) and outcome. Short-term (remission of spasms up to 6 months after the beginning) and long-term outcome (development and seizure status over the age of 2 years) were focused., Results: Of the 37 selected infants, most (29/37, 78.3%) were classified as symptomatic, and neonatal history of hypoxia (10/29) was the most frequent etiology. The majority had a typical hypsarrhythmia EEG pattern. Most used a combination of anti-epileptic drugs and steroids. A favourable short-term outcome occurred in 20 infants, but only three had normal development and were seizure free after the age of 2 years., Conclusion: Early seizure remission is not assurance of normal final outcome in WS., (© 2010 Blackwell Publishing Ltd.)

The affinity of the Ca(2+) ion for a set of substituted carbonyl ligands was analyzed with both the DFT (B3LYP/6-31+G(d)) and semi-empirical (PM6) methods. Two types of ligands were studied: a set of monosubstituted [O=CH(R)] and a set of disubstituted ligands [O=C(R)(2)] (R=H, F, Cl, Br, OH, OCH(3), CH(3), CN, NH(2) and NO(2)), with R either directly bound to the carbonyl carbon atom or to the para position of a phenyl ring. The interaction energy was calculated to quantify the affinity of the Ca(2+) cation for the ligands. Geometric and electronic parameters were correlated with the intensity of the metal-ligand interaction. The electronic nature of the substituent is the main parameter that determines the interaction energy. Donor groups make the interaction energy more negative (stabilizing the complex formed), while acceptor groups make the interaction energy less negative (destabilizing the complex formed).

Purpose: To construct a multidimensional questionnaire that analyses the epileptic child quality of life from the parental point of view., Method: The pilot questionnaire was composed of 157 questions distributed in several dimensions. Fifty-one epileptic children's parents answered the questionnaire. The instrument was tested in its diverse properties: frequency of endorsement, homogeneity (Cronbach alpha), criterion and face validity, and later it was reduced., Results: Endorsement frequency excluded 65 questions that did not attain a minimum of 5% response per item. Cronbach alpha was as follows: physical (0.93), psychological (0.91), social (0.91), familiar (0.70), cognitive (0.92), medical (0.30) and economical (0.37). Patient groups, in relation to seizure control, significantly differed only in physical domain and total score, although there was a trend to differences in other domains. The final questionnaire (QVCE50) has 50 items, with good homogeneity in the physical, psychological and cognitive domains., Conclusion: QVCE-50 is a promissing Brazilian HRQL questionnaire for children with epilepsy. It needs to be applied in a larger population to confirm its psychometric properties.

In order to better understand the relationship between soil characteristics and mobility of some heavy metals, correlation studies were conducted in samples of unlimed and limed A, B and C horizons of three Brazilian soils, representative of the majority of the tropical soils. A number of chemical and mineralogical characteristics of one Oxisol and two Ultisols were related to the retardation factors (Rf) for zinc (Zn), cadmium (Cd), copper (Cu) and lead (Pb). The retardation factors, obtained in leaching column experiments, were used as an estimate of solute movement in the profile. Soil types and soil horizons were found to influence metal retardation factors which, in turn, correlated better with the chemical than the mineralogical soil characteristics. For the unlimed soil samples, the soil characteristics that significantly correlated with Zn-Rf and Cd-Rf were the sum of exchangeable bases (SB), and soil exchangeable (Ca-KCl) and non-exchangeable (Ca-HCl) calcium contents. These results showed the strong influence of the cation exchange phenomenon on the retention and mobility of these two metals. For Cu and Pb, not only SB, cation exchange capacity (CEC) and Ca-KCl and Ca-HCl but also the organic matter correlated well with the Rf, showing that complex or chelate formation may play an important role in the movement of these elements. The important soil chemical characteristics related to the retardation factors in the limed soil samples were SB for Cd, and Ca-HCl for Cu and Pb, suggesting that precipitation may also influence the mobility and retention of the latter two heavy metals in these soil samples. Soil pH influenced the heavy metals adsorption and movement as shown by the significant correlation with the retardation factors when the combined data for the unlimed and limed soil samples was considered.

Rhode Island has rules and regulations for UR, as well as an appeals process. When the appeals process is used, it is more often than not successful. (Table 1) If questions arise concerning the UR Act, the UR process, the appeals process, the rights of patients, physicians, and reviewers, or the authority of the HEALTH, please contact OMCR. For a copy of the Rules and Regulations for the Utilization Review of Health Care Services (R23-17.12-1-UR), please write: Rhode Island Department of Health Office of Managed Care Regulation 3 Capitol Hill Cannon Building, Room 410 Providence, RI 02908.

A study on tick-borne rickettsiosis was developed in the county of Santa Cruz do Escalvado, State of Minas Gerais, Brazil, where a clinical case of the disease, confirmed by necropsy, had been reported. Of the 1,254 ticks collected, 1,061 belonged to the Amblyomma genus, 57 to the Rhipicephalus sanguineus species, 81 to Boophilus microplus, and 46 to Anocentor nitens. The hemolymph test associated with Giménez staining showed that 18 of the 221 A. cajennense specimens, 1 of the 16 R. sanguineus, 1 of the 22 B. microplus, 3 of the A. nitens, and 1 of the A. ovale contained rickettsia-like microorganisms. Only 3 A. cajennense ticks were positive under direct immunofluorescence. A. cajennense was the only species found on humans.

Intra-muscular vincamine in the cat (chronic experimental preparation) causes a change in the equilibrium between sleep and wakefulness. This consists of: (1) an increase in the amount of wakefulness, the duration of which depends on the dose injected (5-10 mg/kg) and the mode of injection (more effective when given in two doses than all at once); (2) a decrease in slow wave sleep (SWS) which often has the appearance of phasic slow wave sleep; (3) a transitory suppression of paradoxical sleep (PS). At the time of recovery there is no rebound either of SWS or PS. The mechanism of vinacamine's action is not understood and some interpretations are suggested.