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Objectives Previous studies in a high-income country have demonstrated that people with and without low back pain (LBP) have an implicit bias that bending and lifting with a flexed lumbar spine is dangerous. These studies present two key limitations: use of a single group per study; people who recovered from back pain were not studied. Our aims were to evaluate: implicit biases between back posture and safety related to bending and lifting in people who are pain-free, have a history of LBP or have current LBP in a middle-income country, and to explore correlations between implicit and explicit measures within groups. Methods Exploratory cross-sectional study including 174 participants (63 pain-free, 57 with history of LBP and 54 with current LBP). Implicit biases between back posture and safety related to bending and lifting were assessed with the Implicit Association Test (IAT). Participants completed paper-based (Bending Safety Belief [BSB]) and online questionnaires (Tampa Scale of Kinesiophobia; Back Pain Attitudes Questionnaire). Results Participants displayed significant implicit bias between images of round-back bending and lifting and words representing “danger” (IATD-SCORE: Pain-free group: 0.56 (IQR=0.31–0.91; 95% CI [0.47, 0.68]); history of LBP group: 0.57 (IQR=0.34–0.84; 95% CI [0.47, 0.67]); current LBP group: 0.56 (IQR=0.24–0.80; 95% CI [0.39, 0.64])). Explicit measures revealed participants hold unhelpful beliefs about the back, perceiving round-back bending and lifting as dangerous (BSBthermometer: Pain-free group: 8 (IQR=7–10; 95% CI [7.5, 8.5]); history of LBP group: 8 (IQR=7–10; 95% CI [7.5, 9.0]); current LBP group: 8.5 (IQR=6.75–10; [7.5, 9.0])). There was no correlation between implicit and explicit measures within the groups. Conclusions In a middle-income country, people with and without LBP, and those who recovered from LBP have an implicit bias that round-back bending and lifting is dangerous.

Introducao A pandemia da COVID-19 mudou o panorama da pratica cirurgica das diversas especialidades medicas no mundo inteiro. – Mudancas nas rotinas dos servicos de estimulacao cardiaca artificial foram apoiadas pelas sociedades medicas da especialidade, que estabeleceram recomendacoes para a definicao da gravidade dos casos e da urgencia dos procedimentos cirurgicos. , O objetivo do presente estudo foi avaliar o impacto das medidas implementadas para enfrentamento da pandemia nos procedimentos cirurgicos realizados na area da estimulacao cardiaca artificial, pela comparacao [...]

BACKGROUND Transvenous lead extraction (TLE) is standard of care for the management of patients with cardiac implantable electronic device infection or lead-related complications. Currently, objective data on TLE in Latin America is lacking. OBJECTIVE To describe the current practice standards in Latin American centers performing TLE. METHODS An online survey was sent through the mailing list of the Latin American Heart Rhythm Society. Online reminders were sent through the mailing list; duplicate answers were discarded. The survey was available for 1 month, after which no more answers were accepted. RESULTS A total of 48 answers were received, from 44 different institutions (39.6% from Colombia, 27.1% from Brazil), with most respondents (82%) being electrophysiologists. Twenty-nine institutions (66%) performed

Background The Back Pain Attitudes Questionnaire (Back-PAQ) was developed to evaluate attitudes and beliefs of the general public, people with back pain, and healthcare professionals about the spine. Objectives To translate and cross-culturally adapt the Back-PAQ (34-item and 10-item versions) into Brazilian-Portuguese (Back-PAQ-Br) and test its measurement properties in a Brazilian sample. Methods The cross-cultural adaptation and testing of the measurement properties followed the recommendations of international guidelines. Members of the general public, people with back pain, and healthcare professionals, for a total of 139 individuals, took part in the assessment of internal consistency, construct validity, and ceiling and floor effects. The Hospital Anxiety and Depression Scale (HADS) and the Brazilian-Portuguese version of the Tampa Scale of Kinesiophobia (TSK) were used to evaluate construct validity. Test-retest reproducibility was determined on 77 participants. Retest was performed a minimum of 1 week and a maximum of 2 weeks from the original test. Results There was very high agreement between translators (88.2%). The Back-PAQ-Br showed excellent internal consistency (Cronbach’s alpha 0.92) and excellent reproducibility (ICC 0.94; SEM 5.14 points on a 136 point scale), with a smallest detectable change (90% confidence level) of 11.93 points. There was strong correlation between Back-PAQ-Br and TSK (r = -0.72) and very weak correlation between Back-PAQ-Br and HADS (r = -0.23 for both depression and anxiety domains). No ceiling/floor effects were observed. Conclusion The translation process and cross-cultural adaptation had very high agreement between translators. The Back-PAQ-Br has excellent measurement properties that are similar to the properties of the original version.

Background Venous obstructions are frequent in patients with transvenous leads, although related clinical findings are rarely reported. After lead replacement or upgrade procedures, these lesions are even more frequent, but there is still no evidence to support this observation. Aim To investigate the incidence and possible risk factors for upper extremity deep venous thrombosis (UEDVT) and pulmonary embolism (PE) after lead replacement or upgrade procedures. Methods Prospective cohort carried out between April 2013 and July 2016. Preoperative evaluation included venous ultrasound and pulmonary angiotomography. Diagnostic exams were repeated postoperatively to detect the study outcomes. Multivariate logistic regression models were used to identify prognostic factors. Results Among the 84 patients included, 44 (52.4%) were female and mean age was 59.3 ± 15.2 years. Lead malfunctioning (75.0%) was the main surgical procedure indication. Lead removal was performed in 44 (52.4%) cases. The rate of postoperative combined events was 32.6%, with 24 (28.6%) cases of UEDVT and six (7.1%) cases of PE. Clinical manifestations of deep venous thrombosis occurred in 10 (11.9%) patients. Independent prognostic factors for UEDVT were severe collateral circulation in the preoperative venography (odds ratio [OR] 4.7; 95% confidence interval [CI] 1.1-19.8; P = .037) and transvenous lead extraction (OR 27.4; 95% CI 5.8-128.8; P Conclusion Reoperations involving previously implanted transvenous leads present high rates of thromboembolic complications. Transvenous lead extraction had a significant impact on the development of UEDVT. These results show the need of further studies to evaluate the role of preventive strategies for this subgroup of patients.

Bone differentiation defects have been recently tied to Wnt signaling alterations occurring in vitro and in vivo Gaucher disease (GD) models. In this work, we provide evidence that the Wnt signaling multi-domain intracellular transducers Dishevelled 1 and 2 (DVL1 and DVL2) may be potential upstream targets of impaired beta glucosidase (GBA1) activity by showing their misexpression in different type 1 GD in vitro models. We also show that in Gba mutant fish a miR-221 upregulation is associated with reduced dvl2 expression levels and that in type I Gaucher patients single-nucleotide variants in the DVL2 3′ untranslated region are related to variable canonical Wnt pathway activity. Thus, we strengthen the recently outlined relation between bone differentiation defects and Wnt/β-catenin dysregulation in type I GD and further propose novel mechanistic insights of the Wnt pathway impairment caused by glucocerebrosidase loss of function.

The emergence and spread of multidrug-resistant (MDR) enterococci and other Gram-positive bacteria represents a severe problem due to the lack of effective therapeutic alternatives. Natural products have long been an important source of new antibacterial scaffolds and can play a key role in the current antibiotic crisis. Enterococci are predominantly non-pathogenic gastrointestinal commensal bacteria, but among them, Enterococcus faecalis and Enterococcus faecium represent the species that account for most clinically relevant infections. The emergence of MDR enterococci has reduced the available antibiotic treatment options and highlights the need to develop new antimicrobial compounds. In the search for new hit compounds against MDR Enterococcus spp., natural-derived compounds represent inspiring scaffolds for drug design studies. In this work, the antimicrobial activity of a fully synthetic chalcone derivative (r4MB) was determined on a clinical panel of 34 MDR Gram-positive bacteria, mostly constituted by E. faecalis and E. faecium, along with Staphylococcus spp., amongst others. Compound r4MB showed activity against 100% of the tested strains, with the minimum inhibitory concentration (MIC) in the range of 5-20 μM. The lethal action of the compound was evaluated using different fluorescent-based assays. The compound showed a time-dependent permeabilisation of the membrane of a vancomycin-resistant E. faecalis, detected by the fluorescent probe SYTOX Green, and digital fluorescent microscopy corroborated the spectrofluorimetric analysis within 6 min of incubation. Flow cytometry analysis of the membrane electric potential demonstrated a significant depolarization, confirming the target of the compound towards the bacterial membrane. No cytotoxic haemolysis was observed with mammalian erythrocytes, and a 99% cytotoxic concentration of 118 μM on NCTC cells demonstrated a promising antimicrobial selectivity. In silico studies using SwissADME and ADMETLabs servers suggest that compound r4MB displayed adequate ADME properties, with no alerts for pan-assay interference compounds (PAINS). Future hit-to-lead optimization of this chalcone derivative can contribute to developing a more potent derivative against infections caused by MDR enterococci.

Studies of critically ill hematopoietic stem cell transplantation (HSCT) recipients have mainly been single-center and focused on allogenic HSCT recipients. We aimed to describe a cohort of autologous HSCT with an unplanned intensive care unit (ICU) admission.This study is a retrospective cohort study of autologous HSCT performed as a treatment for a hematological malignancy, during their first unplanned ICU admission in 50 hospitals in Brazil. We assessed the hospital mortality and the association between mechanical ventilation, vasopressors, and renal replacement therapy and hospital mortality in autologous HSCT recipients, adjusted for potential confounders.We included 301 patients. Multiple myeloma was the most common malignancy driving to HSCT. ICU and hospital mortality were 22.9% and 37.5%, respectively. After adjustment for potential confounders, mechanical ventilation (OR = 9.10; CI 95%, 4.82-17.15) was associated with hospital mortality, but vasopressors (OR = 1.43; CI 95%, 0.77-2.64) and renal replacement therapy (OR = 1.30; CI 95%, 0.63-2.66) were not.In this large cohort of critically ill autologous HSCT recipients, mechanical ventilation was the only organ support-therapy associated with increased mortality in autologous HSCT recipients.

Background There is lack of guidance on specific CT protocols for imaging patients with coronavirus disease 2019 (COVID-19) pneumonia. Purpose To assess international variations in CT utilization, protocols, and radiation doses in patients with COVID-19 pneumonia. Materials and Methods In this retrospective data collection study, the International Atomic Energy Agency (IAEA) coordinated a survey between May and July 2020 regarding CT utilization, protocols, and radiation doses from 62 healthcare sites in 34 countries across five continents for CT exams performed in COVID-19 pneumonia. The questionnaire obtained information on local prevalence, method of diagnosis, most frequent imaging, indications for CT, and specific policies on use of CT in COVID-19 pneumonia. Collected data included general information (patient age, weight, clinical indication), CT equipment (CT make and model, year of installation, number of detector rows), scan protocols (body region, scan phases, tube current and potential), and radiation dose descriptors (CT dose index (CTDIvol) and dose length product (DLP)). Descriptive statistics and generalized estimating equations were performed. Results Data from 782 patients (median age (interquartile range) of 59(15) years) from 54 healthcare sites in 28 countries were evaluated. Less than one-half of the healthcare sites used CT for initial diagnosis of COVID-19 pneumonia and three-fourth used CT for assessing disease severity. CTDIvol varied based on CT vendors (7-11mGy, p

Wnt signaling affects fundamental development pathways and, if aberrantly activated, promotes the development of cancers. Wnt signaling is modulated by different factors, but whether the mitochondrial energetic state affects Wnt signaling is unknown. Here, we show that sublethal concentrations of different compounds that decrease mitochondrial ATP production specifically downregulate Wnt/β-catenin signaling in vitro in colon cancer cells and in vivo in zebrafish reporter lines. Accordingly, fibroblasts from a GRACILE syndrome patient and a generated zebrafish model lead to reduced Wnt signaling. We identify a mitochondria-Wnt signaling axis whereby a decrease in mitochondrial ATP reduces calcium uptake into the endoplasmic reticulum (ER), leading to endoplasmic reticulum stress and to impaired Wnt signaling. In turn, the recovery of the ATP level or the inhibition of endoplasmic reticulum stress restores Wnt activity. These findings reveal a mechanism that links mitochondrial energetic metabolism to the control of the Wnt pathway that may be beneficial against several pathologies., The authors’ work is supported by the Italian Association for Cancer Research (AIRC IG grants 15544 and 20286 to I.S.); the Italian Ministry of University and Education (PRONAT project to M. Zoratti and PRIN 2015795S5W to I.S.); and the CNR (Project of Special Interest on Aging and InterOmics to M. Zoratti). L.L. is grateful for PRID 2017 grant (no. BIRD162511) from the University of Padova.

Pesticides applied indoors may persist longer than they would in outdoor environments, making people more vulnerable to the risk of exposure. Permethrin is a pyrethroid insecticide used in agricultural, residential, and public health sites, and is commonly detected in indoor environments. The objectives of this study were to evaluate the persistence of permethrin indoors and to estimate the levels of possible dermal and non-dietary exposure to this insecticide. Permethrin was applied on aluminum foil and kept in a glass chamber and a test house for 112 days; its concentration was measured at application and after 28, 56, and 112 days. Permethrin persisted for the entire 112 days in concentrations equal to a maximum of 89.6% of the initial concentration. We observed low levels of human dermal and non-dietary exposure to permethrin.

Purpose To evaluate organ doses in routine and low‐dose chest computed tomography (CT) protocols using an experimental methodology. To compare experimental results with results obtained by the National Cancer Institute dosimetry system for CT (NCICT) organ dose calculator. To address the differences on organ dose measurements using tube current modulation (TCM) and fixed tube current protocols. Methods An experimental approach to evaluate organ doses in pediatric and adult anthropomorphic phantoms using thermoluminescent dosimeters (TLDs) was employed in this study. Several analyses were performed in order to establish the best way to achieve the main results in this investigation. The protocols used in this study were selected after an analysis of patient data collected from the Institute of Radiology of the School of Medicine of the University of São Paulo (InRad). The image quality was evaluated by a radiologist from this institution. Six chest adult protocols and four chest pediatric protocols were evaluated. Lung doses were evaluated for the adult phantom and lung and thyroid doses were evaluated for the pediatric phantom. The irradiations were performed using both a GE and a Philips CT scanner. Finally, organ doses measured with dosimeters were compared with Monte Carlo simulations performed with NCICT. Results After analyzing the data collected from all CT examinations performed during a period of 3 yr, the authors identified that adult and pediatric chest CT are among the most applied protocol in patients in that clinical institution, demonstrating the relevance on evaluating organ doses due to these examinations. With regards to the scan parameters adopted, the authors identified that using 80 kV instead of 120 kV for a pediatric chest routine CT, with TCM in both situations, can lead up to a 28.7% decrease on the absorbed dose. Moreover, in comparison to the standard adult protocol, which is performed with fixed mAs, TCM, and ultra low‐dose protocols resulted in dose reductions of up to 35.0% and 90.0%, respectively. Finally, the percent differences found between experimental and Monte Carlo simulated organ doses were within a 20% interval. Conclusions The results obtained in this study measured the impact on the absorbed dose in routine chest CT by changing several scan parameters while the image quality could be potentially preserved.

Wnt signaling is an important pathway mainly active during embryonic development and controlling cell proliferation. This regulatory pathway is aberrantly activated in several human diseases. Ion channels are known modulators of several important cellular functions ranging from the tuning of the membrane potential to modulation of intracellular pathways, in particular the influence of ion channels in Wnt signaling regulation has been widely investigated. This review will discuss the known links between ion channels and canonical Wnt signaling, focusing on their possible roles in human metabolic diseases, neurological disorders, and cancer.

Mitochondrial diseases impair oxidative phosphorylation and ATP production, while effective treatment is still lacking. Defective complex III is associated with a highly variable clinical spectrum. We show that pyocyanin, a bacterial redox cycler, can replace the redox functions of complex III, acting as an electron shunt. Sub-μM pyocyanin was harmless, restored respiration and increased ATP production in fibroblasts from five patients harboring pathogenic mutations in TTC19, BCS1L or LYRM7, involved in assembly/stabilization of complex III. Pyocyanin normalized the mitochondrial membrane potential, and mildly increased ROS production and biogenesis. These in vitro effects were confirmed in both DrosophilaTTC19KO and in Danio rerioTTC19KD, as administration of low concentrations of pyocyanin significantly ameliorated movement proficiency. Importantly, daily administration of pyocyanin for two months was not toxic in control mice. Our results point to utilization of redox cyclers for therapy of complex III disorders., Mitochondrial diseases, including those caused by defects in complex III of the respiratory chain, lack curative treatments. Here the authors report that the small molecule pyocyanin has beneficial effects in cells derived from patients with complex III-deficiency as well as in fly and zebrafish genetic models with reduced complex III activity.

Optimization of imaging examinations is a key requirement of both the International and European Basic Safety Standards, and the focus of much international activity. Although methodologies are well established in principle, there continues to be a variety of practical issues both in collecting and interpreting dose and image quality data and in making successful interventions to optimize exposures. A Coordinated Research Project, involving institutes from ten different countries, was established by the IAEA to assess the efficacy of recommended optimization methodologies in the field of paediatric radiology and to derive practical guidance on their implementation. The steps followed in this process were identification of the imaging process to be investigated (abdomen and chest x-rays, micturating cysto-urethrograms, and brain & thorax CT scans); collection of dose and image quality data; evaluation and comparison of the data between institutes and to standards; identification and implementation of interventions for optimization; and re-evaluation of dose and image quality parameters. The project succeeded both in achieving effective interventions for optimization of specific imaging tasks in individual institutes and in identifying key issues with potential to handicap this process. The main area in which problems were encountered was in the collation of reliable dose and image quality data. The reasons for this were explored and a series of recommendations have been made, summarized into 'ten practical tips' for optimization to assist institutes, particularly those in the early stages of addressing optimization issues.

Resumo Fundamento Remoção de cabos-eletrodos de dispositivos cardíacos eletrônicos implantáveis (DCEI) é procedimento pouco frequente e sua realização exige longo treinamento profissional e infraestrutura adequada. Objetivos Avaliar a efetividade e a segurança da remoção de cabos-eletrodos de DCEI e determinar fatores de risco para complicações cirúrgicas e mortalidade em 30 dias. Métodos Estudo prospectivo com dados derivados da prática clínica. De janeiro/2014 a abril/2020, foram incluídos, consecutivamente, 365 pacientes submetidos à remoção de cabos-eletrodos, independentemente da indicação e técnica cirúrgica utilizada. Os desfechos primários foram: taxa de sucesso do procedimento, taxa combinada de complicações maiores e morte intraoperatória. Os desfechos secundários foram: fatores de risco para complicações intraoperatórias maiores e morte em 30 dias. Empregou-se análise univariada e multivariada, com nível de significância de 5%. Resultados A taxa de sucesso do procedimento foi de 96,7%, sendo 90,1% de sucesso completo e 6,6% de sucesso clínico. Complicações maiores intraoperatórias ocorreram em 15 (4,1%) pacientes. Fatores preditores de complicações maiores foram: tempo de implante dos cabos-eletrodos ≥ 7 anos (OR= 3,78, p= 0,046) e mudança de estratégia cirúrgica (OR= 5,30, p= 0,023). Classe funcional III-IV (OR= 6,98, p

Accepted Manuscript version. The Published Journal Article is available on Materials Science and Engineering: C, Volume 122, Article number 111899 (DOI: https://doi.org/10.1016/j.msec.2021.111899). Supplementary Material available free of charge on the article webpage. © 2021. This Manuscript version is made available under the CC-BY-NC-ND 4.0 license. https://creativecommons.org/licenses/by-nc-nd/4.0/ ABSTRACT The high rates of aggressiveness, drug resistance and relapse of breast cancer (BC) are mainly attributed to the inability of conventional therapies to equally eradicate bulk differentiated cells and cancer stem cells (CSCs). To improve the effectiveness of BC treatments, we report the in-water synthesis of novel keratin-based nanoformulations, loaded with the CSC-specific drug salinomycin (SAL), the photosensitizer chlorin e6 (Ce6) and vitamin E acetate (SAL/Ce6@kVEs), which combine the capability of releasing SAL with the production of singlet oxygen upon light irradiation. In vitro experiments on BC cell lines and CSC-enriched mammospheres exposed to single or combined therapies showed that SAL/Ce6@kVEs determine synergistic cell killing, limit their self-renewal capacity and decrease the stemness potential by eradication of CSCs. In vivo experiments on zebrafish embryos confirmed the capacity of SAL nanoformulations to interfere with the Wnt/β-catenin signaling pathway, which is dysregulated in BC, thus identifying a target for further translation into pre-clinical models.

Resumo Fundamento A despeito da comprovada efetividade do cardioversor-desfibrilador implantável (CDI), as terapias de choque deflagradas pelo dispositivo podem causar níveis elevados de ansiedade e depressão, provocando efeitos deletérios na qualidade de vida. Objetivo Realizar a tradução, adaptação transcultural e validação do instrumento Florida Shock Anxiety Scale (FSAS) para a língua portuguesa falada no Brasil. Métodos Nesse estudo psicométrico, a validade de construto foi realizada pela análise fatorial exploratória (AFE) e confirmatória (AFC) e pela Teoria de Resposta ao Item. Os índices de ajustamento da AFC foram: Robust Mean-Scaled Chi Square/df NNFI, CFI (Comparative Fit Index), GFI (Goodness Fit Index), AGFI (Adjusted Goodness Fit Index), RMSEA (Root Mean Square Error of Approximation) e RMSR (Root Mean Square of Residuals). A confiabilidade foi verificada pelo Alfa de Cronbach, Ômega de McDonald e Greatest Lower Bound. As análises foram realizadas no SPSS 23.0 e Factor 10.8.01, com nível de significância de 5%. Resultados A versão final em português do FSAS foi administrada em 151 portadores de CDI, com idade média de 55,7 ± 14,1 anos e predomínio do sexo masculino. A análise paralela indicou que o FSAS é unidimensional, com variância explicada de 64,4%. As correlações variaram de 0,31 a 0,77; as cargas fatoriais de 0,67 a 0,86 e as comunalidades de 0,46 a 0,74. Os índices de ajustamento da AFC estabeleceram-se acima dos limites de qualidade. Encontramos evidências satisfatórias de confiabilidade da escala FSAS. Conclusão O instrumento FSAS-Br apresentou evidências consistentes de validade e confiabilidade, podendo, portanto, ser utilizado em portadores de CDI do Brasil. (Arq Bras Cardiol. 2020; 114(5):764-772) Abstract Background In spite of proven effectiveness of implantable cardioverter defibrillators (ICDs), shock therapy delivered by the device may result in increased levels of anxiety and depression, leading to deleterious effects on quality of life. Objective To carry out the translation, cross-cultural adaptation and validation of the Florida Shock Anxiety Scale (FSAS) scale into Brazilian Portuguese. Methods In this psychometric study, construct validity was performed by exploratory (EFA) and confirmatory (CFA) factor analyses, and by item response theory (IRT). The adjustment indexes of the CFA were: Robust Mean-Scaled Chi Square/df NNFI, CFI (Comparative Fit Index), GFI (Goodness Fit Index), AGFI (Adjusted Goodness Fit Index), RMSEA (Root Mean Square Error of Approximation) and RMSR (Root Mean Square of Residuals). Reliability was evaluated through Cronbach’s Alpha, McDonald’s Omega and Greatest Lower Bound (GLB). The analyses were carried out with the programs SPSS 23 and Factor 10.8.01. A 5 percent significance level was used. Results The final Portuguese version of the FSAS was administered to 151 ICD patients, with a mean age of 55.7 ± 14.1 years, and predominantly male. The parallel analysis indicated that the FSAS is unidimensional, with an explained variance of 64.4%. The correlations ranged from 0.31 to 0.77, factor loadings from 0.67 to 0.86, and communalities from 0.46 to 0.74. The adjustment indexes of the CFA were above the quality threshold. Satisfactory reliability evidence was provided by the FSAS. Conclusions The FSAS-Br showed consistent validity and reliability evidence. Therefore, it can be used in ICD patients in Brazil. (Arq Bras Cardiol. 2020; 114(5):764-772)

Objective To assess the relationship between human blastocyst chromosomal ploidy established by niPGT-A and increasing age. Methods This is a prospective multicenter study carried out by ten assisted reproduction centers after their embryologists acquired training and validated their results with the previous use of niPGT-A. A total of 94 couples with indication for niPGT-A due to increase maternal age, male factor, repeated implantation failures, recurrent abortion or because they requested niPGT-A were included in this study. The couples had no karyotype abnormalities. After ICSI, the embryos were cultured until blastocyst stage using one or two step culture systems, single or sequential media respectively, at 37°C in an atmosphere of 6-7% CO2 and 5-20% O2 incubators. On day 3, we re-evaluated cleavage embryos to complete cumulus cells removal. The embryos were then cultured in individual well, with 20µl of medium under oil until they reached blastocyst stage. The blastocysts were vitrified and stored in liquid nitrogen. After that, the spent blastocyst culture medium (20µl) was transferred to a PCR tube and sent for analysis in the genetic laboratory, where it was stored at -80°C until sequencing. A total of 243 samples of spent blastocyst culture medium were collected on the 5th/6th day. Cell-free DNA secreted on culture medium was amplified using NICS Sample Preparation Kit (Yikon Genomics), based on the MALBAC technology. After whole genome amplification, the DNA was measured using a Qubit 2.0 fluorometer and subjected to next generation sequencing (NGS) using Illumina MiSeq® platform. The data were analyzed using the ChromGo® software (Yikon Genomics). Results The mean age of the patients was 38±4.08 years with an interval of 20-44 years. The euploid was diagnosed in 36.4% (80/220) of cases, aneuploidy in 31.3% (69/220), and mosaicism in 32.3% (71/220; with ≥60% aneuploidy) of blastocysts. Mosaic values ranged from 29.8% to 33.8% in different age groups. Individually, the most frequent chromosomal abnormality was XXY (Klinefelter Syndrome) occurring in 18 cases, followed by chromosome 21 (trisomy/monosomy) in 8 cases. The niPGT-A data showed a ≥60% incidence of aneuploid cells in all cases of chromosomal mosaicism (n=71). Conclusion A high degree of mosaicism with aneuploidy cells was detected, and some hypotheses were suggested for this data (niPGT-A sensitivity in detecting the self-correction of chromosomal abnormalities phenomenon). However, it did not vary remarkably with age. On the other hand, euploidy levels had a negative correlation with age and aneuploidy levels had a positive relationship. This is the first report in the literature to relate chromosomal ploidy in blastocysts using niPGT-A and increasing patient age.

The neural crest is an important group of cells with pluripotency and migratory ability that is crucially involved in tissue and cell specification during development. Craniofacial shaping, sensory neurons, body asymmetry, and pigmentation are linked to neural crest functionality. Despite its prominent role in embryogenesis, neural crest specification as well as the possible part mitochondria play in such a process remains unclarified. Mitochondria are important organelles not only for respiration, but also for regulation of cell proliferation, differentiation and death. Modulation of mitochondrial fitness and depletion of mitochondrial ATP synthesis has been shown to down-regulate Wnt signaling, both in vitro and in vivo. Since Wnt signaling is one of the crucial players during neural crest induction/specification, we hypothesized a signaling cascade connecting mitochondria to embryonic development and neural crest migration and differentiation. Here, by using pharmacological and genetic modulators of mitochondrial function, we provide evidence that a crosstalk between mitochondrial energy homeostasis and Wnt signaling is important in the development of neural crest-derived tissues. Furthermore, our results highlight the possibility to modulate neural crest cell specification by tuning mitochondrial metabolism via FoxD3, an important transcription factor that is regulated by Wnt. FoxD3 ensures the correct embryonic development and contributes to the maintenance of cell stemness and to the induction of epithelial-to-mesenchymal transition. In summary, our work offers new insights into the molecular mechanism of action of FoxD3 and demonstrates that mitochondrial fitness is linked to the regulation of this important transcription factor via Wnt signaling in the context of neural crest specification.

Numerical models are an alternative to measurements of x-ray energy spectra when validated by comparative methods that assess the similarity of experimental and calculated spectra. In this work, we compared x-ray energy spectra using several methodologies and determined the methodology with highest statistical power among them. Experiments and Monte Carlo (MC) simulations were used to generate a set of 65 experimental and simulated x-ray mammography spectra pairs typically used in mammography applications. They were generated using Tungsten and Molybdenum targets and Molybdenum and Rhodium filters. The x-ray beams were transmitted through breast tissue equivalent material (bTEM) plates with different glandularities and thicknesses, and the transmitted beam was detected using solid-state x-ray spectrometry with a Cadmium Telluride (CdTe) diode. The MC simulations used the PENELOPE code. Additional uncertainties, beyond that from counting, were propagated using the MC method. Quantitative comparative methods based on the [Formula: see text] statistics, the first and second half-value layers, the mean energy, the effective energy, and the non-parametric u-test were applied and their specificity (true negative rate) was assessed. The polyenergetic normalized glandular dose (DgNp) to a 6 cm breast of 50/50 glandularity was derived from the spectra. In this work, the [Formula: see text] statistics attained the highest score; therefore, it is the most indicated metric for the x-ray energy spectra comparative evaluations. The contribution of the additional uncertainties was important, being responsible for up to 98% of the spectra total uncertainty and shifting the mean of the evaluated [Formula: see text] to 1.2(1), compatible with its expected value. The use of non-parametric test is discouraged by our results, since it failed to distinguish spectra pairs that resulted in up to 72% discrepant DgNp.

Aims Cardiac resynchronization therapy (CRT) is an established procedure for patients with heart failure. However, trials evaluating its efficacy did not include patients with chronic Chagas cardiomyopathy (CCC). We aimed to assess the role of CRT in a cohort of patients with CCC. Methods and results This retrospective study compared the outcomes of CCC patients who underwent CRT with those of dilated (DCM) and ischaemic cardiomyopathies (ICM). The primary endpoint was all-cause mortality and the secondary endpoints were the rate of non-advanced New York Heart Association (NYHA) class 12 months after CRT and echocardiographic changes evaluated at least 6 months after CRT. There were 115 patients in the CCC group, 177 with DCM, and 134 with ICM. The annual mortality rates were 25.4%, 10.4%, and 11.3%, respectively (P

Background Chronic Chagas cardiomyopathy (CCC) is the most serious and frequent manifestation of Chagas disease. Conduction abnormalities and bradycardia requiring pacemaker are common. The aim of this study was to determine the rate and predictors of death in CCC patients with pacemaker. Methods In this single-center prospective cohort study we assessed the outcome of 396 CCC patients with pacemaker, followed-up for at least 24months. All patients underwent a clinical and device assessment, 12-lead electrocardiography and echocardiography. Results During the median follow-up of 1.9years (Interquartile range 1.6–2.4), there were 65 (16.4%) deaths, yielding an annual mortality rate of 8.6%. The major cause was sudden death (33.8%), followed by heart failure (HF), 32.3%. All the investigated variables were examined as potential predictors of death. The final multivariate logistic regression model included five independent variables: advanced HF functional class (OR [odds ratio] 6.71; 95% confidence interval [95% CI] 1.95–23.2; P =0.003), renal disease (OR 5.71; 95% CI 1.80–18.0; P =0.003), QRS ≥150ms (OR 2.80; 95% CI 1.08–7.27; P =0.034), left atrial enlargement (OR 2.75; 95% CI 1.09–6.95; P =0.032) and left ventricular ejection fraction ≤43% (OR 2.31; 95% CI 1.07–4.97; P =0.032). The model had good discrimination, confirmed by bootstrap validation (optimism-adjusted c-statistic of 0.78) and the calibration curve showed a proper calibration (slope=0.972). Conclusions CCC patients with pacemaker have a high annual mortality rate despite that the pacemaker related variables were not predictors of death. The independent predictors of death can help us to identify the poor prognosis patients.

Background: Few studies have characterized the surgical outcomes following epicardial pacemaker implantation in neonates with congenital complete atrioventricular block (CCAVB). Objective: This study sought to assess the long-term outcomes of a minimally invasive epicardial approach using a subxiphoid access for pacemaker implantation in neonates. Methods: Between July 2002 and February 2015, 16 consecutive neonates underwent epicardial pacemaker implantation due to CCAVB. Among these, 12 (75.0%) had congenital heart defects associated with CCAVB. The patients had a mean age of 4.7 ± 5.3 days and nine (56.3%) were female. Bipolar steroid-eluting epicardial leads were implanted in all patients through a minimally invasive subxiphoid approach and fixed on the diaphragmatic ventricular surface. The pulse generator was placed in an epigastric submuscular position. Results: All procedures were successful, with no perioperative complications or early deaths. Mean operating time was 90.2 ± 16.8 minutes. None of the patients displayed pacing or sensing dysfunction, and all parameters remained stable throughout the follow-up period of 4.1 ± 3.9 years. Three children underwent pulse generator replacement due to normal battery depletion at 4.0, 7.2, and 9.0 years of age without the need of ventricular lead replacement. There were two deaths at 12 and 325 days after pacemaker implantation due to bleeding from thrombolytic use and progressive refractory heart failure, respectively. Conclusion: Epicardial pacemaker implantation through a subxiphoid approach in neonates with CCAVB is technically feasible and associated with excellent surgical outcomes and pacing lead longevity.

Background: Considering the potential deleterious effects of right ventricular (RV) pacing, the hypothesis of this study is that isolated left ventricular (LV) pacing through the coronary sinus is safe and may provide better clinical and echocardiographic benefits to patients with bradyarrhythmias and normal ventricular function requiring heart rate correction alone. Objective: To assess the safety, efficacy, and effects of LV pacing using an active-fixation coronary sinus lead in comparison with RV pacing, in patients eligible for conventional pacemaker (PM) implantation. Methods: Randomized, controlled, and single-blinded clinical trial in adult patients submitted to PM implantation due to bradyarrhythmias and systolic ventricular function ≥ 0.40. Randomization (RV vs. LV) occurred before PM implantation. The main results of the study were procedural success, safety, and efficacy. Secondary results were clinical and echocardiographic changes. Chi-squared test, Fisher's exact test and Student's t-test were used, considering a significance level of 5%. Results: From June 2012 to January 2014, 91 patients were included, 36 in the RV Group and 55 in the LV Group. Baseline characteristics of patients in both groups were similar. PM implantation was performed successfully and without any complications in all patients in the RV group. Of the 55 patients initially allocated into the LV group, active-fixation coronary sinus lead implantation was not possible in 20 (36.4%) patients. The most frequent complication was phrenic nerve stimulation, detected in 9 (25.7%) patients in the LV group. During the follow-up period, there were no hospitalizations due to heart failure. Reductions of more than 10% in left ventricular ejection fraction were observed in 23.5% of patients in the RV group and 20.6% of those in the LV group (p = 0.767). Tissue Doppler analysis showed that 91.2% of subjects in the RV group and 68.8% of those in the LV group had interventricular dyssynchrony (p = 0.022). Conclusion: The procedural success rate of LV implant was low, and the safety of the procedure was influenced mainly by the high rate of phrenic nerve stimulation in the postoperative period.

Aims Cardiac implantable electronic device (CIED) infection rates are increasing. Worldwide compliance and disparities to published guidelines for the prevention, diagnosis and management of these conditions are not well elucidated. The purpose of this survey, therefore, was to clarify these issues through an inquiry to arrhythmia-related associations and societies worldwide. Methods and results A questionnaire comprising 15 questions related to CIED infections was distributed among members of seven arrhythmia societies worldwide. A total of 234 centres in 62 countries reported implantation rates of which 159 (68.0%) performed more than 200 device implantations per year and 14 (6.0%) performed fewer than 50 implantations per year. The reported rates of CIED infections for 2017 were ≤2% in 78.7% of the centres, while the infection rates exceeded 5% in 7.8% of the centres. Preventive measures for CIED infection differed from published recommendations and varied among different regions mainly in terms of pocket irrigation and administering post-operative antimicrobial therapy the use of which was reported by 39.9% and 44% of the respondents, respectively. Antibacterial envelopes were used by 37.7% of the respondents in selected circumstances. In terms of pocket infection management, 62% of the respondents applied complete system removal as an initial step. Diagnostic pocket needle aspiration and pocket surgical debridement were reported by 15.8% and 11.8% of centres, respectively. Conclusion Clinical practices for prevention and management of CIED do not fully comply with current recommendations and demonstrate considerable regional disparities. Further education and programmes for improved implementation of guidelines are mandatory.

Diagnostic x-ray beams are composed of bremsstrahlung and discrete fluorescence lines. The aim of this study is the development of an efficient model for the evaluation of the fluorescence lines. The most important electron ionization models are analyzed and implemented. The model results were compared with experimental data and with other independent spectra presented in the literature. The implemented peak models allow the discrimination between direct and indirect radiation emitted from tungsten anodes. The comparison with the independent literature spectra indicated a good agreement.

Although the causality between Zika virus, microcephaly, and other central nervous system disorders has been taken for granted by the scientific community, many uncertainties remain. The gap of knowledge at the moment is large enough to remove part of the confidence physicians have on the advice given to patients - and infertile women in particular - on their reproductive plans. Pretreatment serologic screening is a possible strategy to offer more confidence for individuals choosing to bear children regardless of the Zika virus, but the tests currently available do not seem to be sufficiently adequate. Until now, there is no formal recommendation to avoid pregnancy solely because of the Zika virus outbreak, and the choice of becoming pregnant has been regarded as a personal decision to be made by each woman and her family.

Mild gestational hyperglycemia (MGH), as assessed using the normal oral glucose tolerance test (OGTT) and detection of an altered glycemic profile, is associated with adverse perinatal outcome. This study described the results of 40 years of research conducted at the Perinatal Diabetes Research Centre at Sao Paulo State University (UNESP), Brazil, on the maternal MGH environment and placental markers. This study also described the unidirectional relationship between MGH and excessive fetal growth, also supplying moderator analysis. In addition to hyperglycemia, MGH is associated with an increased incidence of hypertension, metabolic syndrome, persistent insulin resistance after pregnancy, and high risk of developing type 2 diabetes mellitus (T2DM) after pregnancy. Structural changes and functional abnormalities resulting from MGH were observed in placenta. The fully adjusted model concluded that the predictor variable (MGH), which creates a complex environment for the fetus, has a direct effect on excessive birth weight and produces a z-score for ratios of birth weight to gestational age of ≥2. Maternal age, pre-pregnancy BMI, number of previous pregnancies, numbers of prenatal visits, and 1 h OGTT are moderator variables that impact MGH and excessive fetal growth. These results show that maternal MGH has some characteristics associated with similar long-term T2DM development and similar adverse perinatal results to those of gestational diabetes mellitus (GDM) mothers, making it an intermediate maternal and placental marker between normoglycemic and GDM mothers.

The number of cardiac implantable electronic device (CIED) implantations has increased over recent years. Transvenous lead extraction (TLE), as a part of an overall lead management strategy, has also been increasing, not only as a consequence of this growth, but also because of increasing rates of infection, lead failure, awareness of indications for lead management, and development of extraction tools. Clinical research is essential for understanding efficacy and risks of TLE.

Detailed information on organization and process of care in intensive care units (ICU) in emerging countries is scarce. Here, we investigated the impact of organizational factors on the outcomes and resource use in a large sample of Brazilian ICUs. Retrospective cohort study of 59,693 patients (medical admissions, 67 %) admitted to 78 ICUs during 2013. We retrieved patients’ data from an ICU quality registry and surveyed ICUs regarding structure, organization, staffing patterns, and process of care. We used multilevel logistic regression analysis to identify factors associated with hospital mortality. Efficient resource use was assessed by estimating standardized resource use and mortality rates adjusted for the SAPS 3 score. ICUs were mostly medical-surgical (79 %) and located at private hospitals (86 %). Median nurse to bed ratio was 0.20 (IQR, 0.15–0.28) and board-certified intensivists were present 24/7 in 16 (21 %) of ICUs. Multidisciplinary rounds occurred in 67 (86 %) and daily checklists were used in 36 (46 %) ICUs. Most frequent protocols focused on sepsis management and prevention of healthcare-associated infections. Hospital mortality was 14.4 %. In multivariable analysis, the number of protocols was the only organizational characteristic associated with mortality [odds ratio = 0.944 (95 % CI 0.904–0.987)]. The effects of protocols were consistent across subgroups including surgical and medical patients as well as the SAPS 3 tertiles. We also observed a significant trend toward efficient resource use as the number of protocols increased. In emerging countries such as Brazil, organizational factors, including the implementation of protocols, are potential targets to improve patient outcomes and resource use in ICUs.

Background: Implantable cardioverter–defibrillator (ICD) therapy significantly improves the survival of patients who are at high risk for sudden cardiac death. However, it is unclear whether this survival is accompanied by impairment on quality of life (QoL). Objectives: This systematic review sought to describe whether ICD therapy, as compared with standard treatment, can have an impact on QoL outcomes. Methods: Extensive literature searches were carried out in PubMed, EMBASE, LILACS and Cochrane Library. Eligible studies were randomized controlled trials (RCTs) of ICD versus medical therapy that reported valid and reliable measures of QoL. Included studies were reviewed to determine baseline patient characteristics, mean duration of follow-up, questionnaires used to assess QoL and association between QoL scores and ICD shock therapy. Results: Seven studies, enrolling a total of 5,701 patients, were included in this review. The analyzed trials showed conflicting results about the impact of ICD on QoL outcomes. Among the secondary prevention studies, CIDS reported a clear benefit from ICD and AVID showed no difference between ICD and amiodarone groups. Of the primary prevention trials, AMIOVIRT, MADIT II, DEFINITE, and SCD-HeFT found no evidence of impaired QoL in patients with an ICD. Evidence for an association between ICD shocks and QoL was mixed and seemed to depend on the interval between shocks and QoL assessment. Conclusion: There was no evidence of impaired QoL in patients with an ICD. However, ICD patients must be educated of all possible risks and benefits, including transitory declines in QoL after ICD shocks.

OBJECTIVE This study aimed to analyze the results of hysterosonography performed prior to in vitro fertilization (IVF) and to correlate anomalous findings with hysteroscopy. METHODS Findings from 197 hysterosonograms of patients examined in an assisted reproduction clinic between January 2012 and August 2014 were included. Enrollment criteria: patients in preparation for IVF not recently submitted to uterine examination through hysterosalpingography or hysteroscopy referred to hysterosonography. Uterine cavity evaluation was considered anomalous when one or more of the following were found: polyps, submucous myomas, uterine synechiae, Mullerian duct anomalies. Individuals with cavity abnormalities that might interfere with IVF results were referred to hysteroscopy. RESULTS Normal test results were seen in 170/197 of the cases (86.3%). Eighteen of the 197 cases (9.1%) were suspected for polyps, two (1%) for submucous myoma, six (3.5%) for synechiae, and one (0.5%) for Mullerian duct anomalies. Sixteen of the patients diagnosed with abnormalities underwent hysteroscopy to confirm or treat the suspected pathology. In only two cases there was no agreement between tests: one patient suspected for synechiae and another for polyps were not confirmed; another individual suspected for polyps was found to have focal endometrial thickening in hysteroscopy. The positive predictive value (PPV) in our study was 93.7%. CONCLUSION In most cases, the diagnoses obtained by hysterosonography showed normal uterine cavities. The most common anomalous findings were polyps, followed by synechiae, submucous myoma, and Mullerian duct anomalies. Hysterosonography is a good option for evaluating the uterus and offers a high positive predictive value, while hysteroscopy stands as the gold standard.

Loss of lysosomal glucocerebrosidase (GBA1) function is responsible for several organ defects, including skeletal abnormalities in type 1 Gaucher disease (GD). Enhanced bone resorption by infiltrating macrophages has been proposed to lead to major bone defects. However, while more recent evidences support the hypothesis that osteoblastic bone formation is impaired, a clear pathogenetic mechanism has not been depicted yet. Here, by combining different molecular approaches, we show that Gba1 loss of function in zebrafish is associated with defective canonical Wnt signaling, impaired osteoblast differentiation and reduced bone mineralization. We also provide evidence that increased reactive oxygen species production precedes the Wnt signaling impairment, which can be reversed upon human GBA1 overexpression. Type 1 GD patient fibroblasts similarly exhibit reduced Wnt signaling activity, as a consequence of increased β-catenin degradation. Our results support a novel model in which a primary defect in canonical Wnt signaling antecedes bone defects in type 1 GD.

Mean glandular dose is the quantity used for dosimetry in mammography and depends on breast-related characteristics, such as thickness and density, and on the x-ray spectrum used for breast imaging. This work aims to present an experimentally-based method to derive polyenergetic normalized glandular dose coefficients (DgNp) from the spectral difference between x-ray spectra incident and transmitted through breast phantoms with glandular/adipose proportions of 30/70 and 50/50 and thicknesses up to 4.5 cm. The spectra were produced by a Mammomat 3000 Nova system using radiographic techniques commonly applied for imaging compressed breast thickness lower than 6 cm (Mo/Mo, Mo/Rh and W/Rh spectra at 26 and 28 kVp). DgNp coefficients were compared with values estimated using Boones' method and data from breast images (DICOM Organ Dose and VolparaDose calculations). The DgNp were also evaluated in layers into the phantoms (depth-DgNp) using both x-ray spectra and thermoluminescent dosimeters (TLD-100). Maximum differences between DgNp from the method presented in this study and results using Boone's method was 11%, with larger differences for Mo/Rh spectra in relation to the Mo/Mo. The DgNp maximum differences to the coefficients obtained using patient images were 8.0%, for the DgN calculated using Volpara and 6.4% for the DgN from DICOM Organ Dose, for a 4.5 cm breast phantom with 30% glandularity. The DgNp estimated from the depth-DgNp distributions differ up to 5.2% to the coefficients obtained using the pair incident-transmitted spectra to calculate the DgNp directly in the whole phantom. The depth-DgNp distributions estimated with TLDs were consistent with the results observed using the experimental spectra, with maximum difference of 3.9%. In conclusion, polyenergetic x-ray spectrometry proved to be an applicable tool for research in dosimetry in mammography allowing spectral characterization. This approach can also be useful for investigation of the influence of x-ray spectra on glandular dose.

Background Limited venous access in certain patients increases the procedural risk and complexity of conventional transvenous pacemaker implantation. Objective The purpose of this study was to determine a minimally invasive epicardial approach using pericardial reflections for dual-chamber pacemaker implantation in patients with limited venous access. Methods Between June 2006 and November 2011, 15 patients underwent epicardial pacemaker implantation. Procedures were performed through a minimally invasive subxiphoid approach and pericardial window with subsequent fluoroscopy-assisted lead placement. Mean patient age was 46.4 ± 15.3 years (9 male [(60.0%], 6 female [40.0%]). The new surgical approach was used in patients determined to have limited venous access due to multiple abandoned leads in 5 (33.3%), venous occlusion in 3 (20.0%), intravascular retention of lead fragments from prior extraction in 3 (20.0%), tricuspid valve vegetation currently under treatment in 2 (13.3%), and unrepaired intracardiac defects in 2 (13.3%). Results All procedures were successful with no perioperative complications or early deaths. Mean operating time for isolated pacemaker implantation was 231.7 ± 33.5 minutes. Lead placement on the superior aspect of right atrium, through the transverse sinus, was possible in 12 patients. In the remaining 3 patients, the atrial lead was implanted on the left atrium through the oblique sinus, the postcaval recess, or the left pulmonary vein recess. None of the patients displayed pacing or sensing dysfunction, and all parameters remained stable throughout the follow-up period of 36.8 ± 25.1 months. Conclusion Epicardial pacemaker implantation through pericardial reflections is an effective alternative therapy for those patients requiring physiologic pacing in whom venous access is limited.

Residential indoor environments are potential sources of exposure to pyrethroids, which have low acute toxicity to humans but are allergenic and suspected endocrine disruptors. The present study evaluated the persistence of the pyrethroids cypermethrin and beta-cyfluthrin on indoor surfaces and in house dust. Cypermethrin and beta-cyfluthrin were applied and maintained on aluminum foils and in dust samples for 112 d under controlled conditions and for 12 mo in a test house; periodically, they were quantified by high-performance liquid chromatography. Cypermethrin and beta-cyfluthrin concentrations showed decreases of 10.1% and 7.7% on aluminum foils, and 12.7% and 16.4% in dust, respectively, at 112 d under controlled conditions. In the test house, cypermethrin and beta-cyfluthrin concentrations decreased by 40.3% and 60.2% on aluminum foils, and 29.6% and 56.2% in dust at the end of the study. The results show the considerable persistence of cypermethrin and beta-cyfluthrin indoors and indicate the risk of exposure to these products. Environ Toxicol Chem 2017;36:2895-2898. © 2017 SETAC.

Purpose To introduce and evaluate a method developed for the direct measurement of mammographic x-ray spectra using a CdTe spectrometer. The assembly of a positioning system and the design of a simple and customized alignment device for this application is described. Methods A positioning system was developed to easily and accurately locate the CdTe detector in the x-ray beam. Additionally, an alignment device to line up the detector with the central axis of the radiation beam was designed. Direct x-ray spectra measurements were performed in two different clinical mammography units and the measured x-ray spectra were compared with computer-generated spectra. In addition, the spectrometer misalignment effect was evaluated by comparing the measured spectra when this device is aligned relatively to when it is misaligned. Results The positioning and alignment of the spectrometer have allowed the measurements of direct mammographic x-ray spectra in agreement with computer-generated spectra. The most accurate x-ray spectral shape, related with the minimal HVL value, and high photon fluence for measured spectra was found with the spectrometer aligned according to the proposed method. The HVL values derived from both simulated and measured x-ray spectra differ at most 1.3 and 4.5% for two mammography devices evaluated in this study. Conclusion The experimental method developed in this work allows simple positioning and alignment of a spectrometer for x-ray spectra measurements given the geometrical constraints and maintenance of the original configurations of mammography machines.

Complications after surgical procedures in patients with cardiac implantable electronic devices (CIED) are an emerging problem due to an increasing number of such procedures and aging of the population, which consequently increases the frequency of comorbidities.To identify the rates of postoperative complications, mortality, and hospital readmissions, and evaluate the risk factors for the occurrence of these events.Prospective and unicentric study that included all individuals undergoing CIED surgical procedures from February to August 2011. The patients were distributed by type of procedure into the following groups: initial implantations (cohort 1), generator exchange (cohort 2), and lead-related procedures (cohort 3). The outcomes were evaluated by an independent committee. Univariate and multivariate analyses assessed the risk factors, and the Kaplan-Meier method was used for survival analysis.A total of 713 patients were included in the study and distributed as follows: 333 in cohort 1, 304 in cohort 2, and 76 in cohort 3. Postoperative complications were detected in 7.5%, 1.6%, and 11.8% of the patients in cohorts 1, 2, and 3, respectively (p = 0.014). During a 6-month follow-up, there were 58 (8.1%) deaths and 75 (10.5%) hospital readmissions. Predictors of hospital readmission included the use of implantable cardioverter-defibrillators (odds ratio [OR] = 4.2), functional class III--IV (OR = 1.8), and warfarin administration (OR = 1.9). Predictors of mortality included age over 80 years (OR = 2.4), ventricular dysfunction (OR = 2.2), functional class III-IV (OR = 3.3), and warfarin administration (OR = 2.3).Postoperative complications, hospital readmissions, and deaths occurred frequently and were strongly related to the type of procedure performed, type of CIED, and severity of the patient's underlying heart disease.Complicações após procedimentos cirúrgicos em portadores de dispositivos cardíacos eletrônicos implantáveis (DCEI) são um problema emergente devido ao aumento crescente na taxa destes procedimentos e ao envelhecimento da população, com consequente aumento de comorbidades.Identificar as taxas de complicações pós-operatórias, mortalidade e readmissão hospitalar, e pesquisar fatores de risco para a ocorrência desses eventos.Registro prospectivo e unicêntrico que incluiu todos os indivíduos submetidos a procedimentos cirúrgicos em DCEI no período de fevereiro a agosto de 2011. Os pacientes foram distribuídos por tipos de procedimento nos seguintes grupos: implantes iniciais (coorte 1), troca de gerador (coorte 2) e procedimentos em cabos-eletrodos (coorte 3). Os desfechos foram avaliados por um comitê independente. Empregou-se a análise univariada e multivariada para a pesquisa de fatores de risco e o método de Kaplan-Meier para análise de sobrevida.Foram incluídos 713 pacientes, sendo 333, 304 e 76 distribuídos nas coortes 1, 2 e 3, respectivamente. Complicações pós-operatórias foram detectadas em 7,5%, 1,6% e 11,8% dos pacientes nas coortes 1, 2 e 3, respectivamente (p = 0,014). Durante os 6 meses de seguimento, houve 58 (8,1%) óbitos e 75 (10,5%) readmissões hospitalares. Preditores de readmissão hospitalar incluíram o uso de cardioversor-desfibrilador implantável ( odds ratio [OR] = 4,2), classe funcional III-IV (OR = 1,8) e uso de warfarina (OR = 1,9). Preditores de mortalidade incluíram idade acima de 80 anos (OR = 2,4), disfunção ventricular (OR = 2,2), classe funcional III-IV (OR = 3,3) e uso de warfarina (OR = 2,3).Complicações pós-operatórias, readmissões hospitalares e óbitos foram frequentes. Esses eventos estiveram fortemente relacionados ao tipo de procedimento realizado, tipo de DCEI e gravidade da doença cardíaca do paciente.

Skeletal abnormalities represent a major clinical burden in patients affected by the lysosomal storage disorder mucopolysaccharidosis type II (MPSII, OMIM #309900). While extensive research has emphasized the detrimental role of stored glycosaminoglycans (GAGs) in the bone marrow (BM), a limited understanding of primary cellular mechanisms underlying bone defects in MPSII has hampered the development of bone-targeted therapeutic strategies beyond enzyme replacement therapy (ERT). We here investigated the involvement of key signaling pathways related to the loss of iduronate-2-sulfatase activity in two different MPSII animal models, D. rerio and M. musculus. We found that FGF pathway activity is impaired during early stages of bone development in IDS knockout mice and in a newly generated Ids mutant fish. In both models the FGF signaling deregulation anticipated a slow but progressive defect in bone differentiation, regardless of any extensive GAGs storage. We also show that MPSII patient fibroblasts harboring different mutations spanning the IDS gene exhibit perturbed FGF signaling-related markers expression. Our work opens a new venue to discover possible druggable novel key targets in MPSII.

The flexion-relaxation phenomenon (FRP) is well documented at end-range lumbar spine flexion in both standing and sitting however, the FRP has been insufficiently investigated in cervico-thoracic musculature. The aim of this study was to determine whether the FRP occurs during forward flexion of the neck, in lumbo-pelvic sitting, amongst a pain-free population. Surface electromyography (EMG) was used to measure muscle activation in 20 (10 men, 10 women) asymptomatic subjects in selected cervico-thoracic muscles during four, 5-s phases (upright posture, forward flexion, full flexion and return to upright) while subjects were positioned in lumbo-pelvic sitting. Spinal kinematics were simultaneously measured using an electromagnetic motion tracking device. No FRP was observed in upper trapezius or thoracic erector spinae (T4). When using visual methods to determine the presence/absence of the FRP, five subjects were believed to show evidence of the FRP in the cervical erector spinae. However, when using various non-visual criteria to determine the existence of the FRP, substantial variations (0-13 subjects) were evident. We recommend that criteria based upon relatively large differences in muscle activation should be considered when defining the FRP. These findings are of significance for future investigations examining specific cervical pain disorders.

Shoulder injuries are often related to rotator cuff muscles. Although there are various models for muscle force estimation, it is difficult to ensure that the results obtained with such models are reliable. The aim of the current study was to compare two models of muscle force estimation. Eight subjects, seven male and one female (mean age of 24 yr; mean height of 1.83 m), performed five isokinetic maximum concentric contractions of internal and external shoulder rotation. Two models with different algorithms were used. In both, the input data consisted of the measured internal rotation moment. Comparisons were made between the difference and the average results obtained with each model of muscle force estimation. There was reasonable agreement among the results for force between the two models for subscapularis, pectoralis major, and anterior deltoideus muscles results. Conversely, poor correlation was found for the latissimus dorsi, teres major, and middle deltoid. These results suggest that the algorithm structure might have a strong effect on muscle force estimation results.

Background— Although routinely administered, definitive evidence for the benefits of prophylactic antibiotics before the implantation of permanent pacemakers and implantable cardioverter-defibrillators from a large double-blinded placebo-controlled trial is lacking. The purpose of this study was to determine whether prophylactic antibiotic administration reduces the incidence of infection related to device implantation. Methods and Results— This double blinded study included 1000 consecutive patients who presented for primary device (Pacemaker and implantable cardioverter-defibrillators) implantation or generator replacement randomized in a 1:1 fashion to prophylactic antibiotics or placebo. Intravenous administration of 1 g of cefazolin (group I) or placebo (group 2) was done immediately before the procedure. Follow-up was performed 10 days, 1, 3, and 6 months after discharge. The primary end point was any evidence of infection at the surgical incision (pulse generator pocket), or systemic infection related to be procedure. The safety committee interrupted the trial after 649 patients were enrolled due to a significant difference in favor of the antibiotic arm (group I: 2 of 314 infected patients—0.63%; group II: 11 of 335 to 3.28%; RR=0.19 ; P =0.016). The following risk factors were positively correlated with infection by univariate analysis: nonuse of preventive antibiotic ( P =0.016); implant procedures (versus generator replacement: P =0.02); presence of postoperative hematoma ( P =0.03) and procedure duration ( P =0.009). Multivariable analysis identified nonuse of antibiotic ( P =0.037) and postoperative hematoma ( P =0.023) as independent predictors of infection. Conclusions— Antibiotic prophylaxis significantly reduces infectious complications in patients undergoing implantation of pacemakers or cardioverter-defibrillators.

Background Imaging with 123I-metalodobenzylguanidine (MIBG) is used for the assessment of cardiac sympathetic activity (CSA). We analyzed CSA before and after cardiac resynchronization therapy (CRT), and correlated these data with CRT response. Methods and Results Thirty patients with chronic heart failure and classic indications for CRT were prospectively studied before and at least 3 months after CRT. The variables analyzed were: QRS width, left-ventricular ejection fraction (LVEF), left-ventricular end-diastolic diameter (LVEDD), heart/mediastinum MIBG uptake ratio (H/M), and washout rate (WR). After CRT, patients were divided into two groups: group 1 (21 patients), responders improving to functional class (FC) I or II; and group 2 (9 patients), nonresponders remaining in FC III or IV. After CRT, only group I showed favorable changes in QRS width (P=.003), LVEF (P=.01), LVEDD (P=.04), and H/M ratio (P=.003). The H/M ratio and WR were associated with CRT response (P=.005 and P=.04, respectively). The H/M ratio was the only independent predictor of CRT response (P=.01). Receiver operating characteristic curves showed that the optimal H/M ratio cutoff point was 1.36 (sensitivity, 75%; specificity, 71%). Conclusions Improvement in CSA correlated with a positive CRT response. Lower MIBG uptake before therapy was associated with CRT nonresponse. The H/M ratio could be helpful in selecting patients for CRT.

Background: Atrial fibrillation (AF) is a common complication after coronary artery bypass grafting (CABG). Since its prevention with prophylactic drug therapy has limited success, alternative approaches are desirable. This study examined the efficacy of atrial or biatrial pacing, compared with no pacing, on the incidence of AF after isolated CABG. Methods: From August 2002 to September 2004, 240 patients underwent CABG. After surgery, right and left atrial epicardial pacing wires were implanted for 72 hours of temporary pacing. Patients were randomly assigned to one of three groups: no pacing (control group), right atrial (RA), and biatrial (BiA) pacing. Cardiac rhythm was monitored continuously during intensive care, or daily on the ward. The primary endpoints of this study were an episode of AF occurring up to 72 hours after CABG and the risk factors correlated with this event. Results: Atrial and BiA pacing significantly lowered the incidence (1.25% vs 25%, P=0.001) of AF episodes, and were both correlated (odd ratio 0.038; 95% confidence interval 0.005–0.29) with a decrease in rates of postoperative AF. Multivariable analysis identified older age (odd ratio 1.074; 95% confidence interval 1.024–1.12) and no pacing as independent risk factors of postoperative AF. Conclusions: Temporary right atrial or biatrial pacing after CABG significantly decreased the postoperative incidence of AF. Multivariable analysis identified older age and no pacing as predictors of AF occurrence.

Background:The recording of arrhythmic events (AE) in renal transplant candidates (RTCs) undergoing dialysis is limited by conventional electrocardiography. However, continuous cardiac rhythm monitoring seems to be more appropriate due to automatic detection of arrhythmia, but this method has not been used.Objective:We aimed to investigate the incidence and predictors of AE in RTCs using an implantable loop recorder (ILR).Methods:A prospective observational study conducted from June 2009 to January 2011 included 100 consecutive ambulatory RTCs who underwent ILR and were followed-up for at least 1 year. Multivariate logistic regression was applied to define predictors of AE.Results:During a mean follow-up of 424 ± 127 days, AE could be detected in 98% of patients, and 92% had more than one type of arrhythmia, with most considered potentially not serious. Sustained atrial tachycardia and atrial fibrillation occurred in 7% and 13% of patients, respectively, and bradyarrhythmia and non-sustained or sustained ventricular tachycardia (VT) occurred in 25% and 57%, respectively. There were 18 deaths, of which 7 were sudden cardiac events: 3 bradyarrhythmias, 1 ventricular fibrillation, 1 myocardial infarction, and 2 undetermined. The presence of a long QTc (odds ratio [OR] = 7.28; 95% confidence interval [CI], 2.01–26.35; p = 0.002), and the duration of the PR interval (OR = 1.05; 95% CI, 1.02–1.08; p < 0.001) were independently associated with bradyarrhythmias. Left ventricular dilatation (LVD) was independently associated with non-sustained VT (OR = 2.83; 95% CI, 1.01–7.96; p = 0.041).Conclusions:In medium-term follow-up of RTCs, ILR helped detect a high incidence of AE, most of which did not have clinical relevance. The PR interval and presence of long QTc were predictive of bradyarrhythmias, whereas LVD was predictive of non-sustained VT. ResumoFundamento:A documentação de eventos arrítmicos (EA) em candidatos a transplante renal (CTR) submetidos à diálise é limitada pelo registro de eletrocardiograma convencional. Um monitoramento contínuo do ritmo cardíaco parece ser o procedimento mais adequado para a detecção automática de arritmia, contudo esse método não foi explorado anteriormente.Objetivo:O objetivo deste estudo foi investigar a incidência e os preditores de EA em CTR usando um gravador de eventos implantável, do inglês, “loop recorder implantável” (ILR).Métodos:Um estudo prospectivo observacional foi conduzido entre Junho/2009 a Janeiro/2011. Cem CTR ambulatoriais consecutivos foram submetidos ao ILR e acompanhados pelo menos por um ano. Uma regressão logística multivariada foi aplicada para definir os preditores de EA.Resultados:Durante o tempo médio de acompanhamento de 424 ± 127 dias, EA foram detectados em 98% dos pacientes, sendo que 92% deles tinham mais de um tipo de arritmia, a maioria não considerada potencialmente séria. Taquicardia atrial sustentada e fibrilação atrial ocorreram respectivamente em 7% e 13% dos pacientes; bradiarritmia em 25% e taquicardia ventricular (TV) não-sustentada ou sustentada em 57%. Ocorreram 18 óbitos, 7 por morte cardíaca súbita, 3 por bradiarritmias, 1 por fibrilação ventricular, 1 por infarto do miocárdio e 2 óbitos devido à causas desconhecidas. A presença de QTc longo (Razão de Probabilidade [RP] = 7,28; intervalo de confiança de 95% [IC] 2,01-26,35; p = 0,002) e duração do intervalo PR (RP = 1,05; IC 95%: 1,02-1,08; p < 0,001) foram associados independentemente a bradiarritmias. A dilatação ventricular esquerda (DVE) foi independentemente associada à TV não-sustentada (RP = 2,83; IC 95%: 1,01-7,96; p = 0,041).Conclusões:Em acompanhamento de médio prazo de CTR, o ILR detectou uma alta incidência de EA, a maioria sem relevância clínica. O intervalo PR e a presença de QTc longo foram preditivos de bradiarritmias e DVE de TV não‑sustentada.

BACKGROUND: Pacemaker with remote monitoring (PRM) may be useful for silent atrial fibrillation (AF) detection. The aims of this study were to evaluate the incidence of silent AF, the role of PRM, and to determine predictors of silent AF occurrence. METHODS: Three hundred elderly patients with permanent pacemaker (PPM) were randomly assigned to the remote group (RG) or control group (CG). All patients received PPM with remote monitoring capabilities. Primary end point was AF occurrence rate and the secondary end points were time to AF detection and number of days with AF. RESULTS: During the average follow‐up of 15.7±7.7 months, AF episodes were detected in 21.6% (RG = 24% vs CG = 19.3%, P = 0.36]. There was no difference in the time to detect the first AF episode. However, the median time to detect AF recurrence in the RG was lower than that in the CG (54 days vs 100 days, P = 0.004). The average number of days with AF was 16.0 and 51.2 in the RG and CG, respectively (P = 0.028). Predictors of silent AF were left atrial diameter (odds ratio [OR] 1.2; 95% CI = 1.1–1.3; P < 0.001) and diastolic dysfunction (OR 4.8; 95% CI = 1.6–14.0; P = 0.005). CONCLUSIONS: The incidence of silent AF is high in elderly patients with pacemaker; left atrial diameter and diastolic dysfunction were predictors of its occurrence. AF monitoring by means of pacemaker is a valuable tool for silent AF detection and continuous remote monitoring allows early AF recurrence detection and reduces the number of days with AF.

Background Left ventricular (LV) dysfunction is the major reason for poor outcomes in patients with congenital complete atrioventricular block (CCAVB) and pacemaker. Long-term pacing has been associated with LV mechanical dyssynchrony. However, the relationship of dyssynchrony and LV dysfunction is not clear. Objective We sought to evaluate the prevalence of LV dyssynchrony by real time three-dimensional echocardiography (RT3DE) in patients with CCAVB and its association with LV dysfunction. In addition, we evaluated the agreement between RT3DE and tissue Doppler imaging (TDI) for detecting LV dyssynchrony. Method We studied 50 patients [median age 20 years old (5 months to 62 years), 68% women] with CCAVB and pacemaker who underwent complete two-dimensional echocardiography and RT3DE. LV dyssynchrony was considered if the systolic dyssynchrony index (SDI) was ≥5%. Intraventricular mechanical delay was defined by TDI when differences in electromechanical activation between LV walls were >65 msec. Results LV systolic dysfunction was present in 16 patients (32%) by two-dimensional and in 20 patients (40%) by RT3DE. There was a good correlation between LV ejection fraction by two-dimensional and RT3DE (r = 0.75; P

The assessment of diurnal preference, or the preferred timing of sleep and activity, is generally based on comprehensive questionnaires such as the Horne-Ostberg (HO). The aim of the present study was to assess the reliability of a subject's self-classification as extremely morning (Self-MM), more morning than evening (Self-M), more evening than morning (Self-E) or extremely evening (Self-EE) type, based on the last question of the HO (Self-ME). A convenience sample of 461 subjects [23.8 ± 4.7 years; 322 females] completed a full sleep-wake assessment, including diurnal preference (HO), night sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime sleepiness (Karolinska Sleepiness Scale, KSS), and habitual sleep-wake timing (12 d sleep diaries; n = 296). Significant differences in HO total score were observed between Self-ME classes, with each class being significantly different from neighboring classes (p