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Backgroung: Sarcopenia has been defined as a progressive and generalized disorder of skeletal muscle that involves accelerated loss of muscle mass and function. The prevalence of sarcopenia worldwide is up to 15% in healthy elderly, approximately 76% of acutely hospitalized elderly patients, and up to 69% of patients admitted for post-acute geriatric rehabilitation. The loss of muscle mass results in serious consequences and several chronic diseases and senility, characterized by functional losses, muscle weakness, loss of independence and increased risk of falls and death. Sarcopenia has been defined as a progressive and generalized muscle disorder. Here we investigate the effects of PEMF in muscle strength and functional capabilities of elderly sarcopenic patients. Methods. Fifteen elderly people of both sexes, aged between 65 and 80 years old, classified according to the degree of muscle weakness. The participants were submitted to PEMF therapy in 12 sessions three times a week with the following parameters. In the first two sessions, only submaximal contraction was applied during 30 min with a frequency of 5 Hz at the sport mode of the equipment. In the following 10 sessions we used cycles of Submaximal contractions – frequency of 5 Hz with 5s duration and Supramaximal contractions – frequency of 30 Hz with 5s duration. The intensity of the equipment was adjusted according to the sensitivity of the patient and session duration was 30 min. Results. the TUG functional tests showed a significant reduction in execution time, with an initial average of 40 ± 10s to 22 ± 6s after treatment sessions. The average increase in muscle strength was 27 ± 9% after PEMF treatment. Conclusions. This case series report is the first in the world scientific literature to demonstrate the effectiveness of PEMF (Supramaximus™) therapy in gaining muscle strength and functionality in elderly sarcopenic patients. PEMF therapy, at least for the treatment of sarcopenia in the elderly, can be considered as the definitive evolution of electrical currents, with greater effectiveness and acceptance by the patient.

Context: Career abandonment (turnaway) among software developers may be associated with many factors related to the profession. Identifying and understanding how these factors can affect those professionals is essential for organizations to design more effective retention policies and better understand the phenomenon. Objective: This study aims to identify motivators that may be associated with the turnaway phenomenon among software developers, in addition to dimensions with which those motivators are associated. Method: A qualitative study was conducted with 15 former software developers from different regions of Brazil. Results: We have identified 49 different motivators, among which the most cited were professional stagnation, lack of financial recognition, lack of professional regulation, and work overload, among others. We classified those motivators into seven software engineering dimensions, mainly: software engineering professional practice, management, and economics. Conclusion: The results of the study suggest, grounded on the collected qualitative data, a number of hypotheses to further research, relating turnaway to the types of activities of software development. We hope these results contribute to devise effective strategies for organizations to retain developers, additionally minimizing the social cost of turnaway to those developers.

Short tandem repeats (STRs) are prone to expansion mutations that cause multiple hereditary neurological and neuromuscular diseases. To study pathomechanisms using mouse models that recapitulate the tissue specificity and developmental timing of an STR expansion gene, we used rolling circle amplification and CRISPR/Cas9-mediated genome editing to generate Dmpk CTG expansion (CTGexp) knockin models of myotonic dystrophy type 1 (DM1). We demonstrate that skeletal muscle myoblasts and brain choroid plexus epithelial cells are particularly susceptible to Dmpk CTGexp mutations and RNA missplicing. Our results implicate dysregulation of muscle regeneration and cerebrospinal fluid homeostasis as early pathogenic events in DM1.

Myotonic dystrophy (DM) is a multisystemic disorder caused by microsatellite expansion mutations in two unrelated genes leading to similar, yet distinct, diseases. DM disease presentation is highly variable and distinguished by differences in age-of-onset and symptom severity. In the most severe form, DM presents with congenital onset and profound developmental defects. At the molecular level, DM pathogenesis is characterized by a toxic RNA gain-of-function mechanism that involves the transcription of noncoding microsatellite expansions. These mutant RNAs disrupt key cellular pathways, including RNA processing, localization, and translation. In DM, these toxic RNA effects are predominantly mediated through the modulation of the muscleblind-like and CUGBP and ETR-3-like factor families of RNA binding proteins (RBPs). Dysfunction of these RBPs results in widespread RNA processing defects culminating in the expression of developmentally inappropriate protein isoforms in adult tissues. The tissue that is the focus of this review, skeletal muscle, is particularly sensitive to mutant RNA-responsive perturbations, as patients display a variety of developmental, structural, and functional defects in muscle. Here, we provide a comprehensive overview of DM1 and DM2 clinical presentation and pathology as well as the underlying cellular and molecular defects associated with DM disease onset and progression. Additionally, fundamental aspects of skeletal muscle development altered in DM are highlighted together with ongoing and potential therapeutic avenues to treat this muscular dystrophy. © 2018 American Physiological Society. Compr Physiol 8:509-553, 2018.

Significance A number of hereditary neurological and neuromuscular diseases are caused by the abnormal expansion of short tandem repeats, or microsatellites, resulting in the expression of repeat expansion RNAs and proteins with pathological properties. Although these microsatellite expansions may occur in either the coding or noncoding regions of the genome, trinucleotide CNG repeats predominate in exonic coding and untranslated regions while intron mutations vary from trinucleotide to hexanucleotide GC-rich, and A/AT-rich, repeats. Here, we use transcriptome analysis combined with complementary experimental approaches to demonstrate that GC-rich intronic expansions are selectively associated with host intron retention. Since these intron retention events are detectable in both affected tissues and peripheral blood, they provide a sensitive and disease-specific diagnostic biomarker.

Submitted by Franciene Aguiar (franciene.aguiar@ucb.br) on 2019-02-22T20:38:19Z No. of bitstreams: 1 GabrielaDeSouzaES XavierTCCGraduacao2018.pdf: 1122919 bytes, checksum: 77057e35d7fb6774ec4b38eebe7cff9e (MD5) Approved for entry into archive by Sara Ribeiro (sara.ribeiro@ucb.br) on 2019-02-27T19:36:18Z (GMT) No. of bitstreams: 1 GabrielaDeSouzaES XavierTCCGraduacao2018.pdf: 1122919 bytes, checksum: 77057e35d7fb6774ec4b38eebe7cff9e (MD5) Made available in DSpace on 2019-02-27T19:36:18Z (GMT). No. of bitstreams: 1 GabrielaDeSouzaES XavierTCCGraduacao2018.pdf: 1122919 bytes, checksum: 77057e35d7fb6774ec4b38eebe7cff9e (MD5) Previous issue date: 2018 Com o avanço das tecnologias na construção civil, a necessidade de utilização de alternativas mais eficazes e modernas vem aumentando gradativamente, buscando uma melhora na produtividade, diminuindo o prazo e custos, consequentemente. O estudo da inserção de argamassas mecanicamente projetadas visa atender dois pilares: técnica e economia. Trata-se da mecanização de um sistema já existente que visa uma melhor qualidade do produto final. Dentro deste contexto, este trabalho apresenta o estudo da viabilidade técnica da aplicação direta do reboco projetado, tendo como base para estudo a construção de um empreendimento, localizado no Setor Noroeste em Brasília no Distrito Federal. Foram realizados ensaios de resistência à tração do reboco para analisar a performance do reboco projetado afim de comprovação do sistema de projeção, obtendo assim êxito na comprovação da produtividade, qualidade e rentabilidade. With the advancement of technologies civil construction, the need to use more effective and modern alternatives has gradually increased, seeking an improvement in productivity, decreasing the time and costs, consequently. The study of the insertion of mechanically designed mortars aims to meet two pillars: technique and economy. This is the mechanization of an existing system that aims at a better quality of the final product. Within this context, this paper presents the study of the technical feasibility of the direct application of the projected plaster, based on the study of construction of a project, located in the Northwest Sector in Brasília at the Distrito Federal. Traction tensile strength tests were carried out to analyze the performance of the plaster designed in order to prove the projection system, thus obtaining success in proving the productivity, quality and profitability.

This chapter illustrates how digital marketplaces may be allied to gamified IT applications/systems to support solutions for complex, costly community challenges in a sustainable manner. A generic modular architectural design for these marketplace‐based games is proposed and instantiated to public health and water management problem scenarios so that the resulting games support expected solutions. Preliminary validation studies of the games’ usefulness as a solution‐support and business‐promotion tool have been carried out for the cases of a game to combat disease‐carrying mosquitoes and of a water conservation game. These games have then been applied to real‐case scenarios pilot tests. The chapter reports on validation results and the contribution the embedded marketplaces may bring to these games and their sustainability.

SummaryTranscription of expanded microsatellite repeats is associated with multiple human diseases, including myotonic dystrophy, Fuchs’ endothelial corneal dystrophy, andC9orf72-ALS/FTD. Eliminating or reducing production of RNA and proteins arising from these expanded loci holds therapeutic benefit. Here, we tested the hypothesis that a deactivated form of the Cas9 enzyme impedes transcription across expanded microsatellites. We observed a repeat length-, PAM-, and strand-dependent reduction in the abundance of repeat-containing RNAs upon targeting dCas9 directly to repeat sequences. Aberrant splicing patterns were rescued in DM1 cells, and production of RAN peptides characteristic of DM1, DM2, andC9orf72-ALS/FTD cells was drastically decreased. Systemic delivery of dCas9/gRNA by adeno-associated virus led to reductions in pathological RNA foci, rescue of chloride channel 1 protein expression, and decreased myotonia. These observations suggest that transcription of microsatellite repeat-containing RNAs is more sensitive to perturbation than transcription of other RNAs, indicating potentially viable strategies for therapeutic intervention.

Background: The incremental prognostic value of plasma levels of C-reactive protein (CRP) in relation to GRACE score has not been established in patients with acute coronary syndrome (ACS) with non-ST segment elevation. Objective: To test the hypothesis that CRP measurements at admission increases the prognostic value of GRACE score in patients with ACS. Methods: A total of 290 subjects, consecutively admitted for ACS, with plasma material obtained upon admission CRP measurement using a high-sensitivity method (nephelometry) were studied. Cardiovascular outcomes during hospitalization were defined by the combination of death, nonfatal myocardial infarction or nonfatal refractory angina. Results: The incidence of cardiovascular events during hospitalization was 15% (18 deaths, 11 myocardial infarctions, 13 angina episodes) with CRP showing C-statistics of 0.60 (95% CI = 0.51-0.70, p = 0.034) in predicting these outcomes. After adjustment for the GRACE score, elevated CRP (defined as the best cutoff point) tended to be associated with hospital events (OR = 1.89, 95% CI = 0.92 to 3.88, p = 0.08). However, the addition of the variable elevated CRP in the GRACE model did not result in significant increase in C-statistics, which ranged from 0.705 to 0.718 (p = 0.46). Similarly, there was no significant reclassification of risk with the addition of CRP in the predictor model (net reclassification = 5.7 %, p = 0.15). Conclusion: Although CRP is associated with hospital outcomes, this inflammatory marker does not increase the prognostic value of the GRACE score.

Background: The TIMI Score for ST-segment elevation myocardial infarction (STEMI) was created and validated specifically for this clinical scenario, while the GRACE score is generic to any type of acute coronary syndrome. Objective: Between TIMI and GRACE scores, identify the one of better prognostic performance in patients with STEMI. Methods: We included 152 individuals consecutively admitted for STEMI. The TIMI and GRACE scores were tested for their discriminatory ability (C-statistics) and calibration (Hosmer-Lemeshow) in relation to hospital death. Results: The TIMI score showed equal distribution of patients in the ranges of low, intermediate and high risk (39 %, 27 % and 34 %, respectively), as opposed to the GRACE Score that showed predominant distribution at low risk (80 %, 13 % and 7%, respectively). Case-fatality was 11%. The C-statistics of the TIMI score was 0.87 (95%CI = 0.76 to 0.98), similar to GRACE (0.87, 95%CI = 0.75 to 0.99) - p = 0.71. The TIMI score showed satisfactory calibration represented by χ2 = 1.4 (p = 0.92), well above the calibration of the GRACE score, which showed χ2 = 14 (p = 0.08). This calibration is reflected in the expected incidence ranges for low, intermediate and high risk, according to the TIMI score (0 %, 4.9 % and 25 %, respectively), differently to GRACE (2.4%, 25% and 73%), which featured middle range incidence inappropriately. Conclusion: Although the scores show similar discriminatory capacity for hospital death, the TIMI score had better calibration than GRACE. These findings need to be validated populations of different risk profiles. Fundamento: O Escore TIMI para infarto com supradesnível do segmento ST (IAMcSST) foi criado e validado especificamente para este cenário clínico, enquanto o Escore GRACE é genérico para qualquer tipo de síndrome coronariana aguda. Objetivo: Identificar qual dos escores, TIMI ou GRACE, apresenta melhor desempenho prognóstico em pacientes com IAMcSST. Métodos: Foram incluídos 152 indivíduos consecutivamente internados por IAMcSST. Os escores TIMI e GRACE foram testados quanto a sua capacidade discriminatória (estatística-C) e calibração (teste Hosmer-Lemeshow), em relação ao desfecho óbito hospitalar. Resultados: O Escore TIMI apresentou distribuição equitativa de pacientes nas faixas de baixo, intermediário e alto risco (39%, 27% e 34%, respectivamente), diferente do Escore GRACE que apresentou distribuição predominante em baixo risco (80%, 13% e 7%, respectivamente). A letalidade da amostra foi de 11%. A estatística-C do Escore TIMI foi de 0,87 (95% IC = 0,76 - 0,98), semelhante ao GRACE (0,87; 95% IC = 0,75-0,99) - p = 0,71. O Escore TIMI apresentou calibração satisfatória, representada por χ2 de 1,4 (p = 0,92), nitidamente superior à calibração do Escore GRACE, que apresentou χ2 de 14 (p = 0,08). Esta calibração se reflete em incidências esperadas para as faixas de baixo, intermediário e alto risco de acordo com o Escore TIMI (0%, 4,9% e 25%, respectivamente), diferente do GRACE (2,4%, 25% e 73%) que caracterizou inadequadamente a faixa intermediária. Conclusão: Os escores TIMI e GRACE apresentam semelhante capacidade discriminatória em relação a óbito hospitalar, porém o Escore TIMI possui calibração superior ao GRACE. Para populações de risco diferente da nossa amostra, esta conclusão deve ser validada por futuros trabalhos.

The Aedes aegypti mosquito transmits the zika, chikungunya, dengue and yellow fever diseases. The mosquito evolves from eggs that hatch in water pooling anywhere. To fight the mosquito effectively, the population must be educated in its biology, health threats and countermeasures and actively engage in reporting hatcheries to sanitary authorities. This paper proposes an IT system to support such education and combat efforts in a sustainable way. The system incorporates concepts from games, crowdsourcing, georeferenced information systems, computer-based education, mobile computing and entrepreneurship. Preliminary validation studies indicate the system to be an efficient and sustainable training and combat tool against Aedes aegytpi.

Os idosos possuem elevada vulnerabilidade a problemas decorrentes do uso de medicamentos. Isso ocorre devido às alterações farmacocinéticas e farmacodinâmicas do próprio envelhecimento, às múltiplas e complexas doenças e uso concomitante de vários medicamentos. Neste sentido, o presente estudo objetivou avaliar potenciais problemas farmacoterapêuticos de idosos atendidos em uma Unidade de Atenção Primária à Saúde de Minas Gerais. Trata-se de um estudo transversal descritivo realizado com 100 idosos. A amostra foi calculada com base no total de idosos cadastrados na Unidade de Saúde. Os dados foram coletados por meio de entrevistas, a partir das quais se obtiveram dados sociodemográficos, relacionados ao uso de medicamentos, condições de saúde, dentre outros. Foram identificados 117 problemas farmacoterapêuticos potenciais, sendo duas duplicidades, sete sobredoses, 72 potenciais interações medicamento-medicamento e prevalência de 8,5% de medicamentos potencialmente inapropriados para idosos, segundo o Critério de Beers. Estes resultados são preocupantes e evidenciam a necessidade de implantação de serviços de acompanhamento da terapia medicamentosa em Unidades de Atenção Primária à Saúde, buscando-se melhorar a qualidade de vida dos idosos. The elderly are highly vulnerable to problems stemming from drug use. This is due to pharmacokinetic and pharmacodynamic changes of aging itself, the multiple and complex diseases and concomitant use of several drugs. In this sense, the present study aimed at evaluating potential pharmacotherapeutic problems of the elderly in a Unit of Primary Healthcare of Minas Gerais. This is a descriptive cross-sectional study of 100 elderly. The convenience sample was calculated based on the total of elderly enrolled in the Health Unit. Data were collected through interviews, from which we obtained sociodemographic data related to the use of medications, health conditions, among others. 117 potential drug therapy problems and 2 duplicates, 7 overdoses, 72 potential drug-drug interactions and 8.5% inappropriate drugs for the elderly, according to the Beers Criteria, were identified. These results are worrying and highlight the need to implement monitoring of drug therapy services in Primary Healthcare Units seeking to improve the quality of life for seniors

Spatial restriction of mRNA to distinct subcellular locations enables local regulation and synthesis of proteins. However, the organizing principles of mRNA localization remain poorly understood. Here we analyzed subcellular transcriptomes of neural projections and soma of primary mouse cortical neurons and two neuronal cell lines and found that alternative last exons (ALEs) often confer isoform-specific localization. Surprisingly, gene-distal ALE isoforms were four times more often localized to neurites than gene-proximal isoforms. Localized isoforms were induced during neuronal differentiation and enriched for motifs associated with muscleblind-like (Mbnl) family RNA-binding proteins. Depletion of Mbnl1 and/or Mbnl2 reduced localization of hundreds of transcripts, implicating Mbnls in localization of mRNAs to neurites. We provide evidence supporting a model in which the linkage between genomic position of ALEs and subcellular localization enables coordinated induction of localization-competent mRNA isoforms through a post-transcriptional regulatory program that is induced during differentiation and reversed in cellular reprogramming and cancer. Taliaferro et al. show that mRNA isoforms that contain gene-distal alternative last exons are preferentially localized to neurites. These isoforms are induced during neuronal differentiation, suggesting that a coordinated post-transcriptional program targets messages to neurites. Localization of many neuronal mRNAs depends on muscleblind proteins.

Rational: The GRACE Score assessed at admission predicts mortality in patients with non-ST elevation acute coronary syndromes (ACS). However, once coronary anatomy is assessed, it is not known whether this score increments prognostic assessment. Objective: To test the hypothesis that the GRACE Score adds prognostic value to coronary anatomy in patients with ACS. Methods: Prospective cohort, including patients with ACS who underwent coronary angiography while admitted to the hospital. Anatomical extension of coronary disease was characterized by the Duke Jeopardy score (DJS) and the number diseased artery (NDA). The primary end-point was the composite of death, non-fatal MI or refractory unstable angina. Results: 112 patients enrolled, aged 70 ± 12, 14% incidence of cardiovascular events. C-statistics for GRACE was 0.68 (95%CI=0.53-0.84), for DJS was 0.78 (95%CI=0.67-0.9) and for NAD was 0.74 (95%CI=0.61-0.88). Logistic regression analysis demonstrated independent predictive value of GRACE in relation to anatomical information. However, when this Score was added to DJS or NDA, no improving in c-statistic was observed: DJS-GRACE had a c-statistics of 0.78 (95%CI=0.64–0.92) and NAD-GRACE of 0.76 (95%CI=0.60–0.92). Conclusion: The GRACE score does not add prognostic value to angiographic data in patients with ACS.

Recent biotechnological advances have permitted the manipulation of genetic sequences to treat several diseases in a process called gene therapy. However, the advance of gene therapy has opened the door to the possibility of using genetic manipulation (GM) to enhance athletic performance. In such ‘gene doping’, exogenous genetic sequences are inserted into a specific tissue, altering cellular gene activity or leading to the expression of a protein product. The exogenous genes most likely to be utilized for gene doping include erythropoietin (EPO), vascular endothelial growth factor (VEGF), insulin-like growth factor type 1 (IGF-1), myostatin antagonists, and endorphin. However, many other genes could also be used, such as those involved in glucose metabolic pathways. Because gene doping would be very difficult to detect, it is inherently very attractive for those involved in sports who are prepared to cheat. Moreover, the field of gene therapy is constantly and rapidly progressing, and this is likely to generate many new possibilities for gene doping. Thus, as part of the general fight against all forms of doping, it will be necessary to develop and continually improve means of detecting exogenous gene sequences (or their products) in athletes. Nevertheless, some bioethicists have argued for a liberal approach to gene doping.