Comparison between GLIM and PG-SGA methods in the nutritional assessment of hospitalized oncological patients / Comparação entre os métodos GLIM e ASG-PPP na avaliação nutricional de pacientes oncológicos hospitalizados

ABSTRACT Objective The aim of this study was to compare the Global Leadership Initiative on Malnutrition and Subjective Global Assessment methods produced by the patient in the nutritional assessment of cancer in-patients. Methods Cross-sectional study with a prospective variable, conducted with patients admitted to a public hospital in Pernambuco, Brazil. The application of these tools and the diagnosis of malnutrition were performed within the first 48 hours of admission. Sociodemographic, clinical and laboratory data were obtained from the medical records and weight, height, arm circumference, triceps skinfold and handgrip strength data were collected. Results The 82 patients evaluated included mostly men aged ≥ 60 years with less than 8 years education. Malnutrition frequency was 93.7% according to the Subjective Global Assessment and including 23.2% severe malnutrition while, according to the Global Leadership Initiative on Malnutrition, 50% of the patients were considered severely malnourished. Malnutrition by the Global Leadership Initiative on Malnutrition showed a sensitivity of 82.9% and when associated with handgrip strength sensitivity was 90.8%, considering the Subjective global assessment produced by the patient as a reference; on the other hand, the specificity was 16.7% independently of adding handgrip strength. None of the anthropometric variables was associated with the reference tool. Conclusion The Global Leadership Initiative on Malnutrition proved to be a very sensitive tool for diagnosing malnutrition when compared to the gold standard, particularly for severe malnutrition, but with little specificity. The need for a comprehensive nutritional assessment in the clinical practice was confirmed, using the parameters available and not interpreting them separately.

RESUMO Objetivo O objetivo deste estudo foi comparar os métodos Global Leadership Initiativeon Malnutrition e Avaliação Subjetiva Global Produzida pelo Próprio Paciente na avaliação nutricional de pacientes oncológicos hospitalizados. Métodos Estudo transversal com uma variável prospectiva, realizado com pacientes internados em um hospital público de Pernambuco. A aplicação dessas ferramentas e o diagnóstico de desnutrição foram realizados nas primeiras 48 horas de admissão. Dados sociodemográficos, clínicos e laboratoriais foram obtidos do prontuário, e dados com peso, altura, circunferência do braço, prega cutânea tricipital e força de preensão palmar foram coletados. Resultados Dos 82 pacientes avaliados, a maioria eram homens com idade ≥60 anos com menos de 8 anos de estudo. A frequência de desnutrição foi de 93,7% pela Avaliação Subjetiva Global; destes, 23,2% com desnutrição grave. Já pela Global Leadership Initiative on Malnutrition, 50% dos pacientes foram considerados desnutridos graves. A desnutrição pela Global Leadership Initiative on Malnutrition apresentou uma sensibilidade de 82,9% e de 90,8% quando associada à força de preensão palmar considerando a Avaliação Subjetiva Global Produzida pelo Próprio Paciente como referência. Por sua vez, a especificidade foi de 16,7% independentemente de adicionar a força de preensão palmar. Nenhuma das variáveis antropométricas apresentou associação com a ferramenta de referência. Conclusão A Global Leadership Initiative on Malnutrition mostrou-se uma ferramenta bastante sensível para diagnosticar desnutrição quando comparada ao padrão ouro, principalmente para desnutrição grave, porém pouco específica. Ratificou-se a necessidade de uma avaliação nutricional ampla na prática clínica, utilizando os parâmetros disponíveis e não os interpretando de forma isolada.

Mouse Neural Stem Cell Differentiation and Human Adipose Mesenchymal Stem Cell Transdifferentiation Into Neuron- and Oligodendrocyte-like Cells With Myelination Potential.

Stem cell therapy is an interesting approach for neural repair, once it can improve and increase processes, like angiogenesis, neurogenesis, and synaptic plasticity. In this regard, adult neural stem cells (NSC) are studied for their mechanisms of proliferation, differentiation and functionality in neural repair. Here, we describe novel neural differentiation methods. NSC from adult mouse brains and human adipose-derived stem cells (hADSC) were isolated and characterized regarding their neural differentiation potential based on neural marker expression profiles. For both cell types, their capabilities of differentiating into neuron-, astrocyte- and oligodendrocytes-like cells (NLC, ALC and OLC, respectively) were analyzed. Our methodologies were capable of producing NLC, ALC and OLC from adult murine and human transdifferentiated NSC. NSC showed augmented gene expression of NES, TUJ1, GFAP and PDGFRA/Cnp. Following differentiation induction into NLC, OLC or ALC, specific neural phenotypes were obtained expressing MAP2, GalC/O4 or GFAP with compatible morphologies, respectively. Accordingly, immunostaining for nestin+ in NSC, GFAP+ in astrocytes and GalC/O4+ in oligodendrocytes was detected. Co-cultured NLC and OLC showed excitability in 81.3% of cells and 23.5% of neuron/oligodendrocyte marker expression overlap indicating occurrence of in vitro myelination. We show here that hADSC can be transdifferentiated into NSC and distinct neural phenotypes with the occurrence of neuron myelination in vitro, providing novel strategies for CNS regeneration therapy. Superior Part: Schematic organization of obtaining and generating hNSC from hADSC and differentiation processes and phenotypic expression of neuron, astrocyte and oligodendrocyte markers (MAP2, GFAP and O4, respectively) and stem cell marker (NES) of differentiating hNSC 14 days after induction. The nuclear staining in blue corresponds to DAPI. bar = 100 µm. Inferior part: Neural phenotype fates in diverse differentiation media. NES: nestin; GFAP: Glial fibrillary acidic protein. MAP2: Microtubule-associated protein 2. TUJ1: ß-III tubulin. PDGFRA: PDGF receptor alpha. Two-way ANOVA with Bonferroni post-test with n = 3. * p < 0.05 and ** p < 0.01: (NSCiM1 NSC induction medium 1) vs differentiation media.

Exercise prevents impaired autophagy and proteostasis in a model of neurogenic myopathy.

Increased proteolytic activity has been widely associated with skeletal muscle atrophy. However, elevated proteolysis is also critical for the maintenance of cellular homeostasis by disposing cytotoxic proteins and non-functioning organelles. We recently demonstrated that exercise activates autophagy and re-establishes proteostasis in cardiac diseases. Here, we characterized the impact of exercise on skeletal muscle autophagy and proteostasis in a model of neurogenic myopathy induced by sciatic nerve constriction in rats. Neurogenic myopathy, characterized by progressive atrophy and impaired contractility, was paralleled by accumulation of autophagy-related markers and loss of acute responsiveness to both colchicine and chloroquine. These changes were correlated with elevated levels of damaged proteins, chaperones and pro-apoptotic markers compared to control animals. Sustained autophagy inhibition using chloroquine in rats (50 mg.kg-1.day-1) or muscle-specific deletion of Atg7 in mice was sufficient to impair muscle contractility in control but not in neurogenic myopathy, suggesting that dysfunctional autophagy is critical in skeletal muscle pathophysiology. Finally, 4 weeks of aerobic exercise training (moderate treadmill running, 5x/week, 1 h/day) prior to neurogenic myopathy improved skeletal muscle autophagic flux and proteostasis. These changes were followed by spared muscle mass and better contractility properties. Taken together, our findings suggest the potential value of exercise in maintaining skeletal muscle proteostasis and slowing down the progression of neurogenic myopathy.

Insect vectors of Chagas disease (Trypanosoma cruzi) in Northeastern Brazil.

INTRODUCTION: Chagas disease remains a public health problem in the rural and urban areas of 19 countries in the Americas. METHODS: The aim of the present study was to investigate the Trypanosoma cruzi infection rate of triatomines collected from both intra- and peridomiciliary areas in eleven municipalities of Southeastern Ceará, Brazil, from 2009 to 2015. RESULTS: A total of 32,364 triatomine specimens, including nymphs and adults, were collected, and 31,736 (98.06%) of these were examined. More nymphs were collected than adults, and the greatest number of triatomines (n = 8,548) was collected in 2010, for which the infection rate was 1.3%, with the highest rate of infections observed for specimens from Quixere. The species collected during the study were identified as Triatoma pseudomaculata, Triatoma brasiliensis, Panstrongylus megistus, Panstrongylus lutzi, and Rhodnius nasutus, with T. pseudomaculata being the most abundant (n = 19,962). CONCLUSIONS: These results verify the presence of triatomines in both intra- and peridomiciliary areas, thereby ensuring persistence of the pathogen and consequently, the disease, as the presence of infected vectors in households is an important risk factor. According to these findings, the Chagas Disease Control Program should intensify its efforts in order to prevent the spread of the disease.

Insect vectors of Chagas disease (Trypanosoma cruzi) in Northeastern Brazil

Abstract INTRODUCTION: Chagas disease remains a public health problem in the rural and urban areas of 19 countries in the Americas. METHODS: The aim of the present study was to investigate the Trypanosoma cruzi infection rate of triatomines collected from both intra- and peridomiciliary areas in eleven municipalities of Southeastern Ceará, Brazil, from 2009 to 2015. RESULTS: A total of 32,364 triatomine specimens, including nymphs and adults, were collected, and 31,736 (98.06%) of these were examined. More nymphs were collected than adults, and the greatest number of triatomines (n = 8,548) was collected in 2010, for which the infection rate was 1.3%, with the highest rate of infections observed for specimens from Quixere. The species collected during the study were identified as Triatoma pseudomaculata, Triatoma brasiliensis, Panstrongylus megistus, Panstrongylus lutzi, and Rhodnius nasutus, with T. pseudomaculata being the most abundant (n = 19,962). CONCLUSIONS: These results verify the presence of triatomines in both intra- and peridomiciliary areas, thereby ensuring persistence of the pathogen and consequently, the disease, as the presence of infected vectors in households is an important risk factor. According to these findings, the Chagas Disease Control Program should intensify its efforts in order to prevent the spread of the disease.

Clinical Evaluation of 10% Hydrogen Peroxide on Tooth Sensitivity and Effectiveness in at Home Dental Bleaching.

AIM: The purpose of this study was to evaluate the dental effect and sensitivity of at-home dental bleaching with 10% hydrogen peroxide (H2O2). MATERIALS AND METHODS: Twenty volunteers with A2 or darker central incisors were selected for this study. Was used 10% H2O2 for thirty minutes twice a day, for two weeks. Shade evaluation was assessed visually by the value-oriented shade guide Vita Classical shade guide, Vita Bleachedguide 3D-MASTER and by the Easyshade spectrophotometer at baseline, during bleaching (first and second weeks), and post-bleaching (one month). The perceptions of sensitivity were recorded by the patients through the numerical rating scale (0 to 4) and 0 to 10 visual analog scales daily. Data from the shade guide units was subjected to a one way repeated measures (RM) analysis of variance (ANOVA) test (a = 5%). The overall AE, absolute risk and intensity of tooth sensitivity were calculated as well as the 95% confidence interval. RESULTS: The absolute risk of tooth sensitivity was 65% and the intensity was mild. Data from ASGU and AE after 1 month of bleaching for H2O2 10% showed significant whitening, 4 units for Vita Classical, 5 units for Vita Bleachedguide and 9.7 units for spectrophotometer. CONCLUSION: At-home bleaching using 10% hydrogen peroxide is effective in 14 days of bleaching. The most common adverse events were mild tooth sensitivity, and no subjects discontinued use early because of a treatment-related adverse event. CLINICAL SIGNIFICANCE: At-home dental bleaching with 10% hydrogen peroxide gel reduces the time of use of the tray, maintaining the effectiveness with low intensity of dental sensitivity. Brazilian clinical trials registry (REBEC) RBR-45xmzj.

Doxycycline induces bone repair and changes in Wnt signalling.

Doxycycline (DOX) exhibits anti-inflammatory and MMP inhibitory properties. The objectives of this study were to evaluate the effects of DOX on alveolar bone repair. Controls (CTL) and DOX-treated (10 and 25 mg·kg-1) molars were extracted, and rats were killed 7 or 14 days later. The maxillae were processed and subjected to histological and immunohistochemical assays. Hematoxylin-eosin staining (7th day) revealed inflammation in the CTL group that was partly reversed after DOX treatment. On the 14th day, the CTL group exhibited bone neoformation, conjunctive tissue, re-epithelization and the absence of inflammatory infiltrate. DOX-treated groups exhibited complete re-epithelization, tissue remodelling and almost no inflammation. Picrosirius red staining in the DOX10 group (7th and 14th days) revealed an increased percentage of type I and III collagen fibres compared with the CTL and DOX25 groups. The DOX10 and DOX25 groups exhibited increases in osteoblasts on the 7th and 14th days. However, there were fewer osteoclasts in the DOX10 and DOX25 groups on the 7th and 14th days. Wnt-10b-immunopositive cells increased by 130% and 150% on the 7th and 14th days, respectively, in DOX-treated groups compared with the CTL group. On the 7th day, Dickkopf (Dkk)-1 immunostaining was decreased by 63% and 46% in the DOX10 and DOX25 groups, respectively. On the 14th day, 69% and 42% decreases in immunopositive cells were observed in the DOX10 and DOX25 groups, respectively, compared with the CTL group. By increasing osteoblasts, decreasing osteoclasts, activating Wnt 10b and neutralising Dkk, DOX is a potential candidate for bone repair in periodontal diseases.

Exercise reestablishes autophagic flux and mitochondrial quality control in heart failure.

We previously reported that facilitating the clearance of damaged mitochondria through macroautophagy/autophagy protects against acute myocardial infarction. Here we characterize the impact of exercise, a safe strategy against cardiovascular disease, on cardiac autophagy and its contribution to mitochondrial quality control, bioenergetics and oxidative damage in a post-myocardial infarction-induced heart failure animal model. We found that failing hearts displayed reduced autophagic flux depicted by accumulation of autophagy-related markers and loss of responsiveness to chloroquine treatment at 4 and 12 wk after myocardial infarction. These changes were accompanied by accumulation of fragmented mitochondria with reduced O2 consumption, elevated H2O2 release and increased Ca2+-induced mitochondrial permeability transition pore opening. Of interest, disruption of autophagic flux was sufficient to decrease cardiac mitochondrial function in sham-treated animals and increase cardiomyocyte toxicity upon mitochondrial stress. Importantly, 8 wk of exercise training, starting 4 wk after myocardial infarction at a time when autophagy and mitochondrial oxidative capacity were already impaired, improved cardiac autophagic flux. These changes were followed by reduced mitochondrial number:size ratio, increased mitochondrial bioenergetics and better cardiac function. Moreover, exercise training increased cardiac mitochondrial number, size and oxidative capacity without affecting autophagic flux in sham-treated animals. Further supporting an autophagy mechanism for exercise-induced improvements of mitochondrial bioenergetics in heart failure, acute in vivo inhibition of autophagic flux was sufficient to mitigate the increased mitochondrial oxidative capacity triggered by exercise in failing hearts. Collectively, our findings uncover the potential contribution of exercise in restoring cardiac autophagy flux in heart failure, which is associated with better mitochondrial quality control, bioenergetics and cardiac function.

Prevalence of intestinal parasitosis and associated factors among the elderly / Prevalência de parasitoses intestinais e fatores associados em idosos

Abstract Objective: To identify the prevalence of intestinal parasitosis and associated factors in elderly persons resident in the community. Methods: A cross-sectional study was performed involving 236 elderly persons in Aiquara, in the state of Bahia, Brazil, in 2015. Data were collected through a coprological survey and a questionnaire for information relating to sociodemographic characteristics, health and lifestyle. The presence of parasites in stools was verified by the Hoffman method. Results: The prevalence of intestinal parasites among the elderly was 30.5%. Among infected elderly persons, 26.3% had monoparasitism, 3.8% biparasitism and 0.4% polyparasitism. There was a predominance of protozoa (80.8%) over helminths (19.2%). The most prevalent parasites were Entamoeba coli (44.6%); Endolimax nana (21.7%) and Iodamoeba bütschlii (14.5%). In the population studied, the independent variables analyzed were not associated (p>0.05) with the presence of intestinal parasites. Conclusion: the prevalence of intestinal parasitic infections in elderly people living in the urban area of the municipal region of Aiquara, Bahia, was high and there was no association between intestinal parasites and sociodemographic characteristics, lifestyle or health. AU

Resumo Objetivo: Identificar a prevalência de parasitoses intestinais e fatores associados em idosos residentes em comunidade. Métodos: estudo transversal, realizado com 236 idosos do município de Aiquara, BA, Brasil, no ano de 2015. Os dados foram coletados por meio de um inquérito coprológico e questionário para obter informações referentes às características sociodemográficas, condições de saúde e estilo de vida. A presença dos parasitas nas fezes foi verificada por meio do método de Hoffman. Resultados: a prevalência de parasitoses intestinais nos idosos foi de 30,5%. Entre os idosos infectados, observou-se 26,3% de monoparasitismo, 3,8% de biparasitismo e 0,4% de poliparasitismo. Houve predominância de protozoários (80,8%), em relação a helmintos (19,2%). Os parasitas mais prevalentes foram Entamoeba coli (44,6%); Endolimax nana (21,7%) e Iodamoeba butschlii (14,5%). Na população avaliada, as variáveis independentes analisadas não foram associadas (p>0,05) à presença de parasitoses intestinais. Conclusão: a prevalência de parasitoses intestinais em idosos residentes na zona urbana do município de Aiquara, BA foi alta e não houve associação entre parasitoses intestinais e características sociodemográficas, estilo de vida e condições de saúde. AU

Analysis of the seroprevalence of and factors associated with Chagas disease in an endemic area in Northeastern Brazil.

INTRODUCTION:: Chagas disease (CD) is currently considered a neglected disease; hence, identifying the factors associated with its high prevalence is essential. This study aimed to identify the seroprevalence of and the possible factors associated with CD in inhabitants of the City of Limoeiro do Norte, Northeastern Brazil. METHODS:: Between April and November 2013, blood collection was conducted and a semi-structured questionnaire was administered. Blood samples that showed positive or possible serology for anti-Trypanosoma cruzi antibodies based on indirect immunofluorescence, hemagglutination indirect, and an enzyme-linked immunosorbent assay were analyzed. Associations between CD positivity and the study variables were analyzed using prevalence ratios (PR) with 95% confidence intervals (CI). RESULTS:: A total of 812 individuals were analyzed, of which T. cruzi seropositivity was determined in 4.2% (34 individuals). Sociodemographic variables showing a significant association with T. cruzi positivity included age >50 years (PR = 27.6; 95% CI = 6.66-114.4), elementary level education (PR = 5.15; 95% CI = 1.83-14.47), and retirement (PR = 7.25; 95% CI = 3.72-14.14). Positivity for T. cruzi was 6.17 times higher in those who had a history of living in rammed earth houses compared with those who did not (95% CI = 2.19-17.37). There was no evidence of vertical transmission in the individuals studied. Among the individuals infected with T. cruzi, the majority reported having a comorbidity (p < 0.01). CONCLUSIONS:: This study demonstrated the seroprevalence of CD and identified factors associated with a high prevalence of CD.

Induced pluripotent stem cells reprogramming: Epigenetics and applications in the regenerative medicine.

Induced pluripotent stem cells (iPSCs) are somatic cells reprogrammed into an embryonic-like pluripotent state by the expression of specific transcription factors. iPSC technology is expected to revolutionize regenerative medicine in the near future. Despite the fact that these cells have the capacity to self-renew, they present low efficiency of reprogramming. Recent studies have demonstrated that the previous somatic epigenetic signature is a limiting factor in iPSC performance. Indeed, the process of effective reprogramming involves a complete remodeling of the existing somatic epigenetic memory, followed by the establishment of a "new epigenetic signature" that complies with the new type of cell to be differentiated. Therefore, further investigations of epigenetic modifications associated with iPSC reprogramming are required in an attempt to improve their self-renew capacity and potency, as well as their application in regenerative medicine, with a new strategy to reduce the damage in degenerative diseases. Our review aimed to summarize the most recent findings on epigenetics and iPSC, focusing on DNA methylation, histone modifications and microRNAs, highlighting their potential in translating cell therapy into clinics.

Induced pluripotent stem cells reprogramming: Epigenetics and applications in the regenerative medicine / Células-tronco de pluripotência induzida: papel da epigenética na reprogramação e sua aplicabilidade clínica

Summary Induced pluripotent stem cells (iPSCs) are somatic cells reprogrammed into an embryonic-like pluripotent state by the expression of specific transcription factors. iPSC technology is expected to revolutionize regenerative medicine in the near future. Despite the fact that these cells have the capacity to self-renew, they present low efficiency of reprogramming. Recent studies have demonstrated that the previous somatic epigenetic signature is a limiting factor in iPSC performance. Indeed, the process of effective reprogramming involves a complete remodeling of the existing somatic epigenetic memory, followed by the establishment of a "new epigenetic signature" that complies with the new type of cell to be differentiated. Therefore, further investigations of epigenetic modifications associated with iPSC reprogramming are required in an attempt to improve their self-renew capacity and potency, as well as their application in regenerative medicine, with a new strategy to reduce the damage in degenerative diseases. Our review aimed to summarize the most recent findings on epigenetics and iPSC, focusing on DNA methylation, histone modifications and microRNAs, highlighting their potential in translating cell therapy into clinics.

Resumo As células-tronco de pluripotência induzida (CTPI) ou do inglês induced pluripotent stem cells (iPSCs) são células somáticas reprogramadas para o estado embrionário por meio da expressão de fatores ectópicos de transcrição específicos, tornando-as um alvo promissor para a medicina regenerativa. Apesar das CTPI compartilharem características embrionárias, como pluripotência e capacidade de autorrenovação, elas possuem uma baixa eficiência de reprogramação, sendo a memória epigenética uma das principais barreiras nesse processo. A epigenética é caracterizada por alterações reversíveis e herdáveis no genoma funcional que não alteram a sequência de nucleotídeos do DNA. Dentre as diferentes modificações epigenéticas, destacam-se metilação de DNA, alterações em histonas e microRNA. Atualmente, sabe-se que o processo de reprogramação efetivo das CTPI envolve um completo remodelamento da memória epigenética somática existente, seguido pelo estabelecimento de uma "assinatura epigenética" que esteja de acordo com o novo tipo de célula a ser diferenciada. Modificações epigenéticas personalizadas são capazes de melhorar o rendimento e a efetividade das CTPI geradas, abrindo uma nova perspectiva para a terapia celular. Nesta revisão reunimos as principais informações sobre os fatores epigenéticos que afetam a reprogramação das CTPI, bem como seus benefícios na aplicação da terapia celular.

Analysis of the seroprevalence of and factors associated with Chagas disease in an endemic area in Northeastern Brazil

ABSTRACT INTRODUCTION: Chagas disease (CD) is currently considered a neglected disease; hence, identifying the factors associated with its high prevalence is essential. This study aimed to identify the seroprevalence of and the possible factors associated with CD in inhabitants of the City of Limoeiro do Norte, Northeastern Brazil. METHODS: Between April and November 2013, blood collection was conducted and a semi-structured questionnaire was administered. Blood samples that showed positive or possible serology for anti-Trypanosoma cruzi antibodies based on indirect immunofluorescence, hemagglutination indirect, and an enzyme-linked immunosorbent assay were analyzed. Associations between CD positivity and the study variables were analyzed using prevalence ratios (PR) with 95% confidence intervals (CI). RESULTS: A total of 812 individuals were analyzed, of which T. cruzi seropositivity was determined in 4.2% (34 individuals). Sociodemographic variables showing a significant association with T. cruzi positivity included age >50 years (PR = 27.6; 95% CI = 6.66-114.4), elementary level education (PR = 5.15; 95% CI = 1.83-14.47), and retirement (PR = 7.25; 95% CI = 3.72-14.14). Positivity for T. cruzi was 6.17 times higher in those who had a history of living in rammed earth houses compared with those who did not (95% CI = 2.19-17.37). There was no evidence of vertical transmission in the individuals studied. Among the individuals infected with T. cruzi, the majority reported having a comorbidity (p < 0.01). CONCLUSIONS: This study demonstrated the seroprevalence of CD and identified factors associated with a high prevalence of CD.

Disruption of mitochondrial quality control in peripheral artery disease: New therapeutic opportunities.

Peripheral artery disease (PAD) is a multifactorial disease initially triggered by reduced blood supply to the lower extremities due to atherosclerotic obstructions. It is considered a major public health problem worldwide, affecting over 200 million people. Management of PAD includes smoking cessation, exercise, statin therapy, antiplatelet therapy, antihypertensive therapy and surgical intervention. Although these pharmacological and non-pharmacological interventions usually increases blood flow to the ischemic limb, morbidity and mortality associated with PAD continue to increase. This scenario raises new fundamental questions regarding the contribution of intrinsic metabolic changes in the distal affected skeletal muscle to the progression of PAD. Recent evidence suggests that disruption of skeletal muscle mitochondrial quality control triggered by intermittent ischemia-reperfusion injury is associated with increased morbidity in individuals with PAD. The mitochondrial quality control machinery relies on surveillance systems that help maintaining mitochondrial homeostasis upon stress. In this review, we describe some of the most critical mechanisms responsible for the impaired skeletal muscle mitochondrial quality control in PAD. We also discuss recent findings on the central role of mitochondrial bioenergetics and quality control mechanisms including mitochondrial fusion-fission balance, turnover, oxidative stress and aldehyde metabolism in the pathophysiology of PAD, and highlight their potential as therapeutic targets.

Exercise reestablishes autophagic flux and mitochondrial quality control in heart failure

We previously reported that facilitating the clearance of damaged mitochondria through macroautophagy/autophagy protects against acute myocardial infarction. Here we characterize the impact of exercise, a safe strategy against cardiovascular disease, on cardiac autophagy and its contribution to mitochondrial quality control, bioenergetics and oxidative damage in a post-myocardial infarction-induced heart failure animal model. We found that failing hearts displayed reduced autophagic flux depicted by accumulation of autophagy-related markers and loss of responsiveness to chloroquine treatment at 4 and 12 wk after myocardial infarction. These changes were accompanied by accumulation of fragmented mitochondria with reduced O-2 consumption, elevated H2O2 release and increased Ca2+-Cinduced mitochondrial permeability transition pore opening. Of interest, disruption of autophagic flux was sufficient to decrease cardiac mitochondrial function in sham-treated animals and increase cardiomyocyte toxicity upon mitochondrial stress. Importantly, 8 wk of exercise training, starting 4 wk after myocardial infarction at a time when autophagy and mitochondrial oxidative capacity were already impaired, improved cardiac autophagic flux. These changes were followed by reduced mitochondrial number: size ratio, increased mitochondrial bioenergetics and better cardiac function. Moreover, exercise training increased cardiac mitochondrial number, size and oxidative capacity without affecting autophagic flux in sham-treated animals. Further supporting an autophagy mechanism for exercise-induced improvements of mitochondrial bioenergetics in heart failure, acute in vivo inhibition of autophagic flux was sufficient to mitigate the increased mitochondrial oxidative capacity triggered by exercise in failing hearts. Collectively, our findings uncover the potential contribution of exercise in restoring cardiac autophagy flux in heart failure, which is associated with better mitochondrial quality control, bioenergetics and cardiac function.

Calcium signaling and cell proliferation.

Cell proliferation is orchestrated through diverse proteins related to calcium (Ca(2+)) signaling inside the cell. Cellular Ca(2+) influx that occurs first by various mechanisms at the plasma membrane, is then followed by absorption of Ca(2+) ions by mitochondria and endoplasmic reticulum, and, finally, there is a connection of calcium stores to the nucleus. Experimental evidence indicates that the fluctuation of Ca(2+) from the endoplasmic reticulum provides a pivotal and physiological role for cell proliferation. Ca(2+) depletion in the endoplasmatic reticulum triggers Ca(2+) influx across the plasma membrane in an phenomenon called store-operated calcium entries (SOCEs). SOCE is activated through a complex interplay between a Ca(2+) sensor, denominated STIM, localized in the endoplasmic reticulum and a Ca(2+) channel at the cell membrane, denominated Orai. The interplay between STIM and Orai proteins with cell membrane receptors and their role in cell proliferation is discussed in this review.

Graphene-based nanomaterials: biological and medical applications and toxicity.

Graphene and its derivatives, due to a wide range of unique properties that they possess, can be used as starting material for the synthesis of useful nanocomplexes for innovative therapeutic strategies and biodiagnostics. Here, we summarize the latest progress in graphene and its derivatives and their potential applications for drug delivery, gene delivery, biosensor and tissue engineering. A simple comparison with carbon nanotubes uses in biomedicine is also presented. We also discuss their in vitro and in vivo toxicity and biocompatibility in three different life kingdoms (bacterial, mammalian and plant cells). All aspects of how graphene is internalized after in vivo administration or in vitro cell exposure were brought about, and explain how blood-brain barrier can be overlapped by graphene nanomaterials.

Adolescência, vulnerabilidade e uso abusivo de drogas: a redução de danos como estratégia de prevenção / Adolescence, vulnerability and drug abuse: harm reduction as a prevention strategy / La adolescencia, la vulnerabilidad y el abuso de drogas: la reducción de daños como estrategia de prevención / L'adolescence, la vulnérabilité et l'utilisation abusive de drogues: réduction des risques et stratégie de prévention

O objetivo desse trabalho é uma reflexão sobre os resultados de uma pesquisa de Iniciação Científica, que teve por objetivo investigar os efeitos da abordagem da Redução de Danos sobre as escolhas e percepção de risco, em relação ao uso abusivo de drogas e conflitos vivenciados por adolescentes em situação de vulnerabilidade. A pesquisa foi realizada em uma instituição pública de ensino da região Sudeste no Estado de São Paulo, utilizando-se os princípios teóricos e técnicos dos Grupos Operativos de Pichon-Rivière. Os sujeitos da pesquisa foram 80 alunos entre 14 e 16 anos, a equipe pedagógica e os professores do ensino médio. Através da análise de conteúdos emergentes em situação de grupo, os principais temas trazidos foram: o conflito responsabilidade x divertimento/prazer; a falta de confiança dos adultos para com os adolescentes; a sexualidade; as drogas; o respeito e os estereótipos. A expressão livre dos adolescentes possibilitou maior adesão às propostas e possibilidade de reflexão, estimulada pela metodologia grupal, contribuindo com uma possível revisão de conceitos pré-estabelecidos.

This article presents the results of a Scientific Initiation Research that investigates the effects of the Harm Reduction approach in reference to the choices and risk perception related to drug abuse and conflicts experienced by adolescents in a vulnerable situation. The research took place at a school in the state of Sao Paulo, based on a methodology of action-research and the theory of Operative Groups. Close to 80 students between the ages of fourteen and sixteen, the pedagogical team, and teachers participated in the research. There were conflictive themes found through analysis of the group's situations, they are as follows: responsibility vs. fun/enjoyment, the adults' lack of reliability towards the adolescents, sex, drugs, respect and stereotypes. The fact that the adolescents were free to express their thoughts made a significant contribution towards our proposals and reflection, enabling greater adhesion. The change of roles, provided for the methodology, contributed to a possible revision of the pre-conceived concepts.

El objetivo de este trabajo es presentar los resultados de una encuesta de Iniciación Científica, cuyo objetivo era investigar los efectos del enfoque de Reducción de Daños sobre las opciones y la percepción de riesgo en relación con el abuso de drogas y los conflictos experimentados por los adolescentes en situación de vulnerabilidad. La investigación fue realizada en una escuela pública en el Sudeste del Estado de Sāo Paulo, basado en la metodología de la investigación-acción y la teoría de los Grupos Operativos. Participaron unos 80 alumnos de entre 14 y 16 años, el personal pedagógico y profesores. A través de las discusiones y análisis de situaciones de grupo, el contenido principal que trajeron fue: el tema conflictivo de responsabilidad x diversion/placer; falta de confianza de los adultos a los adolescentes; sexualidad; drogas; respeto y los estereotipos. La libre expresión de los adolescentes posibilitó una mayor adhesión a las propuestas y a la possibilidade de reflexión, estimulada por la metodologia grupal, contribuyendo con una possible revisión de conceptos pre-estabelecidos.

Le but de ce travail est de faire une réflexion sur les résultats d'une recherche faite par les étudiants du cour de Psychologie, qui cherchait à découvrir les effets de l'approche de Réduction de Risques sur les choix et la perception du risque par rapport à l'usage abusif de drogues et les conflits vécus par des adolescents en situation de vulnérabilité. La recherche a été menée dans une institution d'enseignement public dans la région sud-est de São Paulo et s'est fondée sur les principes théoriques et techniques des Groupes Opératifs de Pichon-Rivière. Ce groupe de sujets de la recherche comportait : 80 éleves âgés de 14 à 16 ans, l'équipe pédagogique et les professeurs du lycée. Par moyen de l'analyse de contenus émergents en situation de groupe, les thémes abordés par les sujets ont été : le conflit responsabilité X plaisir ; la méfiance des adults à l'égard des adolescents ; la sexualité ; les drogues ; le respect et les stéréotypes. La libre expression des adolescents a rendu possible une plus grande adhésion aux propositions et possibilités de reflexion, encouragée par la méthode du groupe et a contribué à une possible modification de concepts préétablis.

Rapid regulation of blood parameters under acute hypoxia in the Amazonian fish Prochilodus nigricans.

Prochilodus nigricans, locally known as curimatã, is an Amazonian commercial fish that endures adverse environmental conditions, in particular low dissolved oxygen, during its migration. Poorer environmental conditions are expected in the near future. Prochilodus nigricans overcomes current seasonal and diurnal changes in dissolved oxygen by adjusting erythrocytic levels of ATP and GTP, modulators of Hb-O2 affinity. Will this fish species be endangered under more extreme environmental conditions as hypoxia and acidification tend to occur in a shorter period of time? As P. nigricans does not exhibit any apparent morphological alterations to exploit the air-water interface, it must rely on fast adjustments of blood properties. To investigate this aspect, basic hematology indices, pHe, pHi, plasma lactate, erythrocytic levels of ATP and GTP and functional properties of the hemolysate of P. nigricans were analyzed over a period of 6h in hypoxia and subsequent recovery in normoxia. The levels of erythrocytic GTP were four times higher than ATP and were reduced to » of the original level after 3h under hypoxia. Erythrocytic levels of ATP were unaffected over the experimental period. All other analyzed blood parameters exhibited a time-course change in animals under hypoxia and returned to normoxic levels. Considering the hemolysate functional properties and the ability to regulate the above mentioned blood characteristics, P. nigricans is able to endure short-term changes in dissolved oxygen.

Aldehydic load and aldehyde dehydrogenase 2 profile during the progression of post-myocardial infarction cardiomyopathy: benefits of Alda-1.

BACKGROUND/OBJECTIVES: We previously demonstrated that reducing cardiac aldehydic load by aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme responsible for metabolizing the major lipid peroxidation product, protects against acute ischemia/reperfusion injury and chronic heart failure. However, time-dependent changes in ALDH2 profile, aldehydic load and mitochondrial bioenergetics during progression of post-myocardial infarction (post-MI) cardiomyopathy are unknown and should be established to determine the optimal time window for drug treatment. METHODS: Here we characterized cardiac ALDH2 activity and expression, lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE) adduct formation, glutathione pool and mitochondrial energy metabolism and H2O2 release during the 4 weeks after permanent left anterior descending (LAD) coronary artery occlusion in rats. RESULTS: We observed a sustained disruption of cardiac mitochondrial function during the progression of post-MI cardiomyopathy, characterized by >50% reduced mitochondrial respiratory control ratios and up to 2 fold increase in H2O2 release. Mitochondrial dysfunction was accompanied by accumulation of cardiac and circulating lipid peroxides and 4-HNE protein adducts and down-regulation of electron transport chain complexes I and V. Moreover, increased aldehydic load was associated with a 90% reduction in cardiac ALDH2 activity and increased glutathione pool. Further supporting an ALDH2 mechanism, sustained Alda-1 treatment (starting 24h after permanent LAD occlusion surgery) prevented aldehydic overload, mitochondrial dysfunction and improved ventricular function in post-MI cardiomyopathy rats. CONCLUSION: Taken together, our findings demonstrate a disrupted mitochondrial metabolism along with an insufficient cardiac ALDH2-mediated aldehyde clearance during the progression of ventricular dysfunction, suggesting a potential therapeutic value of ALDH2 activators during the progression of post-myocardial infarction cardiomyopathy.