Association between religiosity/spirituality and substance use among homeless individuals.

BACKGROUND: Alcohol and illicit drug use are prevalent among homeless people. Religiosity and spirituality (RS) have been widely associated with lower consumption of substances. However, evidence of this relationship among homeless people is still scarce. AIMS: To evaluate the associations between RS and alcohol and illicit drug consumption among homeless people in a large Brazilian urban center. METHOD: This cross-sectional study was carried out in São Paulo city, Brazil. Aspects such as spirituality (FACIT-Sp12), religiosity (DUREL), spiritual-religious coping (Brief-RCOPE), and self-report questions concerning the current substance use (alcohol and illicit substances) were evaluated. Adjusted logistic regression models were used to assess the impact of RS beliefs on alcohol and illicit drug consumption. RESULTS: A total of 456 homeless people were included, of an average age of 44.5 (SD = 12.6) years. More than half of the participants consumed alcohol (55.7%) weekly and 34.2% used illicit drugs weekly. Adjusted logistic regression models identified that aspects of RS were associated with lower likelihood factors for alcohol and illicit drug use; conversely, negative spiritual religious coping (SRC) strategies were associated with a higher likelihood to use both. CONCLUSION: The prevalence of alcohol and illicit drug use among participants was high. RS and positive SRC were important protective factors for lower consumption of these substances. Conversely, negative SRC strategies were associated with risk factors.

Commentary: Aldehyde dehydrogenase, redox balance and exercise physiology: What is missing?

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme involved in reactive aldehyde detoxification. Approximately 560 million people (about 8% of the world's population) carry a point mutation in the aldehyde dehydrogenase 2 gene (ALDH2), identified as ALDH2*2, which leads to decreased ALDH2 catalytic activity. ALDH2*2 variant is associated with an accumulation of toxic reactive aldehydes and consequent disruption of cellular metabolism, which contributes to the establishment and progression of several degenerative diseases. Consequences of aldehyde accumulation include impaired mitochondrial functional, hindered anabolic signaling in the skeletal muscle, impaired cardiovascular and pulmonary function, and reduced osteoblastogenesis. Considering that aldehydes are endogenously produced through redox processes, it is expected that conditions that have a high energy demand, such as exercise, might be affected by impaired aldehyde clearance in ALDH2*2 individuals. Despite the large body of evidence supporting the importance of ALDH2 to ethanol metabolism, redox homeostasis and overall health, specific research investigating the impact of ALDH2*2 on phenotypes relevant to exercise performance are notoriously scarce. In this commentary, we highlight the consolidated knowledge on the impact of ALDH2*2 on physiological processes that are relevant to exercise.

Exercise preserves physical fitness during aging through AMPK and mitochondrial dynamics.

Exercise is a nonpharmacological intervention that improves health during aging and a valuable tool in the diagnostics of aging-related diseases. In muscle, exercise transiently alters mitochondrial functionality and metabolism. Mitochondrial fission and fusion are critical effectors of mitochondrial plasticity, which allows a fine-tuned regulation of organelle connectiveness, size, and function. Here we have investigated the role of mitochondrial dynamics during exercise in the model organism Caenorhabditis elegans. We show that in body-wall muscle, a single exercise session induces a cycle of mitochondrial fragmentation followed by fusion after a recovery period, and that daily exercise sessions delay the mitochondrial fragmentation and physical fitness decline that occur with aging. Maintenance of proper mitochondrial dynamics is essential for physical fitness, its enhancement by exercise training, and exercise-induced remodeling of the proteome. Surprisingly, among the long-lived genotypes we analyzed (isp-1,nuo-6, daf-2, eat-2, and CA-AAK-2), constitutive activation of AMP-activated protein kinase (AMPK) uniquely preserves physical fitness during aging, a benefit that is abolished by impairment of mitochondrial fission or fusion. AMPK is also required for physical fitness to be enhanced by exercise, with our findings together suggesting that exercise may enhance muscle function through AMPK regulation of mitochondrial dynamics. Our results indicate that mitochondrial connectivity and the mitochondrial dynamics cycle are essential for maintaining physical fitness and exercise responsiveness during aging and suggest that AMPK activation may recapitulate some exercise benefits. Targeting mechanisms to optimize mitochondrial fission and fusion, as well as AMPK activation, may represent promising strategies for promoting muscle function during aging.

Experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária / Experience in managing action research on hepatitis C survey in the prison community

Resumo Objetivou-se relatar a experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária no Triângulo Mineiro, Minas Gerais. A proposta foi desenvolvida entre março de 2019 e março de 2020, alcançando 240 pessoas, com o intuito de conter a disseminação do agravo por meio de inquérito, testagem e acompanhamento dos casos positivos. Adotou-se ação intersetorial, com articulação entre universidades, sociedade médica, hospital de ensino e Secretaria de Estado de Justiça e Segurança Pública. As estratégias para o gerenciamento da pesquisa-ação foram: cenários e atores do estudo, registro e formalização da atividade, aplicação dos testes e manejo dos internos reagentes. Dificuldades foram identificadas quanto à acomodação de rotinas entre equipe de pesquisadores e funcionamento próprio da penitenciária, o que exigiu treinamento ostensivo entre as partes e articulações gerenciais. Considera-se que o relato, quando destaca as estratégias adotadas para a condução da pesquisa, colabora para a organização de investigações futuras que visem acessar essa população ainda invisibilizada.

Abstract We aimed to report the experience in managing action research on hepatitis C investigation in the prison community in the Triângulo Mineiro region, Minas Gerais, Brazil. The proposal was developed from March 2019 to March 2020, reaching 240 people to contain the spread of the disease through a survey, testing, and monitoring of positive cases. We adopted intersectoral action with articulation between Universities, Medical Society, Teaching Hospital, and State Secretariat for Justice and Public Security. Strategies for the management of action research are described: study settings and stakeholders, registration and formalization of the activity, application of tests, and management of reagent inmates. We identified difficulties regarding the accommodation of routines among the research team and the proper functioning of the penitentiary, which required extensive training between the parties and managerial articulations. We consider that the report collaborates with the organization of future research aimed at accessing this still invisible population, the prison community when it highlights the strategies adopted to conduct the research.

Experience in managing action research on hepatitis C survey in the prison community. / Experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária.

We aimed to report the experience in managing action research on hepatitis C investigation in the prison community in the Triângulo Mineiro region, Minas Gerais, Brazil. The proposal was developed from March 2019 to March 2020, reaching 240 people to contain the spread of the disease through a survey, testing, and monitoring of positive cases. We adopted intersectoral action with articulation between Universities, Medical Society, Teaching Hospital, and State Secretariat for Justice and Public Security. Strategies for the management of action research are described: study settings and stakeholders, registration and formalization of the activity, application of tests, and management of reagent inmates. We identified difficulties regarding the accommodation of routines among the research team and the proper functioning of the penitentiary, which required extensive training between the parties and managerial articulations. We consider that the report collaborates with the organization of future research aimed at accessing this still invisible population, the prison community when it highlights the strategies adopted to conduct the research.

Objetivou-se relatar a experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária no Triângulo Mineiro, Minas Gerais. A proposta foi desenvolvida entre março de 2019 e março de 2020, alcançando 240 pessoas, com o intuito de conter a disseminação do agravo por meio de inquérito, testagem e acompanhamento dos casos positivos. Adotou-se ação intersetorial, com articulação entre universidades, sociedade médica, hospital de ensino e Secretaria de Estado de Justiça e Segurança Pública. As estratégias para o gerenciamento da pesquisa-ação foram: cenários e atores do estudo, registro e formalização da atividade, aplicação dos testes e manejo dos internos reagentes. Dificuldades foram identificadas quanto à acomodação de rotinas entre equipe de pesquisadores e funcionamento próprio da penitenciária, o que exigiu treinamento ostensivo entre as partes e articulações gerenciais. Considera-se que o relato, quando destaca as estratégias adotadas para a condução da pesquisa, colabora para a organização de investigações futuras que visem acessar essa população ainda invisibilizada.

Mitochondrial Dysfunction in Degenerative Diseases.

Mitochondria are major intracellular hubs distributed throughout the cell that play a key role in the spatiotemporal coordination and propagation of signalling events, ensuring that homeostasis is met at baseline or under environmental pressure [...].

Mitochondrial Fusion, Fission, and Mitophagy in Cardiac Diseases: Challenges and Therapeutic Opportunities.

Significance: Mitochondria play a critical role in the physiology of the heart by controlling cardiac metabolism, function, and remodeling. Accumulation of fragmented and damaged mitochondria is a hallmark of cardiac diseases. Recent Advances: Disruption of quality control systems that maintain mitochondrial number, size, and shape through fission/fusion balance and mitophagy results in dysfunctional mitochondria, defective mitochondrial segregation, impaired cardiac bioenergetics, and excessive oxidative stress. Critical Issues: Pharmacological tools that improve the cardiac pool of healthy mitochondria through inhibition of excessive mitochondrial fission, boosting mitochondrial fusion, or increasing the clearance of damaged mitochondria have emerged as promising approaches to improve the prognosis of heart diseases. Future Directions: There is a reasonable amount of preclinical evidence supporting the effectiveness of molecules targeting mitochondrial fission and fusion to treat cardiac diseases. The current and future challenges are turning these lead molecules into treatments. Clinical studies focusing on acute (i.e., myocardial infarction) and chronic (i.e., heart failure) cardiac diseases are needed to validate the effectiveness of such strategies in improving mitochondrial morphology, metabolism, and cardiac function. Antioxid. Redox Signal. 36, 844-863.

Accuracy of the clinical indicators for Readiness for enhanced health management.

PURPOSE: to analyze accuracy measures of the clinical indicators of Readiness for enhanced health management in patients with arterial hypertension and/or diabetes mellitus METHODS: prospective diagnostic accuracy study conducted with 359 patients with hypertension and/or diabetes mellitus, followed up in primary healthcare. Stratified random sampling was used to recruit participants. An assessment form was applied with sociodemographic data, health conditions, and information related to the clinical indicators under investigation. Sensitivity, specificity, predictive values, and likelihood ratios were analyzed FINDINGS: the sample was composed of 359 participants. The prevalence of Readiness for enhanced health management was 93.8%. There was a statistically significant association between the diagnosis and age under 60 years (p < 0.001), having only one chronic condition (p < 0.001), having normal blood pressure (p = 0.017) and blood glucose (p = 0.013) values, and having a nonsedentary (p = 0.026) and nonalcoholic (p = 0.044) lifestyle. All clinical indicators had high predictive values in predicting the nursing diagnosis under investigation. The indicator expresses desire to enhance management of symptoms was the most sensitive (99.7%) and specific (100%). The indicator expresses desire to enhance management of prescribed regimens was also highly specific (100%) CONCLUSION: all clinical indicators were accurate in predicting Readiness for enhanced health management IMPLICATIONS FOR NURSING PRACTICE: knowing which clinical indicators and sociodemographic/clinical characteristics best predict Readiness for enhanced health management, nurses in primary care can better plan nursing interventions and direct their goals.

Qualidade de vida e condições de saúde de pacientes com hipertensão arterial e diabetes mellitus / Quality of life and health conditions of patients with hypertension arterial and diabetes mellitus

Objetivo: analisar estudos referentes à avaliação da qualidade de vida e as condições de saúde de pacientes hipertensos e diabéticos com disposição para controle da saúde melhorado. Método: revisão integrativa da literatura, realizada no período de junho a julho de 2018. Foram coletados dados nas seguintes bases de dados: PUBMED, LILACS e SciELO. Consoante os critérios de inclusão, estabeleceu-se uma amostra final de 22 artigos. Resultados: Foram encontradas pesquisas que exploraram as medidas de qualidade de vida de pacientes com hipertensão arterial e diabetes. Notou-se que os profissionais da atenção básica atuam como agentes relevantes para o controle dessas doenças. Observou-se a importância da adesão medicamentosa e do perigo que os fatores de risco podem causar nesses pacientes. Conclusão: os principais fatores que influenciam na qualidade de vida e condições de saúde são: maior renda per capita, nível de escolaridade, adesão a medicação, visitas aos profissionais da atenção primária, obesidade, transtornos mentais e idade. (AU)

Objective: to analyze studies related to the assessment of quality of life and health conditions of hypertensive and diabetic patients with a willingness to improve health control. Method: integrative literature review, carried out from June to July 2018. Data were collected in the following databases: PUBMED, LILACS and SciELO. Depending on the inclusion criteria, a final sample of 22 articles was established. Results: Researches were found that explored the quality of life measures of patients with arterial hypertension and diabetes. It was noted that primary care professionals act as relevant agents for the control of these diseases. It was observed the importance of medication adherence and the danger that risk factors can cause in these patients. Conclusion: the main factors that influence quality of life and health conditions are: higher per capita income, education level, medication adherence, visits to primary care professionals, obesity, mental disorders and age. (AU)

Objetivo: analizar estudios relacionados con la evaluación de la calidad de vida y las condiciones de salud de pacientes hipertensos y diabéticos con voluntad de mejorar el control de la salud. Método: revisión integrativa de la literatura, realizada de junio a julio de 2018. Los datos fueron recolectados en las siguientes bases de datos: PUBMED, LILACS y SciELO. Dependiendo de los criterios de inclusión, se estableció una muestra final de 22 artículos. Resultados: Se encontraron investigaciones que exploraron las medidas de calidad de vida de pacientes con hipertensión arterial y diabetes. Se señaló que los profesionales de atención primaria actúan como agentes relevantes para el control de estas enfermedades. Se observó la importancia de la adherencia a la medicación y el peligro que pueden ocasionar los factores de riesgo en estos pacientes. Conclusión: los principales factores que influyen en la calidad de vida y las condiciones de salud son: mayor ingreso per cápita, nivel educativo, adherencia a la medicación, visitas a profesionales de atención primaria, obesidad, trastornos mentales y edad. (AU)

Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel CARNS1 knockout rat model.

Histidine-containing dipeptides (HCDs) are abundantly expressed in striated muscles. Although important properties have been ascribed to HCDs, including H+ buffering, regulation of Ca2+ transients and protection against oxidative stress, it remains unknown whether they play relevant functions in vivo. To investigate the in vivo roles of HCDs, we developed the first carnosine synthase knockout (CARNS1-/-) rat strain to investigate the impact of an absence of HCDs on skeletal and cardiac muscle function. Male wild-type (WT) and knockout rats (4 months-old) were used. Skeletal muscle function was assessed by an exercise tolerance test, contractile function in situ and muscle buffering capacity in vitro. Cardiac function was assessed in vivo by echocardiography and cardiac electrical activity by electrocardiography. Cardiomyocyte contractile function was assessed in isolated cardiomyocytes by measuring sarcomere contractility, along with the determination of Ca2+ transient. Markers of oxidative stress, mitochondrial function and expression of proteins were also evaluated in cardiac muscle. Animals were supplemented with carnosine (1.8% in drinking water for 12 weeks) in an attempt to rescue tissue HCDs levels and function. CARNS1-/- resulted in the complete absence of carnosine and anserine, but it did not affect exercise capacity, skeletal muscle force production, fatigability or buffering capacity in vitro, indicating that these are not essential for pH regulation and function in skeletal muscle. In cardiac muscle, however, CARNS1-/- resulted in a significant impairment of contractile function, which was confirmed both in vivo and ex vivo in isolated sarcomeres. Impaired systolic and diastolic dysfunction were accompanied by reduced intracellular Ca2+ peaks and slowed Ca2+ removal, but not by increased markers of oxidative stress or impaired mitochondrial respiration. No relevant increases in muscle carnosine content were observed after carnosine supplementation. Results show that a primary function of HCDs in cardiac muscle is the regulation of Ca2+ handling and excitation-contraction coupling.

ß2-Adrenergic Signaling Modulates Mitochondrial Function and Morphology in Skeletal Muscle in Response to Aerobic Exercise.

The molecular mechanisms underlying skeletal muscle mitochondrial adaptations induced by aerobic exercise (AE) are not fully understood. We have previously shown that AE induces mitochondrial adaptations in cardiac muscle, mediated by sympathetic stimulation. Since direct sympathetic innervation of neuromuscular junctions influences skeletal muscle homeostasis, we tested the hypothesis that ß2-adrenergic receptor (ß2-AR)-mediated sympathetic activation induces mitochondrial adaptations to AE in skeletal muscle. Male FVB mice were subjected to a single bout of AE on a treadmill (80% Vmax, 60 min) under ß2-AR blockade with ICI 118,551 (ICI) or vehicle, and parameters of mitochondrial function and morphology/dynamics were evaluated. An acute bout of AE significantly increased maximal mitochondrial respiration in tibialis anterior (TA) isolated fiber bundles, which was prevented by ß2-AR blockade. This increased mitochondrial function after AE was accompanied by a change in mitochondrial morphology towards fusion, associated with increased Mfn1 protein expression and activity. ß2-AR blockade fully prevented the increase in Mfn1 activity and reduced mitochondrial elongation. To determine the mechanisms involved in mitochondrial modulation by ß2-AR activation in skeletal muscle during AE, we used C2C12 myotubes, treated with the non-selective ß-AR agonist isoproterenol (ISO) in the presence of the specific ß2-AR antagonist ICI or during protein kinase A (PKA) and Gαi protein blockade. Our in vitro data show that ß-AR activation significantly increases mitochondrial respiration in myotubes, and this response was dependent on ß2-AR activation through a Gαs-PKA signaling cascade. In conclusion, we provide evidence for AE-induced ß2-AR activation as a major mechanism leading to alterations in mitochondria function and morphology/dynamics. ß2-AR signaling is thus a key-signaling pathway that contributes to skeletal muscle plasticity in response to exercise.

Xanthosoma sagittifolium is resistant to Meloidogyne spp. and controls Meloidogyne enterolobii by soil biofumigation.

Meloidogyne is a relevant plant-parasitic nematode that causes enormous damage. It is very challenging to control, and there are not many chemicals available on the market for that. As an alternative method of nematode control, biofumigation is increasingly gaining space. This research aimed to study the reaction of Xanthosoma sagittifolium to Meloidogyne enterolobii, M. incognita, and M. javanica and soil biofumigation with X. sagittifolium leaves for M. enterolobii control. The reaction test was performed in the populations 0 (control), 333, 999, 3,000, 9,000, 27,000 eggs and eventual juveniles. X. sagittifolium did not host the Meloidogyne species studied, even in a high population. X. sagittifolium leaves incorporated in soil at concentrations 0 (control), 0.45, 0.9, 1.8, 3.6 g were also studied to control M. enterolobii, and they were able to reduce galls and eggs. The number of galls and egg masses was reduced to a concentration of 1.8 g. In the maximum concentration, the number of galls was less than 15 galls, and the eggs were also reduced to less than 200 eggs. As these macerates emitted nematicidal volatile organic compounds (VOCs) against M. enterolobii, it reduced the infectivity and reproduction of nematodes.

Hatching and Mortality of Meloidogyne enterolobii Under the Interference of Entomopathogenic Nematodes In vitro.

Plant parasitic nematodes have become one of the main problems in the tomato cultivation. Among these, Meloidogyne enterolobii presents great challenges to the farmer, since it is a polyphagous species and difficult to control. The entomopathogenic nematodes (EPNs) present as potential for biological control of this pathogen. The objective of the study was to evaluate the interference of EPNs S. brazilense, S. feltiae, S. rarum, H. amazonensis and H. bacteriophora on hatching and mortality of M. enterolobii. 500 eggs of this nematode and 1.000 infective juveniles of each EPN species were placed in a plastic pot totaling 25 mL of suspension and kept in an incubator at 25°C. The number of juveniles hatched in the suspension was counted every 2 days, until 10 days. After 10 days of evaluations, the remaining suspension (15 mL) containing M. enterolobii and EPNs was inoculated into Rutgers tomato seedlings. The suspension contained approximately in 300 eggs of M. enterolobii occasional juveniles and 600 IJ of each nematode species. Sixty days after inoculation were evaluated gall indexes, egg mass indexes, total number of eggs and juveniles of M. enterolobii and reproductive factor was calculated. In the mortality experiment, 500 infective juveniles of M. enterolobii and 1.000 juveniles of each EPN species were placed in a plastic pot totaling 25 mL of suspension. The evaluation of juvenile mortality was performed by counting of the mobile and immotile nematodes, by adding two drops of NaOH to the nematode suspension. It was verified that on the 10th day all ENPs provided reduction in the hatching of M. enterolobii. In the pot experiment it was found thato gall index, egg mass indexm, nematodes total number and reproduction factor were significantly reduced in treatments with all species of EPNs tested. However, in the mortality test, only EPNs S. brazilense and S. rarum provided mortality on the second day and H. bacteriophora affected mortality on the 4th day. In the other evaluations, there was no statistical difference. The results highlight the potential of the use of EPNs in programs of integrated management of M. enterolobii in tomato.

Targeting mitochondrial dysfunction and oxidative stress in heart failure: Challenges and opportunities.

Mitochondrial dysfunction characterized by impaired bioenergetics, oxidative stress and aldehydic load is a hallmark of heart failure. Recently, different research groups have provided evidence that selective activation of mitochondrial detoxifying systems that counteract excessive accumulation of ROS, RNS and reactive aldehydes is sufficient to stop cardiac degeneration upon chronic stress, such as heart failure. Therefore, pharmacological and non-pharmacological approaches targeting mitochondria detoxification may play a critical role in the prevention or treatment of heart failure. In this review we discuss the most recent findings on the central role of mitochondrial dysfunction, oxidative stress and aldehydic load in heart failure, highlighting the most recent preclinical and clinical studies using mitochondria-targeted molecules and exercise training as effective tools against heart failure.

Cardioprotection induced by a brief exposure to acetaldehyde: role of aldehyde dehydrogenase 2.

Aims: We previously demonstrated that acute ethanol administration protects the heart from ischaemia/reperfusion (I/R) injury thorough activation of aldehyde dehydrogenase 2 (ALDH2). Here, we characterized the role of acetaldehyde, an intermediate product from ethanol metabolism, and its metabolizing enzyme, ALDH2, in an ex vivo model of cardiac I/R injury. Methods and results: We used a combination of homozygous knock-in mice (ALDH2*2), carrying the human inactivating point mutation ALDH2 (E487K), and a direct activator of ALDH2, Alda-1, to investigate the cardiac effect of acetaldehyde. The ALDH2*2 mice have impaired acetaldehyde clearance, recapitulating the human phenotype. Yet, we found a similar infarct size in wild type (WT) and ALDH2*2 mice. Similar to ethanol-induced preconditioning, pre-treatment with 50 µM acetaldehyde increased ALDH2 activity and reduced cardiac injury in hearts of WT mice without affecting cardiac acetaldehyde levels. However, acetaldehyde pre-treatment of hearts of ALDH2*2 mice resulted in a three-fold increase in cardiac acetaldehyde levels and exacerbated I/R injury. Therefore, exogenous acetaldehyde appears to have a bimodal effect in I/R, depending on the ALDH2 genotype. Further supporting an ALDH2 role in cardiac preconditioning, pharmacological ALDH2 inhibition abolished ethanol-induced cardioprotection in hearts of WT mice, whereas a selective activator, Alda-1, protected ALDH2*2 against ethanol-induced cardiotoxicity. Finally, either genetic or pharmacological inhibition of ALDH2 mitigated ischaemic preconditioning. Conclusion: Taken together, our findings suggest that low levels of acetaldehyde are cardioprotective whereas high levels are damaging in an ex vivo model of I/R injury and that ALDH2 is a major, but not the only, regulator of cardiac acetaldehyde levels and protection from I/R.

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.

Geometry-Aware Neighborhood Search for Learning Local Models for Image Superresolution.

Local learning of sparse image models has proved to be very effective to solve inverse problems in many computer vision applications. To learn such models, the data samples are often clustered using the K-means algorithm with the Euclidean distance as a dissimilarity metric. However, the Euclidean distance may not always be a good dissimilarity measure for comparing data samples lying on a manifold. In this paper, we propose two algorithms for determining a local subset of training samples from which a good local model can be computed for reconstructing a given input test sample, where we consider the underlying geometry of the data. The first algorithm, called adaptive geometry-driven nearest neighbor search (AGNN), is an adaptive scheme, which can be seen as an out-of-sample extension of the replicator graph clustering method for local model learning. The second method, called geometry-driven overlapping clusters (GOCs), is a less complex nonadaptive alternative for training subset selection. The proposed AGNN and GOC methods are evaluated in image superresolution and shown to outperform spectral clustering, soft clustering, and geodesic distance-based subset selection in most settings.

Increased clearance of reactive aldehydes and damaged proteins in hypertension-induced compensated cardiac hypertrophy: impact of exercise training.

BACKGROUND: We previously reported that exercise training (ET) facilitates the clearance of damaged proteins in heart failure. Here, we characterized the impact of ET on cardiac protein quality control during compensated ventricular hypertrophy in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: SHR were randomly assigned into sedentary and swimming-trained groups. Sedentary SHR displayed cardiac hypertrophy with preserved ventricular function compared to normotensive rats, characterizing a compensated cardiac hypertrophy. Hypertensive rats presented signs of cardiac oxidative stress, depicted by increased lipid peroxidation. However, these changes were not followed by accumulation of lipid peroxidation-generated reactive aldehydes and damaged proteins. This scenario was explained, at least in part, by the increased catalytic activity of both aldehyde dehydrogenase 2 (ALDH2) and proteasome. Of interest, ET exacerbated cardiac hypertrophy, improved ventricular function, induced resting bradycardia, and decreased blood pressure in SHR. These changes were accompanied by reduced cardiac oxidative stress and a consequent decrease in ALDH2 and proteasome activities, without affecting small chaperones levels and apoptosis in SHR. CONCLUSION: Increased cardiac ALDH2 and proteasomal activities counteract the deleterious effect of excessive oxidative stress in hypertension-induced compensated cardiac hypertrophy in rats. ET has a positive effect in reducing cardiac oxidative stress without affecting protein quality control.