Ammonium tetrathiomolybdate following ischemia/reperfusion injury: Chemistry, pharmacology, and impact of a new class of sulfide donor in preclinical injury models

Background: Early revascularization of ischemic organs is key to improving outcomes, yet consequent reperfusion injury may be harmful. Reperfusion injury is largely attributed to excess mitochondrial production of reactive oxygen species (ROS). Sulfide inhibits mitochondria and reduces ROS production. Ammonium tetrathiomolybdate (ATTM), a copper chelator, releases sulfide in a controlled and novel manner, and may offer potential therapeutic utility. Methods and findings: In vitro, ATTM releases sulfide in a time-, pH-, temperature-, and thiol-dependent manner. Controlled sulfide release from ATTM reduces metabolism (measured as oxygen consumption) both in vivo in awake rats and ex vivo in skeletal muscle tissue, with a superior safety profile compared to standard sulfide generators. Given intravenously at reperfusion/resuscitation to rats, ATTM significantly reduced infarct size following either myocardial or cerebral ischemia, and conferred survival benefit following severe hemorrhage. Mechanistic studies (in vitro anoxia/reoxygenation) demonstrated a mitochondrial site of action (decreased MitoSOX fluorescence), where the majority of damaging ROS is produced. Conclusions: The inorganic thiometallate ATTM represents a new class of sulfide-releasing drugs. Our findings provide impetus for further investigation of this compound as a novel adjunct therapy for reperfusion injury

Metabolic oscillations on the circadian time scale in Drosophila cells lacking clock genes

Circadian rhythms are cell‐autonomous biological oscillations with a period of about 24 h. Current models propose that transcriptional feedback loops are the primary mechanism for the generation of circadian oscillations. Within this framework, Drosophila S2 cells are regarded as “non‐rhythmic” cells, as they do not express several canonical circadian components. Using an unbiased multi‐omics approach, we made the surprising discovery that Drosophila S2 cells do in fact display widespread daily rhythms. Transcriptomics and proteomics analyses revealed that hundreds of genes and their products, and in particular metabolic enzymes, are rhythmically expressed in a 24‐h cycle. Metabolomics analyses extended these findings and demonstrate that central carbon metabolism and amino acid metabolism are core metabolic pathways driven by protein rhythms. We thus demonstrate that 24‐h metabolic oscillations, coupled to gene and protein cycles, take place in nucleated cells without the contribution of any known circadian regulators. These results therefore suggest a reconsideration of existing models of the clockwork in Drosophila and other eukaryotic systems.Mol Syst Biol. (2018) 14: e837

Biological decolorization of xanthene dyes by anaerobic granular biomass

Biodegradation of a xanthene dyes was investigated for the first time using anaerobic granular sludge. On a first screening, biomass was able to decolorize, at different extents, six azo dye solutions: acid orange 7, direct black 19, direct blue 71, mordant yellow 10, reactive red 2 and reactive red 120 and two xanthene dyes—Erythrosine B and Eosin Y. Biomass concentration, type of electron donor, induction of biomass with dye and mediation with activated carbon (AC) were variables studied for Erythrosine B (Ery) as model dye. Maximum color removal efficiency was achieved with 4.71 g VSS L−1, while the process rates were independent of the biomass concentration above 1.89 g VSS L−1. No considerable effects were observed when different substrates were used as electron donors (VFA, glucose or lactose). Addition of Ery in the incubation period of biomass led to a fivefold increase of the decolorization rate. The rate of Ery decolorization almost duplicated in the presence of commercial AC (0.1 g L−1 AC0). Using different modified AC samples (from the treatment of AC0), a threefold higher rate was obtained with the most basic one, \textAC\textH2ACH2, as compared with non-mediated reaction. Higher rates were obtained at pH 6.0. Chemical reduction using Na2S confirmed the recalcitrant nature of this dye. The results attest that decolorization of Ery is essentially due to enzymatic and adsorption phenomena.This work was supported by the PTDC/AMB/69335/2006 project grants (Fundacao para a Ciencia e Technologia, FCT, Portugal), BRAIN project (ID 6681, European Social Found and Romanian Government and the grant of the Romanian National Authority for Scientific Research, CNCS-UEFISCDI, project number PN-II-ID-PCE-2011-3-0559, Contract 265/2011

High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV

BACKGROUND. People living with HIV (PLHIV) receiving antiretroviral therapy (ART) exhibit persistent immune dysregulation and microbial dysbiosis, leading to development of cardiovascular diseases (CVDs). We initially compared plasma proteomic profiles between 205 PLHIV and 120 healthy control participants (HCs) and validated the results in an independent cohort of 639 PLHIV and 99 HCs. Differentially expressed proteins (DEPs) were then associated to microbiome data. Finally, we assessed which proteins were linked with CVD development in PLHIV. METHODS. Proximity extension assay technology was used to measure 1,472 plasma proteins. Markers of systemic inflammation (C-reactive protein, D-dimer, IL-6, soluble CD14, and soluble CD163) and microbial translocation (IFABP) were measured by ELISA, and gut bacterial species were identified using shotgun metagenomic sequencing. Baseline CVD data were available for all PLHIV, and 205 PLHIV were recorded for development of CVD during a 5-year follow-up. RESULTS. PLHIV receiving ART had systemic dysregulation of protein concentrations, compared with HCs. Most of the DEPs originated from the intestine and lymphoid tissues and were enriched in immune- and lipid metabolism-related pathways. DEPs originating from the intestine were associated with specific gut bacterial species. Finally, we identified upregulated proteins in PLHIV (GDF15, PLAUR, RELT, NEFL, COL6A3, and EDA2R), unlike most markers of systemic inflammation, associated with the presence and risk of developing CVD during 5-year follow-up. CONCLUSION. Our findings suggest a systemic dysregulation of protein concentrations in PLHIV; some proteins were associated with CVD development. Most DEPs originated from the gut and were related to specific gut bacterial species.</p

New insights into the distribution and conservation status of the Golden-White Tassel-Ear Marmoset Mico chrysoleucos (Primates, Callitrichidae)

Among the 13 Mico species recognized by the IUCN Red List of Threatened Species, six are listed as "Data Deficient". The geographic range of most of the Mico species has been estimated from only a few records. We report new localities and the geographic extension of Mico chrysoleucos. In addition, we confirmed the presence of the species in two distinct protected areas. We modeled the habitat suitability of M. chrysoleucos using the maximum entropy method and including new records obtained by the authors in the state of Amazonas, Brazil. From the total area of occurrence calculated for the species, 22.8% is covered by protected areas and indigenous lands. The annual mean deforestation rate estimated between 2000 and 2015 was 2.95%, and the total area deforested by 2015 was 3354 km2 or 8.6% of the total distribution limits of the species. The habitat lost between 2000 and 2015 was 3.2% (1131 km2 ) of the total potential distribution, while the habitat loss area legally protected was 31 km2, and the habitat loss in settlements was equal to 691 km2. Our results extend the geographic distribution of the species about 100 km farther south, with the Maracanã River being a possible geographic barrier for the species. The significantly low rate of habitat loss inside protected areas and indigenous land, when compared to unprotected areas, points out the importance of these areas to M. chrysoleucos conservation. The species is relatively wide-ranging, legally protected, and resilient to regional anthropic threats. However, the hydroelectric schemes and the improvement of the road system in southern Amazonia pose an imminent threat to the species

Estado nutricional e uso de suplementos alimentares por acadêmicos de Nutrição da Universidade Federal do Tocantins

Os estudos sobre o consumo de suplementos alimentares por frequentadores de academias são encontrados em maior número na literatura científica, no entanto, há poucos dados sobre o perfil de consumo destes produtos por universitários ou pela população em geral. Dessa forma, este estudo buscou conhecer a prevalência do uso de suplementos associado ao estado nutricional e percepção corporal de acadêmicos do curso de nutrição. Para obtenção dos resultados foi aplicado um questionário de múltipla escolha, e realizada antropometria em 50 indivíduos de ambos os sexos, com idade de 18 a 35 anos, escolhidos aleatoriamente. Dessa amostra obteve-se que 50% dos estudantes entrevistados utilizavam suplemento alimentar, sendo vitaminas e minerais, ricos em proteínas e fitoterápicos os mais utilizados. Aproximadamente, 26% utilizavam por iniciativa própria. Quanto ao estado nutricional, 72% estavam eutróficos e 74% realizavam alguma atividade física, no entanto, não estavam satisfeitos com o corpo (74%). Sugere-se que a influência do conhecimento científico presente na ciência da nutrição influencie os acadêmicos quanto a alimentação saudável, no entanto, a mesma não está baseada apenas na ingestão de nutrientes específicos e sim na ingestão dos alimentos in natura, com foco nos hábitos alimentares regionais e bem-estar biopsicossocial, fato destoante neste trabalho. Além disso, enfatiza-se sobre a variabilidade da vida dos acadêmicos, embora existam vários meios de se obter uma alimentação saudável, existem vários fatores que podem interferir em uma alimentação variada e balanceada, fazendo assim com que os mesmos invistam na utilização de suplementos alimentares. ABSTRACT Nutritional status and use of food supplements by academics of nutrition of the Federal University of TocantinsStudies on the consumption of dietary supplements by academics are found in greater numbers in the scientific literature, however, there is little data on the profile of consumption of these products by university students or by the general population. Thus, this study sought to know the prevalence of the use of supplements associated with the nutritional status and body perception of the students of the nutrition course. To obtain the results, a multiple-choice questionnaire was applied, and anthropometry was performed in 50 individuals of both sexes, aged 18 to 35 years, randomly selected. From this sample, it was obtained that 50% of the students interviewed used food supplement, being vitamins and minerals, rich in proteins and phototherapy the most used. Approximately 26% used it on their own initiative. Regarding nutritional status, 72% were eutrophic and 74% had some physical activity, however, they were not satisfied with the body (74%). It is suggested that the influence of scientific knowledge present in the science of nutrition influences the academic about healthy eating, however, it is based not only on the ingestion of specific nutrients but on the ingestion of in nature foods, focusing on eating habits And bio psychosocial well-being, a fact that is dis- In addition, emphasis is placed on the variability of academic life, although there are several ways to achieve healthy eating, there are several factors that can interfere with a varied and balanced diet, thus making them invest in the use of food supplements

Evaluation of the health-related quality of life of hematopoietic stem cell transplantation patients

This study evaluates the Health-Related Quality of Life of patients undergoing analogous and allogeneic transplantation at three different points in time: before, 30 and 180 days after transplantation, along with correlated clinical and socio-demographic data. Two questionnaires were used for data collection: the first addressed clinical and socio-demographic data and the second was the Functional Assessment Cancer Therapy translated and validated for Brazilian Portuguese. The initial sample was composed of 30 patients while 26 were ultimately evaluated at the three points. The set of results indicated a positive impact on Health-Related Quality of Life six months after transplantation. Despite the fact that there were additional concerns and some aspects such as physical and functional aspects were affected 30 days after the procedure, the Functional Assessment Cancer Therapy scores obtained six months after HSCT improved in all components, reaching levels above those prior to the procedure, especially physical and emotional aspects and the relationship with the physician.El objetivo de este estudio longitudinal consistió en evaluar la Calidad de Vida relacionada a la Salud de pacientes sometidos a trasplante autólogo y alogénico en tres momentos distintos: en el pre, 30 y 180 días postrasplante. Para la recolección de datos fueron utilizados dos cuestionarios: el primero para obtención de datos clínicos y sociodemográficos, y el segundo una escala específica el Functional Assesment Cancer Therapy. La muestra inicial fue constituida por 30 pacientes, siendo 26 evaluados en los tres momentos. El conjunto de resultados permitió visualizar un impacto positivo de la Calidad de Vida relacionada a la salud al final de los seis meses postrasplante, a pesar de algunas funciones presentarse más perjudicadas, como la función física, funcional y preocupaciones adicionales con 30 días, hubo mejoría en los puntajes del Functional Assesment Cancer Therapy en todos los componentes llegando a alcanzar niveles encima del pretrasplante, especialmente en los aspectos físicos y emocionales, y en la relación con el médico.O objetivo deste estudo longitudinal consistiu em se avaliar a qualidade de vida relacionada à saúde de pacientes submetidos ao transplante autólogo e alogênico, em três momentos distintos: no pré-transplante, 30 e 180 dias pós-transplante . Para a coleta de dados, foram utilizados dois questionários: o primeiro para obtenção de dados clínicos e sociodemográficos, e o segundo constituído por uma escala específica, o Functional Assessment Cancer Therapy. A amostra inicial foi constituída por 30 pacientes, sendo 26 avaliados nos três momentos. O conjunto de resultados permitiu visualizar impacto positivo da qualidade de vida relacionada à saúde, ao final dos seis meses pós-transplante. Apesar de algumas funções se apresentarem mais prejudicadas, como a função física, funcional e preocupações adicionais com 30 dias, houve melhora nos escores do Functional Assessment Cancer Therapy em todos os componentes, chegando-se a alcançar patamares acima dos encontrados na fase do pré-transplante, especialmente nos aspectos físicos, emocionais e relacionamento com o médico

THE SERO-CONVERSION AND EVALUATION OF RENAL ALTERATIONS IN DOGS INFECTED BY Leishmania (Infantum) chagasi

This study investigated the sero-conversion period in which dogs from endemic areas test positive for visceral leishmaniasis (VL) as well as the early post-infection period in which renal alterations are observed. Dogs that were initially negative for Canine Visceral Leishmaniasis (CVL) were clinically evaluated every three months by serological, parasitological and biochemical tests until sero-conversion was confirmed, and six months later a subsequent evaluation was performed. Samples of kidney tissues were processed and stained with Hematoxylin and Eosin (H&E), Periodic Acid Schiff (PAS) and Massons trichrome stain and lesions were classified based on the WHO criteria. Of the 40 dogs that initially tested negative for VL, 25 (62.5%) exhibited positive serological tests during the study period. Of these 25 dogs, 15 (60%) tested positive within three months, five (20%) tested positive within six months and five (20%) tested positive within nine months. The dogs exhibited antibody titers between 1:40 and 1:80 and 72% of the dogs exhibited clinical symptoms. The Leishmania antigen was present in the kidneys of recently infected dogs. We found higher levels of total protein and globulin as well as lower levels of albumin in the infected dogs when compared to the control dogs. Additionally, infected dogs presented levels of urea and creatinine that were higher than those of the uninfected dogs. Glomerulonephritis was detected in some of the dogs examined in this study. These data suggest that in Teresina, the sero-conversion for VL occurs quickly and showed that the infected dogs presented abnormal serum proteins, as well as structural and functional alterations in the kidneys during the early post-infection period

Cultural adaptation and validation of an instrument on barriers for the use of research results

ABSTRACT Objective: to culturally adapt The Barriers to Research Utilization Scale and to analyze the metric validity and reliability properties of its Brazilian Portuguese version. Method: methodological research conducted by means of the cultural adaptation process (translation and back-translation), face and content validity, construct validity (dimensionality and known groups) and reliability analysis (internal consistency and test-retest). The sample consisted of 335 nurses, of whom 43 participated in the retest phase. Results: the validity of the adapted version of the instrument was confirmed. The scale investigates the barriers for the use of the research results in clinical practice. Confirmatory factorial analysis demonstrated that the Brazilian Portuguese version of the instrument is adequately adjusted to the dimensional structure the scale authors originally proposed. Statistically significant differences were observed among the nurses holding a Master's or Doctoral degree, with characteristics favorable to Evidence-Based Practice, and working at an institution with an organizational cultural that targets this approach. The reliability showed a strong correlation (r ranging between 0.77 and 0.84, p<0.001) and the internal consistency was adequate (Cronbach's alpha ranging between 0.77 and 0.82). Conclusion: the Brazilian Portuguese version of The Barriers Scale was valid and reliable in the group studied