Multi-State Gene Cluster Switches Determine the Adaptive Mitochondrial And Metabolic Landscape of Breast Cancer.

Adaptive metabolic switches are proposed to underlie conversions between cellular states during normal development as well as in cancer evolution. Metabolic adaptations represent important therapeutic targets in tumors, highlighting the need to characterize the full spectrum, characteristics, and regulation of the metabolic switches. To investigate the hypothesis that metabolic switches associated with specific metabolic states can be recognized by locating large alternating gene expression patterns, we developed a method to identify interspersed gene sets by massive correlated biclustering (MCbiclust) and to predict their metabolic wiring. Testing the method on breast cancer transcriptome datasets revealed a series of gene sets with switch-like behavior that could be used to predict mitochondrial content, metabolic activity, and central carbon flux in tumors. The predictions were experimentally validated by bioenergetic profiling and metabolic flux analysis of 13C-labelled substrates. The metabolic switch positions also distinguished between cellular states, correlating with tumor pathology, prognosis, and chemosensitivity. The method is applicable to any large and heterogeneous transcriptome dataset to discover metabolic and associated pathophysiological states.

Empowerment-based nutrition interventions on blood pressure: a randomized comparative effectiveness trial.

Introduction: Empowerment lifestyle programs are needed to reduce the risk of hypertension. Our study compared the effectiveness of two empowerment-based approaches toward blood pressure (BP) reduction: salt reduction-specific program vs. healthy lifestyle general program. Methods: Three hundred and eleven adults (median age of 44 years, IQR 34-54 years) were randomly assigned to a salt reduction (n = 147) or a healthy lifestyle program (n = 164). The outcome measures were urinary sodium (Na+) and potassium (K+) excretion, systolic (SBP) and diastolic (DBP) blood pressure, weight, and waist circumference. Results: There were no significant differences in primary and secondary outcomes between the two program groups. When comparing each program to baseline, the program focused on salt reduction was effective in lowering BP following a 12-week intervention with a mean change of -2.5 mm Hg in SBP (95% CI, -4.1 to -0.8) and - 2.7 mm Hg in DBP (95% CI, -3.8 to -1.5) in the intention-to-treat (ITT) analysis. In the complete-case (CC) analysis, the mean change was -2.1 mm Hg in SBP (95% CI, -3.7 to -0.5) and - 2.3 mm Hg in DBP (95% CI, -3.4 to -1.1). This effect increases in subjects with high-normal BP or hypertension [SBP - 7.9 mm Hg (95% CI, -12.5 to -3.3); DBP - 7.3 mm Hg (95% CI, -10.2 to -4.4)]. The healthy lifestyle group also exhibited BP improvements after 12 weeks; however, the changes were less pronounced compared to the salt reduction group and were observed only for DBP [mean change of -1.5 mm Hg (95% CI, -2.6 to -0.4) in ITT analysis and - 1.4 mm Hg (95% CI, -2.4 to -0.3) in CC analysis, relative to baseline]. Overall, improvements in Na+/K+ ratio, weight, and Mediterranean diet adherence resulted in clinically significant SBP decreases. Importantly, BP reduction is attributed to improved dietary quality, rather than being solely linked to changes in the Na+/K+ ratio. Conclusion: Salt-focused programs are effective public health tools mainly in managing individuals at high risk of hypertension. Nevertheless, in general, empowerment-based approaches are important strategies for lowering BP, by promoting health literacy that culminates in adherence to the Mediterranean diet and weight reduction.

Application of an Ultrasonic Nebulizer Closet in the Disinfection of Textiles and Footwear.

The emergence of the coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of disinfection processes in health safety. Textiles and footwear have been identified as vectors for spreading infections. Therefore, their disinfection can be crucial to controlling pathogens' dissemination. The present work aimed to evaluate the effectiveness of a commercial disinfectant aerosolized by an ultrasonic nebulizer closet as an effective method for disinfecting textiles and footwear. The disinfection was evaluated in three steps: suspension tests; nebulization in a 0.08 m3 closet; nebulization in the upscaled 0.58 m3 closet. The disinfection process of textiles and footwear was followed by the use of bacteriophages, bacterial spores, and bacterial cells. The disinfection in the 0.58 m3 closet was efficient for textiles (4 log reduction) when bacteriophage Lambda, Pseudomonas aeruginosa, and Bacillus subtilis were used. The footwear disinfection was achieved (4 log reduction) in the 0.08 m3 closet for Escherichia coli and Staphylococcus aureus. Disinfection in an ultrasonic nebulization closet has advantages such as being quick, not wetting, being efficient on porous surfaces, and is performed at room temperature. Ultrasonic nebulization disinfection in a closet proves to be useful in clothing and footwear stores to prevent pathogen transmission by the items' widespread handling.

Intervenção de enfermagem de reabilitação após artroplastia total da anca: revisão sistemática da literatura / Rehabilitation nursing intervention after total hip arthroplasty: a systematic review of the literature

O presente trabalho prende-se com a temática "Intervenção de Enfermagem de Reabilitação após Artroplastia Total da Anca ­ Revisão Sistemática da Literatura", através de uma revisão sistemática da literatura com caráter descritivo exploratório, pela análise de bases de dados científicas e posteriormente, com a aplicação da estratégia PICO, seguindo o Protocolo da Revisão Sistemática da Literatura publicado pela Cochrane, apresentar e descrever os resultados obtidos. A questão "Quais os ganhos em saúde decorrentes da intervenção do enfermeiro de reabilitação após Artroplastia Total da Anca?" foi claramente respondida, concluindo-se que as intervenções passam essencialmente pela reabilitação do paciente, utilizando para o efeito estratégias e técnicas específicas e altamente qualificadas do Enfermeiro de Reabilitação em conjunto com equipa multidisciplinar que acompanha todos os procedimentos no pós-operatório. De facto, os estudos identificados apresentam, na sua maioria, resultados que comprovam a necessidade de implementação de protocolos multidisciplinares de enfermagem de reabilitação, concluindo-se ainda que a avaliação funcional é essencial para determinar o potencial de reabilitação, implementando técnicas de reeducação funcional, planificando a alta clínica e reinserção na comunidade, com o objetivo de prevenir novas fraturas. No decurso da investigação foram analisados, selecionados e avaliados diversos artigos de investigação, sendo considerados válidos para a presente temática dezoito, sendo nove em língua inglesa e nove em língua portuguesa, publicados nos últimos dez anos e de acesso integral, livre e gratuito. Neste sentido os artigos selecionados e considerados válidos indicam claramente a importância do Enfermeiro de Reabilitação, enquanto contributo direto para uma alta bem-sucedida, particularmente, quando associada a sua intervenção a equipas multidisciplinares, contribuindo diretamente para ganhos globais na saúde e reabilitação de pacientes submetidos a artroplastia total da anca.

The present work deals with the theme "Rehabilitation Nursing Intervention after Total Hip Arthroplasty - Systematic Literature Review", through a systematic literature review with an exploratory descriptive character, through the analysis of scientific databases and later, with the application of the PICO strategy, following the Protocol of Systematic Literature Review published by Cochrane, present and describe the results obtained. The question "What are the health gains resulting from the intervention of the rehabilitation nurse after Total Hip Arthroplasty?" it was clearly answered, concluding that the interventions essentially go through the rehabilitation of the patient, using specific and highly qualified strategies and techniques of the Rehabilitation Nurse in conjunction with a multidisciplinary team that monitors all procedures in the postoperative period. In fact, the studies identified present, for the most part, results that prove the need to implement multidisciplinary rehabilitation nursing protocols, concluding that functional assessment is essential to determine the potential for rehabilitation, implementing functional reeducation techniques, planning hospital discharge and reintegration into the community, with the aim of preventing new fractures. In the course of the investigation, several research articles were analyzed, selected and evaluated, being considered valid for the present topic eighteen, nine in English and nine in Portuguese, published in the last ten years and with full, free and free access. In this sense, the articles selected and considered valid clearly indicate the importance of the Rehabilitation Nurse, as a direct contribution to a successful discharge, particularly when associated with its intervention to multidisciplinary teams, contributing directly to global gains in health and rehabilitation of patients submitted total hip arthroplasty.

TMEM16A calcium-activated chloride currents in supporting cells of the mouse olfactory epithelium.

Glial-like supporting (or sustentacular) cells are important constituents of the olfactory epithelium that are involved in several physiological processes such as production of endocannabinoids, insulin, and ATP and regulation of the ionic composition of the mucus layer that covers the apical surface of the olfactory epithelium. Supporting cells express metabotropic P2Y purinergic receptors that generate ATP-induced Ca2+ signaling through the activation of a PLC-mediated cascade. Recently, we reported that a subpopulation of supporting cells expresses also the Ca2+-activated Cl- channel TMEM16A. Here, we sought to extend our understanding of a possible physiological role of this channel in the olfactory system by asking whether Ca2+ can activate Cl- currents mediated by TMEM16A. We use whole-cell patch-clamp analysis in slices of the olfactory epithelium to measure dose-response relations in the presence of various intracellular Ca2+ concentrations, ion selectivity, and blockage. We find that knockout of TMEM16A abolishes Ca2+-activated Cl- currents, demonstrating that TMEM16A is essential for these currents in supporting cells. Also, by using extracellular ATP as physiological stimuli, we found that the stimulation of purinergic receptors activates a large TMEM16A-dependent Cl- current, indicating a possible role of TMEM16A in ATP-mediated signaling. Altogether, our results establish that TMEM16A-mediated currents are functional in olfactory supporting cells and provide a foundation for future work investigating the precise physiological role of TMEM16A in the olfactory system.

A spatial stream-network approach assists in managing the remnant genetic diversity of riparian forests.

Quantifying the genetic diversity of riparian trees is essential to understand their chances to survive hydroclimatic alterations and to maintain their role as foundation species modulating fluvial ecosystem processes. However, the application of suitable models that account for the specific dendritic structure of hydrographic networks is still incipient in the literature. We investigate the roles of ecological and spatial factors in driving the genetic diversity of Salix salviifolia, an Iberian endemic riparian tree, across the species latitudinal range. We applied spatial stream-network models that aptly integrate dendritic features (topology, directionality) to quantify the impacts of multiple scale factors in determining genetic diversity. Based on the drift hypothesis, we expect that genetic diversity accumulates downstream in riparian ecosystems, but life history traits (e.g. dispersal patterns) and abiotic or anthropogenic factors (e.g. drought events or hydrological alteration) might alter expected patterns. Hydrological factors explained the downstream accumulation of genetic diversity at the intermediate scale that was likely mediated by hydrochory. The models also suggested upstream gene flow within basins that likely occurred through anemophilous and entomophilous pollen and seed dispersal. Higher thermicity and summer drought were related to higher population inbreeding and individual homozygosity, respectively, suggesting that increased aridity might disrupt the connectivity and mating patterns among and within riparian populations.

Demonstration of glucose-6-phosphate hydrogen 5 enrichment from deuterated water by transaldolase-mediated exchange alone.

PURPOSE: Enrichment of glucose position 5 (H5) from deuterated water ((2)H2O) is widely used for quantifying gluconeogenesis. Exchanges of hexose and triose phosphates mediated by transaldolase have been postulated to enrich H5 independently of gluconeogenesis, but to date this mechanism has not been proven. We determined the enrichment of glucose-6-phosphate (G6P), the immediate precursor of endogenously produced glucose, from (2)H2O in erythrocyte hemolysate preparations. Here, transaldolase exchange is active but gluconeogenesis is absent. METHODS: Hemolysates were prepared from human erythrocytes and incubated with a buffer containing 5% [U-(13)C]G6P, unlabeled fructose 1,6-bisphosphate, and 10% (2)H2O. G6P (2)H-enrichment and (13)C-isotopomer distributions were analyzed by (2)H and (13)C NMR following derivatization to monoacetone glucose. RESULTS: (2)H NMR analysis revealed high (2)H-enrichment of G6P hydrogens 2, 4, and 5; low enrichment of hydrogen 3, and residual enrichments of hydrogens 1, 6R, and 6S. (13)C NMR isotopomer analysis revealed that [U-(13)C]G6P was converted to [1,2,3-(13)C3]G6P, a predicted product of transaldolase-mediated exchange, as well as [1,2-(13)C2]G6P and [3-(13)C]G6P, predicted products of combined transaldolase and transketolase exchanges. CONCLUSION: Hydrogen 5 of G6P was enriched from (2)H2O through exchanges mediated by transaldolase. These studies prove that G6P can be enriched in hydrogen 5 by (2)H2O independently of gluconeogenesis.

Development of the Olfactory Epithelium and Nasal Glands in TMEM16A-/- and TMEM16A+/+ Mice.

TMEM16A/ANO1 is a calcium-activated chloride channel expressed in several types of epithelia and involved in various physiological processes, including proliferation and development. During mouse embryonic development, the expression of TMEM16A in the olfactory epithelium is dynamic. TMEM16A is expressed at the apical surface of the entire olfactory epithelium at embryonic day E12.5 while from E16.5 its expression is restricted to a region near the transition zone with the respiratory epithelium. To investigate whether TMEM16A plays a role in the development of the mouse olfactory epithelium, we obtained the first immunohistochemistry study comparing the morphological properties of the olfactory epithelium and nasal glands in TMEM16A-/- and TMEM16A+/+ littermate mice. A comparison between the expression of the olfactory marker protein and adenylyl cyclase III shows that genetic ablation of TMEM16A did not seem to affect the maturation of olfactory sensory neurons and their ciliary layer. As TMEM16A is expressed at the apical part of supporting cells and in their microvilli, we used ezrin and cytokeratin 8 as markers of microvilli and cell body of supporting cells, respectively, and found that morphology and development of supporting cells were similar in TMEM16A-/- and TMEM16A+/+ littermate mice. The average number of supporting cells, olfactory sensory neurons, horizontal and globose basal cells were not significantly different in the two types of mice. Moreover, we also observed that the morphology of Bowman's glands, nasal septal glands and lateral nasal glands did not change in the absence of TMEM16A. Our results indicate that the development of mouse olfactory epithelium and nasal glands does not seem to be affected by the genetic ablation of TMEM16A.