An IoT-fuzzy intelligent approach for holistic management of COVID-19 patients.

In this study, an internet of things (IoT)-enabled fuzzy intelligent system is introduced for the remote monitoring, diagnosis, and prescription of treatment for patients with COVID-19. The main objective of the present study is to develop an integrated tool that combines IoT and fuzzy logic to provide timely healthcare and diagnosis within a smart framework. This system tracks patients' health by utilizing an Arduino microcontroller, a small and affordable computer that reads data from various sensors, to gather data. Once collected, the data are processed, analyzed, and transmitted to a web page for remote access via an IoT-compatible Wi-Fi module. In cases of emergencies, such as abnormal blood pressure, cardiac issues, glucose levels, or temperature, immediate action can be taken to monitor the health of critical COVID-19 patients in isolation. The system employs fuzzy logic to recommend medical treatments for patients. Sudden changes in these medical conditions are remotely reported through a web page to healthcare providers, relatives, or friends. This intelligent system assists healthcare professionals in making informed decisions based on the patient's condition.

Safety, Efficacy, and Visual Performance of an Orthokeratology Lens with Increased Compression Factor.

The aim was to evaluate the safety, efficacy, and visual performance of an orthokeratology lens with an increased compression factor (ICF) of 1.25 D in a 3-month follow-up. Thirty-six myopic patients (5 males and 31 females; 24.2 ± 5.8 years) were fitted with Alexa AR (Tiedra Farmacéutica S.L., Madrid, Spain) contact lenses (CLs) and twenty participants finished the follow-up. Visual acuity (VA), subjective refraction, primary spherical and primary coma aberrations, keratometry, central pachymetry, and ocular surface evaluation were performed at baseline and after 1 night, 1 week, 1 month, and 3 months of CL wear. The differences among visits were analyzed using a repeated-measures analysis of variance or the Friedman test. The spherical equivalent decreased (p ≤ 0.005), and the uncorrected VA improved (p < 0.001) until the first week. Corneal and ocular aberrations showed a significant increase (p ≤ 0.02). A significant decrease (p < 0.001) was found for keratometry values. No significant changes were observed in either central pachymetry or ocular surface parameters among study visits. In conclusion, an orthokeratology CL with an ICF of 1.25 D provides good safety, efficacy, and visual performance in a 3-month follow-up. Seven days of orthokeratology wear are enough to achieve the full myopic compensation, resulting in satisfactory VA.

Evaluation of hemostatic devices in a randomized porcine model of junctional hemorrhage and 72-hour prolonged field care.

BACKGROUND: Hemorrhage control in prolonged field care (PFC) presents unique challenges that drive the need for enhanced point of injury treatment capabilities to maintain patient stability beyond the Golden Hour. To address this, two hemostatic agents, Combat Gauze (CG) and XSTAT, were evaluated in a porcine model of uncontrolled junctional hemorrhage for speed of deployment and hemostatic efficacy over 72 hours. METHODS: The left subclavian artery and subscapular vein were isolated in anesthetized male Yorkshire swine (70-85 kg) and injured via 50% transection, followed by 30 seconds of hemorrhage. Combat Gauze (n = 6) or XSTAT (n = 6) was administered until bleeding stopped and remained within subjects for observation over 72 hours. Physiologic monitoring, hemostatic efficacy, and hematological parameters were measured throughout the protocol. Gross necropsy and histology were performed following humane euthanasia. RESULTS: Both CG and XSTAT maintained hemostasis throughout the full duration of the protocol. There were no significant differences between groups in hemorrhage volume (CG: 1021.0 ± 183.7 mL vs. XSTAT: 968.2 ± 243.3 mL), total blood loss (CG: 20.8 ± 2.7% vs. XSTAT: 20.1 ± 5.1%), or devices used (CG: 3.8 ± 1.2 vs. XSTAT: 5.3 ± 1.4). XSTAT absorbed significantly more blood than CG (CG: 199.5 ± 50.3 mL vs. XSTAT: 327.6 ± 71.4 mL) and was significantly faster to administer (CG: 3.4 ± 1.6 minutes vs. XSTAT: 1.4 ± 0.5 minutes). There were no significant changes in activated clot time, prothrombin time, or international normalized ratio between groups or compared with baseline throughout the 72-hour protocol. Histopathology revealed no evidence of microthromboemboli or disseminated coagulopathies across evaluated tissues in either group. CONCLUSION: Combat Gauze and XSTAT demonstrated equivalent hemostatic ability through 72 hours, with no overt evidence of coagulopathies from prolonged indwelling. In addition, XSTAT offered significantly faster administration and the ability to absorb more blood. Taken together, XSTAT offers logistical and efficiency advantages over CG for immediate control of junctional noncompressible hemorrhage, particularly in a tactical environment. In addition, extension of indicated timelines to 72 hours allows translation to PFC.

On the Use of Machine Learning Techniques and Non-Invasive Indicators for Classifying and Predicting Cardiac Disorders.

This research aims to enhance the classification and prediction of ischemic heart diseases using machine learning techniques, with a focus on resource efficiency and clinical applicability. Specifically, we introduce novel non-invasive indicators known as Campello de Souza features, which require only a tensiometer and a clock for data collection. These features were evaluated using a comprehensive dataset of heart disease cases from a machine learning data repository. Our findings highlight the ability of machine learning algorithms to not only streamline diagnostic procedures but also reduce diagnostic errors and the dependency on extensive clinical testing. Three key features-mean arterial pressure, pulsatile blood pressure index, and resistance-compliance indicator-were found to significantly improve the accuracy of machine learning algorithms in binary heart disease classification. Logistic regression achieved the highest average accuracy among the examined classifiers when utilizing these features. While such novel indicators contribute substantially to the classification process, they should be integrated into a broader diagnostic framework that includes comprehensive patient evaluations and medical expertise. Therefore, the present study offers valuable insights for leveraging data science techniques in the diagnosis and management of cardiovascular diseases.

Similarity-Based Predictive Models: Sensitivity Analysis and a Biological Application with Multi-Attributes.

Predictive models based on empirical similarity are instrumental in biology and data science, where the premise is to measure the likeness of one observation with others in the same dataset. Biological datasets often encompass data that can be categorized. When using empirical similarity-based predictive models, two strategies for handling categorical covariates exist. The first strategy retains categorical covariates in their original form, applying distance measures and allocating weights to each covariate. In contrast, the second strategy creates binary variables, representing each variable level independently, and computes similarity measures solely through the Euclidean distance. This study performs a sensitivity analysis of these two strategies using computational simulations, and applies the results to a biological context. We use a linear regression model as a reference point, and consider two methods for estimating the model parameters, alongside exponential and fractional inverse similarity functions. The sensitivity is evaluated by determining the coefficient of variation of the parameter estimators across the three models as a measure of relative variability. Our results suggest that the first strategy excels over the second one in effectively dealing with categorical variables, and offers greater parsimony due to the use of fewer parameters.

An Epidemiological Analysis for Assessing and Evaluating COVID-19 Based on Data Analytics in Latin American Countries.

This research provides a detailed analysis of the COVID-19 spread across 14 Latin American countries. Using time-series analysis and epidemic models, we identify diverse outbreak patterns, which seem not to be influenced by geographical location or country size, suggesting the influence of other determining factors. Our study uncovers significant discrepancies between the number recorded COVID-19 cases and the real epidemiological situation, emphasizing the crucial need for accurate data handling and continuous surveillance in managing epidemics. The absence of a clear correlation between the country size and the confirmed cases, as well as with the fatalities, further underscores the multifaceted influences on COVID-19 impact beyond population size. Despite the decreased real-time reproduction number indicating quarantine effectiveness in most countries, we note a resurgence in infection rates upon resumption of daily activities. These insights spotlight the challenge of balancing public health measures with economic and social activities. Our core findings provide novel insights, applicable to guiding epidemic control strategies and informing decision-making processes in combatting the pandemic.

Parent Perception of School Meals in the San Joaquin Valley during COVID-19: A Photovoice Project.

School-based nutrition programs are crucial to reducing food insecurity. The COVID-19 pandemic adversely impacted students' school meal participation. This study seeks to understand parent views of school meals during COVID-19 to inform efforts to improve participation in school meal programs. Photovoice methodology was used to explore parental perception of school meals in San Joaquin Valley, California, a region of predominately Latino farmworker communities. Parents in seven school districts photographed school meals for a one-week period during the pandemic and then participated in focus group discussions and small group interviews. Focus group discussions and small group interviews were transcribed, and data were analyzed using a team-based, theme-analysis approach. Three primary domains emerged: benefits of school meal distribution, meal quality and appeal, and perceived healthfulness. Parents perceived school meals as beneficial to addressing food insecurity. However, they noted that meals were unappealing, high in added sugar, and unhealthy, which led to discarded meals and decreased participation in the school meal program. The transition to grab-and-go style meals was an effective strategy for providing food to families during pandemic school closures, and school meals remain an important resource for families experiencing food insecurity. However, negative parental perceptions of the appeal and nutritional content of school meals may have decreased school meal participation and increased food waste that could persist beyond the pandemic.

Seguridad de las drogas biológicas y sintéticas dirigidas utilizadas en pacientes con enfermedades reumáticas inmunomediadas. Datos del registro BIOBADASAR 3.0 / Safety of biological and targeted synthetic drugs in patients with immune-mediated rheumatic diseases. Data from the BIOBADASAR 3.0 registry

Introducción: conocer la seguridad de las drogas actualmente disponibles para el tratamiento de las enfermedades reumáticas es muy importante al momento de tomar decisiones terapéuticas objetivas e individualizadas en la consulta médica diaria. Asimismo, datos de la vida real amplían el conocimiento revelado por los ensayos clínicos. Objetivos: describir los eventos adversos (EA) reportados, estimar su frecuencia e identificar los factores relacionados con su desarrollo. Materiales y métodos: se utilizaron datos BIOBADASAR, un registro voluntario y prospectivo de seguimiento de EA de tratamientos biológicos y sintéticos dirigidos en pacientes con enfermedades reumáticas inmunomediadas. Los pacientes son seguidos hasta la muerte, pérdida de seguimiento o retiro del consentimiento informado. Para este análisis se extrajeron datos recopilados hasta el 31 de enero de 2023. Resultados: se incluyó un total de 6253 pacientes, los cuales aportaron 9533 ciclos de tratamiento, incluyendo 3647 (38,3%) ciclos sin drogas modificadoras de la enfermedad biológicas y sintéticas dirigidas (DME-b/sd) y 5886 (61,7%) con DME-b/sd. Dentro de estos últimos, los más utilizados fueron los inhibidores de TNF y abatacept. Se reportaron 5890 EA en un total de 2701 tratamientos (844 y 1857 sin y con DME-b/sd, respectivamente), con una incidencia de 53,9 eventos cada 1000 pacientes/año (IC 95% 51,9-55,9). La misma fue mayor en los ciclos con DME-b/sd (71,1 eventos cada 1000 pacientes/año, IC 95% 70,7-77,5 versus 33,7, IC 95% 31,5-36,1; p<0,001). Las infecciones, particularmente las de la vía aérea superior, fueron los EA más frecuentes en ambos grupos. El 10,9% fue serio y el 1,1% provocó la muerte del paciente. El 18,7% de los ciclos con DME-b/sd fue discontinuado a causa de un EA significativamente mayor a lo reportado en el otro grupo (11,5%; p<0,001). En el análisis ajustado, las DME-b/sd se asociaron a mayor riesgo de presentar al menos un EA (HR 1,82, IC 95% 1,64-1,96). De igual manera, la mayor edad, el mayor tiempo de evolución, el antecedente de enfermedad pulmonar obstructiva crónica, el diagnóstico de lupus eritematoso sistémico y el uso de corticoides se asociaron a mayor riesgo de EA. Conclusiones: la incidencia de EA fue significativamente superior durante los ciclos de tratamientos que incluían DME-b/sd.

Introduction: knowing the efficacy and safety of the drugs currently available for the treatment of rheumatic diseases is very important when making objective and individualized therapeutic decisions in daily medical consultation. Likewise, real-life data extends the knowledge revealed by clinical trials. Objectives: to describe the reported adverse events (AEs), estimate their frequency and identify factors associated to them. Materials and methods: BIOBADASAR data were used, which is a voluntary, prospective follow-up registry of AEs of biological and synthetic treatments in patients with immune-mediated rheumatic diseases. Patients are followed until death, loss of followup, or withdrawal of informed consent. To carry out this analysis, the data collected up to January 31, 2023 was extracted. Results: a total of 6253 patients were included, who contributed with 9533 treatment periods, including 3647 (38.3%) periods without b/ts-DMARDs and 5886 (61.7%) with b/ts-DMARDs. Among the latter, the most used were TNF inhibitors and abatacept. A total of 5890 AEs were reported in a total of 2701 treatments (844 and 1857 without and with b/ts-DMARDs, respectively), with an incidence of 53.9 events per 1000 patients/ year (95% CI 51.9-55.9). It was higher during the periods with b/ts-DMARDs (71.1 events per 1000 patients/year, 95% CI 70.7-77.5 vs 33.7, 95% CI 31.5-36.1, p<0.001). Infections, particularly those of the upper respiratory tract, were the most frequent AEs in both groups. 10.9% were severe and 1.1% were associated with the death of the patient. 18.7% of the periods with b/ts-DMARDs were discontinued due to an AE, significantly higher than that reported in the other group (11.5%; p<0.001). In the adjusted analysis, b/ts-DMARDs were associated with a higher risk of presenting at least one AE (HR 1.82, 95% CI 1.64-1.96). Similarly, older age, longer evolution time, history of chronic obstructive pulmonary disease, diagnosis of systemic lupus erythematosus, and use of corticosteroids were associated with a higher risk of AE. Conclusions: the incidence of AEs was significantly higher during those treatment periods that included DME-b/sd.

Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells.

Current understanding of tumor immunosuppressive mechanisms forms the basis for modern day immunotherapies. Immunoregulatory role of platelets in cancer remains largely elusive. Platelets from non-small cell lung cancer (NSCLC) patients revealed a distinct activation phenotype. TREM-like transcript 1 (TLT-1), a platelet protein, was increased along with enhanced extracellular release from NSCLC platelets. The increased platelet TLT-1 was also evident in humanized mice with patient-derived tumors. In immunocompetent mice with syngeneic tumors, TLT-1 binding to T cells, in vivo, led to suppression of CD8 T cells, promoting tumor growth. We identified direct interaction between TLT-1 and CD3ε on T cells, implicating the NF-κB pathway in CD8 T cell suppression. Anti-TLT-1 antibody rescued patients' T cells from platelet-induced suppression ex vivo and reduced tumors in mice in vivo. Clinically, higher TLT-1 correlated with reduced survival of NSCLC patients. Our findings thus identify TLT-1 as a platelet-derived immunosuppressor that suppresses CD8 T cells and demonstrate its therapeutic and prognostic significance in cancer.

Cysteine and iron accelerate the formation of ribose-5-phosphate, providing insights into the evolutionary origins of the metabolic network structure.

The structure of the metabolic network is highly conserved, but we know little about its evolutionary origins. Key for explaining the early evolution of metabolism is solving a chicken-egg dilemma, which describes that enzymes are made from the very same molecules they produce. The recent discovery of several nonenzymatic reaction sequences that topologically resemble central metabolism has provided experimental support for a "metabolism first" theory, in which at least part of the extant metabolic network emerged on the basis of nonenzymatic reactions. But how could evolution kick-start on the basis of a metal catalyzed reaction sequence, and how could the structure of nonenzymatic reaction sequences be imprinted on the metabolic network to remain conserved for billions of years? We performed an in vitro screening where we add the simplest components of metabolic enzymes, proteinogenic amino acids, to a nonenzymatic, iron-driven reaction network that resembles glycolysis and the pentose phosphate pathway (PPP). We observe that the presence of the amino acids enhanced several of the nonenzymatic reactions. Particular attention was triggered by a reaction that resembles a rate-limiting step in the oxidative PPP. A prebiotically available, proteinogenic amino acid cysteine accelerated the formation of RNA nucleoside precursor ribose-5-phosphate from 6-phosphogluconate. We report that iron and cysteine interact and have additive effects on the reaction rate so that ribose-5-phosphate forms at high specificity under mild, metabolism typical temperature and environmental conditions. We speculate that accelerating effects of amino acids on rate-limiting nonenzymatic reactions could have facilitated a stepwise enzymatization of nonenzymatic reaction sequences, imprinting their structure on the evolving metabolic network.

ß-hydroxybutyrate accumulates in the rat heart during low-flow ischaemia with implications for functional recovery.

Extrahepatic tissues which oxidise ketone bodies also have the capacity to accumulate them under particular conditions. We hypothesised that acetyl-coenzyme A (acetyl-CoA) accumulation and altered redox status during low-flow ischaemia would support ketone body production in the heart. Combining a Langendorff heart model of low-flow ischaemia/reperfusion with liquid chromatography coupled tandem mass spectrometry (LC-MS/MS), we show that ß-hydroxybutyrate (ß-OHB) accumulated in the ischaemic heart to 23.9 nmol/gww and was secreted into the coronary effluent. Sodium oxamate, a lactate dehydrogenase (LDH) inhibitor, increased ischaemic ß-OHB levels 5.3-fold and slowed contractile recovery. Inhibition of ß-hydroxy-ß-methylglutaryl (HMG)-CoA synthase (HMGCS2) with hymeglusin lowered ischaemic ß-OHB accumulation by 40%, despite increased flux through succinyl-CoA-3-oxaloacid CoA transferase (SCOT), resulting in greater contractile recovery. Hymeglusin also protected cardiac mitochondrial respiratory capacity during ischaemia/reperfusion. In conclusion, net ketone generation occurs in the heart under conditions of low-flow ischaemia. The process is driven by flux through both HMGCS2 and SCOT, and impacts on cardiac functional recovery from ischaemia/reperfusion.

Nrf2 activation does not affect adenoma development in a mouse model of colorectal cancer.

Transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) and its main negative regulator, Kelch-like ECH associated protein 1 (Keap1), are at the interface between redox and intermediary metabolism. Nrf2 activation is protective in models of human disease and has benefits in clinical trials. Consequently, the Keap1/Nrf2 protein complex is a drug target. However, in cancer Nrf2 plays a dual role, raising concerns that Nrf2 activators may promote growth of early neoplasms. To address this concern, we examined the role of Nrf2 in development of colorectal adenomas by employing genetic, pharmacological, and metabolomic approaches. We found that colorectal adenomas that form in Gstp-/-: ApcMin/+ mice are characterized by altered one-carbon metabolism and that genetic activation, but not disruption of Nrf2, enhances these metabolic alterations. However, this enhancement is modest compared to the magnitude of metabolic differences between tumor and peri-tumoral tissues, suggesting that the metabolic changes conferred by Nrf2 activation may have little contribution to the early stages of carcinogenesis. Indeed, neither genetic (by Keap1 knockdown) nor pharmacological Nrf2 activation, nor its disruption, affected colorectal adenoma formation in this model. We conclude that pharmacological Nrf2 activation is unlikely to impact the early stages of development of colorectal cancer.

Downregulation of Keap1 Confers Features of a Fasted Metabolic State.

Transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) and its main negative regulator, Kelch-like ECH-associated protein 1 (Keap1), are at the interface between redox and intermediary metabolism, allowing adaptation and survival under conditions of oxidative, inflammatory, and metabolic stress. Nrf2 is the principal determinant of redox homeostasis, and contributes to mitochondrial function and integrity and cellular bioenergetics. Using proteomics and lipidomics, we show that genetic downregulation of Keap1 in mice, and the consequent Nrf2 activation to pharmacologically relevant levels, leads to upregulation of carboxylesterase 1 (Ces1) and acyl-CoA oxidase 2 (Acox2), decreases triglyceride levels, and alters the lipidome. This is accompanied by downregulation of hepatic ATP-citrate lyase (Acly) and decreased levels of acetyl-CoA, a trigger for autophagy. These findings suggest that downregulation of Keap1 confers features of a fasted metabolic state, which is an important consideration in the drug development of Keap1-targeting pharmacologic Nrf2 activators.

Percepção e Vivência da Morte de Estudante de Medicina durante a Graduação / Medical Undergraduate Student's Perception and Experience of Death

Resumo: Introdução: o estudo da morte envolve a exploração que o indivíduo faz na busca de si mesmo. A Medicina tende a negá-la e controlá-la por meio de avanços tecnológicos e medicalização, o que leva ao pensamento de que o médico pode regular a duração dela. A morte é carregada de significados simbólicos e faz parte do processo de desenvolvimento humano, contudo muitas vezes é desconhecida do estudante de Medicina, o que leva ao temor pela indefinição do momento em que ocorrerá o encontro. Inerente às atividades do médico, há a crença de que poderá ser sempre evitada, sendo entendida como falha ou insucesso do tratamento, ou como desconhecimento do profissional, provocando ansiedade e cobrança tanto por parte da população como dos médicos. Este estudo objetivou relatar a vivência e percepção sobre a morte entre estudantes de Medicina. Método: trata-se se um estudo qualitativo, observacional, realizado com 50 alunos de três períodos de um curso de Medicina em Alagoas, em 2018. Usou-se um questionário com a seguinte pergunta aberta: "Após a vivência da morte durante o curso, o que mudou na sua atuação como estudante e na sua vida?". Os dados foram analisados manualmente em quatro etapas. A primeira fase consistiu na organização dos dados, procurando ideias que emergiram das respostas à questão norteadora, quando foi realizada a pré-análise, por meio de uma leitura aprofundada, na busca da criação das categorias, uma vez que elas não foram elaboradas previamente. A segunda fase correspondeu à elaboração da segunda planilha que armazenou as ideias explícitas (categorias provisórias) e implícitas (focos) com a identificação dos sentidos. A terceira fase procurou responder à pergunta da pesquisa por meio das unidades de registro, em que se relacionou a fala com o foco/tema e se identificou o sentido da inferência. A quarta fase compreendeu duas planilhas: uma com a interpretação dos focos e suas unidades de registros e outra com elaboração de síntese para cada foco. A vivência da morte pode acontecer em relação ao outro ou à própria morte, ocorrendo diferenças nos dois processos. Aqui abordagem concentrou-se na morte do outro e em como ela é vivenciada pelo estudante de Medicina durante a graduação. Resultados: Os dados obtidos resultaram em três categorias relacionadas à vivência da morte durante a graduação, refletindo o preparo ou não para lidar com o fenômeno. Cada categoria apresentou duas subcategorias: significação da morte, com as subcategorias "vida pessoal" e "vida profissional"; qualificação profissional, com as subcategorias "limites de atuação profissional" e "curso em relação à morte"; humanização, com as subcategorias "relação médico-paciente" e "cuidados paliativos". Conclusão: A pesquisa mostrou que os discentes modificaram sua visão da morte após a vivência durante o curso e que estão despertos para o tema, revelando a importância deste para sua formação e também a necessidade da ampliação de sua discussão durante a graduação.

Abstract Introduction: the study of death involves the exploration in the search of oneself. Medicine tends to deny death and control it through technological advances and medicalization, leading to the thought that the doctor can regulate the duration of the process. Death is full of symbolic meanings and it is an important part of the human development process, often unknown by the medical students, which makes them fearful for not knowing when this meeting is going to happen. It is inherent to the doctor's activities, believing it can be always avoided, being understood as a failure or unsuccessful treatment, or lack of knowledge by the professional, generating anxiety and demands, by the population and the doctors themselves. This research aims to report the experience and perception of death among medical students. Methods: it is a qualitative, observational study carried out with 50 students from three different semesters from a School of Medicine in the state of Alagoas, Brazil, in 2018. It was applied an instrument with an open question: After the experience of death during the course, what has changed in your performance as a student and in your life? The data was analyzed manually during four steps. The first phase consisted of organizing the data, looking for ideas that emerged from the answers to the guiding question, when the pre-analysis was carried out, through a deep reading aiming to define categories, since they had not been previously created; the second phase corresponded to the preparation of the second worksheet that stored the explicit and implicit ideas, the former being the temporary categories and the latter being the focus along with identification of the senses; the third phase sought to answer the study question through the record units, associating the speech to the focus/theme, identifying the sense of inference; the fourth phase was based on two spreadsheets, the first one with the interpretation of the main topics and their record units, and the second one with the creation of the synthesis for each focus. The experience of death may occur in relation to the other or to death itself, with differences between them. This research focus on the death of others and how undergraduate medical students experience it during the course, of which data resulted in three categories related to the experience of death during medical school, reflecting their capacity or not to deal with the phenomenon. Results: the three categories showed two subcategories, as follows: Acceptance of death, with subcategories in personal and professional life; Professional qualification with two subcategories: limits of professional performance and of the course in relation to death. The last category was Humanization, with two more subcategories: medical-patient relationship and palliative care. Conclusion: the research showed that the students modified their views about death during the course, and that they are aware of the topic, disclosing the value of this subject and also the need to discuss it during undergraduate school.

NMR-Based Metabolomics in Cardiac Research.

Proton (1H) nuclear magnetic resonance (NMR) spectroscopy can measure a range of metabolites in both cardiac tissue and blood plasma for following cardiovascular disease. For solution-state NMR spectroscopy, it is necessary to create a tissue extract, with perchloric acid, acetonitrile/water, and chloroform/methanol being popular extraction media. Alternatively, high-resolution magic angle spinning (HRMAS) 1H NMR spectroscopy can be used to derive a metabolic profile directly from intact cardiac tissue. This chapter will discuss the practical methods used for 1H NMR spectroscopy to follow cardiovascular diseases both in terms of metabolic changes in cardiac tissue and changes in blood plasma.

Dysbiosis associated with acute helminth infections in herbivorous youngstock - observations and implications.

A plethora of data points towards a role of the gastrointestinal (GI) microbiota of neonatal and young vertebrates in supporting the development and regulation of the host immune system. However, knowledge of the impact that infections by GI helminths exert on the developing microbiota of juvenile hosts is, thus far, limited. This study investigates, for the first time, the associations between acute infections by GI helminths and the faecal microbial and metabolic profiles of a cohort of equine youngstock, prior to and following treatment with parasiticides (ivermectin). We observed that high versus low parasite burdens (measured via parasite egg counts in faecal samples) were associated with specific compositional alterations of the developing microbiome; in particular, the faecal microbiota of animals with heavy worm infection burdens was characterised by lower microbial richness, and alterations to the relative abundances of bacterial taxa with immune-modulatory functions. Amino acids and glucose were increased in faecal samples from the same cohort, which indicated the likely occurrence of intestinal malabsorption. These data support the hypothesis that GI helminth infections in young livestock are associated with significant alterations to the GI microbiota, which may impact on both metabolism and development of acquired immunity. This knowledge will direct future studies aimed to identify the long-term impact of infection-induced alterations of the GI microbiota in young livestock.

XBP-1 Remodels Lipid Metabolism to Extend Longevity.

The endoplasmic reticulum unfolded protein response (UPRER) is a cellular stress response that maintains homeostasis within the secretory pathway, regulates glucose and lipid metabolism, and influences longevity. To ask whether this role in lifespan determination depends upon metabolic intermediaries, we metabotyped C. elegans expressing the active form of the UPRER transcription factor XBP-1, XBP-1s, and found many metabolic changes. These included reduced levels of triglycerides and increased levels of oleic acid (OA), a monounsaturated fatty acid associated with lifespan extension in C. elegans. Here, we show that constitutive XBP-1s expression increases the activity of lysosomal lipases and upregulates transcription of the Δ9 desaturase FAT-6, which is required for the full lifespan extension induced by XBP-1s. Dietary OA supplementation increases the lifespan of wild-type, but not xbp-1s-expressing animals and enhances proteostasis. These results suggest that modulation of lipid metabolism by XBP-1s contributes to its downstream effects on protein homeostasis and longevity.

Cytosine-5 RNA methylation links protein synthesis to cell metabolism.

Posttranscriptional modifications in transfer RNA (tRNA) are often critical for normal development because they adapt protein synthesis rates to a dynamically changing microenvironment. However, the precise cellular mechanisms linking the extrinsic stimulus to the intrinsic RNA modification pathways remain largely unclear. Here, we identified the cytosine-5 RNA methyltransferase NSUN2 as a sensor for external stress stimuli. Exposure to oxidative stress efficiently repressed NSUN2, causing a reduction of methylation at specific tRNA sites. Using metabolic profiling, we showed that loss of tRNA methylation captured cells in a distinct catabolic state. Mechanistically, loss of NSUN2 altered the biogenesis of tRNA-derived noncoding fragments (tRFs) in response to stress, leading to impaired regulation of protein synthesis. The intracellular accumulation of a specific subset of tRFs correlated with the dynamic repression of global protein synthesis. Finally, NSUN2-driven RNA methylation was functionally required to adapt cell cycle progression to the early stress response. In summary, we revealed that changes in tRNA methylation profiles were sufficient to specify cellular metabolic states and efficiently adapt protein synthesis rates to cell stress.

Author Correction: A comprehensive analysis of the faecal microbiome and metabolome of Strongyloides stercoralis infected volunteers from a non-endemic area.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.