Next-generation sequencing reveals that miR-16-5p, miR-19a-3p, miR-451a, and miR-25-3p cargo in plasma extracellular vesicles differentiates sedentary young males from athletes.

A sedentary lifestyle and Olympic participation are contrary risk factors for global mortality and incidence of cancer and cardiovascular disease. Extracellular vesicle miRNAs have been described to respond to exercise. No molecular characterization of young male sedentary people versus athletes is available; so, our aim was to identify the extracellular vesicle miRNA profile of chronically trained young endurance and resistance male athletes compared to their sedentary counterparts. A descriptive case-control design was used with 16 sedentary young men, 16 Olympic male endurance athletes, and 16 Olympic male resistance athletes. Next-generation sequencing and RT-qPCR and external and internal validation were performed in order to analyze extracellular vesicle miRNA profiles. Endurance and resistance athletes had significant lower levels of miR-16-5p, miR-19a-3p, and miR-451a compared to sedentary people. Taking all together, exercise-trained miRNA profile in extracellular vesicles provides a differential signature of athletes irrespective of the type of exercise compared to sedentary people. Besides, miR-25-3p levels were specifically lower in endurance athletes which defines its role as a specific responder in this type of athletes. In silico analysis of this profile suggests a role in adaptive energy metabolism in this context that needs to be experimentally validated. Therefore, this study provides for the first time basal levels of circulating miRNA in extracellular vesicles emerge as relevant players in intertissue communication in response to chronic exercise exposure in young elite male athletes.

Pharmacokinetic evaluation of a single chain antibody fragment against scorpion toxins in sheep.

A key aspect during the development of antivenoms is the evaluation of the efficiency and security of the therapeutic molecules. In this work, we report the pharmacokinetic analysis of a neutralizing single chain antibody fragment named LR (scFv LR) where three sheep were used as a large animal model. The animals were injected through i.v. route with 2 mg of scFv LR. Blood samples were drawn every minute within the first 15 min, the sampling continues at 20, 25, 30, 45, 60, 90, 120 min, subsequently at 1-h intervals, 3, 4, 5, 6 h, two more samples at 9 and 12 h and, two more samples at 24 and 48 h and finally at one-day intervals during 4 days. scFv LR levels were measured from blood serum and urine samples by an ELISA. The pharmacokinetics of the experimental data was analyzed using the three-exponential kinetics. The value of the fast initial component (τ1=0.409±0.258min) indicated that the scFv is distributed rapidly into the tissues. The mean residence time, MRT, was 45 ± 0.51 min and the clearance (CL), 114.3 ± 14.3 mL/min. From urine samples it was possible to detect significant amounts of scFv LR, which is evidence of renal elimination.

Molecular identification and lipolytic potential of filamentous fungi isolated from residual cooking oil.

Filamentous fungi, microorganisms that develop and are located in different habitats, are considered important producers of enzymes and metabolites with potential for the biotechnology industry. The objective of this work was to isolate and identify filamentous fungi that grow in used oil. Two fungal species were characterised through their morphology and molecular identification. The DNA of each extracted strain was amplified by PCR using primers ITS1 and ITS4, obtaining sequences that were later in GenBank (NCBI). A white coloured strain (HB) with a cottony, white, hyaline morphology and irregular borders was observed; so too, a brown colony (HC) with a sandy surface, a well-defined border of beige colour in early growth until it became a dark brown colour. The identity result by homology of the sequences in the BLASTn database was 100% and 99.55%, indicating that they correspond to Cladosporiumtenuissimum and Fomitopsismeliae, respectively. Finally, the results in lipolytic activity show greater potential for Fomitopsismeliae with 0.61 U/l in residual oil. Thus, it is important to highlight the potential of this type of waste to favour the prospection of microorganisms for a sustainable alternative for future studies of biological conversion.

Smartphone-based procedure to determine content of single synthetic dyes in food using the Arata-Possetto extraction method.

The use of additives, including dyes, is common in the preparation of food products. The analytical control of artificial food dye content is relevant since some, such as azo dyes, may produce cancer and attention deficit disorders and hyperactivity in children. Consequently, the maximum permitted concentration of azo dyes in food is regulated by current legislation. Therefore, it is of interest to find simple and fast procedures for the control of these compounds. The aim of this study is to determine the concentration of azo dyes in food samples by the Arata-Possetto method - based on the extraction of azo dyes employing natural wool -, followed by the analysis of an image captured by a smartphone camera. After experimentally determining the optimal extraction conditions, the calibration curves for standard solutions of different food dyes and the color of the dyed wool were obtained. Results from dyed wool image processing were compared with the absorbance spectra of the solutions before extraction as measured by a diode array spectrophotometer. The spectrophotometric and the image processing procedures were employed to obtain the calibration curves for different food dyes, which were subsequently employed to analyze food samples. Statistical treatment shows that the results of both methods are comparable.

ATP1A1-linked diseases require a malfunctioning protein product from one allele.

Heterozygous germline variants in ATP1A1, the gene encoding the α1 subunit of the Na+/K+-ATPase (NKA), have been linked to diseases including primary hyperaldosteronism and the peripheral neuropathy Charcot-Marie-Tooth disease (CMT). ATP1A1 variants that cause CMT induce loss-of-function of NKA. This heterodimeric (αß) enzyme hydrolyzes ATP to establish transmembrane electrochemical gradients of Na+ and K+ that are essential for electrical signaling and cell survival. Of the 4 catalytic subunit isoforms, α1 is ubiquitously expressed and is the predominant paralog in peripheral axons. Human population sequencing datasets indicate strong negative selection against both missense and protein-null ATP1A1 variants. To test whether haploinsufficiency generated by heterozygous protein-null alleles are sufficient to cause disease, we tested the neuromuscular characteristics of heterozygous Atp1a1+/- knockout mice and their wildtype littermates, while also evaluating if exercise increased CMT penetrance. We found that Atp1a1+/- mice were phenotypically normal up to 18 months of age. Consistent with the observations in mice, we report clinical phenotyping of a healthy adult human who lacks any clinical features of known ATP1A1-related diseases despite carrying a plasma-membrane protein-null early truncation variant, p.Y148*. Taken together, these results suggest that a malfunctioning gene product is required for disease induction by ATP1A1 variants and that if any pathology is associated with protein-null variants, they may display low penetrance or high age of onset.

Engaging communities to inform the development of a diverse cohort of cancer survivors: formative research for the eat move sleep study (EMOVES).

BACKGROUND: There are more than 18 million cancer survivors in the United States. Yet, survivors of color remain under-represented in cancer survivorship research (Saltzman et al. in Contemp Clin Trials Commun 29:100986, 2022; Pang et al. in J Clin Oncol 34:3992-3999, 2016; Lythgoe et al. in Prostate Cancer Prostatic Dis 24:1208-1211, 2021). Our long-term goal is to enroll and follow a cohort of historically under-represented cancer survivors, to better understand modifiable risk factors that influence clinical and quality of life outcomes in these populations. Towards that goal, we describe herein how we applied community-based participatory research approaches to develop inclusive study materials for enrolling such a cohort. METHODS: We implemented community engagement strategies to inform and enhance the study website and recruitment materials for this cohort including: hiring a dedicated engagement coordinator/community health educator as a member of our team; working with the Helen Diller Family Comprehensive Cancer Center Office of Community Engagement (OCE) and Community Advisory Board members; presenting our educational, research, and study recruitment materials at community events; and establishing a community advisory group specifically for the study (4 individuals). In parallel with these efforts, 20 semi-structured user testing interviews were conducted with diverse cancer survivors to inform the look, feel, and usability of the study website. RESULTS: Engagement with community members was a powerful and important approach for this study's development. Feedback was solicited and used to inform decisions regarding the study name (eat move sleep, EMOVES), logo, study website content and imagery, and recruitment materials. Based on community feedback, we developed additional educational materials on healthy groceries and portion size in multiple languages and created a study video. CONCLUSIONS: Including an engagement coordinator as a permanent team member, partnering with the institutional community outreach and engagement resources (i.e., OCE), and allocating dedicated time and financial support for cultivating relationships with stakeholders outside the university were critical to the development of the study website and materials. Our community guided strategies will be tested as we conduct enrollment through community advisor networks and via the state cancer registry.

Under-represented racial and ethnic populations are diagnosed with and die from cancer at higher rates than white Americans but are less likely to be included in research studies. This has resulted in limited data on these populations, especially regarding cancer survivorship and lifestyle factors such as diet, exercise, and sleep. Our aim was to develop inclusive and appealing study materials for enrolling a diverse cancer survivorship cohort by integrating a community engagement coordinator/health educator into the research team and collaborating with our cancer center's office of community engagement community advisory board. An additional bridge was developed between community partners and the research team by establishing a community advisory board specifically for the study. We also conducted 20 user testing interviews with cancer survivors and community stakeholders to inform the look, feel, and usability of the study website during development. Our community partnerships and interviews assisted with decisions on our study name, Eat Move Sleep Study (EMOVES), logo, redesigning the study website, and study format. Our partners also provided guidance that highlighted community need and development of new educational materials for healthy diet (postcard sized grocery list on healthy eating) and a video-based recruitment tool for the study. Incorporation of an engagement coordinator into the research team, building an ongoing relationship with our cancer center's office of community engagement, and adding community advisors onto our study team has greatly impacted our study approach and design.

Machine learning combining multi-omics data and network algorithms identifies adrenocortical carcinoma prognostic biomarkers.

Background: Rare endocrine cancers such as Adrenocortical Carcinoma (ACC) present a serious diagnostic and prognostication challenge. The knowledge about ACC pathogenesis is incomplete, and patients have limited therapeutic options. Identification of molecular drivers and effective biomarkers is required for timely diagnosis of the disease and stratify patients to offer the most beneficial treatments. In this study we demonstrate how machine learning methods integrating multi-omics data, in combination with system biology tools, can contribute to the identification of new prognostic biomarkers for ACC. Methods: ACC gene expression and DNA methylation datasets were downloaded from the Xena Browser (GDC TCGA Adrenocortical Carcinoma cohort). A highly correlated multi-omics signature discriminating groups of samples was identified with the data integration analysis for biomarker discovery using latent components (DIABLO) method. Additional regulators of the identified signature were discovered using Clarivate CBDD (Computational Biology for Drug Discovery) network propagation and hidden nodes algorithms on a curated network of molecular interactions (MetaBase™). The discriminative power of the multi-omics signature and their regulators was delineated by training a random forest classifier using 55 samples, by employing a 10-fold cross validation with five iterations. The prognostic value of the identified biomarkers was further assessed on an external ACC dataset obtained from GEO (GSE49280) using the Kaplan-Meier estimator method. An optimal prognostic signature was finally derived using the stepwise Akaike Information Criterion (AIC) that allowed categorization of samples into high and low-risk groups. Results: A multi-omics signature including genes, micro RNA's and methylation sites was generated. Systems biology tools identified additional genes regulating the features included in the multi-omics signature. RNA-seq, miRNA-seq and DNA methylation sets of features revealed a high power to classify patients from stages I-II and stages III-IV, outperforming previously identified prognostic biomarkers. Using an independent dataset, associations of the genes included in the signature with Overall Survival (OS) data demonstrated that patients with differential expression levels of 8 genes and 4 micro RNA's showed a statistically significant decrease in OS. We also found an independent prognostic signature for ACC with potential use in clinical practice, combining 9-gene/micro RNA features, that successfully predicted high-risk ACC cancer patients. Conclusion: Machine learning and integrative analysis of multi-omics data, in combination with Clarivate CBDD systems biology tools, identified a set of biomarkers with high prognostic value for ACC disease. Multi-omics data is a promising resource for the identification of drivers and new prognostic biomarkers in rare diseases that could be used in clinical practice.

Genetic variability of the honey bee mite, Varroa destructor, from a humid continental climatic region of Canada, and temperate and tropical climatic regions of Mexico.

Varroa destructor is a damaging mite of Western honey bees (Apis mellifera). Genetic variability of the mite in different regions of the world could be related to the movement of infested bees or other factors, such as climate. In this study, V. destructor samples were collected from tropical and temperate climate regions of Mexico, and a humid continental climate region of Canada. COX-1 AFLPs showed that all the mites were the Korean haplotype. Four microsatellites revealed nine haplogroups from the continental climate region of Canada, compared to three haplogroups from the tropical and temperate climate regions of Mexico. CytII-ATP sequences showed seven haplogroups from the humid continental climate region vs. two haplogroups from the temperate region and one haplogroup from the tropical region. CytB sequences revealed seven haplogroups from Canada vs. three from Mexico. A comparison of the cytB sequences of the samples from Canada and Mexico to those from a worldwide collection showed that one sequence, designated the cytB1 type, predominated, comprising 57% of the 86 sequences; it clustered with similar sequences that comprised 80% of the sequences, designated family A. CytB1 was predominant in Mexico, but not in Canada. The other 20% of sequences were in families B and C, and all those samples originated from East and Southeast Asia. The microsatellite, cytII-ATP, and cytB markers, all showed higher variability in mites collected in Canada than in Mexico, which could be related to the cooler climate or an earlier invasion and/or multiple mite invasions in Canada.

Repurposing of rabeprazole as an anti-Trypanosoma cruzi drug that targets cellular triosephosphate isomerase.

Trypanosoma cruzi is the causative agent of American trypanosomiasis, which mainly affects populations in Latin America. Benznidazole is used to control the disease, with severe effects in patients receiving this chemotherapy. Previous studies have demonstrated the inhibition of triosephosphate isomerase from T. cruzi, but cellular enzyme inhibition has yet to be established. This study demonstrates that rabeprazole inhibits both cell viability and triosephosphate isomerase activity in T. cruzi epimastigotes. Our results show that rabeprazole has an IC50 of 0.4 µM, which is 14.5 times more effective than benznidazole. Additionally, we observed increased levels of methyl-glyoxal and advanced glycation end products after the inhibition of cellular triosephosphate isomerase by rabeprazole. Finally, we demonstrate that the inactivation mechanisms of rabeprazole on triosephosphate isomerase of T. cruzi can be achieved through the derivatization of three of its four cysteine residues. These results indicate that rabeprazole is a promising candidate against American trypanosomiasis.

Wnt7a deficit is associated with dysfunctional angiogenesis in pulmonary arterial hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is characterised by loss of microvessels. The Wnt pathways control pulmonary angiogenesis but their role in PAH is incompletely understood. We hypothesised that Wnt activation in pulmonary microvascular endothelial cells (PMVECs) is required for pulmonary angiogenesis, and its loss contributes to PAH. METHODS: Lung tissue and PMVECs from healthy and PAH patients were screened for Wnt production. Global and endothelial-specific Wnt7a -/- mice were generated and exposed to chronic hypoxia and Sugen-hypoxia (SuHx). RESULTS: Healthy PMVECs demonstrated >6-fold Wnt7a expression during angiogenesis that was absent in PAH PMVECs and lungs. Wnt7a expression correlated with the formation of tip cells, a migratory endothelial phenotype critical for angiogenesis. PAH PMVECs demonstrated reduced vascular endothelial growth factor (VEGF)-induced tip cell formation as evidenced by reduced filopodia formation and motility, which was partially rescued by recombinant Wnt7a. We discovered that Wnt7a promotes VEGF signalling by facilitating Y1175 tyrosine phosphorylation in vascular endothelial growth factor receptor 2 (VEGFR2) through receptor tyrosine kinase-like orphan receptor 2 (ROR2), a Wnt-specific receptor. We found that ROR2 knockdown mimics Wnt7a insufficiency and prevents recovery of tip cell formation with Wnt7a stimulation. While there was no difference between wild-type and endothelial-specific Wnt7a -/- mice under either chronic hypoxia or SuHx, global Wnt7a +/- mice in hypoxia demonstrated higher pulmonary pressures and severe right ventricular and lung vascular remodelling. Similar to PAH, Wnt7a +/- PMVECs exhibited an insufficient angiogenic response to VEGF-A that improved with Wnt7a. CONCLUSIONS: Wnt7a promotes VEGF signalling in lung PMVECs and its loss is associated with an insufficient VEGF-A angiogenic response. We propose that Wnt7a deficiency contributes to progressive small vessel loss in PAH.

Clinical factors influencing long-term survival in a real-life cohort of early stage non-small-cell lung cancer patients in Spain.

Background: Current prognosis in oncology is reduced to the tumour stage and performance status, leaving out many other factors that may impact the patient´s management. Prognostic stratification of early stage non-small-cell lung cancer (NSCLC) patients with poor prognosis after surgery is of considerable clinical relevance. The objective of this study was to identify clinical factors associated with long-term overall survival in a real-life cohort of patients with stage I-II NSCLC and develop a prognostic model that identifies features associated with poor prognosis and stratifies patients by risk. Methods: This is a cohort study including 505 patients, diagnosed with stage I-II NSCLC, who underwent curative surgical procedures at a tertiary hospital in Madrid, Spain. Results: Median OS (in months) was 63.7 (95% CI, 58.7-68.7) for the whole cohort, 62.4 in patients submitted to surgery and 65 in patients submitted to surgery and adjuvant treatment. The univariate analysis estimated that a female diagnosed with NSCLC has a 0.967 (95% CI 0.936 - 0.999) probability of survival one year after diagnosis and a 0.784 (95% CI 0.712 - 0.863) five years after diagnosis. For males, these probabilities drop to 0.904 (95% CI 0.875 - 0.934) and 0.613 (95% CI 0.566 - 0.665), respectively. Multivariable analysis shows that sex, age at diagnosis, type of treatment, ECOG-PS, and stage are statistically significant variables (p<0.10). According to the Cox regression model, age over 50, ECOG-PS 1 or 2, and stage ll are risk factors for survival (HR>1) while adjuvant chemotherapy is a good prognostic variable (HR<1). The prognostic model identified a high-risk profile defined by males over 71 years old, former smokers, treated with surgery, ECOG-PS 2. Conclusions: The results of the present study found that, overall, adjuvant chemotherapy was associated with the best long-term OS in patients with resected NSCLC. Age, stage and ECOG-PS were also significant factors to take into account when making decisions regarding adjuvant therapy.

Participatory intervention to improve nutrition and physical activity of school-age children in Mexico.

Obesity is one of the major public health problems of the 21st century, affecting every country in the world. In Mexico, the prevalence of overweight and obesity in children (5 to 11 years) was 35.5%. Childhood obesity is a chronic disease itself; and is associated with other chronic conditions. OBJECTIVE: To assess the effect and feasibility of a participatory intervention to improve nutrition and physical activity within the school environment in children in public elementary schools in Mexico. METHODS: The present study is a cluster trial. The intervention focused on; changes in food offered, training the schools' food service staff, promoting water consumption and physical activity at the community level, implementing healthy spaces inside the school, improving the quality of physical education within schools, among others. The main outcomes will focus on rate of weight gain, time devoted to physical activity, sedentary behaviors, diet quality and response feeding behaviors. We also will assess the time and personnel involved in the intervention development, maintenance, and dissemination. CONCLUSION: Findings from this trial will generate new translational knowledge in Mexico; if the results are positive, this participatory intervention could serve as a basis for designing multidimensional interventions that could be scaled up at the national level.

Sociodemographic inequalities in cardiovascular risk factors among adolescents from indigenous areas in Chiapas, Mexico / Desigualdades sociodemográficas como factores de riesgo cardiovascular para adolescentes de zonas indígenas de Chiapas, México / Desigualdades sociodemográficas como fatores de risco cardiovascular para adolescentes de áreas indígenas de Chiapas, México

Abstract: This study was aimed to determine the prevalence of cardiovascular risk factors among different sociodemographic groups of adolescents from indigenous communities in Chiapas, Mexico. A cross-sectional prevalence study was performed in urban and rural communities in the Tzotzil-Tzeltal and Selva regions of Chiapas. A sample of 253 adolescents was studied, of whom 48% were girls and 52% were boys. A descriptive analysis of quantitative variables was performed using measures of central tendency and dispersion. The prevalence of cardiovascular risk factors stratified by sex, geographical area, years of schooling, and ethnicity of the mothers was estimated. The prevalence of cardiovascular risk factors was analyzed in relation to the sociodemographic characteristics of the study population. Low HDL-c (51%) was the predominant cardiovascular risk factor. Girls had a higher prevalence of abdominal obesity, hypertriglyceridemia, and borderline total cholesterol than boys. High diastolic blood pressure was more prevalent in boys. Adolescents from urban areas had a higher prevalence of overweight/obesity and insulin resistance than adolescents from rural areas. The prevalence of overweight/obesity and abdominal obesity was higher in adolescents whose mothers had ≥ 7 years of schooling compared with adolescents with less educated mothers. Differences by maternal ethnicity also influenced the prevalence of insulin resistance. Among the main findings, this study associated sociodemographic and geographical inequalities with cardiovascular risk factors. Promoting a healthy lifestyle for this young population is absolutely necessary to prevent cardiovascular diseases in adulthood.

Resumen: El objetivo de este estudio fue estimar la prevalencia de los factores de riesgo cardiovascular entre diferentes grupos sociodemográficos de adolescentes de comunidades indígenas de Chiapas, México. Se realizó un estudio transversal de prevalencia en comunidades urbanas y rurales de las regiones Tzotzil-Tzeltal y Selva, en Chiapas. Participó una muestra de 253 adolescentes, en la cual el 48% eran niñas y el 52% niños. Se realizó un análisis descriptivo de las variables cuantitativas utilizando medidas de tendencia central y dispersión. Se estimó la prevalencia de los factores de riesgo cardiovascular, estratificados por sexo, área geográfica, nivel de estudios y etnia de las madres. Se analizó la prevalencia de los factores de riesgo cardiovascular con relación a las características sociodemográficas de la población estudiada. El HDL-c bajo (51%) fue el factor de riesgo cardiovascular predominante. Se observó una mayor prevalencia de obesidad abdominal, hipertrigliceridemia y colesterol total en las niñas que en los niños. La alta presión arterial diastólica prevaleció en los niños. Los adolescentes del área urbana tuvieron una mayor prevalencia de sobrepeso/obesidad y resistencia a la insulina que los del área rural. La prevalencia de sobrepeso/obesidad y obesidad abdominal fue mayor en los adolescentes cuyas madres tenían nivel de estudios ≥ 7 años que aquellos cuyas madres tenían bajo nivel de estudios. Las diferencias en la etnicidad materna también influyeron en la prevalencia de resistencia a la insulina. Entre las principales conclusiones de este estudio, se destacan las desigualdades sociodemográficas y geográficas entre los factores de riesgo cardiovascular. La promoción de un estilo de vida saludable entre la población joven es lo indicado para prevenir las enfermedades cardiovasculares en la edad adulta.

Resumo: O objetivo deste estudo foi determinar a prevalência de fatores de risco cardiovascular entre diferentes grupos sociodemográficos de adolescentes de comunidades indígenas em Chiapas, México. Foi realizado um estudo transversal de prevalência em comunidades urbanas e rurais das regiões de Tzotzil-Tzeltal e Selva de Chiapas. Foi estudada uma amostra de 253 adolescentes, sendo 48% meninas e 52% meninos. Foi realizada uma análise descritiva das variáveis quantitativas por meio de medidas de tendência central e dispersão. Foram estimadas as prevalências de fatores de risco cardiovascular, estratificadas por sexo, área geográfica, escolaridade e etnia das mães. A prevalência dos fatores de risco cardiovascular foi analisada em relação às características sociodemográficas da população estudada. O HDL-c baixo (51%) foi o fator de risco cardiovascular predominante. Prevalências mais elevadas de obesidade abdominal, hipertrigliceridemia e colesterol total limítrofe foram mais observadas em meninas do que em meninos. A pressão arterial diastólica elevada prevaleceu nos meninos. Adolescentes da área urbana apresentaram prevalências de sobrepeso/obesidade e resistência à insulina maiores do que os da área rural. A prevalência de sobrepeso/obesidade e obesidade abdominal foi maior nos adolescentes cujas mães possuíam escolaridade ≥ 7 anos do que naqueles indivíduos cujas mães tinham baixa escolaridade. As diferenças de etnia das mães também foram observadas na prevalência de resistência à insulina. Dentre as principais conclusões, foram encontradas, neste estudo, desigualdades sociodemográficas e geográficas entre fatores de risco cardiovascular. Promover estilos de vida saudáveis entre a população jovem é o ideal para prevenir doenças cardiovasculares na vida adulta.

Assessing the risk of cardiovascular events in patients receiving immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, despite their excellent therapeutic effect, these medications typically result in a broad spectrum of toxicity reactions. Immune-related cardiotoxicity is uncommon but can be potentially fatal, and its true incidence is underestimated in clinical trials. The aim of this study is to assess the incidence and identify risk factors for developing a cardiac event in patients treated with ICIs. Methods: We conducted a single-institution retrospective study, including patients treated with ICIs in our center. The main outcomes were cardiac events (CE) and cardiovascular death. Results: A total of 378 patients were analyzed. The incidence of CE was 16.7%, during a median follow-up of 50.5 months. The multivariable analysis showed that age, a history of arrhythmia or ischemic heart disease, and prior immune-related adverse events were significantly associated with CE. Conclusion: CE during ICI treatment are more common than currently appreciated. A complete initial cardiovascular evaluation is recommended, especially in high-risk patients, being necessary a multidisciplinary approach of a specialized cardio-oncology team.

Percepciones de atletas de slackline en relación con los efectos en el entrenamiento y calidad de vida en situación de covid-19 / Perceptions of Slackline Athletes in Relation to Effects onTraining and Quality of Life in a COVID-19

Resumen La pandemia generada por el COVID-19 se ha convertido en un desafío para atletas de la mayoría de las disciplinas. La incertidumbre frente al contagio ha repercutido física y psicológicamente, y ha provocado un deterioro de la calidad de vida no solo en quienes han contraído la enfermedad sino también en quienes han tenido que vivir el confinamiento. El presente estudio tiene como objetivo conocer las percepciones de atletas de Slackline respecto a los efectos en los entrenamientos y calidad de vida derivados de dicha situación. La investigación se sustenta en un método cuantitativo exploratorio-descriptivo de corte transversal; el instrumento utilizado fue una encuesta autoaplicada con tres dimensiones la cual fue contestada correctamente por 229 personas de 28 países, 176 hombres (15 - 57 años) y 51 mujeres (20 - 43 años), pertenecientes a Europa, América, Asia y Oceanía. Los resultados arrojan que el 97,8% señala haber perdido la motivación, el 60,2% declara tener malas condiciones de infraestructura o poco acceso a sus lugares de entrenamiento, el 65,5% tiene inconvenientes económicos y el 88,2% ha presentado problemas de salud: se destaca que el 10% de las personas encuestadas han sido diagnosticado con COVID-19 positivo. Se concluye que el confinamiento y situación de pandemia han creado un ambiente desfavorable para los atletas y las atletas de Slackline debido a las complicaciones para realizar sus entrenamientos dada la ausencia de acceso a espacios públicos, desmotivación, pérdida de capacidad física y aumento de lesiones.

Abstract The COVID-19 disease is an emerging pandemic challenge, which has physical and psychological repercussions, deteriorating the quality of life in those who have been infected and, in turn, in those who have had to live in confinement. The objective of this study is to know the perceptions of Slackline athletes regarding the effects on training and quality of life derived from the COVID-19 situation. The research is based on a cross-sectional exploratory-descriptive quantitative method. The instrument used was a self-applied survey with three dimensions; 229 people from 28 countries correctly answered it, 176 men (15 - 57 years) and 51 women (20 - 43 years), belonging to Europe, America, Asia, and Oceania. The results show that 97.8% say they have lost motivation, 60.2% declare they have poor infrastructure conditions and / or little access to their training places, 65.5% have financial problems, and 88.2 % have presented health problems, highlighting that 10% of those surveyed have been diagnosed with positive COVID-19. It is concluded that the confinement and pandemic situation has created an unfavorable environment for Slackline athletes due to the complications to carry out their training sessions, lack of access to public spaces, demotivation, loss of physical capacity, and increase in injuries.

Resumo A COVID-19 é um desafio pandêmico emergente, que tem repercussões físicas e psicológicas, prejudicando a qualidade de vida daqueles que foram infectados e daqueles que tiveram que viver em confinamento. O objetivo deste estudo é descobrir as percepções dos atletas de slackline sobre os efeitos no treinamento e na qualidade de vida derivados da situação da COVID-19. A pesquisa é baseada em um método transversal exploratório-descritivo quantitativo, o instrumento utilizado foi uma pesquisa auto-administrada com três dimensões que foi respondida corretamente por 229 pessoas de 28 países, 176 homens (15 - 57 anos) e 51 mulheres (20 - 43 anos), pertencentes à Europa, América, Ásia e Oceania. Os resultados mostram que 97,8% relataram uma perda de motivação, 60,2% relataram más condições de infraestrutura e/ou mau acesso a seus locais de treinamento, 65,5% tiveram problemas financeiros e 88,2% tiveram problemas de saúde, com 10% dos entrevistados sendo diagnosticados com COVID-19 positivos. Conclui-se que a situação de confinamento e pandemia criou um ambiente desfavorável para os atletas da Slackline devido a complicações no treinamento, falta de acesso aos espaços públicos, falta de motivação, perda de capacidade física e um aumento de lesões.

Twenty Years of Abdominal Wall Allotransplantation: A Systematic Review of the Short- and Long-Term Outcomes.

BACKGROUND: Abdominal wall allotransplantation following intestinal and multivisceral transplant procedures has proven to be successful in achieving adequate closure in patients in whom other techniques have proven inadequate. Thus far, the focus of these abdominal wall allotransplants has been on graft and overall patient survival following surgery and the implementation of immunosuppression. The purpose of this study was to review the outcomes of abdominal wall allotransplantation reported in the literature. METHODS: The PubMed database was queried, and 2595 articles were found. Search criteria used were "abdominal wall transplant" and "abdominal wall allotransplant." Of these, eight met inclusion/exclusion criteria. RESULTS: In the present study, eight publications were identified reporting abdominal wall allotransplants, for a total of 38 full-thickness abdominal wall allotransplantations performed worldwide. All studies reported abdominal wall allotransplantation in combination with visceral organ allotransplantation. Abdominal wall allotransplantations reported thus far have been nonneurotized. Abdominal wall allotransplantations have proven to be beneficial both in terms of abdominal wall closure and acting as a sentinel marker for rejection for underlying visceral organ allotransplantation. The success of abdominal wall allotransplants and their long-term survival has introduced the question of functionality and long-term durability. Cadaveric studies have shown that it is possible to neurotize abdominal wall allotransplants, and future direction toward neurotized abdominal wall allotransplantation requires tools to assess functional outcomes of these transplants. CONCLUSIONS: Abdominal wall allotransplantation is an important reconstructive option when abdominal wall closure is challenging and should be considered in combination with visceral organ allotransplantations. There may be potential benefit in neurotizing the abdominal wall allotransplant for functional use, and future studies should aim to include functional outcomes.

An Artificial Intelligence-Based Tool for Data Analysis and Prognosis in Cancer Patients: Results from the Clarify Study.

BACKGROUND: Artificial intelligence (AI) has contributed substantially in recent years to the resolution of different biomedical problems, including cancer. However, AI tools with significant and widespread impact in oncology remain scarce. The goal of this study is to present an AI-based solution tool for cancer patients data analysis that assists clinicians in identifying the clinical factors associated with poor prognosis, relapse and survival, and to develop a prognostic model that stratifies patients by risk. MATERIALS AND METHODS: We used clinical data from 5275 patients diagnosed with non-small cell lung cancer, breast cancer, and non-Hodgkin lymphoma at Hospital Universitario Puerta de Hierro-Majadahonda. Accessible clinical parameters measured with a wearable device and quality of life questionnaires data were also collected. RESULTS: Using an AI-tool, data from 5275 cancer patients were analyzed, integrating clinical data, questionnaires data, and data collected from wearable devices. Descriptive analyses were performed in order to explore the patients' characteristics, survival probabilities were calculated, and a prognostic model identified low and high-risk profile patients. CONCLUSION: Overall, the reconstruction of the population's risk profile for the cancer-specific predictive model was achieved and proved useful in clinical practice using artificial intelligence. It has potential application in clinical settings to improve risk stratification, early detection, and surveillance management of cancer patients.

Iron availability enhances the cellular energetics of aerobic Escherichia coli cultures while upregulating anaerobic respiratory chains.

Aerobic Escherichia coli growth at restricted iron concentrations (≤ 1.75 ± 0.04 µM) is characterized by lower biomass yield, higher acetate accumulation and higher activation of the siderophore iron-acquisition systems. Although iron homeostasis in E. coli has been studied intensively, previous studies focused only on understanding the regulation of the iron import systems and the iron-requiring enzymes. Here, the effect of iron availability on the energy metabolism of E. coli has been investigated. It was established that aerobic cultures growing under limiting iron conditions showed lower ATP yield per glucose, lower growth rate and lower TCA cycle activity and respiration, at the same time as increased glucose consumption, acetate and pyruvate accumulation, practically mimicking microaerobic growth. However, at excess iron, independent of oxygen availability, the cultures showed high cellular energetics (5.8 ATP/mol of glucose) by using pathways requiring iron-rich complex proteins found in the TCA cycle and respiratory chain. In conditions of iron excess, some iron-requiring terminal reductases of the respiratory chain, that were thought to function only under anaerobiosis, were used by the E. coli, when in aerobic conditions, to maintain high respiratory activity. This allowed it to produce more biomass and more reactive oxygen species that were controlled by the higher activity of the antioxidant defenses (SOD, peroxidase and catalase) and the iron-sulfur cluster repair systems.

Recovery of polyclonal immunoglobulins during treatment in patients ineligible for autologous stem-cell transplantation is a prognostic marker of longer progression-free survival and overall survival.

Immunoparesis is the suppression of normal polyclonal immunoglobulins and is present in most patients with newly diagnosed multiple myeloma (MM). The association of immunoparesis at diagnosis, and particularly its recovery along with treatment, with survival in patients ineligible for autologous stem-cell transplantation (ASCT) has not been well established. This retrospective study evaluated the impact of immunoparesis in 431 patients diagnosed with MM, ineligible for ASCT, with a median overall survival of 36 months [95% confidence interval (CI): 31-40]. Immunoparesis was present in 81.2% of patients at diagnosis and was associated with a trend to a worse overall response rate (ORR: 84.8% vs. 74.9%; OR 1.88 (95% CI: 0.97-3.63), shorter progression-free survival (PFS) [22.0 vs. 18.2 months; hazard ratio (HR) 0.775; 95%CI: 0.590-1.018; p = 0.066], and overall survival (OS) (45.9 vs. 34.2 months; HR 0.746; 95% CI: 0.551-1.010; p = 0.057). Twenty-four per cent of patients who had immunoparesis at diagnosis recovered polyclonal immunoglobulins in the follow-up period. Interestingly, these patients had a better ORR (96.3% vs. 68.2%; OR 12.29 (95% CI: 3.77-40.06), PFS (HR 0.703; 95CI%: 0.526-0.941; p = 0.018) and OS (HR 0.678; 95 CI%: 0.503-0.913; p = 0.011) than patients who did not recover it. In summary, restoring a healthy immune system along with first-line treatment in patients with MM, not receiving ASCT, is associated with better outcomes.

Plan de acción para el control de la hipertensión arterial en pacientes de Arame-Maranhão, Brasil

RESUMEN Introducción: La hipertensión arterial es una condición clínica que provoca el ingreso de un gran número de pacientes en los sectores de emergencia y urgencia de los servicios hospitalarios. El número de hipertensos en el grupo de edad de 18 a 90 años es cada vez mayor en la Unidad Básica de Salud João Paulo II, Arame, estado de Maranhão. Objetivo: Implementar un plan de acción para el óptimo control de la hipertensión arterial sistémica en las comunidades de cobertura del puesto de salud en estudio durante el periodo diciembre de 2017 hasta junio de 2018. Método: Se realizó un estudio de intervención en 467 hipertensos, de un universo de 935 pacientes. El dato primario se obtuvo de las historias clínicas. Se estudiaron las variables: edad, sexo, hábitos tóxicos, índice de masa corporal, hábitos dietéticos, actividad física y cumplimiento del tratamiento médico. Resultados: Después de la intervención, la asistencia al puesto de salud, la reevaluación del tratamiento, los ingresos y el control arterial mejoraron sustancialmente a 4,0 %, 3,7 %, 0,2 % y 9,8 %, respectivamente. Conclusiones: Existe la necesidad de intervenir en el cuidado de los pacientes hipertensos y de la población en general para transformar los estilos de vida y los factores de riesgo que garanticen la reducción de la incidencia de la hipertensión arterial sistémica, todo esto favorece el aumento de la adherencia al tratamiento, mejora el seguimiento médico y contribuye a disminuir las complicaciones y los ingresos hospitalarios.

ABSTRACT Introduction: Arterial hypertension is a clinical condition that causes the admission of a large number of patients in the emergency and urgency areas of the hospital services. The number of hypertensive patients in the age group from 18 to 90 years of age is increasing in the João Paulo Basic Health Unit II, in Arame, Maranhão state. Objective: To implement an action plan for the optimal control of systemic arterial hypertension in the communities covered by the health institution under study, during the period from December 2017 to June 2018. Method: An intervention study was carried out in 467 hypertensive patients, out of a population of 935 individuals. The primary data was obtained from the medical records. The variables studied were: age, sex, toxic habits, body mass index, dietary habits, physical activity and compliance with medical treatment. Results: After the intervention, the attendance, treatment reassessment, admissions, and control of arterial figures improved substantially to 4.0%, 3.7%, 0.2%, and 9.8%, respectively. Conclusions: There is a need to intervene in the care of hypertensive patients and the general population to transform lifestyles and risk factors that guarantee the reduction of the incidence of systemic arterial hypertension, all of which favors the increase in adherence to treatment, improves medical follow-up and contributes to reducing complications and hospital admissions.

RESUMO Introdução: A hipertensão arterial é uma condição clínica que ocasiona a admissão de grande número de pacientes nos setores de urgência e emergência dos serviços hospitalares. O número de hipertensos na faixa etária de 18 a 90 anos está aumentando na Unidade Básica de Saúde João Paulo II, Arame, Maranhão. Objetivo: Implementar um plano de ação para o controle ótimo da hipertensão arterial sistêmica nas comunidades abrangidas pelo posto de saúde em estudo durante o período de dezembro de 2017 a junho de 2018. Método: Foi realizado um estudo de intervenção em 467 hipertensos, de um universo de 935 pacientes. Os dados primários foram obtidos dos prontuários médicos. As variáveis estudadas foram: idade, sexo, hábitos tóxicos, índice de massa corporal, hábitos alimentares, atividade física e adesão ao tratamento médico. Resultados: Após a intervenção, o atendimento ao posto de saúde, a reavaliação do tratamento, as admissões e o controle do controle arterial melhoraram substancialmente para 4,0%, 3,7%, 0,2% e 9,8%, respectivamente. Conclusões: Há necessidade de intervir no cuidado dos hipertensos e da população em geral para transformar estilos de vida e fatores de risco que garantam a redução da incidência de hipertensão arterial sistêmica, o que favorece o aumento da adesão ao tratamento, melhora o acompanhamento médico -up e contribui para a redução de complicações e internações hospitalares.