Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation

Abstract Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing V max and K m. Pharmacological activation of AMP‐activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia. Cr supplementation increases ATP and PCr content in cardiomyocytes subjected to hypoxia, while also significantly augmenting the cellular adaptive response to hypoxia mediated by HIF‐1 activation. Our results indicate that: (1) hypoxia reduces Cr transport in cardiomyocytes in culture, (2) the cytoprotective effects of Cr supplementation are related to enhanced adaptive physiological responses to hypoxia mediated by HIF‐1, and (3) Cr supplementation increases the cellular ATP and PCr content in RNCMs exposed to hypoxia

Enlightening decisions and public interventions for the older adult population : Sabe Bogotá study

Objetivo: Destacar los resultados de mayor impacto para la población adulta mayor en Bogotá, de ma-nera que sirvan como referencias para priorizar las decisiones y las medidas públicas en su beneficio. Materiales y métodos: Estudio de cohorte transversal, con un muestreo probabilístico por conglome-rados, polietápico, con un nivel de confiabilidad del 95% y un tamaño de 2000 personas entre 60 y 100 años. Se realizó un análisis descriptivo de todas las variables, calculando distribuciones de frecuencias simples y posteriormente se hizo un análisis de dependencia y asociación con Chi cuadrado, T-test y regresiones logísticas multivariadas según correspondiera para cada caso. Adicionalmente se utilizan pruebas de Spearman Rho para analizar correlaciones. Se analizaron los temas principales: fragilidad, sarcopenia, nutrición, hipertensión arterial (HTA), depresión, violencia, discapacidad, vivir solo y pobreza. Resultados: Cerca del 40% de la población tenía desnutrición o estaba en riesgo de desnutri-ción, más del 60% era prefrágil o frágil y más del 11% tenía sarcopenia. La HTA se presentó en el 58% de los ancianos; la depresión estaba presente en uno de cada cuatro; 42% había sido víctima de agre-sión en el último año y el 43% desplazado por violencia en el transcurso de su vida. Más de la mitad tenía una discapacidad, 12,6% vivía solo y el 7,8% estaba en pobreza extrema. Conclusiones: Cada una de las temáticas desarrolladas aporta individualmente en la selección de los mejores derroteros de la política pública para el Distrito Capital, pues sólo su integración, bajo la tutela de los gestores de la misma y la participación ciudadana desde los diferentes escenarios y participantes, logrará el mejor impacto en la aplicabilidad de este trabajo de investigación.Artículo de investigación191-207Objective: this work highlights the results with the greatest impact for the older adult population in Bogotá.These results should serveas references to prioritize decisions and develop public health interventions to benefit these older adults. Materials and methods: We used data from across sectional study, with a multistage probabilistic sampling by conglomerates. A of reliability level of 95% was established and the sample size was 2000 individuals between the ages of 60 and 100 years. A descriptive analys is of all the variables was conducted, estimating frequencies and subsequently analyzing dependency and association with Chisquare, T-tests and multivariate logistic regressions as appropriate for each case. Additionally, Spearman Rho tests were used to analyze correlations. The main topics analyzed were: frailty, sarcopenia, nutrition, hypertension(HTN), depression, violence, disability, livingalone and poverty. Results: about 40% of the population was malnourished or a trisk of malnutrition, morethan 60% was pre-frail or frailand more than 11% had sarcopenia. HTN was reported in 58% of older adults, 42% had been victims of violence in the last year and 43% had been displaced by violence during their life. More than half had disability, 12,6% lived alone and 7,8% had extreme poverty. Conclusions: these results should help identify the most pressing issues faced by older adults in the capital of Colombia and should drive the development of public health interventions for the city. Only integration of these results with active participation of policy makers and the community will resultin improvements for older adults and the population at large

Paisaje Cultural Urbano e Identitad Territorial

Linguaggio contemporaneo e preesistenze: dialogo in un mondo globalizzato Il tema del rapporto con l’antico trova una giusta dimensione operativa quando, superando la sfera delle ideologie e quella delle opposte ragioni della memoria e dello sviluppo, indirizza positivamente l’azione progettuale ora per differenza ora per empatia, a seconda delle circostanze, ma crea sempre una forte tensione tra le ragioni dell’esistente e le necessità del nuovo. Intervenire nell’antico e per l’antico significa, pertanto, riprogettare il nostro modo di relazionarci con il passato, rinegoziandone identità e valori alla luce del nostro presente. Da questa angolazione il patrimonio non è solo lo spazio della memoria o quello della storia, ma diviene lo spazio del desiderio che trae alimento dal mito dell’araba fenice: esso, come principio evolutivo, rappresenta l’inizio di un incessante ricominciamento e l'occasione per una mediazione tra globale e locale

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study

Background: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. Methods: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. Findings: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). Interpretation: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. Funding: None