Nuevas estrategias terapéuticas en diabetes mellitus tipo 1

El principal determinante del riesgo de complicaciones derivadas de la diabetes mellitus tipo 1 se debe a los altos niveles de glucosa en sangre mantenidos durante largo tiempo. Para conseguir un beneficio terapéutico en pacientes con diabetes mellitus es necesario desarrollar tratamientos que permitan de manera segura, efectiva y estable mantener la normoglucemia. Lamentablemente, el tratamiento de la diabetes mellitus tipo 1 mediante el aporte exógeno de insulina no es capaz de conseguir niveles estables de glucosa en sangre, de manera que con frecuencia se producen casos de severa hipoglucemia o hiperglucemia. Hasta la fecha la única solución para reestablecer de manera permanente la normoglucemia se consigue mediante el trasplante de páncreas o de islotes pancreáticos. Sin embargo, a medida que se incrementa el número de centros especializados en el trasplante de islotes, mayor es la necesidad de islotes para su trasplante. Así pues, el estudio de nuevas fuentes de células productoras de insulina así como de nuevos tratamientos que permitan preservar o incluso aumentar la masa de células beta en los pacientes con diabetes mellitus representa un objetivo de primera necesidad en este campo. En este sentido, en la última década ha habido un avance significativo en el campo de la biología de las células madre. Sin embargo, la identificación de células apropiadas para la generación de nuevas células beta, además del desarrollo de técnicas para la caracterización de estas células, así como de ensayos y modelos animales apropiados para probar su capacidad de diferenciación tanto in vitro como in vivo son de vital importancia para la puesta en marcha de nuevas estrategias terapéuticas basadas en la aplicación de las células madre para el tratamiento de la diabetes mellitus tipo 1

The HIF1A Functional Genetic Polymorphism at Locus +1772 Associates with Progression to Metastatic Prostate Cancer and Refractoriness to Hormonal Castration

The hypoxia inducible factor 1 alpha (HIF1a) is a key regulator of tumour cell response to hypoxia, orchestrating mechanisms known to be involved in cancer aggressiveness and metastatic behaviour. In this study we sought to evaluate the association of a functional genetic polymorphism in HIF1A with overall and metastatic prostate cancer (PCa) risk and with response to androgen deprivation therapy (ADT). The HIF1A +1772 C>T (rs11549465) polymorphism was genotyped, using DNA isolated from peripheral blood, in 1490 male subjects (754 with prostate cancer and 736 controls cancer-free) through Real-Time PCR. A nested group of cancer patients who were eligible for androgen deprivation therapy was followed up. Univariate and multivariate models were used to analyse the response to hormonal treatment and the risk for developing distant metastasis. Age-adjusted odds ratios were calculated to evaluate prostate cancer risk. Our results showed that patients under ADT carrying the HIF1A +1772 T-allele have increased risk for developing distant metastasis (OR, 2.0; 95%CI, 1.1-3.9) and an independent 6-fold increased risk for resistance to ADT after multivariate analysis (OR, 6.0; 95%CI, 2.2-16.8). This polymorphism was not associated with increased risk for being diagnosed with prostate cancer (OR, 0.9; 95%CI, 0.7-1.2). The HIF1A +1772 genetic polymorphism predicts a more aggressive prostate cancer behaviour, supporting the involvement of HIF1a in prostate cancer biological progression and ADT resistance. Molecular profiles using hypoxia markers may help predict clinically relevant prostate cancer and response to ADT

An Inka Offering at Yayno (North Highlands, Peru): Objects, Subjects and Gifts in the Ancient Andes

While Marcel Mauss's landmark essay on The Gift has been vital in social anthropology, inspiring a vast and influential secondary literature, the gift has been much less prominent in archaeological interpretation. This study considers evidence for an ancient Andean gift economy, a system of reciprocal exchanges focused on making people and ensuring group social relations, rather than accumulating wealth/capital. Excavations at Yayno (north highlands, Ancash, Peru) revealed two features dating to the time of the Inkas: 1) a slab-lined cist burial; and 2) an offering deposit containing abundant long-distance trade and sumptuary items. Besides its mountaintop location, the burial's intrusive character and foreign items indicate that the offerings were made to propitiate the place, ruins and their divine aspect. This essay studies the reciprocal acts that led to the offerings, comparing them to gifting patterns in Inka human sacrifices known as capac hucha. The key actors in the exchange were children, divinities, Inka bureaucrats, local leaders and state subjects

Statistical Coding and Decoding of Heartbeat Intervals

The heart integrates neuroregulatory messages into specific bands of frequency, such that the overall amplitude spectrum of the cardiac output reflects the variations of the autonomic nervous system. This modulatory mechanism seems to be well adjusted to the unpredictability of the cardiac demand, maintaining a proper cardiac regulation. A longstanding theory holds that biological organisms facing an ever-changing environment are likely to evolve adaptive mechanisms to extract essential features in order to adjust their behavior. The key question, however, has been to understand how the neural circuitry self-organizes these feature detectors to select behaviorally relevant information. Previous studies in computational perception suggest that a neural population enhances information that is important for survival by minimizing the statistical redundancy of the stimuli. Herein we investigate whether the cardiac system makes use of a redundancy reduction strategy to regulate the cardiac rhythm. Based on a network of neural filters optimized to code heartbeat intervals, we learn a population code that maximizes the information across the neural ensemble. The emerging population code displays filter tuning proprieties whose characteristics explain diverse aspects of the autonomic cardiac regulation, such as the compromise between fast and slow cardiac responses. We show that the filters yield responses that are quantitatively similar to observed heart rate responses during direct sympathetic or parasympathetic nerve stimulation. Our findings suggest that the heart decodes autonomic stimuli according to information theory principles analogous to how perceptual cues are encoded by sensory systems

Age, Successive Waves, Immunization, and Mortality in Elderly COVID-19 Haematological Patients: EPICOVIDEHA Findings

Introduction: elderly patients with haematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection impact in different age groups remains unstudied in detail. Methods: We analysed elderly patients (age groups: 65-70, 71-75, 76-80 and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with haematological malignancy. results: the study included data from 3,603 elderly patients (aged 65 or older) with haematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves.tThe 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukaemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusions: These data underscore the heterogeneity of elderly haematological patients, highlight the different impact of COVID waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts

Reviewing the use of resilience concepts in forest sciences

Purpose of the review Resilience is a key concept to deal with an uncertain future in forestry. In recent years, it has received increasing attention from both research and practice. However, a common understanding of what resilience means in a forestry context, and how to operationalise it is lacking. Here, we conducted a systematic review of the recent forest science literature on resilience in the forestry context, synthesising how resilience is defined and assessed. Recent findings Based on a detailed review of 255 studies, we analysed how the concepts of engineering resilience, ecological resilience, and social-ecological resilience are used in forest sciences. A clear majority of the studies applied the concept of engineering resilience, quantifying resilience as the recovery time after a disturbance. The two most used indicators for engineering resilience were basal area increment and vegetation cover, whereas ecological resilience studies frequently focus on vegetation cover and tree density. In contrast, important social-ecological resilience indicators used in the literature are socio-economic diversity and stock of natural resources. In the context of global change, we expected an increase in studies adopting the more holistic social-ecological resilience concept, but this was not the observed trend. Summary Our analysis points to the nestedness of these three resilience concepts, suggesting that they are complementary rather than contradictory. It also means that the variety of resilience approaches does not need to be an obstacle for operationalisation of the concept. We provide guidance for choosing the most suitable resilience concept and indicators based on the management, disturbance and application context