Morbid liver manifestations are intrinsically bound to metabolic syndrome and nutrient intake based on a machine-learning cluster analysis

Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient ' s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients

One-year longitudinal association between changes in dietary choline or betaine intake and cardiometabolic variables in the PREvención con DIeta MEDiterránea-Plus (PREDIMED-Plus) trial

Choline and betaine intakes have been related to cardiovascular health. We aimed to explore the relation between 1-y changes in dietary intake of choline or betaine and 1-y changes in cardiometabolic and renal function traits within the frame of the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial. We used baseline and 1-y follow-up data from 5613 participants (48.2% female and 51.8% male; mean ± SD age: 65.01 ± 4.91 y) to assess cardiometabolic traits, and 3367 participants to assess renal function, of the Spanish PREDIMED-Plus trial. Participants met ≥3 criteria of metabolic syndrome and had overweight or obesity [BMI (in kg/m 2) ≥27 and ≤40]. These criteria were similar to those of the PREDIMED parent study. Dietary intakes of choline and betaine were estimated from the FFQ. The greatest 1-y increase in dietary choline or betaine intake (quartile 4) was associated with improved serum glucose concentrations (−3.39 and −2.72 mg/dL for choline and betaine, respectively) and HbA1c levels (−0.10% for quartile 4 of either choline or betaine intake increase). Other significant changes associated with the greatest increase in choline or betaine intake were reduced body weight (−2.93 and −2.78 kg, respectively), BMI (−1.05 and −0.99, respectively), waist circumference (−3.37 and −3.26 cm, respectively), total cholesterol (−4.74 and −4.52 mg/dL, respectively), and LDL cholesterol (−4.30 and −4.16 mg/dL, respectively). Urine creatinine was reduced in quartile 4 of 1-y increase in choline or betaine intake (−5.42 and −5.74 mg/dL, respectively). Increases in dietary choline or betaine intakes were longitudinally related to improvements in cardiometabolic parameters. Markers of renal function were also slightly improved, and they require further investigation. This trial was registered at as ISRCTN89898870

Dietary Iron, Anemia Markers, Cognition, and Quality of Life in Older Community-Dwelling Subjects at High Cardiovascular Risk

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55-75 years (men) and 60-75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality

The uprise of RNA biology in neuroendocrine neoplasms: altered splicing and RNA species unveil translational opportunities.

Neuroendocrine neoplasms (NENs) comprise a highly heterogeneous group of tumors arising from the diffuse neuroendocrine system. NENs mainly originate in gastrointestinal, pancreatic, and pulmonary tissues, and despite being rare, show rising incidence. The molecular mechanisms underlying NEN development are still poorly understood, although recent studies are unveiling their genomic, epigenomic and transcriptomic landscapes. RNA was originally considered as an intermediary between DNA and protein. Today, compelling evidence underscores the regulatory relevance of RNA processing, while new RNA molecules emerge with key functional roles in core cell processes. Indeed, correct functioning of the interrelated complementary processes comprising RNA biology, its processing, transport, and surveillance, is essential to ensure adequate cell homeostasis, and its misfunction is related to cancer at multiple levels. This review is focused on the dysregulation of RNA biology in NENs. In particular, we survey alterations in the splicing process and available information implicating the main RNA species and processes in NENs pathology, including their role as biomarkers, and their functionality and targetability. Understanding how NENs precisely (mis)behave requires a profound knowledge at every layer of their heterogeneity, to help improve NEN management. RNA biology provides a wide spectrum of previously unexplored processes and molecules that open new avenues for NEN detection, classification and treatment. The current molecular biology era is rapidly evolving to facilitate a detailed comprehension of cancer biology and is enabling the arrival of personalized, predictive and precision medicine to rare tumors like NENs

Diseño universal de aprendizaje y accesibilidad (DUA-A) en la enseñanza universitaria

Se trata de un proyecto de innovación docente desarrollado en el curso 2021/22, en el que se ha aplicado una metodología innovadora como es el Diseño universal de aprendizaje y accesibilidad (DUA-A) para tratar de eliminar las barreras que dificultan el acceso al currículo de nuestro alumnado. Pretendemos un diseño docente tal que nos permita partir de la diversidad de nuestro alumnado, para propiciar un desarrollo pleno de nuestro alumnado y de las disciplinas implicadas. El objetivo global de este proyecto ha sido conseguir una enseñanza universitaria más inclusiva que mejore el desarrollo profesional de nuestro alumnado y de nuestras disciplinas. Para ello, es necesario un esfuerzo de formación del profesorado. La elaboración de la línea base, del punto de partida, una detección de las barreras que dificultan el acceso al currículo: barreras físicas, sensoriales, psicoemocionales, y todas aquellas que invisibilizan la diversidad (diversidad funcional, psico-emocional, alumnado TEA, altas capacidades, etc) , para elaborar un plan de mejora de la práctica docente, con la visibilización y posterior eliminación de las barreras y que nos permita una planificación inclusiva.UCMDepto. de Psicología Experimental, Procesos Cognitivos y LogopediaFac. de PsicologíaFALSEsubmitte

Altered splicing machinery in lung carcinoids unveils NOVA1, PRPF8 and SRSF10 as novel candidates to understand tumor biology and expand biomarker discovery

Abstract Background Lung neuroendocrine neoplasms (LungNENs) comprise a heterogeneous group of tumors ranging from indolent lesions with good prognosis to highly aggressive cancers. Carcinoids are the rarest LungNENs, display low to intermediate malignancy and may be surgically managed, but show resistance to radiotherapy/chemotherapy in case of metastasis. Molecular profiling is providing new information to understand lung carcinoids, but its clinical value is still limited. Altered alternative splicing is emerging as a novel cancer hallmark unveiling a highly informative layer. Methods We primarily examined the status of the splicing machinery in lung carcinoids, by assessing the expression profile of the core spliceosome components and selected splicing factors in a cohort of 25 carcinoids using a microfluidic array. Results were validated in an external set of 51 samples. Dysregulation of splicing variants was further explored in silico in a separate set of 18 atypical carcinoids. Selected altered factors were tested by immunohistochemistry, their associations with clinical features were assessed and their putative functional roles were evaluated in vitro in two lung carcinoid-derived cell lines. Results The expression profile of the splicing machinery was profoundly dysregulated. Clustering and classification analyses highlighted five splicing factors: NOVA1, SRSF1, SRSF10, SRSF9 and PRPF8. Anatomopathological analysis showed protein differences in the presence of NOVA1, PRPF8 and SRSF10 in tumor versus non-tumor tissue. Expression levels of each of these factors were differentially related to distinct number and profiles of splicing events, and were associated to both common and disparate functional pathways. Accordingly, modulating the expression of NOVA1, PRPF8 and SRSF10 in vitro predictably influenced cell proliferation and colony formation, supporting their functional relevance and potential as actionable targets. Conclusions These results provide primary evidence for dysregulation of the splicing machinery in lung carcinoids and suggest a plausible functional role and therapeutic targetability of NOVA1, PRPF8 and SRSF10