NAD+ regulates nucleotide metabolism and genomic DNA replication.

The intricate orchestration of enzymatic activities involving nicotinamide adenine dinucleotide (NAD+) is essential for maintaining metabolic homeostasis and preserving genomic integrity. As a co-enzyme, NAD+ plays a key role in regulating metabolic pathways, such as glycolysis and Kreb's cycle. ADP-ribosyltransferases (PARPs) and sirtuins rely on NAD+ to mediate post-translational modifications of target proteins. The activation of PARP1 in response to DNA breaks leads to rapid depletion of cellular NAD+ compromising cell viability. Therefore, the levels of NAD+ must be tightly regulated. Here we show that exogenous NAD+, but not its precursors, has a direct effect on mitochondrial activity. Short-term incubation with NAD+ boosts Kreb's cycle and the electron transport chain and enhances pyrimidine biosynthesis. Extended incubation with NAD+ results in depletion of pyrimidines, accumulation of purines, activation of the replication stress response and cell cycle arrest. Moreover, a combination of NAD+ and 5-fluorouridine selectively kills cancer cells that rely on de novo pyrimidine synthesis. We propose an integrated model of how NAD+ regulates nucleotide metabolism, with relevance to healthspan, ageing and cancer therapy.

The relapsed acute lymphoblastic leukemia network (ReALLNet): a multidisciplinary project from the spanish society of pediatric hematology and oncology (SEHOP).

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, with survival rates exceeding 85%. However, 15% of patients will relapse; consequently, their survival rates decrease to below 50%. Therefore, several research and innovation studies are focusing on pediatric relapsed or refractory ALL (R/R ALL). Driven by this context and following the European strategic plan to implement precision medicine equitably, the Relapsed ALL Network (ReALLNet) was launched under the umbrella of SEHOP in 2021, aiming to connect bedside patient care with expert groups in R/R ALL in an interdisciplinary and multicentric network. To achieve this objective, a board consisting of experts in diagnosis, management, preclinical research, and clinical trials has been established. The requirements of treatment centers have been evaluated, and the available oncogenomic and functional study resources have been assessed and organized. A shipping platform has been developed to process samples requiring study derivation, and an integrated diagnostic committee has been established to report results. These biological data, as well as patient outcomes, are collected in a national registry. Additionally, samples from all patients are stored in a biobank. This comprehensive repository of data and samples is expected to foster an environment where preclinical researchers and data scientists can seek to meet the complex needs of this challenging population. This proof of concept aims to demonstrate that a network-based organization, such as that embodied by ReALLNet, provides the ideal niche for the equitable and efficient implementation of "what's next" in the management of children with R/R ALL.

The favourable association of self-reported physical fitness with depression and anxiety during pregnancy. The GESTAFIT project.

We explored the association of self-reported physical fitness with depressive symptoms and anxiety levels during pregnancy. One hundred fifty-five pregnant women (32.9 ± 4.7 years old) participated in the study. Self-reported physical fitness was assessed with the International Fitness Scale, depressive symptoms and state anxiety levels with the Center for Epidemiological Studies-Depression Scale and the State Trait Anxiety Index, respectively, at the 16 and 34 weeks of gestation. In model 1 (adjusted for age and gestational weight gain), greater overall self-reported physical fitness was associated with fewer depressive symptoms at the 16 weeks (p = .004). Greater self-reported cardiorespiratory fitness and muscular strength were associated with lower anxiety levels at the 16 weeks (all, p > .05). Greater overall self-reported physical fitness, cardiorespiratory fitness and speed-agility were associated with lower anxiety levels at the 34 weeks (all, p > .05). These results were also confirmed in model 2 (additionally adjusted for the exercise intervention, sleep quality, educational level, working status and cohabitating), except for cardiorespiratory fitness and anxiety levels at the 16 weeks (p = .09). Greater self-reported physical fitness was associated with lower psychological ill-being during pregnancy. Specifically, at the 16 weeks, greater self-reported overall physical fitness was associated with fewer depressive symptoms, greater self-reported muscular strength with lower anxiety levels; greater self-reported overall physical fitness and speed-agility with lower anxiety levels at the 34 weeks and greater self-reported cardiorespiratory fitness with lower anxiety levels during the pregnancy. Screening of physical fitness may reduce the risk of depression and anxiety and generally improve pregnancy mental health-related quality of life.Highlights Maternal depression and anxiety have prevalence rates between 8 and 36%.Physical fitness enhancement during pregnancy results in less depression and anxiety.Greater physical fitness may provide benefits for the mother mental health.Self-reported physical fitness screening during pregnancy may be useful in clinical settings.

Glycemic variability in type 2 diabetes mellitus and acute coronary syndrome: liraglutide compared with insulin glargine: a pilot study.

OBJECTIVE: To explore the glucagon-like peptide-1 analogue liraglutide in the hospital setting in patients with type 2 diabetes mellitus (T2DM) and acute coronary syndrome and to evaluate the safety and efficacy and its impact on hospitalization and short-term glycemic variability (GV). METHODS: A 12-week, open-label, prospective, randomized pilot clinical study with parallel groups that compared liraglutide (group 1) with glargine (group 2) and its impact on glycemic control and GV. RESULTS: Thirteen patients were included. During hospitalization, mean glucose was 164.75 mg/dL (standard deviation [SD] 19.94) in group 1 and 166.69 mg/dL (38.22) in group 2. GV determined by CV and SD was 20.98 (7.68) vs. 25.48 (7.19) and 34.37 (13.05) vs. 43.56 (19.53) in groups 1 and 2, respectively. Group 1 prandial insulin requirements during hospitalization were lower compared with group 2. Follow-up A1c in group 1 was 6.9% (-1.51%) and 6.5% in group 2 (-1.27). GV after discharge and hypoglycemia were lower in group 1 compared with group 2. CONCLUSIONS: Liraglutide seems to reduce GV in the acute phase of acute coronary syndrome, and patients achieved optimal control with a low incidence of hypoglycemia. These results support the need to explore liraglutide in a larger multicenter trial. Trial registration: The study was approved by the National Medical Ethics Committee of Spain. The study was registered at European Clinical Trials Database (EudraCT): 2014003298-40.

Implicit Attitudes to Female Body Shape in Spanish Women With High and Low Body Dissatisfaction.

Research on implicit attitudes to body image has grown substantially in recent years. The extant evidence reveals an implicit weight bias in the general population that has generally been interpreted in terms of anti-fat attitudes. However, research with the Implicit Relational Assessment Procedure (IRAP) shows that this bias appears to be driven by pro-slim rather than anti-fat implicit attitudes. Besides, the only IRAP study of this sort conducted in Spain found no evidence of such implicit weight bias (with similarly positive attitudes to thinness and fatness). Given the existing differences in body dissatisfaction (BD) among diverse cultural contexts, we predicted that discrepancies in findings about implicit weight bias might be related to differences in BD amongst the samples in the different studies. This study explores whether women with extreme scores in BD (High vs. Low) show different patterns of attitudes to female body shape. Spanish female college students with extreme scores in the Body Shape Questionnaire (BSQ: high ≥ 104, percentile 80; low ≤ 52, percentile 20) completed an IRAP with pictures of overweight and underweight women as target stimuli and the words pleasant and unpleasant as labels. Participants also completed explicit ratings to the same stimuli and clinically relevant measures of body image related distress. Results showed an implicit weight bias only for women high in BD. While both groups showed equally positive implicit attitudes to thinness, only women with low BD showed implicit positive attitudes to fatness (and hence no bias). In turn, both groups presented a clear pro-thin/anti-fat explicit bias with positive ratings for underweight pictures and negative ratings for overweight pictures. The latter were stronger for the high BD group. Therefore, between-group differences were mainly driven by differences in attitudes to fatness (both implicit and explicit). Both implicit and explicit attitudes to fatness independently predicted eating disorders symptoms and other clinically relevant measures. These results are discussed in terms of their clinical implications.

Tumor Neuroectodérmico primitivo melanótico de la infancia: reporte de un Caso / Neuroectodermal tunmor melanotic

El tumor neuroectodérmico primitivo melanótico de la infancia es una neoplasia poco común, originada en la cresta neural. Se presenta frecuentemente en los huesos orofaciales, pero se ha informado en múltiples localizaciones. La mayoría de las veces afecta a lacatantes menores de 12 meses de edad. Tiene un curso benigno, por lo cual el tratamiento es fundamentalmente la resección completa de la lesión. Se describe el caso de un niño de 4 meses de edad con un tumor orbitario con extensión intracraneana manejado quirúrgicamente con buena evolución.

Ecografía intraoperatoria en la detección de nódulos pulmonares metastásicos

El pulmón es el segundo órgano en frecuencia de metástasis de todas las neoplasias del organismo. Por años el examen bimanual se consideró el método más sensible. in embargo la recidiva de metástasis y la necesidad de reintervenciones, obligaron a la búsqueda de nuevas alternativas diagnósticas. Introdujimos la ecografía intraoperatoria como una herramienta diagnóstica de lesiones metastásicas pulmonares en pacientes que cumplieron los criterios de inclusión y fueron sometidos a metastectomía entre agosto de 1997 y mayo de 1998. Mediante técnicas de abordaje quirúrgico convencional, se practicó examen bimanual del pulmón colpasado. Posteriormente se realizó la ecografía intraoperatoria previa infusión de solución salina en la cavidad pleural empleando un equipo de ecografía con transductor multipropósito sectorial de alta resolución de 7.5 Mhz. todas las lesiones detectadas por ambos métodos fueron identificadas y su tamaño y localiazación registrados. se practicó resección cuneiforme y estudio histopatológico en todos los casos. El estudio incluyó 11 pacientes, seis fueron hombres (55 por ciento) y cienco mujeres (45 por ciento); en total se resecaron 50 nódulos. El cirujano detectó 35 (78 por ciento) y la ecografía 45 (90 por ciento). En total 42 fueron reportados como metastásicos, de éstos sólo 27 (64 por ciento) fueron localizados por el cirujano, en comparación con 42 (100 por ciento) evidenciados por la ecografía. La ecografiía diagnosticó 13 nódulos menores de 5 mm (29.5 por ciento) contra 2 (7.5 por ciento) detectados por el cirujano lo cual fue estadisticamente significativo (Chi cuadrado 1 g.-=7.2; p.007) el tiempo prometido de realización de la ecografía fue de 9 minutos (rango 5 a 15 minutos)

Hemorragia del tracto gastrointestinal inferior: enfoque imaginológico

Se revisa la historia clínica, hallazgos imaginológicos y evolución en tres pacientes con hemorragia del tracto gastrointestinal inferior de diferentes etiologías que fueron estudiados con glóbulos rojos radiomarcados y angiografía selectiva con terapia endovascular mediante infusión intrarterial de vasopresina en el Hospital San Juan de Dios en santafé de Bogotá, entre Agosto de 1996 y Marzo de 1997. se revisa la literatura reciente y el abordaje diagnóstico y terapéutico utilizado como flujograma de manejo