Local administration of IL-12 with an HC vector results in local and metastatic tumor control in pediatric osteosarcoma.

Osteosarcoma is the most frequent and aggressive bone tumor in children and adolescents, with a long-term survival rate of 30%. Interleukin-12 (IL-12) is a potent cytokine that bridges innate and adaptive immunity, triggers antiangiogenic responses, and achieves potent antitumor effects. In this work, we evaluated the antisarcoma effect of a high-capacity adenoviral vector encoding mouse IL-12.

Renal tubule Cpt1a overexpression protects from kidney fibrosis by restoring mitochondrial homeostasis.

Chronic kidney disease (CKD) remains a major epidemiological, clinical, and biomedical challenge. During CKD, renal tubular epithelial cells (TECs) present a persistent inflammatory and profibrotic response. Fatty acid oxidation (FAO), the main source of energy for TECs, is reduced in kidney fibrosis and contributes to its pathogenesis.

Delta-24-RGD, an Oncolytic Adenovirus, Increases Survival and Promotes Proinflammatory Immune Landscape Remodeling in Models of AT/RT and CNS-PNET.

Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) and central nervous system primitive neuroectodermal tumors (CNS-PNET) are pediatric brain tumors with poor survival and life-long negative side effects. Here, the aim was to characterize the efficacy and safety of the oncolytic adenovirus, Delta-24-RGD, which selectively replicates in and kills tumor cells.

Experimental Design: Delta-24-RGD determinants for infection and replication were evaluated in patient expression datasets.

Effects of 2 physical exercise programs (circuit training and brisk walk) carried out during working hours on multidimensional components of workers' health: a pilot study.

Objectives: The objective of this study was to determine the effects of 2 physical exercise programs carried out during working hours in an office work environment on health-related parameters of employees.

Material And Methods: The participants included 47 healthy office worker volunteers (aged 45±11.95 years, 27% males) who formed 3 groups: circuit training (CT), brisk walk (BW), and control (C) groups.

miR-425-5p, a SOX2 target, regulates the expression of FOXJ3 and RAB31 and promotes the survival of GSCs.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults and prognosis is poor despite maximum therapeutic efforts. GBM is composed of heterogeneous cell populations, among which the glioma stem-like cells (GSCs) play an important role in tumor cell self-renewal and the ability to initiate and drive tumor growth and recurrence. The transcription factor SOX2 is enriched in GSCs where it controls the stem cell phenotype, invasion and maintenance of tumorigenicity.

RNU6-1 in circulating exosomes differentiates GBM from non-neoplastic brain lesions and PCNSL but not from brain metastases.

Background: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Circulating biomarkers may assist in the processes of differential diagnosis and response assessment. GBM cells release extracellular vesicles containing a subset of proteins and nucleic acids.

Genetic driver mutations introduced in identical cell-of-origin in murine glioblastoma reveal distinct immune landscapes but similar response to checkpoint blockade.

Glioblastoma (GBM) is the most aggressive primary brain tumor. In addition to being genetically heterogeneous, GBMs are also immunologically heterogeneous. However, whether the differences in immune microenvironment are driven by genetic driver mutation is unexplored.

The Effect of 12 Weeks of Different Exercise Training Modalities or Nutritional Guidance on Cardiometabolic Risk Factors, Vascular Parameters, and Physical Fitness in Overweight Adults: Cardiometabolic High-Intensity Interval Training-Resistance Training Randomized Controlled Study.

Ramírez-Vélez, R, Castro-Astudillo, K, Correa-Bautista, JE, González-Ruíz, K, Izquierdo, M, García-Hermoso, A, Álvarez, C, Ramírez-Campillo, R, and Correa-Rodríguez, M. The effect of 12 weeks of different exercise training modalities or nutritional guidance on cardiometabolic risk factors, vascular parameters and physical fitness in overweight adults: cardiometabolic high-intensity interval training-resistance training randomized controlled study. J Strength Cond Res 34(8): 2178-2188, 2020-Evidence suggests that exercise training improves cardiometabolic risk factors.

Clinical and Neuropsychological Predictors of Methylphenidate Response in Children and Adolescents with ADHD: A Naturalistic Follow-up Study in a Spanish Sample.

Background: Methylphenidate (MPH) is the most commonly used medication for Attention-Deficit/Hyperactivity Disorder (ADHD), but to date, there are neither consistent nor sufficient findings on conditions differentiating responsiveness to MPH response in ADHD.

Objective: To develop a predictive model of MPH response, using a longitudinal and naturalistic follow-up study, in a Spanish sample of children and adolescents with ADHD.

Methods: We included all children and adolescents with ADHD treated with MPH in our outpatient Clinic (2005 to 2015), evaluated with the K-SADS interview.

International and multicenter real-world study of sorafenib-treated patients with hepatocellular carcinoma under dialysis.

Background & Aims: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population.

Methods: We report a multicenter study comprising patients from Latin America and Europe.

Glycolysis/gluconeogenesis- and tricarboxylic acid cycle-related metabolites, Mediterranean diet, and type 2 diabetes.

Background: Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear.

Objectives: We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions.

The value of the ethnographic approach to research issues in palliative care.

Purpose Of Review: Qualitative research in the field of palliative care allows for a crucial study of the final stage of life from a social point of view and cultural perspective. This review evaluates the advantages and challenges of applying an ethnographic approach to palliative care research.

Recent Findings: Thirteen ethnographic articles on organization or quality of care, decision-making, delirium, death, and the process of dying, were reviewed.

Recalibrating the 'world map' of palliative care development.

: Despite growing interest from policy makers, researchers and activists, there is still little science to underpin the global development of palliative care. This study presents the methods deployed in the creation of a 'world map' of palliative care development. Building on two previous iterations, with improved rigour and taking into account reviewers' feedback, the aim of the study is to determine the level of palliative care development in 198 countries in 2017, whilst ensuring comparability with previous versions.

Multitarget Approach for the Treatment of Alzheimer's Disease: Inhibition of Phosphodiesterase 9 (PDE9) and Histone Deacetylases (HDACs) Covering Diverse Selectivity Profiles.

Here, we present a series of dual-target phosphodiesterase 9 (PDE9) and histone deacetylase (HDAC) inhibitors devised as pharmacological tool compounds for assessing the implications of these two targets in Alzheimer's disease (AD). These novel inhibitors were designed taking into account the key pharmacophoric features of known selective PDE9 inhibitors as well as privileged chemical structures, bearing zinc binding groups (hydroxamic acids and -amino anilides) that hit HDAC targets. These substituents were selected according to rational criteria and previous knowledge from our group to explore diverse HDAC selectivity profiles (pan-HDAC, HDAC6 selective, and class I selective) that were confirmed in biochemical screens.

Definition of nutritionally qualitative categorizing (proto)nutritypes and a pilot quantitative nutrimeter for mirroring nutritional well-being based on a quality of life health related questionnaire.

Background: there are numerous approaches to assess nutritional status, which are putatively applied to nutritionally classify diseased people, but less information is available to study the role of environmental factors on nutritional well-being. A qualitative (nutritypes) and quantitative (nutrimeter) nutritional categorization based on dietary, lifestyle and disease criteria can be a useful nutritional approach to personalize health interventions and identify at risk individuals. Methods: cross-sectional study conducted on 102 patients (60 women), evaluating quality of life using the Short-Form 36 questionnaire (SF-36) and lifestyle factors with a general questionnaire, the Mediterranean Diet Adherence Screener (MEDAS) and the Global Physical Activity Questionnaire (GPAQ).

Taking Advantage of the Selectivity of Histone Deacetylases and Phosphodiesterase Inhibitors to Design Better Therapeutic Strategies to Treat Alzheimer's Disease.

The discouraging results with therapies for Alzheimer's disease (AD) in clinical trials, highlights the urgent need to adopt new approaches. Like other complex diseases, it is becoming clear that AD therapies should focus on the simultaneous modulation of several targets implicated in the disease. Recently, using reference compounds and the first-in class CM-414, we demonstrated that the simultaneous inhibition of histone deacetylases [class I histone deacetylases (HDACs) and HDAC6] and phosphodiesterase 5 (PDE5) has a synergistic therapeutic effect in AD models.

Burnout Syndrome and Increased Insulin Resistance.

Objective: Our aim was to measure the association of burnout syndrome with insulin resistance in the context of a workplace health intervention.

Methods: One-year intervention program (2015 to 2016) within a university workplace. Participants (n=55) were categorized by the presence or absence of burnout syndrome at baseline using the Maslach Burnout Inventory.

Programmed death-ligand 1 expression on direct Pap-stained cytology smears from non-small cell lung cancer: Comparison with cell blocks and surgical resection specimens.

Background: Programmed death-ligand 1 (PD-L1) expression, as assessed by immunohistochemistry (IHC), is used to select patients with non-small cell lung cancer (NSCLC) for anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy. The current study evaluated the feasibility and efficacy of PD-L1 immunostaining and quantitation on direct Papanicolaou-stained cytological smears compared with formalin-fixed paraffin-embedded samples (cytological cell blocks and surgical resection specimens) in NSCLC cases using 2 commercially available assays: the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies/Dako, Carpinteria, CA, USA) and the Ventana SP263 Assay (Ventana Medical Systems Inc, Tucson, Arizona).

Methods: PD-L1 immunostaining using either both or one of the assays was tested in 117 sets of paired samples obtained from 62 NSCLC cases.

The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models.

Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway.

Delta-24-RGD combined with radiotherapy exerts a potent antitumor effect in diffuse intrinsic pontine glioma and pediatric high grade glioma models.

Pediatric high grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPGs), are aggressive tumors with a dismal outcome. Radiotherapy (RT) is part of the standard of care of these tumors; however, radiotherapy only leads to a transient clinical improvement. Delta-24-RGD is a genetically engineered tumor-selective adenovirus that has shown safety and clinical efficacy in adults with recurrent gliomas.

Identification of mutations associated with acquired resistance to sunitinib in renal cell cancer.

Sunitinib is one of the most widely used targeted therapeutics for renal cell carcinoma (RCC), but acquired resistance against targeted therapies remains a major clinical challenge. To dissect mechanisms of acquired resistance and unravel reliable predictive biomarkers for sunitinib in RCC, we sequenced the exons of 409 tumor-suppressor genes and oncogenes in paired tumor samples from an RCC patient, obtained at baseline and after development of acquired resistance to sunitinib. From newly arising mutations, we selected, using in silico prediction models, six predicted to be deleterious, located in G6PD, LRP1B, SETD2, TET2, SYNE1, and DCC.

Plasma Acylcarnitines and Risk of Type 2 Diabetes in a Mediterranean Population at High Cardiovascular Risk.

Context: The potential associations between acylcarnitine profiles and incidence of type 2 diabetes (T2D) and whether acylcarnitines can be used to improve diabetes prediction remain unclear.

Objective: To evaluate the associations between baseline and 1-year changes in acylcarnitines and their diabetes predictive ability beyond traditional risk factors.

Design, Setting, And Participants: We designed a case-cohort study within the PREDIMED Study including all incident cases of T2D (n = 251) and 694 randomly selected participants at baseline (follow-up, 3.