Very Broadly Effective Hemagglutinin-Directed Influenza Vaccines with Anti-Herpetic Activity.

A universal vaccine that generally prevents influenza virus infection and/or illness remains elusive. We have been exploring a novel approach to vaccination involving replication-competent controlled herpesviruses (RCCVs) that can be deliberately activated to replicate efficiently but only transiently in an administration site in the skin of a subject. The RCCVs are derived from a virulent wild-type herpesvirus strain that has been engineered to contain a heat shock promoter-based gene switch that controls the expression of, typically, two replication-essential viral genes.

Efficacy and safety of autologous or allogeneic mesenchymal stromal cells from adult adipose tissue expanded and combined with tricalcium phosphate biomaterial for the surgical treatment of atrophic nonunion of long bones: a phase II clinical trial.

Background: Autologous bone grafting is the standard treatment for the surgical management of atrophic nonunion of long bones. Other solutions, such as bone marrow mesenchymal stem cells (BM-MSC) combined with phospho-calcium material, have also been used. Here we evaluate the safety and early efficacy of a novel procedure using autologous or allogenic adipose tissue mesenchymal stromal cells (AT-MSC) seeded in a patented tricalcium phosphate-based biomaterial for the treatment of bone regeneration in cases of atrophic nonunion.

Behavioral Problems and Family Impact in Congenital Cytomegalovirus Infection.

We examined behavior (Child Behavior Checklist) and family functioning (Family Impact Questionnaire) in 65 children with congenital cytomegalovirus. Behavioral problems were present in 30.8%.

Motivation and Confidence about Physical Activity in Chronic Obstructive Pulmonary Disease Patients: Health Benefits Matter to Patients.

Introduction: Physical activity (PA) has shown great benefits in patients with chronic obstructive pulmonary disease (COPD); however, their PA is below average. Motivational factors associated with PA in COPD have not been widely studied and could be a target for improving adherence to PA. The objective of our study was to identify and understand the different motivational and confidence factors related to low levels of PA in a COPD cohort.

The evolutionary conserved miR-137/325 tandem mediates obesity-induced hypogonadism and metabolic comorbidities by repressing hypothalamic kisspeptin.

Background: Obesity-induced hypogonadism (OIH) is a prevalent, but often neglected condition in men, which aggravates the metabolic complications of overweight. While hypothalamic suppression of Kiss1-encoded kisspeptin has been suggested to contribute to OIH, the molecular mechanisms for such repression in obesity, and the therapeutic implications thereof, remain unknown.

Methods: A combination of bioinformatic, expression and functional analyses was implemented, assessing the role of the evolutionary-conserved miRNAs, miR-137 and miR-325, in mediating obesity-induced suppression of hypothalamic kisspeptin, as putative mechanism of central hypogonadism and metabolic comorbidities.

Evaluation of the transition from intravenous to subcutaneous vedolizumab in patients with inflammatory bowel disease.

Aims: The aim of the study is to evaluate the clinical and biochemical response of inflammatory bowel disease patients treated with vedolizumab, 16 weeks after transitioning from intravenous (iv) to subcutaneous (sc).

Methods: An observational, prospective, single-center cohort study was performed. Patients with inflammatory bowel disease and maintenance treatment with vedolizumab, stable for at least 4 months, were offered to switch to sc formulation.

Spinopelvic interactions in total hip arthroplasty: 295 patients followed for a minimum follow-up of 10 years.

Background: Concurrent spinal pathology is frequent in patients undergoing total hip arthroplasty (THA). In this study we examined whether spinopelvic interactions affect THA outcomes at a minimum follow-up of 10 years.

Patients And Methods: 295 patients with a mean age of 63.

Real-life effectiveness of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients previously treated with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir.

Background: Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is the recommended rescue therapy for patients with chronic hepatitis C infection who fail direct-acting antivirals (DAAs). Data are limited on the effectiveness of this treatment after the current first-line therapies. Our aim was to analyse the effectiveness and safety of SOF/VEL/VOX among patients failing sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB).

Immunomodulatory Activity of Cytokines in Hypertension: A Vascular Perspective.

Cytokines play a crucial role in the structure and function of blood vessels in hypertension. Hypertension damages blood vessels by mechanisms linked to shear forces, activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, oxidative stress, and a proinflammatory milieu that lead to the generation of neoantigens and damage-associated molecular patterns, ultimately triggering the release of numerous cytokines. Damage-associated molecular patterns are recognized by PRRs (pattern recognition receptors) and activate inflammatory mechanisms in endothelial cells, smooth muscle cells, perivascular nerves, and perivascular adipose tissue.

Vitamin D opposes multilineage cell differentiation induced by Notch inhibition and BMP4 pathway activation in human colon organoids.

Understanding the mechanisms involved in colonic epithelial differentiation is key to unraveling the alterations causing inflammatory conditions and cancer. Organoid cultures provide an unique tool to address these questions but studies are scarce. We report a differentiation system toward enterocytes and goblet cells, the two major colonic epithelial cell lineages, using colon organoids generated from healthy tissue of colorectal cancer patients.

Spanish translation and validation of the Music-Related Quality of Life Questionnaire (MuRQoL) in postlingually deaf cochlear implant users.

Purpose: The aim of this study was to translate and validate the "Music-Related Quality of Life Questionnaire" into Spanish (sMuRQoL) and assess its convergent validity and discriminative capacity by comparing its scores with the outcomes of the musical perception test Meludia.

Methods: The sMuRQoL was completed by 129 patients: 55 cochlear implant (CI) users and 74 normal hearing (NH) individuals. Conducted in this study were an exploratory factor analysis, an evaluation of internal consistency, an assessment of score stability through test-retest reliability, a comparison of sMuRQoL scores between CI users and NH individuals and an examination of potential evidence of convergent validity and discriminative capacity of sMuRQoL in relation to other tools.

Resolvin D2 prevents vascular remodeling, hypercontractility and endothelial dysfunction in obese hypertensive mice through modulation of vascular and proinflammatory factors.

During resolution of inflammation, specialized proresolving mediators (SPMs), including resolvins, are produced to restore tissue homeostasis. We hypothesized that there might be a dysregulation of SPMs pathways in pathological vascular remodeling and that resolvin D2 (RvD2) might prevent vascular remodeling and contractile and endothelial dysfunction in a model of obesity and hypertension. In aortic samples of patients with or without abdominal aortic aneurysms (AAA), we evaluated gene expression of enzymes involved in SPMs synthesis (ALOXs), SPMs receptors and pro-inflammatory genes.

Non-suppressible viraemia during HIV-1 therapy: a challenge for clinicians.

In individuals receiving antiretroviral therapy (ART), persistent low-level viraemia not attributed to suboptimal ART adherence, detrimental pharmacological interactions, or drug resistance is referred to as non-suppressible viraemia (NSV). This Review presents recent findings in the virological characterisation of NSV, revealing that it consists of one or a few identical populations of plasma viruses without signs of evolution. This finding suggests that NSV originates from virus production by expanded HIV-infected cell clones, reflecting the persistence of the HIV reservoir despite ART.

Multidisciplinary consensus document on the current treatment of bacille Calmette-Guérin-unresponsive non-muscle invasive bladder tumor.

Radical cystectomy is the current treatment of choice for patients with BCG-unresponsive non-muscle invasive bladder tumor (NMIBC). However, the high comorbidity of this surgery and its effects on the quality of life of patients require the investigation and implementation of bladder-sparing treatment options. These must be evaluated individually by the uro-oncology committee based on the characteristics of the BCG failure, type of tumor, patient preferences and treatment options available in each center.

Microevolution, reinfection and highly complex genomic diversity in patients with sequential isolates of Mycobacterium abscessus.

Mycobacterium abscessus is an opportunistic, extensively drug-resistant non-tuberculous mycobacterium. Few genomic studies consider its diversity in persistent infections. Our aim was to characterize microevolution/reinfection events in persistent infections.

Variant characterisation and clinical profile in a large cohort of patients with Ellis-van Creveld syndrome and a family with Weyers acrofacial dysostosis.

Background: Ellis-van Creveld syndrome (EvC) is a recessive disorder characterised by acromesomelic limb shortening, postaxial polydactyly, nail-teeth dysplasia and congenital cardiac defects, primarily caused by pathogenic variants in or . Weyers acrofacial dysostosis (WAD) is an ultra-rare dominant condition allelic to EvC. The present work aimed to enhance current knowledge on the clinical manifestations of EvC and WAD and broaden their mutational spectrum.