Photoswitchable Diazocine Derivative for Adenosine A Receptor Activation in Psoriasis.

Incorporating photoisomerizable moieties within drugs offers the possibility of rapid and reversible light-dependent switching between active and inactive configurations. Here, we developed a photoswitchable adenosine A receptor (AR) agonist that confers optical control on this G protein-coupled receptor through noninvasive topical skin irradiation in an animal model of psoriasis. This was achieved by covalently bonding an adenosine-5'-methyluronamide moiety to a diazocine photochrome, whose singular photoswitching properties facilitated repeated interconversion between a thermally stable, biologically inactive agonist form and a photoinduced, pharmacologically active configuration.

Attitude of general dental practitioners, oral surgeons, and dentistry students towards oral lesions and oral biopsy.

Background: Oral biopsy is a fundamental surgical procedure used to obtain a histopathological result that assists clinicians in establishing a definitive diagnosis of oral mucosal lesions. The aim of this study was to asses the knowledge and attitudes of dental students, general dentists, and oral surgery experts regarding the detection of oral lesions and the use of biopsy as a diagnostic tool.

Material And Methods: a self-administered questionnaire consisting of 26 questions and 3 clinical cases on oral lesions was distributed to general dentists, oral surgery specialists and final-year dentistry students at the University of Barcelona.

Exploring Biginelli-based scaffolds as A adenosine receptor antagonists: Unveiling novel structure-activity relationship trends, lead compounds, and potent colorectal anticancer agents.

Antagonists of the A adenosine receptor have recently emerged as targeted anticancer agents and immune checkpoint inhibitors within the realm of cancer immunotherapy. This study presents a comprehensive evaluation of novel Biginelli-assembled pyrimidine chemotypes, including mono-, bi-, and tricyclic derivatives, as AAR antagonists. We conducted a comprehensive examination of the adenosinergic profile (both binding and functional) of a large compound library consisting of 168 compounds.

Imaging of chronic thromboembolic pulmonary hypertension before, during and after balloon pulmonary angioplasty.

Balloon pulmonary angioplasty (BPA) has recently been elevated as a class I recommendation for the treatment of inoperable or residual chronic thromboembolic pulmonary hypertension (CTEPH). Proper patient selection, procedural safety, and post-procedural evaluation are crucial in the management of these patients, with imaging work-up playing a pivotal role. Understanding the diagnostic and therapeutic imaging algorithms of CTEPH, the imaging features of patients amenable to BPA, all imaging findings observed during and immediately after the procedure and the changes observed during the follow-up is crucial for all interventional radiologists involved in the care of patients with CTEPH.

In vivo photopharmacology with light-activated opioid drugs.

Traditional methods for site-specific drug delivery in the brain are slow, invasive, and difficult to interface with recordings of neural activity. Here, we demonstrate the feasibility and experimental advantages of in vivo photopharmacology using "caged" opioid drugs that are activated in the brain with light after systemic administration in an inactive form. To enable bidirectional manipulations of endogenous opioid receptors in vivo, we developed photoactivatable oxymorphone (PhOX) and photoactivatable naloxone (PhNX), photoactivatable variants of the mu opioid receptor agonist oxymorphone and the antagonist naloxone.

Understanding the neurological implications of acute and long COVID using brain organoids.

As early as in the acute phase of the coronavirus disease 2019 (COVID-19) pandemic, the research community voiced concerns about the long-term implications of infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), like many other viruses, can trigger chronic disorders that last months or even years. Long COVID, the chronic and persistent disorder lasting more than 12 weeks after the primary infection with SARS-CoV-2, involves a variable number of neurological manifestations, ranging from mild to severe and even fatal.

Endothelial deletion of Wt1 disrupts coronary angiogenesis and myocardium development.

Wt1 encodes a zinc finger protein that is crucial for epicardium development. Although WT1 is also expressed in coronary endothelial cells (ECs), the abnormal heart development observed in Wt1 knockout mice is mainly attributed to its functions in the epicardium. Here, we have generated an inducible endothelial-specific Wt1 knockout mouse model (Wt1KOΔEC).

Short-term outcomes by chronic betablocker treatment in patients presenting to emergency departments with acute heart failure: BB-EAHFE.

Aims: To evaluate the association between chronic treatment with betablockers (BB) and the severity of decompensation and short-term outcomes of patients with acute heart failure (AHF).

Methods And Results: We consecutively included all patients presenting with AHF to 45 Spanish emergency departments (ED) during six different time-periods between 2007 and 2018. Patients were stratified according to whether they were on chronic treatment with BB at the time of ED consultation.

Advances and Pitfalls of Specialized Pain Care through Public and Private Health Care Providers in Catalonia and the Balearic Islands: A Physician's Survey.

Optimal diagnosis and treatment of pain require a multidisciplinary approach that demands considerable coordination and forethought. A cross-sectional physician survey based on an online questionnaire was carried out to assess the adoption of multidisciplinary working patterns, compare the public and private models, and provide an update on the resources and organization of specialized pain care in Catalonia and the Balearic Islands. Active pain practitioners identified through the Catalan Health Service and Pain Society databases were sent an invitation in December 2020.

Ligand with Two Modes of Interaction with the Dopamine D Receptor-An Induced-Fit Mechanism of Insurmountable Antagonism.

A solid understanding of the mechanisms governing ligand binding is crucial for rational design of therapeutics targeting the dopamine D receptor (DR). Here, we use G protein-coupled inward rectifier potassium (GIRK) channel activation in oocytes to measure the kinetics of DR antagonism by a series of aripiprazole analogues, as well as the recovery of dopamine (DA) responsivity upon washout. The aripiprazole analogues comprise an orthosteric and a secondary pharmacophore and differ by the length of the saturated carbon linker joining these two pharmacophores.

Burden of cancer mortality attributable to carcinogenic infections in Spain.

Introduction: The impact of carcinogenic infections on cancer-related mortality is unknown.

Methods: The mortality due to cancers attributable to carcinogenic infections was estimated. The attributable fraction for the infectious agents classified as group 1 carcinogenic in human beings was applied to yearly data on causes of cancer mortality over the period 2013-2017 in Spain according to the International Classification of Diseases (ICD-10).

Brain Functional Connectivity Is Modified by a Hypocaloric Mediterranean Diet and Physical Activity in Obese Women.

Functional magnetic resonance imaging (fMRI) in the resting state has shown altered brain connectivity networks in obese individuals. However, the impact of a Mediterranean diet on cerebral connectivity in obese patients when losing weight has not been previously explored. The aim of this study was to examine the connectivity between brain structures before and six months after following a hypocaloric Mediterranean diet and physical activity program in a group of sixteen obese women aged 46.

Romiplostim therapy as a second-line treatment before splenectomy for refractory immune thrombocytopenia in a cirrhotic patient with iatrogenic Cushing syndrome secondary to corticosteroids.

Our case report discusses the usefulness of administering romiplostim as a second-line treatment before splenectomy in a cirrhotic patient with immune thrombocytopenia who developed corticosteroid-induced Cushing's syndrome. Corticosteroids were tapered and consequently withdrawn. The patient made a full recovery postsplenectomy.

MxA mRNA expression as a biomarker of interferon beta response in multiple sclerosis patients.

Myxovirus resistance protein A (MxA) is a molecule induced after interferon-β injection. The aim of this study was to investigate whether MxA determination one year after starting interferon-β can predict treatment response in multiple sclerosis patients. MxA mRNA expression was evaluated in blood samples obtained at baseline and at month 12.

Aberrant DNA methylation in non-small cell lung cancer-associated fibroblasts.

Epigenetic changes through altered DNA methylation have been implicated in critical aspects of tumor progression, and have been extensively studied in a variety of cancer types. In contrast, our current knowledge of the aberrant genomic DNA methylation in tumor-associated fibroblasts (TAFs) or other stromal cells that act as critical coconspirators of tumor progression is very scarce. To address this gap of knowledge, we conducted genome-wide DNA methylation profiling on lung TAFs and paired control fibroblasts (CFs) from non-small cell lung cancer patients using the HumanMethylation450 microarray.

Novel Regulation of the Synthesis of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Subunit GluA1 by Carnitine Palmitoyltransferase 1C (CPT1C) in the Hippocampus.

The regulation of AMPA-type receptor (AMPAR) abundance in the postsynaptic membrane is an important mechanism involved in learning and memory formation. Recent data suggest that one of the constituents of the AMPAR complex is carnitine palmitoyltransferase 1C (CPT1C), a brain-specific isoform located in the endoplasmic reticulum of neurons. Previous results had demonstrated that CPT1C deficiency disrupted spine maturation in hippocampal neurons and impaired spatial learning, but the role of CPT1C in AMPAR physiology had remained mostly unknown.

Improved image quality in pinhole SPECT by accurate modeling of the point spread function in low magnification systems.

Purpose: Single photon emission computed tomography (SPECT) has become an important noninvasive imaging technique in small-animal research. Due to the high resolution required in small-animal SPECT systems, the spatially variant system response needs to be included in the reconstruction algorithm. Accurate modeling of the system response should result in a major improvement in the quality of reconstructed images.

Combined intermittent hypobaric hypoxia and muscle electro-stimulation: a method to increase circulating progenitor cell concentration?

Background: Our goal was to test whether short-term intermittent hypobaric hypoxia (IHH) at a level well tolerated by healthy humans could, in combination with muscle electro-stimulation (ME), mobilize circulating progenitor cells (CPC) and increase their concentration in peripheral circulation.

Methods: Nine healthy male subjects were subjected, as the active group (HME), to a protocol involving IHH plus ME. IHH exposure consisted of four, three-hour sessions at a barometric pressure of 540 hPa (equivalent to an altitude of 5000 m).

Inverted CD4:CD8 ratio is not associated with three-year mortality in a sample of community-dwelling oldest old: the OCTABAIX immune study.

Background: The presence of an immune risk phenotype (IRP) has been correlated with survival rates in elderly people.

Objective: To determine whether an inverted CD4:CD8 ratio might be a marker of IRP in a sample of oldest old by assessing its relationship with mortality.

Design: Prospective cohort study.

Impact of non-neurological complications in severe traumatic brain injury outcome.

Introduction: Non-neurological complications in patients with severe traumatic brain injury (TBI) are frequent, worsening the prognosis, but the pathophysiology of systemic complications after TBI is unclear. The purpose of this study was to analyze non-neurological complications in patients with severe TBI admitted to the ICU, the impact of these complications on mortality, and their possible correlation with TBI severity.

Methods: An observational retrospective cohort study was conducted in one multidisciplinary ICU of a university hospital (35 beds); 224 consecutive adult patients with severe TBI (initial Glasgow Coma Scale (GCS) < 9) admitted to the ICU were included.

Performance of the digene LQ, RH and PS HPVs genotyping systems on clinical samples and comparison with HC2 and PCR-based Linear Array.

Background: Certain Human Papillomaviruses (HPVs) are the infectious agents involved in cervical cancer development. Detection of HPVs DNA is part of the cervical cancer screening protocols and HPVs genotyping has been proposed for its inclusion in these preventive programs. The aim of this study was to evaluate three novel genotyping tests, namely Qiagen LQ, RH and PS, in clinical samples with and without abnormalities.

Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial.

Introduction: The benefit of corticosteroids as adjunctive treatment in patients with severe community-acquired pneumonia (CAP) requiring hospital admission remains unclear. This study aimed to evaluate the impact of corticosteroid treatment on outcomes in patients with CAP.

Methods: This was a prospective, double-blind and randomized study.

Predictors of 3-year mortality in subjects over 95 years of age. The NonaSantfeliu study.

Objectives: To examine the survival rates of subjects aged 95 or over after a follow-up period of 3 years, and to determine predictive factors for mortality risk.

Design: A prospective cohort study.

Setting: A community-based study.

Serum levels of organochlorine pesticides in healthy adults from five regions of Spain.

The aim of this study was to measure of serum levels of p,p'-dichlorodiphenyl trichloroethane (p,p'-DDT), p,p'-dichlorodiphenyl dichlorethylene (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), and hexachlorobenzene (HCB) in healthy adults in Spain. Furthermore, we also analyzed these levels according to dietary, other lifestyle factors and anthropometric characteristics. We measured the concentrations of such organochlorine pesticides (OCPs) in serum samples collected during 1992-1996 from 953 subjects aged 35-64 years, they were residents of five Spanish regions, they were randomly selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.