Appropriateness of behavioural scales in the monitoring of pain in the critically ill patient unable to self-report.

Appropriateness is a dimension of quality that evaluates the effective use of technologies, resources or interventions in specific situations or populations, assessing whether our interventions do more benefit than harm. The evidence regarding pain monitoring in the critically ill patient points to the periodic assessment of pain using appropriate tools, with the aim of improving pain management and more efficient use of analgesics in the intensive care unit. The first step would be to assess the patient's ability to communicate or self-report and, based on this, to select the most appropriate pain assessment tool.

Pregnancy, Reproductive Factors, and Female Heart Failure Risk and Outcomes.

Purpose Of Review: The purpose of this review is to provide an overview of recent evidence on female-specific risk factors related to reproductive status or pregnancy.

Recent Findings: Pregnancy-related factors, including hypertensive disorders and gestational diabetes, increase the risk of heart failure in women, while breastfeeding and hormone therapy may offer protection. Hypertensive disorders of pregnancy, gestational diabetes, polycystic ovarian syndrome, placental abruption, younger maternal age at first live birth, younger maternal age at last live birth, number of stillbirths, number of pregnancies, onset of menstruation before 12 years of age, shorter reproductive age, ovariectomy, and prolonged absence of ovarian hormones may increase the risk of heart failure in women.

Marizomib for patients with newly diagnosed glioblastoma: A randomized phase 3 trial.

Background: Standard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT), and temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood-brain barrier.

The ATPase Inhibitory Factor 1 (IF1) Contributes to the Warburg Effect and Is Regulated by Its Phosphorylation in S39 by a Protein Kinase A-like Activity.

The relevant role played by the ATPase Inhibitory Factor 1 (IF1) as a physiological in vivo inhibitor of mitochondrial ATP synthase in cancer and non-cancer cells, and in the mitochondria of different mouse tissues, as assessed in different genetic loss- and gain-of-function models of IF1 has been extensively documented. In this review we summarize our findings and those of others that favor the implication of IF1 in metabolic reprogramming to an enhanced glycolytic phenotype, which is mediated by its binding and inhibition of the ATP synthase. Moreover, we emphasize that IF1 is phosphorylated in vivo in its S39 by the c-AMP-dependent PKA activity of mitochondria to render an inactive inhibitor that is unable to interact with the enzyme, thus triggering the activation of ATP synthase.

Biodegradable polydioxanone stents: histologic and structural effects in an experimental model of tracheal stenosis.

Objectives: To evaluate the biologic impact of polydioxanone (PDO) stenting in an animal model of inflammatory tracheal stenosis (TS). Additionally, to compare these results with those obtained in the same model without a stent and after placing one PDO stent in a healthy trachea.

Methods: 40 adult NZ rabbits were distributed into 3 groups: Group A, 8 animals with a healthy trachea and a PDO stent; group B, 17 rabbits with a TS and no stent; and group C, 15 animals with TS and a PDO stent.

Clinical outcomes and prognostic factors after HCV clearance with DAA in HIV/HCV-coinfected patients with advanced fibrosis/cirrhosis.

Background And Aims: We assessed long-term clinical outcomes and prognostic factors for liver disease progression after sustained viral response with direct-acting antivirals in patients coinfected with HIV/HCV with advanced fibrosis or cirrhosis.

Approach And Results: A total of 1300 patients who achieved sustained viral response with direct-acting antivirals from 2014 to 2017 in Spain were included: 1145 with compensated advanced chronic liver disease (384 advanced fibrosis and 761 compensated cirrhosis) and 155 with decompensated cirrhosis. The median follow-up was 40.

Lifestyle and cardiovascular risk in working young adults: insights from a nationwide Spanish cohort.

Introduction And Objectives: This study aimed to describe the cardiovascular risk profile of working young adults from Spain and its association with lifestyle.

Methods: Participants (18-30 years) were recruited from a nationwide cohort of economically active adults insured by a large occupational risk prevention company, with data obtained from routine medical assessments. The participants were categorized as having an "unhealthy" cardiovascular risk profile based on the presence of prediabetes/diabetes, prehypertension/hypertension, or hypercholesterolemia, or a "healthy" profile if these conditions were completely absent.

Expanding the genetic and phenotypic spectrum of congenital myasthenic syndrome: new homozygous VAMP1 splicing variants in 2 novel individuals.

We report the cases of two Spanish pediatric patients with hypotonia, muscle weakness and feeding difficulties at birth. Whole-exome sequencing (WES) uncovered two new homozygous VAMP1 (Vesicle Associated Membrane Protein 1) splicing variants, NM_014231.5:c.

Kidney Diseases Associated With Inflammatory Bowel Disease: Impact of Chronic Histologic Damage, Treatments, and Outcomes.

Introduction: Kidney disease is a well-known extraintestinal manifestation (EIM) associated with inflammatory bowel disease (IBD), with a variety of underlying etiologies. However, little is known about the overall outcomes and predictors.

Methods: This is a retrospective, observational cohort study.

Targeting cancer stem cell OXPHOS with tailored ruthenium complexes as a new anti-cancer strategy.

Background: Previous studies by our group have shown that oxidative phosphorylation (OXPHOS) is the main pathway by which pancreatic cancer stem cells (CSCs) meet their energetic requirements; therefore, OXPHOS represents an Achille's heel of these highly tumorigenic cells. Unfortunately, therapies that target OXPHOS in CSCs are lacking.

Methods: The safety and anti-CSC activity of a ruthenium complex featuring bipyridine and terpyridine ligands and one coordination labile position (Ru1) were evaluated across primary pancreatic cancer cultures and in vivo, using 8 patient-derived xenografts (PDXs).

Solid Lipid Nanoparticles Enhancing the Leishmanicidal Activity of Delamanid.

Leishmaniasis, a zoonotic parasitic disease transmitted by infected sandflies, impacts nearly 1 million people yearly and is endemic in many countries across Asia, Africa, the Americas, and the Mediterranean; despite this, it remains a neglected disease with limited effective treatments, particularly in impoverished communities with limited access to healthcare. This study aims to repurpose approved drugs for an affordable leishmaniasis treatment. After the screening of potential drug candidates by reviewing databases and utilizing molecular docking analysis, delamanid was chosen to be incorporated into solid lipid nanoparticles (SLNPs).

An ETFDH-driven metabolon supports OXPHOS efficiency in skeletal muscle by regulating coenzyme Q homeostasis.

Coenzyme Q (Q) is a key lipid electron transporter, but several aspects of its biosynthesis and redox homeostasis remain undefined. Various flavoproteins reduce ubiquinone (oxidized form of Q) to ubiquinol (QH); however, in eukaryotes, only oxidative phosphorylation (OXPHOS) complex III (CIII) oxidizes QH to Q. The mechanism of action of CIII is still debated.

Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation.

Mammary gland development occurs primarily in adulthood, undergoing extensive expansion during puberty followed by cycles of functional specialization and regression with every round of pregnancy/lactation/involution. This process is ultimately driven by the coordinated proliferation and differentiation of mammary epithelial cells. However, the endogenous molecular factors regulating these developmental dynamics are still poorly defined.

The splicing factor SF3B1 is involved in brown adipocyte thermogenic activation.

The ability of alternative splicing mechanisms to control gene expression is increasingly being recognized as relevant for adipose tissue function. The expression of SF3B1, a key component of the SF3B complex directly involved in spliceosome formation, was previously reported to be significantly induced in brown adipose tissue under cold-induced thermogenic activation. Here, we identify that noradrenergic cAMP-mediated thermogenic stimulation increases SF3B1 expression in brown and beige adipocytes.

Preclinical immune efficacy against SARS-CoV-2 beta B.1.351 variant by MVA-based vaccine candidates.

The constant appearance of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs) has jeopardized the protective capacity of approved vaccines against coronavirus disease-19 (COVID-19). For this reason, the generation of new vaccine candidates adapted to the emerging VoCs is of special importance. Here, we developed an optimized COVID-19 vaccine candidate using the modified vaccinia virus Ankara (MVA) vector to express a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, containing 3 proline (3P) substitutions in the S protein derived from the beta (B.

Effect of Asymptomatic and Symptomatic COVID-19 on Acute Ischemic Stroke Revascularization Outcomes.

Background: The association of COVID-19 with higher bleeding risk and worse outcomes in acute ischemic stroke (AIS) undergoing revascularization may be related to the presence of infection symptoms. We aimed to assess the safety and outcomes of revascularization treatments in patients with AIS with asymptomatic COVID-19 (AS-COVID) or symptomatic COVID-19 (S-COVID).

Methods: We conducted an international multicenter retrospective cohort study of consecutive AIS tested for SARS-CoV-2, receiving intravenous thrombolysis and endovascular treatment between 2020 and 2021.

Short-Chain Fatty Acid Production by Gut Microbiota Predicts Treatment Response in Multiple Myeloma.

Purpose: The gut microbiota plays important roles in health and disease. We questioned whether the gut microbiota and related metabolites are altered in monoclonal gammopathies and evaluated their potential role in multiple myeloma and its response to treatment.

Experimental Design: We used 16S rRNA sequencing to characterize and compare the gut microbiota of patients with monoclonal gammopathy of undetermined significance (n = 11), smoldering multiple myeloma (n = 9), newly diagnosed multiple myeloma (n = 11), relapsed/refractory multiple myeloma (n = 6), or with complete remission (n = 9).

Renal Function Impairment in Children With Congenital Cytomegalovirus Infection: A Cross-sectional Study.

Background: We aimed to determine the prevalence and severity of glomerular and tubular renal dysfunction by means of urinalysis in infants and toddlers with congenital cytomegalovirus infection (cCMV) and their association with cCMV disease, viruria and antiviral treatment.

Methods: This cross-sectional study was done using the Spanish Registry of Congenital Cytomegalovirus Infection. First-morning urine samples were collected from January 2016 to December 2018 from patients <5 years old enrolled in Spanish Registry of Congenital Cytomegalovirus Infection.

Symptom burden guiding invasive electrophysiological study in paroxysmal supraventricular tachycardia: The believe SVT registry.

Background And Objective: Patients with palpitations clinically suggestive of paroxysmal supraventricular tachycardia (PSVT) are often managed conservatively until ECG-documentation of the tachycardia, leading to high impact on life quality and healthcare resource utilization. We evaluated results of electrophysiological study (EPS), and ablation when appropriate, among these patients, with special focus on gender differences in management.

Methods: BELIEVE SVT is a European multicenter, retrospective registry in tertiary hospitals performing EPS in patients with palpitations, without ECG-documentation of tachycardia or preexcitation, and considered highly suggestive of PSVT by a cardiologist or cardiac electrophysiologist.

Congenital cytomegalovirus infection: the state of the art and future perspectives.

Congenital cytomegalovirus (cCMV) infection is the most common congenital infection, with an estimated incidence of approximately one in 200 infants in high-income settings. Approximately one in four children may experience life-long consequences, including sensorineural hearing loss and neurodisability. Knowledge regarding prevention, diagnosis, and treatment increased in the recent years, but some challenges remain.

Efficacy of immune checkpoint inhibitors in alveolar soft-part sarcoma: results from a retrospective worldwide registry.

Background: Conventional cytotoxic drugs are not effective in alveolar soft-part sarcoma (ASPS). Immune checkpoint (programmed cell death protein 1/programmed death-ligand 1) inhibitors (ICIs) are promising drugs in ASPS. A worldwide registry explored the efficacy of ICI in ASPS.