Value contribution of leniolisib in the Treatment of Activated PI3Kδ syndrome (APDS) in Spain using Multi-Criteria Decision Analysis (MCDA).

Background: Activated phosphoinositide 3-kinase (PI3K) δ Syndrome (APDS) is an ultra-rare, potentially life-threatening disease that lacks approved treatments in Spain. This study aimed to apply Multi-Criteria Decision Analysis (MCDA) to assess the value of the first pharmacological treatment for APDS in Spain.

Methods: A multidisciplinary group of 8 experts evaluated the selective PI3Kδ inhibitor leniolisib against Standard of Care (SoC).

Thermal-crosslinked acellular dermal matrix combined with adipose-derived stem cells to regenerate vascularized adipose tissue.

The reconstruction of large-sized soft tissue defects remains a substantial clinical challenge, with adipose tissue engineering emerging as a promising solution. The acellular dermal matrix (ADM), known for its intricate spatial arrangement and active cytokine involvement, is widely employed as a scaffold in soft tissue engineering. Since ADM shares high similarity with decellularized adipose matrix, it holds potential as a substitute for adipose tissue.

Delirium and Cognitive Screening in National Hip Fracture Registries: Scoping Review Protocol.

Background: Delirium and cognitive impairment are common in hip fracture populations and are associated with significant adverse patient outcomes. National hip fracture registries facilitate improvements in patient outcomes and care quality, such as reduced mortality and the development of specialist multidisciplinary services. However, there is substantial variation in the data collected and reported in relation to delirium and cognition, which impedes international comparison and may reduce quality of care.

Pathogenicity assessment of genetic variants identified in patients with severe hypertriglyceridemia: novel cases of Familial Chylomicronemia Syndrome from the Dyslipidemia Registry of the Spanish Atherosclerosis Society.

Purpose: Genetic testing is required to confirm a diagnosis of familial chylomicronemia syndrome (FCS). We assessed the pathogenicity of variants identified in the FCS canonical genes to diagnose FCS cases.

Methods: 245 patients with severe hypertriglyceridemia underwent next-generation sequencing.

Multi-center benchmarking of cervical spinal cord RF coils for 7 T MRI: A traveling spines study.

Purpose: The depth within the body, small diameter, long length, and varying tissue surrounding the spinal cord impose specific considerations when designing radiofrequency coils. The optimal coil configuration for 7 T cervical spinal cord MRI is unknown and, currently, there are very few coil options. The purpose of this work was (1) to establish a quality control protocol for evaluating 7 T cervical spinal cord coils and (2) to use that protocol to evaluate the performance of 4 different coil designs.

Development of a versatile system for evaluating the target protein degradation activity of novel ubiquitin ligases utilizing existing PROTACs.

Proteolysis-Targeting Chimeras (PROTAC) are a bifunctional molecule that binds to a protein of interest (POI) and a ubiquitin ligase, thereby inducing the ubiquitination and degradation of POI. Many PROTACs currently utilize a limited number of ubiquitin ligases, such as von Hippel-Lindau (VHL) and Cereblon. Because these ubiquitin ligases are widely expressed in normal tissues, unexpected side effects can occur.

Increased fecal glycocholic acid levels correlate with obesity in conjunction with the depletion of archaea: the DOSANCO Health Study.

Background: Recent studies have focused on the relationship between obesity and gut microbiota. This study aims to identify fecal components and gut bacterial species associated with different BMI categories.

Methods: In this study, 538 participants aged ≥18 years were categorized into underweight, normal, and obese groups based on BMI (cutoffs: 18.

Unique considerations in the assessment and management of traumatic brain injury in older adults.

The age-specific incidence of traumatic brain injury in older adults is rising in high-income countries, mainly due to an increase in the incidence of falls. The severity of traumatic brain injury in older adults can be underestimated because of a delay in the development of mass effect and symptoms of intracranial haemorrhage. Management and rehabilitation in older adults must consider comorbidities and frailty, the treatment of pre-existing disorders, the reduced potential for recovery, the likelihood of cognitive decline, and the avoidance of future falls.

Efficacy of -Acetylcysteine in Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age and requires better treatment. -acetylcysteine (NAC) is known to be beneficial under such conditions owing to its antioxidant potential and insulin-sensitizing properties. The effect of NAC on the reproductive outcomes of PCOS patients was examined in this meta-analysis.

Impact of Earthquakes During COVID-19 Lockdown on the Pediatric Injury Pattern in the Zagreb Urban Area.

: Previous works on the epidemiology of pediatric trauma during the COVID-19 lockdown observed a decrease in pediatric surgical emergency consultations and fracture referrals. None of those works describes a unique situation in which there is the coexistence of another opposing factor, like an earthquake, that influences the number of injured children's referrals. Therefore, this study aimed to investigate the influence of earthquakes during the COVID-19 lockdown on pediatric injury pattern referrals at a tertiary care hospital in a urban setting.

T Cell-Specific Inactivation of the PI3K p110α Catalytic Subunit: Effect in T Cell Differentiation and Antigen-Specific Responses.

Class IA PI3K p110δ and p110α subunits participate in TCR and costimulatory receptor signals involved in T cell-mediated immunity, but the role of p110α is not completely understood. Here, we analyzed a mouse model of the Cre-dependent functional inactivation of p110α (kinase dead) in T lymphocytes (p110αKD-T, KD). KD mice showed increased cellularity in thymus and spleen and altered T cell differentiation with increased number of CD4CD8 DP thymocytes, enhanced proportion of CD4 SP lymphocytes linked to altered apoptosis, lower Treg cells, and increased AKT and ERK phosphorylation in activated thymocytes.

Harnessing Artificial Intelligence to Enhance Global Breast Cancer Care: A Scoping Review of Applications, Outcomes, and Challenges.

Background: In recent years, Artificial Intelligence (AI) has shown transformative potential in advancing breast cancer care globally. This scoping review seeks to provide a comprehensive overview of AI applications in breast cancer care, examining how they could reshape diagnosis, treatment, and management on a worldwide scale and discussing both the benefits and challenges associated with their adoption.

Methods: In accordance with PRISMA-ScR and ensuing guidelines on scoping reviews, PubMed, Web of Science, Cochrane Library, and Embase were systematically searched from inception to end of May 2024.

Is There a Role for Daratumumab Retreatment in Patients with Relapsed/Refractory Multiple Myeloma?

Multiple myeloma (MM) is a hematologic disease characterized by the clonal expansion of malignant plasma cells that accumulate in the bone marrow, leading to osteolytic bone disease, hypercalcemia, anemia, and renal dysfunction. Daratumumab was the first monoclonal anti-CD38 antibody approved for the treatment of MM, initially in relapse/refractory settings and, more recently, for newly diagnosed patients. Increased first-line usage of daratumumab will also substantially change treatment approaches for patients with relapsed/refractory disease.

Hyperbaric Oxygen Therapy in the Treatment of Crohn's Disease.

: Our study describes hyperbaric oxygen therapy (HBOT) as an additional therapy in the conservative treatment of Crohn's disease (CD) and its benefit in the early postoperative period to prevent surgical complications and improve gastrointestinal motility. : This retrospective study evaluated HBOT in patients hospitalized at the Clinical Hospital Center Split for complications of CD between 2015 and 2020. Patients (N = 61) aged 19 to 67 with perianal fistulas, abscesses, fistulas, obstruction, stenosis, or bleeding were included, excluding those with ulcerative colitis or requiring intensive care.

A point-based cognitive impairment scoring system for Southeast Asian adults short title: Cognitive impairment scoring system.

Background: Cognitive impairment is a growing concern in Southeast Asian populations, where the burden of cerebrovascular disease (CeVD) is high. Currently, there is no point-based scoring system for identifying cognitive impairment in these populations.

Objective: To develop and validate a simple point-based Cognitive Impairment Scoring System (CISS) for identifying individuals with cognitive impairment no dementia (CIND) and concomitant CeVD in Southeast Asian populations.

Diffusion weighted imaging to predict longer term response in Crohn's disease patients commencing biological therapy: Results from the MOTILITY Trial.

Objectives: Predicting longer term response to biological therapy for small bowel Crohn's disease (SBCD) is an unmet clinical need. Diffusion-weighted MR imaging (DWI) may indicate disease activity, but its predictive ability, if any, is unknown. We investigated the prognostic value of DWI for one year response or remission (RoR) in SBCD patients commencing biologic therapy, including incremental value over C-reactive protein (CRP) and faecal calprotectin (FC).

bFGF-Chitosan "brain glue" promotes functional recovery after cortical ischemic stroke.

The mammalian brain has an extremely limited ability to regenerate lost neurons and to recover function following ischemic stroke. A biomaterial strategy of slowly-releasing various regeneration-promoting factors to activate endogenous neurogenesis represents a safe and practical neuronal replacement therapy. In this study, basic fibroblast growth factor (bFGF)-Chitosan gel is injected into the stroke cavity.

Microbiota translocation following intestinal barrier disruption promotes Mincle-mediated training of myeloid progenitors in the bone marrow.

Impairment of the intestinal barrier allows the systemic translocation of commensal bacteria, inducing a proinflammatory state in the host. Here, we investigated innate immune responses following increased gut permeability upon administration of dextran sulfate sodium (DSS) in mice. We found that Enterococcus faecalis translocated to the bone marrow following DSS treatment and induced trained immunity (TI) hallmarks in bone-marrow-derived mouse macrophages and human monocytes.

Endocrine Disrupting Toxicity of Bisphenol A and Its Analogs: Implications in the Neuro-Immune Milieu.

Endocrine-disrupting chemicals (EDCs) are natural or synthetic substances that are able to interfere with hormonal systems and alter their physiological signaling. EDCs have been recognized as a public health issue due to their widespread use, environmental persistence and the potential levels of long-term exposure with implications in multiple pathological conditions. Their reported adverse effects pose critical concerns about their use, warranting their strict regulation.

Sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles of autism candidate genes in neural stem cells from offspring hippocampus.

Bisphenol A (BPA), an endocrine-disrupting chemical, is increasingly linked to the pathogenesis of autism spectrum disorder (ASD). This study investigates the effects of prenatal BPA exposure on neural stem cells (NSCs) from the hippocampi of rat offspring, a brain region critical for neurodevelopment and implicated in ASD. Pregnant rats were administered with BPA or vehicle control once daily via oral gavage from gestational day 1 until parturition.

Pseudoprecocious puberty and gynaecomastia as presenting features of Peutz-Jeghers syndrome.

A boy in mid-childhood presented with right-sided gynaecomastia, which was excised. He represented and, on review by endocrinology, Tanner staging showed stage 2 left-sided glandular breast tissue and some features of virilisation. His testicular volumes remained prepubertal (3 mL).

Metabolism and effects of acetoaceto--toluidine in the urinary bladder of humanized-liver mice.

Occupational exposure to aromatic amines is a major risk factor for urinary bladder cancer. Our previous studies showed that acetoaceto--toluidine, which is produced using -toluidine as a raw material, promotes urinary bladder carcinogenesis in rats. We also found high concentrations of -toluidine, a human bladder carcinogen, in the urine of acetoaceto--toluidine-treated rats, indicating that urinary -toluidine derived from acetoaceto--toluidine may play an important role in bladder carcinogenesis.

Physical activity-the past, present and potential future: a state-of-the-art review.

This is a state-of-the-art review of historical developments, current approaches and recommended future directions in physical activity (PA) research, practice and policy. Since the early epidemiological studies in the 1950s, PA research has developed from within a biomedical paradigm. There is now a strong evidence base linking PA with positive health outcomes.

Comprehensive Clinical and Genetic Characterization of a Spanish Cohort of 22 Patients With Bainbridge-Ropers Syndrome.

Bainbridge-Ropers Syndrome (BRPS) is a genetic condition resulting from truncating variants in the ASXL3 gene. The clinical features include neurodevelopmental and language impairments, behavioral issues, hypotonia, feeding difficulties, and distinctive facial features. In this retrospective study, we analyzed 22 Spanish individuals with BRPS, aiming to perform a detailed clinical and molecular description and establish a genotype-phenotype correlation.