Extracellular Vesicles as Tools for Crossing the Blood-Brain Barrier to Treat Lysosomal Storage Diseases.

Extracellular vesicles (EVs) are nanosized, membrane-bound structures that have emerged as promising tools for drug delivery, especially in the treatment of lysosomal storage disorders (LSDs) with central nervous system (CNS) involvement. This review highlights the unique properties of EVs, such as their biocompatibility, capacity to cross the blood-brain barrier (BBB), and potential for therapeutic cargo loading, including that of enzymes and genetic material. Current therapies for LSDs, like enzyme replacement therapy (ERT), often fail to address neurological symptoms due to their inability to cross the BBB.

Mechanical Behavior of PEEK and PMMA Graphene and Ti6Al4V Implant-Supported Frameworks: In Silico Study.

A comparative analysis has been carried out between three different dental materials suitable for the prostheses manufacturing. The analysis performed is based on the finite elements method (FEM) and was made to evaluate their performance under three different loading conditions. Three different materials were modeled with 3D CAD geometry, all of them suitable to be simulated by means of a linear elastic model.

Clinical and Genomic Features of Androgen Indifferent Prostate Cancer.

Androgen-indifferent prostate cancer (AIPC) is increasingly common and particularly lethal. Data describing these tumors are sparse, and AIPC remains a poorly understood malignancy. Utilizing the Oncology Research Information Exchange Network (ORIEN) database, we enriched for tumors with features of AIPC using previously described characteristics.

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.

Risk Factors and Circulating Subtypes of spp. and in Hospitalized Children in Mozambique.

spp. and are important diarrheal agents in children in developing countries. Little is known about their molecular epidemiology; as such, the objective of this study was to determine the risk factors and genetic diversity of both parasites in diarrheal samples in Mozambique.

Low-Cost and Portable Biosensor Based on Monitoring Impedance Changes in Aptamer-Functionalized Nanoporous Anodized Aluminum Oxide Membrane.

We report a low-cost, portable biosensor composed of an aptamer-functionalized nanoporous anodic aluminum oxide (NAAO) membrane and a commercial microcontroller chip-based impedance reader suitable for electrochemical impedance spectroscopy (EIS)-based sensing. The biosensor consists of two chambers separated by an aptamer-functionalized NAAO membrane, and the impedance reader is utilized to monitor transmembrane impedance changes. The biosensor is utilized to detect amodiaquine molecules using an amodiaquine-binding aptamer (OR7)-functionalized membrane.

Novel Splice-Altering Variants in the and Genes Causative of X-Linked Choroideremia and Cone Dystrophy.

Background: An estimated 10-15% of all genetic diseases are attributable to variants in noncanonical splice sites, auxiliary splice sites and deep-intronic variants. Most of these unstudied variants are classified as variants of uncertain significance (VUS), which are not clinically actionable. This study investigated two novel splice-altering variants, NM_000390.

A Longer Duration of Intravenous Antibiotic Treatment for Patients with Early Periprosthetic Joint Infections Is Not Associated with a Lower Failure Rate.

Background: In recent years, many studies have demonstrated the efficacy of an early switch to oral antibiotics after surgical treatment in orthopedic-related infections. However, large analyses on periprosthetic joint infections (PJIs) are lacking.

Material And Methods: We conducted a retrospective observational multicenter study in patients diagnosed with an early post-operative PJI, defined as one occurring <3 months after the index arthroplasty and treated with debridement, antibiotics, and implant retention (DAIR).

Logistic Stewardship: Supporting Antimicrobial Stewardship Programs Based on Antibiotics Goods Flow.

Background/objectives: Antimicrobial resistance is a global threat to safe health care, and a reduction in antibiotic consumption seems to be an appropriate preventive measure. In Germany, the reporting of hospital antibiotics consumption to an independent institution is only voluntary. Although a high level of willingness to improve can be assumed in the case of participation, the median consumptions of reporting hospitals change only slightly.

Analysis of TERT mRNA Levels and Clinicopathological Features in Patients with Peritoneal Mesothelioma.

Background/objectives: Telomerase reverse transcriptase (TERT) is the catalytic subunit of the telomerase enzyme responsible for telomere length maintenance and is an important cancer hallmark. Our study aimed to clarify the mRNA expression of TERT in peritoneal mesothelioma (PeM), and to explore the relationship between its expression and the clinicopathological parameters and prognosis of patients with PeM.

Methods: In a cohort of 13 MpeM patients, we evaluated histotype, nuclear grade, mitotic count, necrosis, inflammation, Ki67, BAP1, MTAP and p16 expression by immunohistochemistry, / status by FISH and TERT mRNA expression by RNAscope.

Squamous Cell Bladder Cancer: A Rare Histological Variant with a Demand for Modern Cancer Therapeutics.

Bladder cancer is among the most common form of cancer worldwide and is predicted to increase in incidence and mortality over the next decade. Squamous cell carcinoma of the bladder is a rare histological variant typically associated with schistosomiasis, also known as bilharzia, a parasitic infection caused by flatworms called schistosomes or blood flukes, and is generally seen in underdeveloped nations. However, squamous cell carcinoma of the bladder still represents nearly 5% of bladder cancer diagnoses in the western world.

Association of Corticosteroid Inhaler Type with Saliva Microbiome in Moderate-to-Severe Pediatric Asthma.

: Metered-dose inhalers (MDIs) and dry powder inhalers (DPIs) are common inhaled corticosteroid (ICS) inhaler devices. The difference in formulation and administration technique of these devices may influence oral cavity microbiota composition. We aimed to compare the saliva microbiome in children with moderate-to-severe asthma using ICS via MDIs versus DPIs.

Disease-Associated Dopamine Receptor D2 Variants Exhibit Functional Consequences Depending on Different Heterotrimeric G-Protein Subunit Combinations.

Dopamine receptors (DRs) are G-protein-coupled receptors (GPCRs) found in the central nervous system (CNS). DRs are essential for mediating various downstream signaling cascades and play a critical role in regulating the dopaminergic nigrostriatal pathway, which is involved in motor control. Recently, mutations in DRD2 (WT), p.

"My Husband Is a 'Mama's Boy'": Women's Views on Male Engagement in Maternal, Newborn, and Child Health in Western Kenya.

There is an increasing global acknowledgment of the critical role that men have as key partners in maternal, newborn, and child health (MNCH). Most male-engagement initiatives do not address the perceived benefits and risks that women may experience because of increased male participation in MNCH, especially in Kenya. The aim of this study, therefore, is to qualitatively assess how women perceive and experience increased male engagement in MNCH in western Kenya.

A Multi- Mediation Analysis on the Impact of Social Media and Internet Addiction on University and High School Students' Mental Health Through Social Capital and Mindfulness.

Introduction: Social media addiction (SMA) and internet addiction (IA) are increasingly prevalent, impacting mental health (MH) globally. This study investigates the mediating roles of mindfulness and social capital (SC) in the relationship between SMA, IA, and MH among Ethiopian high school and university students, contributing to the Sustainable Development Goal (SDG) 3 of good health and well-being.

Methods: A cross-sectional study was conducted with 1160 university and 1473 high school students in Dessie, Ethiopia.

Current Practices and Perceived Effectiveness of Clinicians Regarding Polynucleotide Injection for Knee Osteoarthritis: A Survey-Based Evaluation.

Intra-articular (IA) injection therapy, particularly IA hyaluronic acid (HA), is a common treatment for knee osteoarthritis, but it does have limitations. The injection of IA polynucleotide (PN) has emerged as an alternative, potentially offering superior clinical outcomes. This study investigates current practice patterns and the perceived effectiveness of PN among clinicians for treating knee osteoarthritis in the Republic of Korea.

Deep Learning in Oral Hygiene: Automated Dental Plaque Detection via YOLO Frameworks and Quantification Using the O'Leary Index.

: Oral diseases such as caries, gingivitis, and periodontitis are highly prevalent worldwide and often arise from plaque. This study focuses on detecting three plaque stages-new, mature, and over-mature-using state-of-the-art YOLO architectures to enhance early intervention and reduce reliance on manual visual assessments. : We compiled a dataset of 531 RGB images from 177 individuals, captured via multiple mobile devices.

Effect of a Nutritional Education Intervention on the Reduction of Added Sugar Consumption in Schoolchildren in Southeastern Mexico: Community Study.

Consumption of added sugars negatively affects schoolchildren's health, making it essential to promote strategies designed to reduce their intake through educational interventions. This study aimed to evaluate the effect of a nutritional education intervention, INCAI, on the consumption of added sugars among schoolchildren in southeastern Mexico. A 9-month educational intervention was designed to promote healthy eating, physical activity, and the development of socio-emotional skills among primary school children.

Activity of Aztreonam-avibactam and other β-lactamase inhibitor combinations against Gram-negative bacteria isolated from patients hospitalized with pneumonia in United States medical centers (2020-2022).

Background: Initial antimicrobial therapy for pneumonia is frequently empirical and resistance to antimicrobial agents represents a great challenge to the treatment of patients hospitalized with pneumonia. We evaluated the frequency and antimicrobial susceptibility of Gram-negative bacteria causing pneumonia in US hospitals.

Methods: Bacterial isolates were consecutively collected (1/patient) from patients hospitalized with pneumonia and the susceptibility of Gram-negative bacilli (3,911 Enterobacterales and 2,753 non-fermenters) was evaluated by broth microdilution in a monitoring laboratory.

Trust: an essential component in nursing crisis leadership; a hybrid concept analysis.

Background: Given the increasing trend of disasters, terrorist attacks, pandemics and other crises, crisis leadership is crucial for nurses who lead others and for those working in such situations. There is a need to define and explore the concept of trust as a component of crisis leadership in nursing. This concept analysis aimed to explore the concept of trust in crisis leadership from a nursing perspective.

Increased aqueous humor levels of endothelin-1 in patients with open angle glaucoma.

Background: Endothelin is a potent vasoconstrictor and contributes to the regulation of vascular perfusion. Aberrant endothelin-1 (ET-1) levels in aqueous humor have been reported across a variety of vascular diseases of the eye, including glaucoma. These findings suggest that dysregulation of ET-1 production may contribute to glaucoma pathophysiology.

Symptom representations in people with multimorbidity undergoing treatment for cancer: a qualitative descriptive study.

Purpose: The symptom representations (i.e., beliefs and attitudes) that people with cancer hold about their symptom experience can impact how they self-manage their symptoms.

Increased use of damage control laparotomy for emergency small bowel or colon surgery: does it affect patient outcomes?

Purpose: Evidence to guide the application of damage control laparotomy (DCL) in emergency surgery patients is limited. We assessed whether DCL use for emergent small bowel or colon surgery increased over time and its impact on outcomes. We hypothesized that DCL would be utilized more often in patients with significant comorbidities or septic shock with improved outcomes.

Autosomal and Y-STR genetic database from a population of the Spanish Civil War (1936-1939) and the postwar period.

Under the initiative of the "Direcció General de Memòria democràtica-Departament de Justícia" (Generalitat of Catalonia, Spain), a multi-disciplinar project was funded to identify the remains of people disappeared in Catalonia during and after the Spanish Civil War (1936-1939). Samples were officially sent by Autonomous Government of Catalonia to the Laboratory of Forensic and Population Genetics at Complutense University, Madrid, Spain, to be genotyped. Our study presents a database of 343 victims genotyped for STRs comprised in GlobalFiler™ PCR Amplification Kit (Thermofisher Scientific) and a subset of 292 typed with Y-STRs from Yfiler™ Plus PCR Amplification Kit (Thermofisher Scientific).