Understanding glucose metabolism and insulin action at the blood-brain barrier: Implications for brain health and neurodegenerative diseases.

The blood-brain barrier (BBB) is a highly selective, semipermeable barrier critical for maintaining brain homeostasis. The BBB regulates the transport of essential nutrients, hormones, and signaling molecules between the bloodstream and the central nervous system (CNS), while simultaneously protecting the brain from potentially harmful substances and pathogens. This selective permeability ensures that the brain is nourished and shielded from toxins.

Plasma proteomic biomarkers as mediators or moderators for the association between poor cardiovascular health and white matter microstructural integrity: The UK Biobank study.

Introduction: The plasma proteome's mediating or moderating roles in the association between poor cardiovascular health (CVH) and brain white matter (WM) microstructural integrity are largely unknown.

Methods: Data from 3953 UK Biobank participants were used (40-70 years, 2006-2010), with a neuroimaging visit between 2014 and 2021. Poor CVH was determined using Life's Essential 8 (LE8) and reversing standardized z-scores (LE8 ).

Enhancing quality and yield of recombinant secretory IgA antibodies in Nicotiana benthamiana by endoplasmic reticulum engineering.

The production of complex multimeric secretory immunoglobulins (SIgA) in Nicotiana benthamiana leaves is challenging, with significant reductions in complete protein assembly and consequently yield, being the most important difficulties. Expanding the physical dimensions of the ER to mimic professional antibody-secreting cells can help to increase yields and promote protein folding and assembly. Here, we expanded the ER in N.

Current and novel biomarkers in cardiogenic shock.

Cardiogenic shock (CS) carries a 30-50% in-hospital mortality rate, with little improvement in outcomes in the last decade. Challenges in improving outcomes are closely linked to the frequent late presentation or diagnosis of CS where the 'point of no return' has often passed, leading to haemodynamic dysregulation, progressive myocardial depression, hypotension, and a downward spiral of hypoperfusion, organ dysfunction and decreasing myocardial function, driven by inflammation and metabolic derangements. Novel therapeutic interventions may have varying efficacy depending on the type and stage of shock in which they are applied.

A roadmap to sustainable management of commercial medicinal and aromatic plants, fungi, and lichens in Nepal.

Thousands of plants, fungi, and lichen species are traded every year. Although sustainable use is critical for livelihoods and biodiversity conservation, insufficient data prevent detailed sustainability assessments for most species. How can the sustainability of trade in such data-deficient species be enhanced? We considered a country-level example of 300 medicinal and aromatic plant, fungus, and lichen species traded in tens of thousands of tons worth tens of millions of US dollars in and from Nepal annually.

Unifying biology of neurodegeneration in lysosomal storage diseases.

There are currently at least 70 characterised lysosomal storage diseases (LSD) resultant from inherited single-gene defects. Of these, at least 30 present with central nervous system (CNS) neurodegeneration and overlapping aetiology. Substrate accumulation and dysfunctional neuronal lysosomes are common denominator, but how variants in 30 different genes converge on this central cellular phenotype is unclear.

Should We Be Treating Affective Symptoms, Like Anxiety and Depression Which May Be Related to LUTD in Patients With OAB? ICI-RS 2024.

Aims: To discuss the role of screening and treatment of affective symptoms, like anxiety and depression in patients with LUTD. A review of the literature regarding the bidirectional association and multidisciplinary approaches integrating psychometric assessments with personalized treatment plans to improve diagnostic accuracy and therapeutic outcomes of LUTD.

Methods: This review summarizes discussions and a narrative review of (recent) literature during an International Consultation on Incontinence-Research Society 2024 research proposal with respect to the role of screening for anxiety and depression, effect of mental health symptoms on treatment outcomes and future implications.

Clinical Relevance of 'Cap' and 'Track' Development after Recent Small Subcortical Infarct.

Objective: After a recent small subcortical infarct (RSSI), some patients develop perilesional or remote hyperintensities ('caps/tracks') to the index infarct on T2/FLAIR MRI. However, their clinical relevance remains unclear. We investigated the clinicoradiological correlates of 'caps/tracks', and their impact on long-term outcomes following RSSI.

Reversal of Roux-en-Y Gastric Bypass: A Multi-Centric Analysis of Indications, Techniques, and Surgical Outcomes.

Background: Roux-en-Y gastric bypass may present long-term complications that require revisional surgery or even reversal to normal anatomy. Data on the indications, surgical technique, and outcomes of RYGB reversal remain scarce.

Methods: We identified 48 cases of RYGB reversals with complete 90-day follow-up within a multi-centric international retrospective database of elective secondary bariatric surgery.

Compact and cGMP-compliant automated synthesis of [F]FSPG on the Trasis AllinOne™.

Background: (S)-4-(3-F-Fluoropropyl)-ʟ-glutamic acid ([F]FSPG) is a positron emission tomography radiotracer used to image system x, an antiporter that is upregulated in several cancers. Not only does imaging system x with [F]FSPG identify tumours, but it can also provide an early readout of response and resistance to therapy. Unfortunately, the clinical production of [F]FSPG has been hampered by a lack of robust, cGMP-compliant methods.

Management of Recurrent Clostridioides difficile Infection (rCDI): A Systematic Literature Review to Assess the Feasibility of Indirect Treatment Comparison (ITC).

Recurrent Clostridioides difficile infection (rCDI) is a major cause of increased morbidity, mortality, and healthcare costs. Fecal-microbiota-based therapies are recommended for rCDI on completion of standard-of-care (SoC) antibiotics to prevent further recurrence: these therapies include conventional fecal-microbiota transplantation and the US Food and Drug Administration-approved therapies REBYOTA® (RBL) and VOWST Oral Spores™ (VOS). As an alternative to microbiota-based therapies, bezlotoxumab, a monoclonal antibody, is used as adjuvant to SoC antibiotics to prevent rCDI.

Accelerated epigenetic ageing after burn injury.

Individuals who suffer a major burn injury are at higher risk of developing a range of age-associated diseases prematurely leading to an increase in mortality in adult and juvenile burn injury survivors. One possible explanation is that injury is accelerating the biological ageing process. To test this hypothesis, we analysed DNA methylation in peripheral blood mononuclear cells from adult burn-injured patients (> 5%TBSA) upon admission to hospital and 6 months later, to calculate an epigenetic clock value which can be used to determine biological age.

Epidemiological and genotypic assessment of cystic echinococcosis in ruminant populations of Northern Punjab, Pakistan: a neglected zoonotic disease.

Echinococcus granulosus is a zoonotic dog parasite, which causes cystic echinococcosis in humans and animals, adversely affecting health and food production. The resultant socio-economic impacts in lower-middle-income countries and the paucity of epidemiology data prompted the World Health Organization to classify cystic echinococcosis as a neglected tropical disease. Between November 2019 and December 2020, the prevalence of cystic echinococcosis was assessed from 3600 post-slaughter livestock (1142 sheep, 1258 goats and 1200 buffalo) from three districts, Narowal, Sheikhupura and Sialkot, in Northern Punjab, Pakistan.

Functional Imaging Methods for Investigating 3D Choroid Plexus Organoids.

The choroid plexus (ChP) is a vital brain structure that produces cerebrospinal fluid (CSF) and forms a selective barrier between the blood and CSF, essential for brain homeostasis. Composed of secretory epithelial cells, connective stroma, and a fenestrated vascular network, the ChP supports nutrient transport, immune surveillance, and the clearance of toxic by-products. Despite its significance in maintaining cerebral function, the mechanisms underlying its development and maturation remain poorly understood.

The Renaissance of Reproductive Science: Leonardo da Vinci's Anatomical Contributions.

Leonardo de Vinci is considered one of the greatest artists that has ever lived. His work includes the Mona Lisa and The Last Supper are celebrated worldwide. His talents expand beyond his art and his contributions to disciplines such as engineering, astronomy, geometry, botany, geology have revealed is him as a polymath.

Non-smoking, non-drinking, oral squamous cell carcinoma patients are a distinct and clinically significant group.

Purpose: Carcinogenesis of oral squamous cell carcinoma (OSCC) has long been associated with exposure to tobacco smoke and alcohol consumption. Some centres have reported that non-smoking non-drinking (NSND) patients represent a significant and increasing proportion of OSCC cases with reports of poorer outcomes. Demographic characteristics are variably reported for this group and carcinogenesis is not fully understood.

Self-Bias and Self-Related Mentalizing are Unaltered in Adolescents with Autism.

Purpose: The self is a multidimensional concept that can be represented at a pre-reflective (first-order) level, at a deeper, reflective level (second-order), or even at a meta-level (representing one's own thoughts, i.e. self-related mentalizing).

Co-expression of the RPS6KB1 and PDPK1 genes for production of activated p70S6K1 using bac-to-bac baculovirus expression system.

Background: Ribosomal protein S6 kinase 1 (p70S6K1) is a member of the AGC family of serine/threonine kinases which plays a role in various cellular processes, including protein synthesis, cell growth, and survival. Dysregulation of p70S6K1, characterized by its overexpression and/or hyperactivation, has been implicated in numerous human pathologies, particularly in several types of cancer. Therefore, generating active, recombinant p70S6K1 is critical for investigating its role in cancer biology and for developing novel diagnostic or therapeutic approaches.

Population pharmacokinetics and exposure-response analysis of durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer.

Purpose: Durvalumab in combination with gemcitabine/cisplatin has shown a favorable benefit-risk profile in the TOPAZ-1 study for advanced biliary tract cancers (BTC). This analysis evaluated the population pharmacokinetics (PopPK) of durvalumab, and exposure-response for efficacy and safety (ERES) of TOPAZ-1.

Methods: The PopPK model for durvalumab was updated using data from 5 previously analysed studies and TOPAZ-1.