Sex differences in mitochondrial free-carnitine levels in subjects at-risk and with Alzheimer's disease in two independent study cohorts.

A major challenge in the development of more effective therapeutic strategies for Alzheimer's disease (AD) is the identification of molecular mechanisms linked to specific pathophysiological features of the disease. Importantly AD has a two-fold higher incidence in women than men and a protracted prodromal phase characterized by amnestic mild-cognitive impairment (aMCI) suggesting that biological processes occurring early can initiate vulnerability to AD. Here, we used a sample of 125 subjects from two independent study cohorts to determine the levels in plasma (the most accessible specimen) of two essential mitochondrial markers acetyl-L-carnitine (LAC) and its derivative free-carnitine motivated by a mechanistic model in rodents in which targeting mitochondrial metabolism of LAC leads to the amelioration of cognitive function and boosts epigenetic mechanisms of gene expression.

Endocannabinoid involvement in beneficial effects of caloric restriction in a rodent model of comorbid depression and epilepsy.

Clinically, patients with depression are at a heightened risk for developing epilepsy, and vice versa, suggesting shared mechanisms for this bidirectional comorbidity. Unfortunately, comorbid depression and epilepsy is associated with worsened quality of life and treatment refractoriness, highlighting the need for novel treatment targets and nonpharmacologic supplements to existing therapies. The present study used the Swim-Low Active rat, a well-validated model of depression and epilepsy comorbidity that was selectively bred based on forced swim test behavior, to assess the safety and efficacy of caloric restriction in treating this comorbidity.

An alcohol-related liver disease multi-stakeholder hub (ARMS-Hub) to enhance research activity in underserved communities in the UK.

Background: Alcohol use is the third leading risk factor of death and disability in the UK and costs the NHS £3.5 billion per year. Despite the high prevalence and healthcare burden of Alcohol-related Liver Disease (ArLD), there has been minimal research addressing prevention, morbidity and mortality.

Driving DNA Nanopore Membrane Insertion through Dipolar Coupling.

DNA nanopores appear to be a plausible alternative to the use of transmembrane proteins. The specificity and programmability of DNA interactions allow the design of synthetic channels that insert into lipid bilayers and can regulate the ionic transport across them. In this Communication, we investigate the dependence of insertion capabilities on the electrostatic properties of the nanopore and show that the presence of a permanent electric dipole is an important factor for the nanopore to insert into the membrane.

Voucher-based contingency management to promote treatment engagement in comorbid alcohol use disorder and alcohol-related liver disease: A pilot theory-informed qualitative study with service users.

Background: Effective interventions for the management of alcohol-related liver disease (ARLD) remain a gap in clinical practice, and patients' engagement with alcohol services is suboptimal. Based upon the principles of operant conditioning, contingency management (CM) is a psychosocial intervention th at involves gradual, increasing incentives upon completion of treatment-related goals such as treatment attendance.

Methods: A pilot feasibility trial was conducted with 30 adult patients recruited from an inpatient clinical setting.

Cytotoxicity and cell membrane interactions of choline-based ionic liquids: Comparing amino acids, acetate, and geranate anions.

Ionic liquids (ILs) have found diverse applications in research and industry. Biocompatible ILs, a subset considered less toxic than traditional ILs, have expanded their applications into biomedical fields. However, there is limited understanding of the toxicity profiles, safe concentrations, and underlying factors driving their toxicity.

Treatment engagement in comorbid alcohol use disorder and alcohol-related liver disease: A qualitative exploration of barriers and facilitators with service users.

Background: Effective interventions to improve patient outcomes in comorbid alcohol use disorder (AUD) and alcohol-related liver disease (ARLD) remain a clinical unmet need. While the choice of abstinence is the cornerstone for the prevention of disease progression and mortality, evidence suggests a suboptimal engagement with treatment supporting recovery. This qualitative investigation aims to understand barriers and facilitators to treatment as experienced by this clinical population by applying a multidimensional adherence model proposed by the World Health Organization.

Graphene in Water is Hardly Ever Neutral.

Graphene in water is electrically charged in most conditions. The level of charge can be large enough to stabilize single (or few) layer graphene colloidal dispersions in water, without the need of using any other additive. In this work, potentiometric titration, isothermal titration calorimetry, electrokinetic measurements, Density Functional Theory calculations, Raman Spectroscopy, and direct force measurements using Atomic Force Microscopy to investigate this charge and explore its origin are combined.

Use of Transdermal Alcohol Sensors in Conjunction With Contingency Management to Reduce Alcohol Consumption in People With Alcohol Dependence Attending Alcohol Treatment Services: Protocol for a Pilot Feasibility Randomized Controlled Trial.

Background: Wearable technology for objective, continuous, and reliable alcohol monitoring has been developed. These are known as transdermal alcohol sensors (TASs). They can be worn on the wrist or ankle with the sensor pressed against the skin and can measure sweat vapors being emitted from the skin, to record transdermal alcohol concentration (TAC).

Scattering approaches to unravel protein solution behaviors in ionic liquids and deep eutectic solvents: From basic principles to recent developments.

Proteins in ionic liquids (ILs) and deep eutectic solvents (DESs) have gained significant attention due to their potential applications in various fields, including biocatalysis, bioseparation, biomolecular delivery, and structural biology. Scattering approaches including dynamic light scattering (DLS) and small-angle X-ray and neutron scattering (SAXS and SANS) have been used to understand the solution behavior of proteins at the nanoscale and microscale. This review provides a thorough exploration of the application of these scattering techniques to elucidate protein properties in ILs and DESs.

Inequity in clinical research access for service users presenting comorbidity within alcohol treatment settings: findings from a focused ethnographic study.

Background: While healthcare policy has fostered implementation strategies to improve inclusion and access of under-served groups to clinical care, systemic and structural elements still disproportionately prevent service users from accessing research opportunities embedded within clinical settings. This contributes to the widening of health inequalities, as the absence of representativeness prevents the applicability and effectiveness of evidence-based interventions in under-served clinical populations. The present study aims to identify the individual (micro), organisational (meso) and structural (macro) barriers to clinical research access in patients with comorbid alcohol use disorder and alcohol-related liver disease.

Overcoming Therapeutic Challenges of Antibiotic Delivery with Cubosome Lipid Nanocarriers.

Low discovery rates for new antibiotics, commercial disincentives to invest, and inappropriate use of existing drugs have created a perfect storm of antimicrobial resistance (AMR). This "silent pandemic" of AMR looms as an immense, global threat to human health. In tandem, many potential novel drug candidates are not progressed due to elevated hydrophobicity, which may result in poor intracellular internalization and undesirable serum protein binding.

A qualitative exploration of the experiences of transdermal alcohol sensor devices amongst people in receipt of treatment for alcohol use disorder.

Introduction: Transdermal alcohol sensors (TAS) have the potential to be used as a clinical tool in alcohol treatment, but there is limited research with individuals with alcohol dependence using TAS. Our study is a qualitative evaluation of the views of people attending alcohol treatment and their experiences of wearing the BACtrack Skyn, within alcohol services in South London.

Methods: Participants with alcohol dependence wore a BACtrack Skyn TAS for one week and met with the researcher every two days, for a total of four meetings (for example: Monday, Wednesday, Friday, and Monday).

Advancing Wearable Biosensors for Congenital Heart Disease: Patient and Clinician Perspectives: A Science Advisory From the American Heart Association.

Wearable biosensors (wearables) enable continual, noninvasive physiologic and behavioral monitoring at home for those with pediatric or congenital heart disease. Wearables allow patients to access their personal data and monitor their health. Despite substantial technologic advances in recent years, issues with hardware design, data analysis, and integration into the clinical workflow prevent wearables from reaching their potential in high-risk congenital heart disease populations.

Angiopep-2-Functionalized Lipid Cubosomes for Blood-Brain Barrier Crossing and Glioblastoma Treatment.

Glioblastoma multiforme (GBM) is an aggressive brain cancer with high malignancy and resistance to conventional treatments, resulting in a bleak prognosis. Nanoparticles offer a way to cross the blood-brain barrier (BBB) and deliver precise therapies to tumor sites with reduced side effects. In this study, we developed angiopep-2 (Ang2)-functionalized lipid cubosomes loaded with cisplatin (CDDP) and temozolomide (TMZ) for crossing the BBB and providing targeted glioblastoma therapy.

A systematic study of the effect of lipid architecture on cytotoxicity and cellular uptake of cationic cubosomes.

Hypothesis: Lipid nanoparticles containing a cationic lipid are increasingly used in drug and gene delivery as they can display improved cellular uptake, enhanced loading for anionic cargo such as siRNA and mRNA or exhibit additional functionality such as cytotoxicity against cancer cells. This research study tests the hypothesis that the molecular structure of the cationic lipid influences the structure of the lipid nanoparticle, the cellular uptake, and the resultant cytotoxicity.

Experiments: Three potentially cytotoxic cationic lipids, with systematic variations to the hydrophobic moiety, were designed and synthesised.

Influence of Defects and Charges on the Colloidal Stabilization of Graphene in Water.

Mastering graphene preparation is an essential step to its integration into practical applications. For large-scale purposes, full graphite exfoliation appears as a suitable route for graphene production. However, it requires overpowering attractive van der Waals forces demanding large energy input, with the risk of introducing defects in the material.

Comparison of transdermal alcohol concentration and self-reported alcohol consumption in people with alcohol dependence attending community alcohol treatment services.

Aim: We aimed to assess the accuracy and wearability of a transdermal alcohol sensor (TAS) (BACtrack Skyn) with people currently receiving treatment at alcohol services.

Method: A mixed methods observational study involving three NHS alcohol services in south London was conducted. All participants (7=male, 9=female) wore a TAS for 1 week and met with the researcher every other weekday to complete the TAS data download and a TimeLine Follow Back (TLFB).

pH-Dependent Lyotropic Liquid Crystalline Mesophase and Ionization Behavior of Phytantriol-Based Ionizable Lipid Nanoparticles.

Self-assembled lipid nanoparticles (LNPs), serving as essential nanocarriers in recent COVID-19 mRNA vaccines, provide a stable and versatile platform for delivering a wide range of biological materials. Notably, LNPs with unique inverse mesostructures, such as cubosomes and hexosomes, are recognized as fusogenic nanocarriers in the drug delivery field. This study delves into the physicochemical properties, including size, lyotropic liquid crystalline mesophase, and apparent pK of LNPs with various lipid components, consisting of two ionizable lipids (ALC-0315 and SM-102) used in commercial COVID-19 mRNA vaccines and a well-known inverse mesophase structure-forming helper lipid, phytantriol (PT).

Adapting a measure of gross motor skills for individuals with CDKL5 deficiency disorder: A psychometric study.

Purpose: Validated measures capable of demonstrating meaningful interventional change in the CDKL5 deficiency disorder (CDD) are lacking. The study objective was to modify the Rett Syndrome Gross Motor Scale (RSGMS) and evaluate its psychometric properties for individuals with CDD.

Methods: Item and scoring categories of the RSGMS were modified.

Regulating the structural polymorphism and protein corona composition of phytantriol-based lipid nanoparticles using choline ionic liquids.

Lipid-based lyotropic liquid crystalline nanoparticles (LCNPs) face stability challenges in biological fluids during clinical translation. Ionic Liquids (ILs) have emerged as effective solvent additives for tuning the structure of LCNP's and enhancing their stability. We investigated the effect of a library of 21 choline-based biocompatible ILs with 9 amino acid anions as well as 10 other organic/inorganic anions during the preparation of phytantriol (PHY)-based LCNPs, followed by incubation in human serum and serum proteins.