Emerging medications and pharmacological treatment approaches for substance use disorders.

Medications to treat substance use disorders remain suboptimal or, in the case of stimulants and cannabis, non-existent. Many factors have contributed to this paucity, including the biological complexity of addiction, regulatory challenges, and a historical lack of enthusiasm among pharmaceutical companies to commit resources to this disease space. Despite these headwinds, the recent opioid crisis has highlighted the devastating consequences of SUDs for both individuals and society, stimulating urgent efforts to identify novel treatment approaches.

Reliability and applicability of angiographic outcome scales in WEB device-treated aneurysms: a systematic review.

Purpose: Various angiographic assessment scales have been used to report the results of endovascular treatment with the WEB device. We aimed to review the use and reliability of these scales.

Methods: We systematically reviewed studies reporting angiographic outcomes of WEB-treated aneurysms from January 2010 to May 2023.

Flow diversion for the treatment of distal circulation aneurysms: A randomized comparison.

Background And Purpose: Flow diversion (FD) has expanded beyond initial indications (proximal carotid artery aneurysms) to include distal circulation aneurysms (on the anterior, middle, or posterior cerebral arteries). Our objective was to examine results obtained from aneurysms in these locations in the Flow Diversion in the Treatment of Intracranial Aneurysms Trial (FIAT) which compared FD with alternative standard management options (ASMO).

Materials And Methods: FIAT was an all-inclusive parallel-group 1:1 randomized study comparing FD with one of 4 ASMOs (coiling +/-stenting, parent vessel occlusion (PVO), clipping, or observation, pre-specified by clinical judgment).

Variations on a theme: non-canonical DUF3494 ice-binding proteins.

Among the many ice-binding proteins (IBPs) found in microorganisms (bacteria, archaea, fungi and algae), the canonical DUF3494 beta-barrel type is the most common. Until now, little variation has been found in this structure: an initial coil leads into an alpha helix that directs the following coils into a reverse stack, with the final coil ending up next to the initial coil. Here, I show that there exist many bacterial proteins whose AlphaFold-predicted structures deviate from the DUF3494 structure so that they are not recognized as belonging to an existing DUF or Pfam family.

Computational analysis of Urolithin A as a potential compound for anti-inflammatory, antioxidant, and neurodegenerative pathways.

Urolithin A, an active precursor derived from the metabolism of ellagitanins in rats and humans, is known for its potential health benefits, including stimulating mitophagy and promoting muscular skeletal function. While experimental studies have demonstrated Urolithin A's potential to enhance cellular health, the detailed molecular interactions through which Urolithin A exerts its effects are not fully elucidated. In this study, we investigated the anti-inflammatory, antioxidation and neuroprotective abilities of Urolithin A in selected targets using molecular docking and molecular dynamics simulation methods.

Insights from Team Clinic: A Person-Centered Virtual Peer Group Care Model Adapted for Marginalized and Historically Excluded Youth with Type 1 Diabetes (T1D).

Background: Despite advancements in T1D care regimens, racially and ethnically diverse youth with low income continue to experience worse health outcomes, more psychosocial challenges, and higher barriers to care. Alternative care models are needed to address the needs of this population.

Methods: Team Clinic is a person-centered virtual peer group (VPG) care model that was assessed in a 15-month, pragmatic randomized controlled trial.

The interpretation-use argument- the essential ingredient for high quality assessment design and validation.

There is increasing interest in health professions education (HPE) in applying argument-based validity approaches, such as Kane's, to assessment design. The critical first step in employing Kane's approach is to specify the interpretation-use argument (IUA). However, in the HPE literature, this step is often poorly articulated.

Controlled Delivery of Paclitaxel via Stable Synthetic Protein Nanoparticles.

Despite decades of intense research, glioma remains a disease for which no adequate clinical treatment exists. Given the ongoing therapeutic failures of conventional treatment approaches, nanomedicine may offer alternative options because it can increase the bioavailability of drugs and alter their pharmacokinetics. Here, a new type of synthetic protein nanoparticles (SPNPs) is reported that allow for effective loading and controlled release of the potent cancer drug, paclitaxel (PTX) - a drug that so far has been unsuccessful in glioma treatment due to hydrophobicity, low solubility, and associated delivery challenges.

International practice patterns and perspectives on endovascular therapy for the treatment of cerebral venous thrombosis.

Background: Cerebral venous thrombosis (CVT) accounts for 0.5-1% of all strokes. The role of endovascular therapy (EVT) in the management of CVT remains controversial and variations in practice patterns are not well known.

Catheter Ablation or Antiarrhythmic Drugs for Ventricular Tachycardia.

Background: Patients with ventricular tachycardia and ischemic cardiomyopathy are at high risk for adverse outcomes. Catheter ablation is commonly used when antiarrhythmic drugs do not suppress ventricular tachycardia. Whether catheter ablation is more effective than antiarrhythmic drugs as a first-line therapy in patients with ventricular tachycardia is uncertain.

A sleepy cannabis constituent: cannabinol and its active metabolite influence sleep architecture in rats.

Medicinal cannabis is being used worldwide and there is increasing use of novel cannabis products in the community. Cannabis contains the major cannabinoids, Δ-tetrahydrocannabinol (Δ-THC) and cannabidiol (CBD), but also an array of minor cannabinoids that have undergone much less pharmacological characterization. Cannabinol (CBN) is a minor cannabinoid used in the community in "isolate' products and is claimed to have pro-sleep effects comparable to conventional sleep medications.

Understanding the role of induction, intensions and extensions in pragmatic clinical research and practice.

Background: Pragmatic clinical research methods are poorly understood, but essential to practice outcome-based medical or surgical care. Pragmatic research aims to verify the connections between medical knowledge and the reality of practice. Its methods can be understood by reviewing the problems of induction, as well as the related linguistic and mathematical notions of intensions and extensions.

Understanding statistical populations and inferences.

Background: The term population is frequently used in clinical research and statistics, but concepts are multiple and confusing. Populations are a roundabout way of conceiving classifications, generalizations and inductive inferences. When misapplied, the term can lead to serious errors in study design, analysis and interpretation.

The Lipid Droplet Protein DHRS3 Is a Regulator of Melanoma Cell State.

Lipid droplets are fat storage organelles composed of a protein envelope and lipid-rich core. Regulation of this protein envelope underlies differential lipid droplet formation and function. In melanoma, lipid droplet formation has been linked to tumor progression and metastasis, but it is unknown whether lipid droplet proteins play a role.

Randomized Controlled Feasibility Trial of Late 8-Hour Time-Restricted Eating for Adolescents With Type 2 Diabetes.

Background: No trial to date has tested the effects of late time-restricted eating (lTRE) on glycemic control or body composition in adolescents with type 2 diabetes (T2D).

Objective: The objective of the current study was to examine the feasibility, acceptability, and preliminary efficacy of lTRE compared to a prolonged eating window in adolescents with T2D.

Design: A 12-week, randomized, controlled, feasibility study of lTRE compared to control in adolescents with obesity and new onset T2D was conducted.

UVB radiation suppresses Dicer expression through β-catenin.

Ultraviolet (UV) rays prompt a natural response in epidermal cells, particularly within melanocytes. The changes in gene expression and related signaling pathways in melanocytes following exposure to UV radiation are still not entirely understood. Our findings reveal that UVB irradiation suppresses the expression of Dicer (also known as Dicer1).

General practitioners' experiences delivering essential care services during the 2020 and 2021 COVID-19-related lockdowns.

Background And Objectives: The UK provided guidance for general practitioners (GPs) to deliver essential care services during the COVID-19 pandemic. Our objective was to describe local GP experiences and approaches to delivering care while similar formal guidance in Australia was unavailable.

Method: Two hundred and ninety-one GPs who practised during the March 2020 to December 2021 COVID-19 lockdowns in Melbourne and Sydney undertook an electronic survey exploring perceptions of essential care service delivery.

Strategies for Equitable Recruitment to Engage Underrepresented Youth and Their Families into Clinical Research: Findings from the BEAD-T1D Pilot Study.

Introduction: To address disparities in clinical research, we present strategies to optimize recruitment of underrepresented families into the Building the Evidence to Address Disparities in Type 1 Diabetes (BEAD-T1D) study.

Methods: A bilingual/bicultural Latino research assistant (RA) was hired to facilitate culturally congruent recruitment for pediatric type 1 diabetes families. The RA screened, approached, and consented families using their preferred language, time of contact, and answered personal concerns around research.

Synaptic weight dynamics underlying memory consolidation: Implications for learning rules, circuit organization, and circuit function.

Systems consolidation is a common feature of learning and memory systems, in which a long-term memory initially stored in one brain region becomes persistently stored in another region. We studied the dynamics of systems consolidation in simple circuit architectures with two sites of plasticity, one in an early-learning and one in a late-learning brain area. We show that the synaptic dynamics of the circuit during consolidation of an analog memory can be understood as a temporal integration process, by which transient changes in activity driven by plasticity in the early-learning area are accumulated into persistent synaptic changes at the late-learning site.

Janus Swarm Metamaterials for Information Display, Memory, and Encryption.

Metamaterials are emerging as an unconventional platform to perform computing abstractions in physical systems by processing environmental stimuli into information. While computation functions have been demonstrated in mechanical systems, they rely on compliant mechanisms to achieve predefined states, which impose inherent design restrictions that limit their miniaturization, deployment, reconfigurability, and functionality. Here, a metamaterial system is described based on responsive magnetoactive Janus particle (MAJP) swarms with multiple programmable functions.

Trial selection criteria should not be used for clinical decisions and recommendations: the thrombectomy trials example.

Background: Despite multiple calls for more inclusive studies, most clinical trial eligibility criteria remain too restrictive. Thrombectomy trials have been no exception.

Methods: We review the landmark trials that have shown the benefits of thrombectomy, their eligibility criteria, and consequences on clinical practice.