Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.

Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).

Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.

Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.

Psychological and interpersonal dimensions of sexual function and dysfunction: recommendations from the fifth international consultation on sexual medicine (ICSM 2024).

Introduction: Sexual health concerns are common and significantly impact quality of life, but many people do not seek treatment due to embarrassment and other barriers. A biopsychosocial model of assessment and treatment acknowledges the biological, psychological, and social contributors to sexual difficulties and suggests that all these domains should be evaluated.

Objectives: This paper provides an overview of the major psychological factors contributing to sexual difficulties and offer an evidence-based approach for primary care clinicians to assess and treat these issues.

Engaging dystonia networks with subthalamic stimulation.

Deep brain stimulation is an efficacious treatment for dystonia. While the internal pallidum serves as the primary target, recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its surroundings have not been studied in depth.

Sebaceous carcinoma in immunosuppressed patients: a narrative review.

Sebaceous carcinoma is a rare cutaneous malignancy of sebaceous glands, but it is up to 25-fold more common in immunosuppressed individuals. In this narrative review, we examine the current literature on the pathogenesis, incidence, risk factors, prognosis, treatment, and surveillance of sebaceous carcinoma in immunosuppression and highlight practical considerations for providers who care for these patients. Increased incidence may be related to decreased immune surveillance, susceptibility to an unknown viral trigger, microsatellite instability, immunosuppressive medications, and unmasking of occult Muir-Torre Syndrome.

The brain's action-mode network.

The brain is always intrinsically active, using energy at high rates while cycling through global functional modes. Awake brain modes are tied to corresponding behavioural states. During goal-directed behaviour, the brain enters an action-mode of function.

Novel variant alters splicing of in family with features of Loeys-Dietz syndrome.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder representing a wide spectrum of phenotypes, ranging from isolated thoracic aortic aneurysm or dissection to a more severe syndromic presentation with multisystemic involvement. Significant clinical variability has been noted for both related and unrelated individuals with the same pathogenic variant. We report a family of five affected individuals with notable phenotypic variability who appear to have two distinct molecular causes of LDS, one attributable to a missense variant in and the other an intronic variant 6 bp upstream from a splice junction in .

From Moral Injury Vulnerability to Protective Equity: The Voyage Every Surgeon Must Take.

Objective: To examine the relationship between moral injury and surgical practice, further explore the concept of protective equity, and understand its role in mitigating the impact of morally injurious events throughout a surgical career.

Background: Moral injury in healthcare settings has evolved from Jonathan Shay's original definition, modified by Brett Litz and others, to encompass the psychological impact of adverse patient outcomes on medical practitioners. Early career surgeons may be particularly susceptible to moral injury, yet the factors influencing this vulnerability remain poorly understood.

Surrogates may not accurately estimate resilience and spirituality in neurologically critically ill patients.

Background: Surrogates often provide substituted judgement for neurologically critically ill patients. Resilience and spirituality are understudied constructs in this patient population. In this study we examine how accurately surrogates estimate measures of resilience and spirituality for neurologically critically ill patients.

Clinical researchers' insights on key data for eligibility screening in clinical studies.

Introduction: Clinical research is critical for healthcare advancement, but participant recruitment remains challenging. Clinical research professionals (CRPs; e.g.

Impact of ChatGPT and Large Language Models on Radiology Education: Association of Academic Radiology-Radiology Research Alliance Task Force White Paper.

Generative artificial intelligence, including large language models (LLMs), holds immense potential to enhance healthcare, medical education, and health research. Recognizing the transformative opportunities and potential risks afforded by LLMs, the Association of Academic Radiology-Radiology Research Alliance convened a task force to explore the promise and pitfalls of using LLMs such as ChatGPT in radiology. This white paper explores the impact of LLMs on radiology education, highlighting their potential to enrich curriculum development, teaching and learning, and learner assessment.

Moral enhancement and cheapened achievement: Psychedelics, virtual reality and AI.

A prominent critique of cognitive or athletic enhancement claims that certain performance-improving drugs or technologies may 'cheapen' resulting achievements. Considerably less attention has been paid to the impact of enhancement on the value of moral achievements. Would the use of moral enhancement (bio)technologies, rather than (solely) 'traditional' means of moral development like schooling and socialization, cheapen the 'achievement' of morally improving oneself? We argue that, to the extent that the 'cheapened achievement' objection succeeds in the domains of cognitive or athletic enhancement, it could plausibly also succeed in the domain of moral enhancement-but only regarding certain forms.

Brain functional connectivity, but not neuroanatomy, captures the interrelationship between sex and gender in preadolescents.

Understanding sex differences in the adolescent brain is crucial, as these differences are linked to neurological and psychiatric conditions that vary between males and females. Predicting sex from adolescent brain data may offer valuable insights into how these variations shape neurodevelopment. Recently, attention has shifted toward exploring socially-identified gender, distinct from sex assigned at birth, recognizing its additional explanatory power.

Charge-Stabilized Nanodiscs as a New Class of Lipid Nanoparticles.

Nanoparticles have the potential to improve disease treatment and diagnosis due to their ability to incorporate drugs, alter pharmacokinetics, and enable tissue targeting. While considerable effort is placed on developing spherical lipid-based nanocarriers, recent evidence suggests that high aspect ratio lipid nanocarriers can exhibit enhanced disease site targeting and altered cellular interactions. However, the assembly of lipid-based nanoparticles into non-spherical morphologies has typically required incorporating additional agents such as synthetic polymers, proteins, lipid-polymer conjugates, or detergents.

Frailty Trajectories Preceding Dementia in the US and UK.

Importance: An accessible marker of both biological age and dementia risk is crucial to advancing dementia prevention and treatment strategies. Although frailty is a candidate for that role, the nature of the relationship between frailty and dementia is not well understood.

Objective: To clarify the temporal relationship between frailty and incident dementia by investigating frailty trajectories in the years preceding dementia onset.

Febrile Seizures, Ongoing Epileptiform Activity, and the Resulting Long-Term Consequences: Lessons From Animal Models.

Febrile seizures affect 2% to 14% of children. Prospective studies indicate that following a relatively prolonged febrile seizure there are long-term consequences. Although controlled experiments in children have ethical limitations, nonhuman animal models give us the ability to discover new phenomena, determine their mechanisms, and test treatments that can potentially translate to the human clinical population.