The Emerging Role of Neurosteroids: Novel Drugs Brexanalone, Sepranolone, Zuranolone, and Ganaxolone in Mood and Neurological Disorders.

This review investigates the potential of neurosteroids, including brexanolone, zuranolone, sepranolone, and ganaxalone, as therapeutic agents for a range of mood and neurological disorders. Notably, these disorders encompass postpartum depression, post-traumatic stress disorder (PTSD), major depressive disorder (MDD), epilepsy, and Alzheimer's disease. Brexanolone and zuranolone have emerged as frontrunners in the treatment of postpartum depression, offering rapid relief from debilitating symptoms. Their mechanism of action involves modulation of the gamma-aminobutyric acid (GABA) system, which plays a pivotal role in mood regulation. Clinical trials have demonstrated their efficacy, heralding a potential breakthrough in addressing this often-overlooked condition. In the context of PTSD and MDD, neurosteroids have demonstrated significant promise. Their positive allosteric modulation of GABA-A receptors translates into improved mood stabilization and reduced symptoms. This novel approach represents a departure from conventional treatments and could offer newfound hope for individuals grappling with these disorders. Beyond mood disorders, neurosteroids, especially ganaxalone, exhibit potential in the realm of epilepsy management. Ganaxalone's capacity to control seizures is attributed to its GABAergic activity, which helps restore the delicate balance of neurotransmission in epileptic brains. Moreover, neurosteroids have revealed neuroprotective properties in Alzheimer's disease models. By influencing the GABAergic system, they mitigate excitotoxicity, a hallmark of Alzheimer's pathology. This neuroprotection opens a novel avenue for slowing neurodegeneration, although further research and clinical validation are essential. In conclusion, this review underscores the substantial therapeutic promise of neurosteroids in mood and neurological disorders. Their modulation of the GABA system emerges as a central mechanism of action, emphasizing the importance of GABAergic signaling in these conditions. The path forward entails continued investigation and clinical trials to fully unlock the potential of neurosteroids, offering hope for enhanced treatments in these challenging clinical domains.

Understanding the Interplay Between Premenstrual Dysphoric Disorder (PMDD) and Female Sexual Dysfunction (FSD).

Premenstrual dysphoric disorder (PMDD) is a severe variant of premenstrual syndrome (PMS), categorized as a mood disorder due to marked symptoms of depression and anxiety, compounded with severe physical symptoms. Female sexual dysfunction (FSD) can manifest as low libido, difficulty achieving sexual pleasure, and dyspareunia, causing functional and psychological distress. PMDD and FSD are globally prevalent conditions with postulated biological, psychological, and social associations between them. Nevertheless, sexual dysfunction in PMDD is an important aspect of women's health that has been understudied and has notable methodological limitations. In this narrative review, we summarize the existing literature on sexual function in women with PMDD and PMS, specify the distinctions between PMDD and other general symptoms of PMS, highlight the significance of understanding sexual dysfunction in the female population, and outline some available therapeutic options. Studies show that women frequently experience debilitating sexual distress during the premenstrual phase; however, there is an essential need to formulate standardized tools for definite diagnosis. Selective serotonin re-uptake inhibitors (SSRIs) and combined oral contraceptive pills (COCPs) are approved medications for PMDD, while flibanserin and bremelanotide are effective in treating FSD. However, the potential effects of these treatment modalities on the two comorbid conditions render them inconclusive. Awareness of PMDD and FSD among clinicians and society can allow the implementation of targeted interventions to alleviate the suffering of women and enhance their quality of life.

Heart Failure With Improved Ejection Fraction: Prevalence, Predictors, and Guideline-Directed Medical Therapy.

Recently, a new category of heart failure with improved ejection fraction (HFimpEF) has emerged in the classification system. This is defined as the subgroup of patients with heart failure with reduced ejection fraction (HFrEF) whose left ventricular ejection fraction has recovered partially or completely, with no specific cut-off values established yet in the guidelines. In our review, we aim to provide an overview of prevalence, predictors, mechanism of remodeling, and management strategies regarding HFimpEF. These patients constitute a sizeable cohort among patients with reduced ejection fraction. Certain patient characteristics including younger age and female gender, absence of comorbid conditions, low levels of biomarkers, and non-ischemic etiology were identified as positive predictors. The heart undergoes significant maladaptive changes post failure leading to adverse remodeling influenced etiology and duration. Goal-directed medical therapy including beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin II receptor blockers (ARBs) have notably improved cardiac function by inducing reverse remodeling. Despite a more favorable prognosis compared to HFrEF, patients with improved ejection fraction (EF) still face clinical events and reduced quality of life, and remain at risk of adverse outcomes. Although the evidence is scarce, it is advisable to continue treatment modalities despite improvement in EF, including device therapies, to prevent relapse and clinical deterioration. It is imperative to conduct further research to understand the mechanism leading to EF amelioration and establish guidelines to identify and direct management strategies.

Gender Disparities in First Authorship in Publications Related to Attention Deficit Hyperkinetic Disorder (ADHD) and Artificial Intelligence (AI).

The medical profession has experienced a significant increase in the number of women practitioners in recent decades, leading to a reduction in the gender gap. According to the United States Medical Association, approximately 25% of physicians in the United States are now women. Although this progress is evident in the clinical setting, women's representation in academic medicine remains disproportionately low. The underrepresentation of women in academia has various consequences, including limited access to academic resources and hindered career growth. Previous studies have attempted to analyze these disparities, but results have been inconsistent, and the issue's complexity has not been fully understood. This study aims to examine the disparity in the gender of first authors in academic publications related to " Artificial intelligence (AI) and Attention Deficit Hyperkinetic Disorder (ADHD)" between 2010 and 2023. Analysis was conducted on June 21st, 2023, using the database PubMed. The search term "AI" AND "ADHD" was used to derive all articles over a period of 13 years, from January 1st, 2010, to December 31st, 2022, excluding the year 2023 due to limited available publications. The relevant articles were downloaded in Microsoft Excel sheets. The gender of the first authors was determined using the NamSor app V.2, an application programming interface (API) with a large dataset of names and countries of origin. A total of 204 articles were considered for this study. There were 78 female first authors and 126 male first authors. The highest number of publications with a male first author occurred in 2022, with 32 publications. The Netherlands, Singapore, Turkey, and China have the highest gender ratios, indicating a more favourable representation of both genders. The p-value of 0.2664 suggests that there is no significant association between gender and country. The findings revealed a gender disparity, with a higher number of male first authors. By addressing and rectifying these disparities, we can enhance the overall quality, diversity, and inclusivity of research in the field of ADHD and Artificial Intelligence.

Gains Across WHO Dimensions of Function After Robot-Based Therapy in Stroke Subjects.

BACKGROUND: Studies examining the effects of therapeutic interventions after stroke often focus on changes in loss of body function/structure (impairment). However, improvements in activities limitations and participation restriction are often higher patient priorities, and the relationship that these measures have with loss of body function/structure is unclear. OBJECTIVE: This study measured gains across WHO International Classification of Function (ICF) dimensions and examined their interrelationships. METHODS: Subjects were recruited 11 to 26 weeks after hemiparetic stroke. Over a 3-week period, subjects received 12 sessions of intensive robot-based therapy targeting the distal arm. Each subject was assessed at baseline and at 1 month after end of therapy. RESULTS: At baseline, subjects (n = 40) were 134.7 ± 32.4 (mean ± SD) days poststroke and had moderate-severe arm motor deficits (arm motor Fugl-Meyer score of 35.6 ± 14.4) that were stable. Subjects averaged 2579 thumb movements and 1298 wrist movements per treatment session. After robot therapy, there was significant improvement in measures of body function/structure (Fugl-Meyer score) and activity limitations (Action Research Arm Test, Barthel Index, and Stroke Impact Scale-Hand), but not participation restriction (Stroke Specific Quality of Life Scale). Furthermore, while the degree of improvement in loss of body function/structure was correlated with improvement in activity limitations, neither improvement in loss of body function/structure nor improvement in activity limitations was correlated with change in participation restriction. CONCLUSIONS: After a 3-week course of robotic therapy, there was improvement in body function/structure and activity limitations but no reduction in participation restriction.

Changes in Coronary Plaque Volume: Comparison of Serial Measurements on Intravascular Ultrasound and Coronary Computed Tomographic Angiography.

Serial measurements of coronary plaque volume have been used to evaluate drug efficacy in atherosclerotic progression. However, the usefulness of computed tomography for this purpose is unknown. We investigated whether the change in total plaque volume on coronary computed tomographic angiography is associated with the change in segment plaque volume on intravascular ultrasound. We prospectively enrolled 11 consecutive patients (mean age, 56.3 ± 5 yr; 6 men) who were to undergo serial invasive coronary angiographic examinations with use of grayscale intravascular ultrasound and coronary computed tomography, performed <180 days apart at baseline and from 1 to 2 years later. Subjects underwent 186 serial measurements of total plaque volume on coronary computed tomography and 22 of segmental plaque volume on intravascular ultrasound. We used semiautomated software to examine percentage relationships and changes between total plaque and segmental plaque volumes. No significant correlations were found between percentages of total coronary and segment coronary plaque volume, nor between normalized coronary plaque volume. However, in the per-patient analysis, there were strong correlations between the imaging methods for changes in total coronary and segment coronary plaque volume (r=0.62; P=0.04), as well as normalized plaque volume (r=0.82; P=0.002). Per-patient change in plaque volume on coronary computed tomography is significantly associated with that on intravascular ultrasound. Computed tomographic angiography may be safer and more widely available than intravascular ultrasound for evaluating atherosclerotic progression in coronary arteries. Larger studies are warranted.

Aged Garlic Extract Reduces Low Attenuation Plaque in Coronary Arteries of Patients with Metabolic Syndrome in a Prospective Randomized Double-Blind Study.

BACKGROUND: Although several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification, its effect on noncalcified plaque (NCP) has been unclear. OBJECTIVE: This study investigated whether AGE reduces coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with metabolic syndrome (MetS). METHODS: Fifty-five patients with MetS (mean ± SD age: 58.7 ± 6.7 y; 71% men) were prospectively assigned to consume 2400 mg AGE/d (27 patients) or placebo (28 patients) orally. Both groups underwent CCTA at baseline and follow-up 354 ± 41 d apart. Coronary plaque volume, including total plaque volume (TPV), dense calcium (DC), NCP, and low-attenuation plaque (LAP), were measured based upon predefined intensity cutoff values. Multivariable linear regression analysis, adjusted for age, gender, number of risk factors, hyperlipidemia medications, history of coronary artery disease, scan interval time, and baseline %TPV, was performed to examine whether AGE affected each plaque change. RESULTS: The %LAP change was significantly reduced in the AGE group compared with the placebo group (-1.5% ± 2.3% compared with 0.2% ± 2.0%, P = 0.0049). In contrast, no difference was observed in %TPV change (0.3% ± 3.3% compared with 1.6% ± 3.0%, P = 0.13), %NCP change (0.2% ± 3.3% compared with 1.4% ± 2.9%, P = 0.14), and %DC change (0.2% ± 1.4%, compared with 0.2% ± 1.7%, P = 0.99). Multivariable linear regression analysis found a beneficial effect of AGE on %LAP regression (ß: -1.61; 95% CI: -2.79, -0.43; P = 0.008). CONCLUSIONS: This study indicates that the %LAP change was significantly greater in the AGE group than in the placebo group. Further studies are needed to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events. This trial was registered at clinicaltrials.gov as NCT01534910.