Sex differences in the structure and function of the vasopressin system in the ventral pallidum are associated with the sex-specific regulation of social play behavior in juvenile rats.

Vasopressin (AVP) regulates various social behaviors, often in sex-specific ways, including social play behavior, a rewarding behavior displayed primarily by juveniles. Here, we examined whether and how AVP acting in the brain's reward system regulates social play behavior in juvenile rats. Specifically, we focused on AVP signaling in the ventral pallidum (VP), a brain region that is a part of the reward system. First, we examined the organization of the VP-AVP system in juvenile rats and found sex differences, with higher density of both AVP-immunoreactive fibers and AVP V1a receptor (V1aR) binding in males compared to females while females show a greater number of V1aR-expressing cells compared to males. We further found that, in both sexes, V1aR-expressing cells co-express a GABA marker to a much greater extent (approx. 10 times) than a marker for glutamate. Next, we examined the functional involvement of V1aR-expressing VP cells in social play behavior. We found that exposure to social play enhanced the proportion of activated V1aR-expressing VP cells in males only. Finally, we showed that infusion of a specific V1aR antagonist into the VP increased social play behaviors in juvenile male rats while decreasing these behaviors in juvenile female rats. Overall, these findings reveal structural and functional sex differences in the AVP-V1aR system in the VP that are associated with the sex-specific regulation of social play behavior.

MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement.

Microtubule doublets (MTDs) comprise an incomplete microtubule (B-tubule) attached to the side of a complete cylindrical microtubule. These compound microtubules are conserved in cilia across the tree of life; however, the mechanisms by which MTDs form and are maintained in vivo remain poorly understood. Here, we identify microtubule-associated protein 9 (MAP9) as an MTD-associated protein. We demonstrate that C. elegans MAPH-9, a MAP9 homolog, is present during MTD assembly and localizes exclusively to MTDs, a preference that is in part mediated by tubulin polyglutamylation. We find that loss of MAPH-9 causes ultrastructural MTD defects, including shortened and/or squashed B-tubules with reduced numbers of protofilaments, dysregulated axonemal motor velocity, and perturbed cilia function. Because we find that the mammalian ortholog MAP9 localizes to axonemes in cultured mammalian cells and mouse tissues, we propose that MAP9/MAPH-9 plays a conserved role in regulating ciliary motors and supporting the structure of axonemal MTDs.

Assisted Reproductive Technology Treatment Outcomes in Women With Liver Disease.

INTRODUCTION: There is a need for evidence-based counseling for women with chronic liver disease (LD) who may experience impaired fertility. Currently, the literature on assisted reproductive technology (ART) treatment in women with LD has been limited to a single European case series. We evaluated ART treatment outcomes in patients with LD and compared with controls. METHODS: The retrospective study evaluated women with and without LD who had normal ovarian reserve and underwent ART treatment in a high-volume fertility practice from 2002 to 2021. RESULTS: We identified 295 women with LD (mean age 37.8 ± 5.2 years) who underwent 1,033 ART treatment cycles; of these women, 115 underwent 186 in vitro fertilization (IVF) cycles. Six women (2.0%) had cirrhosis, 8 (2.7%) were postliver transplantation, and 281 (95.3%) had chronic LD, with viral hepatitis (B and C) being the most prevalent. In the subgroup who underwent IVF and embryo biopsy, the median fibrosis-4 score was 0.81 (0.58-1.03), and there were no statistically significant differences in response to controlled ovarian stimulation, embryo fertilization rate, or ploidy outcome in patients with LD compared with controls. In those who subsequently underwent a single thawed euploid embryo transfer to achieve pregnancy, there were no statistically significant differences in rates of clinical pregnancy, clinical pregnancy loss, or live birth in patients with LD compared with controls. DISCUSSION: To the best of our knowledge, this study is the largest to date to evaluate IVF efficacy in women with LD. Our study demonstrates that patients with LD have similar ART treatment outcomes compared with those without LD.

Translating Animal Models of Ischemic Stroke to the Human Condition.

Ischemic stroke is a leading cause of death and disability. However, very few neuroprotective agents have shown promise for treatment of ischemic stroke in clinical trials, despite showing efficacy in many successful preclinical studies. This may be attributed, at least in part, to the incongruency between experimental animal stroke models used in preclinical studies and the manifestation of ischemic stroke in humans. Most often the human population selected for clinical trials are more diverse than the experimental model used in a preclinical study. For successful translation, it is critical to develop clinical trial designs that match the experimental animal model used in the preclinical study. This review aims to provide a comprehensive summary of commonly used animal models with clear correlates between rodent models used to study ischemic stroke and the clinical stroke pathologies with which they most closely align. By improving the correlation between preclinical studies and clinical trials, new neuroprotective agents and stroke therapies may be more accurately and efficiently identified.

Paradoxical Cerebral Air Embolism after Cardiac Ablation in Williams-Beuren Syndrome: A Clinico-Pathological Correlation.

Non-traumatic neurological deterioration is a medical emergency that may arise from diverse causes, to include cerebral infarction or intracranial hemorrhage, meningoencephalitis, seizure, hypoxic-ischemic or toxic/metabolic encephalopathy, poisoning, or drug intoxication. We describe the abrupt onset of neurological deterioration in a 53-year-old man with Williams-Beuren syndrome, a sporadically occurring genetic disorder caused by chromosomal microdeletion at 7q11.23. The clinical phenotype of Williams-Beuren syndrome is suggested by distinctive elfin facies, limited intellect, unique personality features, growth abnormalities, and endocrinopathies. The causative microdeletion of chromosomal material will frequently involve loss of the elastin gene, ELN, with resulting arteriopathy, supravalvular aortic stenosis, non-ischemic cardiopathy, and atrial fibrillation. Our patient sustained acute neurological decline within one month after undergoing a cardiac ablative procedure to convert atrial fibrillation to sinus rhythm. We present our findings in the setting of a clinico-pathological correlation, in which we reveal the cause of the abrupt neurological deterioration and discuss how our patient was affected by an uncommon stroke disorder.

Suicidality in a 27-year-old Male with Obsessive Compulsive Disorder.

This is a case report of a 27-year-old male with obsessive compulsive disorder (OCD) and anxiety who presented to a community hospital with suicidality. OCD is a rare psychiatric disorder characterized by recurrent and intrusive thoughts or obsessions and/or repetitive behaviors aimed at alleviating these thoughts known as compulsions. Management of this condition includes comprehensive evaluation of comorbidities and suicidality along with pharmacotherapy and a specific form of cognitive behavioral therapy (CBT) called exposure and response prevention (EX/RP or ERP). This unique case report highlights the necessity of a thorough and individualized approach to treatment for each patient in order to maximize the outcomes of care.

Contribution of Secreted NADase and Streptolysin O to the Pathogenesis of Epidemic Serotype M1 Streptococcus pyogenes Infections.

Streptococcus pyogenes secretes many toxins that facilitate human colonization, invasion, and dissemination. NADase (SPN) and streptolysin O (SLO) are two toxins that play important roles in pathogenesis. We previously showed that increased production of SPN and SLO in epidemic serotype M1 and M89 S. pyogenes strains is associated with rapid intercontinental spread and enhanced virulence. The biological functions of SPN and SLO have been extensively studied using eukaryotic cell lines, but the relative contribution of each of these two toxins to pathogenesis of epidemic M1 or M89 strains remains unexplored. Herein, using a genetically representative epidemic M1 strain and a panel of isogenic mutant derivative strains, we evaluated the relative contributions of SPN and SLO toxins to virulence in mouse models of necrotizing myositis, bacteremia, and skin and soft tissue infection. We found that isogenic mutants lacking SPN, SLO, and both toxins are equally impaired in ability to cause necrotizing myositis. In addition, mutants lacking either SPN or SLO are significantly attenuated in the bacteremia and soft tissue infection models, and the mutant strain lacking production of both toxins is further attenuated. The mutant strain lacking both SPN and SLO production is severely attenuated in ability to resist killing by human polymorphonuclear leukocytes. We conclude that both SPN and SLO contribute significantly to S. pyogenes pathogenesis in these virulence assays.

Caenorhabditis elegans glutamylating enzymes function redundantly in male mating.

Microtubule glutamylation is an important modulator of microtubule function and has been implicated in the regulation of centriole stability, neuronal outgrowth and cilia motility. Glutamylation of the microtubules is catalyzed by a family of tubulin tyrosine ligase-like (TTLL) enzymes. Analysis of individual TTLL enzymes has led to an understanding of their specific functions, but how activities of the TTLL enzymes are coordinated to spatially and temporally regulate glutamylation remains relatively unexplored. We have undertaken an analysis of the glutamylating TTLL enzymes in C. elegans We find that although all five TTLL enzymes are expressed in the embryo and adult worm, loss of individual enzymes does not perturb microtubule function in embryonic cell divisions. Moreover, normal dye-filling, osmotic avoidance and male mating behavior indicate the presence of functional amphid cilia and male-specific neurons. A ttll-4(tm3310); ttll-11(tm4059); ttll-5(tm3360) triple mutant, however, shows reduced male mating efficiency due to a defect in the response step, suggesting that these three enzymes function redundantly, and that glutamylation is required for proper function of the male-specific neurons.

Advanced Practice Provider Utilization in the Neurocritical Care Unit.

This article discusses the role of advanced practice providers (APPs) in the interprofessional team management of patients with critical neurologic illnesses and how this role has evolved through the years. There is increasing demand for these types of practitioners, formerly termed midlevel providers. Furthermore, the use of APPs appears to have a positive impact on patient satisfaction, reduced costs, and reduced length of stays.

Communication challenges in complex medical environments.

The provision of health care is becoming increasingly complex and can involve multiple providers and care setting transitions, particularly as the population is living longer, and often with chronic disease. The Electronic Health Record (EHR) was intended to provide a comprehensive documentation of a patient's health-related information; however, health care systems often function in isolation with EHRs that are unique only to that system. The EHR may also limit face-to-face communication between treating physicians within the same system. It is only with diligent effort that changes in medical management plans are conveyed among providers. When multiple providers are involved in a patient's care, physician-to-patient communication may also suffer, which can impact patient satisfaction and outcome. This article describes a scenario in which several lapses in communication occurred, and it outlines other common pitfalls while providing possible solutions for improving communication across the health care spectrum.

Neurologic complications of infective endocarditis.

Infective endocarditis is an infection of the inner surface or endocardium of the heart, in most instances involving the heart valves or the mural portion of the endocardium. As nonbacterial organisms such as rickettsia, fungi, and even viruses may also cause endocarditis, the term "infective endocarditis" is preferred over the older terminology of "bacterial endocarditis." Despite advancements in medical treatment and surgical therapies over the last few decades, infective endocarditis continues to be associated with a poor prognosis. There are many different factors affecting the clinical outcome in patient with infective endocarditis, including the type of organism and its virulence, patient characteristics, comorbid illness, time to diagnosis and treatment, indications for surgery, and time to surgery when indicated. In this article, we will review the epidemiology of endocarditis, the neurologic complications of infective endocarditis, and the current therapeutic strategies.

Sex differences in the association of regional fat distribution with the severity of obstructive sleep apnea.

STUDY OBJECTIVES: To describe sex differences in the associations between severity of obstructive sleep apnea (OSA) and measures of obesity in body regions defined using both dual-energy absorptiometry and traditional anthropometric measures in a sleep-clinic sample. DESIGN: A prospective case-series observational study. SETTING: The Western Australian Sleep Health Study operating out of the Sir Charles Gairdner Hospital Sleep Clinic, Perth, Western Australia. PARTICIPANTS: Newly referred clinic patients (60 men, 36 women) suspected of having OSA. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Obstructive sleep apnea severity was defined by apnea-hypopnoea index from laboratory-based overnight polysomnography. Body mass index, neck, waist and hip circumference, neck-to-waist ratio, and waist-to-hip ratio were measured. Dual energy absorptiometry measurements included percentage fat and lean tissue. Multivariate regression models for each sex were developed. In women, percentage of fat in the neck region and body mass index together explained 33% of the variance in apnea-hypopnea index. In men, percentage of fat in the abdominal region and neck-to-waist ratio together accounted for 37% of the variance in apnea-hypopnea index. CONCLUSIONS: Regional obesity is associated with obstructive sleep apnea severity, although differently in men and women. In women, a direct influence of neck fat on the upper airway patency is implicated. In men, abdominal obesity appears to be the predominant influence. The apnea-hypopnea index was best predicted by a combination of Dual Energy Absorptiometry-measured mass and traditional anthropometric measurements.

Education research: evaluating acute altered mental status: are incoming interns prepared?

BACKGROUND: Clinical evaluation of hospitalized patients with acute altered mental status (AMS) is a common task of interns, regardless of medical specialty. The effectiveness of medical education to ensure competence in this area is unknown. OBJECTIVE: To measure competency of new interns in the evaluation and management of AMS using an Objective Structured Clinical Examination (OSCE). METHODS: A cohort study was conducted with 61 medical school graduates entering internship at a single teaching hospital in 2006. Interns from all major specialty fields were included. The OSCE consisted of a 12-minute simulated encounter with a human patient simulator and nurse actor. Each intern's performance was graded by the same neurologist, using criteria agreed upon by consensus of the neurology faculty. Competency in obtaining a history, performing a neurologic examination, generating a differential diagnosis, and ordering diagnostic studies was graded. Overall performance was scored on a percentage scale from 0 to 100. RESULTS: Overall performance scores ranged from 19 to 43 with a mean of 31.4 (SD +/- 5.6). Hypoglycemia was identified as a potential cause of AMS by 72.1% of interns, while fewer identified urinary tract infection (45.9%) and seizure (13.1%). While many interns ordered a CXR (86.9%) and head CT (80.3%), few requested a toxicology screen (21.3%) or lumbar puncture (3.3%). Only 41% of interns performed a neurologic examination. CONCLUSION: New interns are not well-prepared to evaluate patients with altered mental status in the inpatient setting as measured by an Objective Structured Clinical Examination.

The Western Australian Twin Register: a population-based register of adult and child multiples.

The Western Australian Twin Register (WATR) was established in 1997 to study the health of all child multiples born in Western Australia (WA). The Register has until recently consisted of all multiples born in WA between 1980 and 1997. Using unique record linkage capacities available through the WA data linkage system, we have subsequently been able to identify all multiple births born in WA since 1974. New affiliations with the Australian Twin Registry and the WA Institute for Medical Research are further enabled by the use of the WA Genetic Epidemiology Resource--a high-end bioinformatics infrastructure that allows efficient management of health datasets and facilitates collaborative research capabilities. In addition to this infrastructure, funding provided by these institutions has allowed the extension of the WATR to include a greater number of WA multiples, including those born between 1974 and 1979, and from 1998 onwards. These resources are in the process of being enabled for national and international access.