Discriminative Stimulus Effects of Magnesium Chloride: Substitution Studies with Monoamine Uptake Inhibitors and N-Methyl-D-Aspartate Antagonists 1

ABSTRACT Previous studies suggest that magnesium chloride may have discriminative stimulus effects that partially overlap with those of noncompetitive N-methyl-D-aspartate antagonists as well as certain monoamine uptake inhibitors. In our study, rats were trained to discriminate 100 mg/kg magnesium chloride from saline and its discriminative stimulus effects were characterized with respect to N-methyl-D-aspartate receptor and monoamine transporter functions in substitution tests. The discriminative stimulus effects of magnesium chloride were acquired within a moderate number of training sessions and showed dose-related substitution after either subcutaneous (3-300 mg/kg) or intracerebroventricular (0.3-300 g) administration. The intracerebroventricular administration of magnesium chloride was over 4000 times more potent than its s.c. administration. The monoamine uptake inhibitors cocaine, GBR 12909, talsupram and citalopram fully substituted (Ն90% magnesium-appropriate responses) for magnesium chloride in the majority of subjects tested and the group averages reached a maximum of 72 to 82% responses on the magnesium-appropriate lever. Based on relative potency analysis, the rank order of potency of these four drugs for producing magnesium-appropriate responses was talsupram ϭ cocaine Ͼ citalopram ϭ GBR 12909. The N-methyl-D-aspartate receptor antagonists dizocilpine, phencyclidine and NPC 17742 engendered maximum group averages of 49 to 65% responses on the magnesium-appropriate lever. The results suggest that the centrally mediated discriminative stimulus effects of magnesium chloride may be more directly related to interactions with monoamine neurotransmitter functions than to N-methyl-D-aspartate receptor blockade

The National COVID Cohort Collaborative (N3C): Rationale, design, infrastructure, and deployment.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) poses societal challenges that require expeditious data and knowledge sharing. Though organizational clinical data are abundant, these are largely inaccessible to outside researchers. Statistical, machine learning, and causal analyses are most successful with large-scale data beyond what is available in any given organization. Here, we introduce the National COVID Cohort Collaborative (N3C), an open science community focused on analyzing patient-level data from many centers. MATERIALS AND METHODS: The Clinical and Translational Science Award Program and scientific community created N3C to overcome technical, regulatory, policy, and governance barriers to sharing and harmonizing individual-level clinical data. We developed solutions to extract, aggregate, and harmonize data across organizations and data models, and created a secure data enclave to enable efficient, transparent, and reproducible collaborative analytics. RESULTS: Organized in inclusive workstreams, we created legal agreements and governance for organizations and researchers; data extraction scripts to identify and ingest positive, negative, and possible COVID-19 cases; a data quality assurance and harmonization pipeline to create a single harmonized dataset; population of the secure data enclave with data, machine learning, and statistical analytics tools; dissemination mechanisms; and a synthetic data pilot to democratize data access. CONCLUSIONS: The N3C has demonstrated that a multisite collaborative learning health network can overcome barriers to rapidly build a scalable infrastructure incorporating multiorganizational clinical data for COVID-19 analytics. We expect this effort to save lives by enabling rapid collaboration among clinicians, researchers, and data scientists to identify treatments and specialized care and thereby reduce the immediate and long-term impacts of COVID-19

A View from the Past Into our Collective Future: The Oncofertility Consortium Vision Statement

Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future

Increased Incidence of Vestibular Disorders in Patients With SARS-CoV-2

OBJECTIVE: Determine the incidence of vestibular disorders in patients with SARS-CoV-2 compared to the control population. STUDY DESIGN: Retrospective. SETTING: Clinical data in the National COVID Cohort Collaborative database (N3C). METHODS: Deidentified patient data from the National COVID Cohort Collaborative database (N3C) were queried based on variant peak prevalence (untyped, alpha, delta, omicron 21K, and omicron 23A) from covariants.org to retrospectively analyze the incidence of vestibular disorders in patients with SARS-CoV-2 compared to control population, consisting of patients without documented evidence of COVID infection during the same period. RESULTS: Patients testing positive for COVID-19 were significantly more likely to have a vestibular disorder compared to the control population. Compared to control patients, the odds ratio of vestibular disorders was significantly elevated in patients with untyped (odds ratio [OR], 2.39; confidence intervals [CI], 2.29-2.50; CONCLUSIONS: The incidence of vestibular disorders differed between COVID-19 variants and was significantly elevated in COVID-19-positive patients compared to the control population. These findings have implications for patient counseling and further research is needed to discern the long-term effects of these findings

Pelvic Floor Dysfunction in the Female Athlete

Pelvic floor dysfunction (PFD) is a term used to describe a variety of disorders involving moderate to severe impairment of the pelvic floor muscles. It can be divided into two broad categories. Relaxing PFD is more common, presenting with urinary incontinence, fecal incontinence, or pelvic organ prolapse. Nonrelaxing PFD symptoms include impaired ability to evacuate urine or stool, sexual dysfunction, and pelvic pain. Unfamiliarity with this diagnosis among medical providers along with nonspecific symptoms often lead to a delayed or missed diagnosis for patients. Here, we present the case of a collegiate soccer player with PFD to illustrate the severity of presentation and progression of this disorder. We review the current literature regarding nonrelaxing PFD and all types of PFD in female athletes to raise awareness and recognition of this condition

MOTherhood: How Occupational Therapy Can Support the Role of Mothers with a Disability

Problem Statement Women with disabilities experience challenges with participating in meaningful occupations of motherhood; therefore, there is a need to determine what occupational therapy interventions are effective to promote increased participation within the role of motherhood PICO Question For women with disabilities, what are effective interventions within the scope of occupational therapy practice that increase participation in the role of motherhood? Objectives By the end of the presentation participants will be able to: Recognize the prevalence of disability on mothers and how disability impacts participation in occupations relating to motherhood Discuss the need for occupational therapy (OT) interventions that are effective in facilitating participation in occupations relating to the role of motherhood Describe the role of OT services for mothers with disabilitie