ABSTRACT
Psychiatric and obstetric diseases are growing threats to public health and share high rates of co-morbidity. G protein-coupled receptor signaling (e.g., vasopressin, serotonin) may be a convergent psycho-obstetric risk mechanism. Regulator of G Protein Signaling 2 (RGS2) mutations increase risk for both the gestational disease preeclampsia and for depression. We previously found preeclampsia-like, anti-angiogenic obstetric phenotypes with reduced placental Rgs2 expression in mice. Here, we extend this to test whether conserved cerebrovascular and serotonergic mechanisms are also associated with risk for neurobiological phenotypes in the Rgs2 KO mouse. Rgs2 KO exhibited anxiety-, depression-, and hedonic-like behaviors. Cortical vascular density and vessel length decreased in Rgs2 KO; cortical and white matter thickness and cell densities were unchanged. In Rgs2 KO, serotonergic gene expression was sex-specifically changed (e.g., cortical Htr2a, Maoa increased in females but all serotonin targets unchanged or decreased in males); redox-related expression increased in paraventricular nucleus and aorta; and angiogenic gene expression was changed in male but not female cortex. Whole-cell recordings from dorsal raphe serotonin neurons revealed altered 5-HT1A receptor-dependent inhibitory postsynaptic currents (5-HT1A-IPSCs) in female but not male KO neurons. Additionally, serotonin transporter blockade by the SSRI sertraline increased the amplitude and time-to-peak of 5-HT1A-IPSCs in KO neurons to a greater extent than in WT neurons in females only. These results demonstrate behavioral, cerebrovascular, and sertraline hypersensitivity phenotypes in Rgs2 KOs, some of which are sex-specific. Disruptions may be driven by vascular and cell stress mechanisms linking the shared pathogenesis of psychiatric and obstetric disease to reveal future targets.
Subject(s)
Pre-Eclampsia , Serotonin , Humans , Female , Male , Mice , Pregnancy , Animals , Serotonin/metabolism , Sertraline , Pre-Eclampsia/metabolism , Placenta/metabolism , Dorsal Raphe Nucleus/metabolism , Mice, Knockout , Receptor, Serotonin, 5-HT1A/metabolismABSTRACT
Purpose: To report a case of an elderly man who presented with a choroidal metastasis from renal cell carcinoma that spontaneously regressed prior to any local or systemic treatment. Observations: An 82-year-old man without a history of metastatic cancer was referred to the ocular oncology service for evaluation of a newly noted amelanotic choroidal lesion. Examination and imaging findings were concerning for choroidal metastasis. Systemic workup revealed previously undiagnosed widely metastatic renal cell carcinoma. The lesion spontaneously regressed prior to the initiation of any treatment for his tumor. Conclusions and importance: This is a unique case of choroidal metastases from renal cell carcinoma that spontaneously regressed prior to medical or surgical treatment of the primary tumor.
ABSTRACT
A rise in international medical volunteering (IMV) poses complex issues for organizations, clinicians, and trainees to navigate. This article explores ethical implications of IMV, such as scope of practice, continuity of care, and erosion of local health systems, and offers a personal perspective from a related field.
Subject(s)
Health Personnel/ethics , Travel/ethics , Volunteers , Developing Countries , Humans , International Cooperation , International Educational Exchange , Medical Missions/ethicsABSTRACT
Federal health care reform has expanded medical insurance to millions of people, altering the role that hospitals play in improving community health. However, current federal and state community benefit policy is an ineffective tool for ensuring that hospitals address the social determinants of health afflicting their communities. Policy shifts and other incentives that promote improved population health outcomes can encourage health care organizations to do the same.
Subject(s)
Hospitals/ethics , Social Determinants of Health , Community-Institutional Relations , Health Care Reform/organization & administration , Health Services Needs and Demand , Health Status , Hospital Administration/ethics , HumansABSTRACT
As capabilities of predictive algorithms improve, machine learning will become an important element of physician practice and patient care. Implementation of artificial intelligence (AI) raises complex legal questions regarding health care professionals' and technology manufacturers' liability, particularly if they cannot explain recommendations generated by AI technology. The limited literature on liability for innovation provides opportunities to consider possible implications of AI for medical malpractice and products liability and new legal solutions for addressing liability issues surrounding "black-box" medicine.
