Women's Health Policy in the United States: An American College of Physicians Position Paper.

In this position paper, the American College of Physicians (ACP) examines the challenges women face in the U.S. health care system across their lifespans, including access to care; sex- and gender-specific health issues; variation in health outcomes compared with men; underrepresentation in research studies; and public policies that affect women, their families, and society. ACP puts forward several recommendations focused on policies that will improve the health outcomes of women and ensure a health care system that supports the needs of women and their families over the course of their lifespans.

Achieving Gender Equity in Physician Compensation and Career Advancement: A Position Paper of the American College of Physicians.

Women comprise more than one third of the active physician workforce, an estimated 46% of all physicians-in-training, and more than half of all medical students in the United States. Although progress has been made toward gender diversity in the physician workforce, disparities in compensation exist and inequities have contributed to a disproportionately low number of female physicians achieving academic advancement and serving in leadership positions. Women in medicine face other challenges, including a lack of mentors, discrimination, gender bias, cultural environment of the workplace, imposter syndrome, and the need for better work-life integration. In this position paper, the American College of Physicians summarizes the unique challenges female physicians face over the course of their careers and provides recommendations to improve gender equity and ensure that the full potential of female physicians is realized.

Addressing Social Determinants to Improve Patient Care and Promote Health Equity: An American College of Physicians Position Paper.

Social determinants of health are nonmedical factors that can affect a person's overall health and health outcomes. Where a person is born and the social conditions they are born into can affect their risk factors for premature death and their life expectancy. In this position paper, the American College of Physicians acknowledges the role of social determinants in health, examines the complexities associated with them, and offers recommendations on better integration of social determinants into the health care system while highlighting the need to address systemic issues hindering health equity.

Autoimmune Schizophrenia? Psychiatric Manifestations of Hashimoto's Encephalitis.

Hashimoto's encephalitis (HE), also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), can be a debilitating manifestation of an autoimmune reaction against the thyroid that is often under-diagnosed primarily due to a lack of definitive diagnostic criteria. This is a case of a 52-year-old woman who has been diagnosed with HE after presenting with recurrent and severe psychosis in conjunction with paranoia and a thyroidopathy. Her symptoms are chronic, having first been documented as presenting 15 years prior and showing progressive exacerbation in both frequency and severity. The patient's paranoia often manifested as delusions involving family members or close friends and consequently introduced an opportunity for harm to herself and others. She showed great conviction with self-diagnoses that were proven incorrect, resulting in occasional non-compliance. Between episodes, the patient did not show evidence of symptoms. This patient struggled with several incorrect diagnoses and treatments for several years before the correct diagnosis of HE was made and displayed extreme improvement upon corticosteroid administration. This case illustrates the importance of increasing awareness of HE as well as including HE in a differential diagnosis when any patient presents with psychosis and concurrent thyroidopathy. Hashimoto's encephalitis follows putative characteristics of autoimmune diseases, exhibiting a higher incidence in women as compared to men, presenting with increased titers of autoantibodies, and showing dramatic amelioration when treated with corticosteroids.

Donor T cells lacking Fas ligand and perforin retain the capacity to induce severe GvHD in minor histocompatibility antigen mismatched bone-marrow transplantation recipients.

Graft-versus-host disease (GvHD) is a frequent impediment to therapeutically successful allogeneic bone-marrow transplantation (BMT). This investigation further examines the roles of two potential donor cytotoxic effector mechanisms previously implicated in tissue pathogenesis. Cytotoxically double deficient (B6-cdd) T cells (lacking functional fas ligand and perforin) and wild-type (B6-wt) donor T-cell transplantation in a minor antigen-mismatched BMT model (C57BL/6 --> C3H.SW) resulted in similar mortality and weight loss. Histopathologic findings revealed mononuclear infiltrates and cellular atrophy in GvHD target tissues (liver, stomach) in recipients of B6-wt and B6-cdd donor T cells. Both recipients also exhibited GvH-associated lymphohematopoietic compartment (LHC) alterations as evidenced by inverted CD4:CD8 ratios and B-cell hypoplasia. Notably, transplants using recombinant inbred mHAg disparate recipients demonstrated that B6-cdd T cells induced lethal GvHD in CXBE but not CXBG recipients: the same pattern induced by B6-wt T cells. This observation is consistent with previous findings that cytotoxic T lymphocyte (CTL) responses against CXBG and CXBE antigens did not correlate with GvH responses in these strains. In contrast with the typical pattern of donor T-cell expansion and contraction, T cells lacking perforin and FasL function exhibited extensive expansion postBMT. In summary, these findings support the notion that donor anti-host cytotoxicity by way of the two major pathways is not a prerequisite for induction of GvHD. In addition, the results suggest that this model will be useful to investigate the regulation of allogeneic donor T-cell expansion after major histocompatibility complex-matched allogeneic BMT.

The cytotoxic potential of regulatory T cells: what has been learned from gene knockout model systems?

The mechanisms of T-cell regulation are difficult to elucidate because of their complexity and the numerous subcategories of cell populations. There are two fundamental approaches to address this conundrum. First, it is possible to use a purified cell population and submit these cells to various assays. The second approach is to manipulate a target molecule and determine what effect this has on T-cell homeostasis in vitro and in vivo. This molecular strategy may help characterize multiple regulatory populations that use the same pathway for controlling T-cell function. Through a concerted two-pronged effort, the authors' laboratory and others have attempted to decipher different molecular pathways for regulatory cell function. Several gene knockout mouse models display a phenotype of profound lack of homeostasis in which T cells accumulate, presumably because of a defect in regulation. Dependent on the molecule disrupted, the immune cell subset being examined may no longer be appropriately regulated. Accordingly, the phenotype of exogenously added "putative" regulatory cells can then be examined by assessing their ability to control this aberrant accumulation. By using co-transplantation techniques, much information can be postulated regarding potential regulatory cell phenotype and function. Model systems with target gene manipulations involving Fas ligand, Fas, perforin, interleukin-2, and cytotoxic T-lymphocyte-associated antigen-4 exist and in all cases appear to disrupt critical cytotoxic regulatory cell function.