The IWill MCW Campaign: Individual Actions to Advance Gender Equity.

Advancing equity for women remains an urgent and complex problem at academic health centers. Attempts to mitigate gender gaps have ranged widely and have been both slow to occur and limited in effect. Recognizing the limitations of previously attempted solutions and fueled by the #MeToo and #TimesUp movements, the Medical College of Wisconsin (MCW) stepped outside known approaches (e.

The Great Mask Debate: A Debate That Shouldn't Be a Debate at All.

Background: Despite a rapidly growing and evolving literature, there continues to be a vigorous public debate about whether the community use of face coverings can mitigate the spread of COVID-19 ten months into the pandemic.

Objectives: This article describes a semi-structured literature review of the use of face coverings to prevent the spread of coronaviruses and similar respiratory pathogens, with a focus on SARS-CoV-2 (COVID-19).

Methods: : The author conducted a semi-structured literature review using search terms "COVID19" or "SARS-CoV-2" crossed with "mask/s" or "face covering/s.

Racial/Ethnic Differences In COVID-19 Screening, Hospitalization, And Mortality In Southeast Wisconsin.

This study aimed to understand racial/ethnic differences in coronavirus disease 2019 (COVID-19) screening, symptom presentation, hospitalization, and mortality, using data from 31,549 adults tested for COVID-19 between March 1 and July 10, 2020, in Milwaukee and Southeast Wisconsin. Racial/ethnic differences existed in adults who screened positive for COVID-19 (4.5 percent of non-Hispanic Whites, 14.

Drug Regimen Individualization for Attention-Deficit/Hyperactivity Disorder: Guidance for Methylphenidate and Dexmethylphenidate Formulations.

In 2000, the first biphasic modified-release (MR) formulation of methylphenidate (MPH) was approved for the treatment of attention-deficit/hyperactivity disorder (ADHD). An immediate-release (IR) MPH pulse (22% of the dose) facilitates rapid onset of stimulant action, while the remaining MR portion of the dose provides for day-long duration of efficacy. A wide array of oral MR-MPH products has subsequently been approved that also allows for once-daily dosing, though each product is characterized by distinctive exposure time courses.

Expanding the Health-care Pipeline through Innovation: The MCW model.

In 2016, the Association of American Medical Colleges projected a physician shortage in the United States of approximately 90,000; in the same year, the Wisconsin Hospital Association projected a shortage of 2,000 physicians in Wisconsin. The Medical College of Wisconsin has begun to address these shortages in three ways: 1) creation of immersive regional medical school campuses in Green Bay and Central Wisconsin, in partnership with rural serving health systems; 2) creation of rural-based psychiatry and family medicine residency programs in Green Bay and central Wisconsin; and 3) expansion of the scope of practice of pharmacists through creation of a new School of Pharmacy in collaboration with the Medical College of Wisconsin School of Medicine. This article will discuss those approaches, history and progress to date, principles used, and future plans to address the impending physician shortages.

Three-Year Experience of an Academic Medical Center Ombuds Office.

An ombuds is an individual who informally helps people or groups (visitors) resolve disputes and/or interpersonal conflicts as an alternative to formal dispute resolution mechanisms within an organization. Ombuds are nearly ubiquitous in many governmental, business, and educational settings but only recently have gained visibility at medical schools. Medical schools in the United States are increasingly establishing ombuds offices as part of comprehensive conflict management systems to address concerns of faculty, staff, students, and others.

The Advancing a Healthier Wisconsin Endowment: How a Health Care Conversion Foundation Is Transforming a Medical School.

Health care conversion foundations, such as the Advancing a Healthier Wisconsin Endowment (the endowment) at the Medical College of Wisconsin (MCW), result from the conversion of nonprofit health organizations to for-profit corporations. Over the past several decades, nearly 200 of these foundations have been created, and they have had a substantial impact on the field of health philanthropy. The MCW was a recipient of funds resulting from Blue Cross & Blue Shield United of Wisconsin's conversion from a nonprofit to a for-profit status in 1999.

The Merits and Challenges of Three-Year Medical School Curricula: Time for an Evidence-Based Discussion.

The debate about three-year medical school curricula has resurfaced recently, driven by rising education debt burden and a predicted physician shortage. In this Perspective, the authors call for an evidence-based discussion of the merits and challenges of three-year curricula. They examine published evidence that suggests that three-year curricula are viable, including studies on three-year curricula in (1) U.

Isoproterenol acts as a biased agonist of the alpha-1A-adrenoceptor that selectively activates the MAPK/ERK pathway.

The α1A-AR is thought to couple predominantly to the Gαq/PLC pathway and lead to phosphoinositide hydrolysis and calcium mobilization, although certain agonists acting at this receptor have been reported to trigger activation of arachidonic acid formation and MAPK pathways. For several G protein-coupled receptors (GPCRs) agonists can manifest a bias for activation of particular effector signaling output, i.e.

Epidermal growth factor-induced proliferation of collecting duct cells from Oak Ridge polycystic kidney mice involves activation of Na+/H+ exchanger.

Epidermal growth factor (EGF) is linked to the pathogenesis of polycystic kidney disease (PKD). We explored signaling pathways activated by EGF in orpk cilia (-) collecting duct cell line derived from a mouse model of PKD (hypomorph of the Tg737/Ift88 gene) with severely stunted cilia, and in a control orpk cilia (+) cell line with normal cilia. RT-PCR demonstrated mRNAs for EGF receptor subunits ErbB1, ErbB2, ErbB3, ErbB4, and mRNAs for Na(+)/H(+) exchangers (NHE), NHE-1, NHE-2, NHE-3, NHE-4, and NHE-5 in both cell lines.

Suppression of GNAI2 message in ovarian cancer.

Background: Understanding the integration of hormone signaling and how it impacts oncogenesis is critical for improved cancer treatments. Here we elucidate GNAI2 message alterations in ovarian cancer (OvCa). GNAI2 is a heterotrimeric G protein which couples cell surface hormone receptors to intracellular enzymes, and is best characterized for its direct role in regulating cAMP response element-binding protein (CREB) function by decreasing intracellular cAMP through inhibiting adenylyl cyclase.

The bradykinin B(2) receptor induces multiple cellular responses leading to the proliferation of human renal carcinoma cell lines.

Background: The vasoactive peptide bradykinin (BK) acts as a potent growth factor for normal kidney cells, but there have been few studies on the role of BK in renal cell carcinomas.

Purpose: In this study, we tested the hypothesis that BK also acts as a mitogen in kidney carcinomas, and explored the effects of BK in human renal carcinoma A498 cells.

Methods: The presence of mRNAs for BK B(1) and BK B(2) receptors in A498 cells was demonstrated by reverse transcription-polymerase chain reaction.

Enzymatic processing of angiotensin peptides by human glomerular endothelial cells.

The intraglomerular renin-angiotensin system (RAS) is linked to the pathogenesis of progressive glomerular diseases. Glomerular podocytes and mesangial cells play distinct roles in the metabolism of angiotensin (ANG) peptides. However, our understanding of the RAS enzymatic capacity of glomerular endothelial cells (GEnCs) remains incomplete.

Role of c-Cbl carboxyl terminus in serotonin 5-HT2A receptor recycling and resensitization.

The 5-hydroxytryptamine 2A receptor (5-HT(2A)R) undergoes constitutive and agonist-dependent internalization. Despite many advances in our understanding of G protein-coupled receptor trafficking, the exact mechanism of endocytic sorting of G protein-coupled receptors remains obscure. Recently, we have reported a novel finding documenting a global role for the ubiquitin ligase c-Cbl in regulating vesicular sorting of epidermal growth factor receptor (Baldys, A.

Role of integrins in angiotensin II-induced proliferation of vascular smooth muscle cells.

Angiotensin II (AII) binds to G protein-coupled receptor AT(1) and stimulates extracellular signal-regulated kinase (ERK), leading to vascular smooth muscle cells (VSMC) proliferation. Proliferation of mammalian cells is tightly regulated by adhesion to the extracellular matrix, which occurs via integrins. To study cross-talk between G protein-coupled receptor- and integrin-induced signaling, we hypothesized that integrins are involved in AII-induced proliferation of VSMC.

Novel mechanisms in the regulation of G protein-coupled receptor trafficking to the plasma membrane.

β(2)-adrenergic receptors (β(2)-AR) are low abundance, integral membrane proteins that mediate the effects of catecholamines at the cell surface. Whereas the processes governing desensitization of activated β(2)-ARs and their subsequent removal from the cell surface have been characterized in considerable detail, little is known about the mechanisms controlling trafficking of neo-synthesized receptors to the cell surface. Since the discovery of the signal peptide, the targeting of the integral membrane proteins to plasma membrane has been thought to be determined by structural features of the amino acid sequence alone.

Bradykinin decreases podocyte permeability through ADAM17-dependent epidermal growth factor receptor activation and zonula occludens-1 rearrangement.

Recent data show that increases in bradykinin (BK) concentration contribute to the beneficial effects of angiotensin-converting enzyme inhibitor (ACEI) treatment in chronic kidney disease. However, the possible role of BK in attenuated proteinuria, often seen in ACEI-treated patients, is not well studied. Here, we report that BK decreases mouse podocyte permeability through rearrangement of the tight junction protein zonula occludens-1 (ZO-1) and identify some of the major signaling events leading to permeability change.

Bradykinin B2 receptor interacts with integrin alpha5beta1 to transactivate epidermal growth factor receptor in kidney cells.

We have shown previously that the vasoactive peptide bradykinin (BK) stimulates proliferation of a cultured murine cell model of the inner medullary collecting duct (mIMCD-3 cells) via transactivation of epidermal growth factor receptor (EGFR) by a mechanism that involves matrix metalloproteinases (collagenase-2 and -3). Because collagenases lack an integral membrane domain, we hypothesized that receptors for extracellular matrix proteins, integrins, may play a role in BK-induced signaling by targeting collagenases to the membrane, thus forming a functional signaling complex. BK-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) in mIMCD-3 cells was reduced by approximately 65% by synthetic peptides containing an Arg-Gly-Asp sequence, supporting roles for integrins in BK-induced signaling.

Preventing and responding to complaints of sexual harassment in an academic health center: a 10-year review from the Medical University of South Carolina.

There is a high incidence of sexual harassment and gender discrimination in academic health center (AHC) settings according to multiple surveys of medical students. Therefore, it is incumbent on AHCs to develop programs both to educate faculty, residents, and students and to handle complaints of possible episodes of sexual harassment or gender discrimination. Despite the apparent high prevalence of gender discrimination and sexual harassment, and the importance of handling complaints of gender discrimination and sexual harassment in a prompt, consistent, and rational manner, there are few descriptions of programs that address those concerns in AHCs.

Critical role of ESCRT machinery in EGFR recycling.

The molecular mechanisms of EGFR vesicular trafficking to lysosomes have recently received considerable attention. It is now clear that endosomal sorting complexes required for transport (ESCRTs) are critical for EGFR degradation. Although an increasing number of membrane receptors also undergo recycling via specific pathways, little information is available regarding regulated recycling of EGFR.

Sustained receptor stimulation leads to sequestration of recycling endosomes in a classical protein kinase C- and phospholipase D-dependent manner.

Considerable insight has been garnered on initial mechanisms of endocytosis of plasma membrane proteins and their subsequent trafficking through the endosomal compartment. It is also well established that ligand stimulation of many plasma membrane receptors leads to their internalization. However, stimulus-induced regulation of endosomal trafficking has not received much attention.