Outcomes of Student-Driven, Faculty-Mentored Research and Impact on Postgraduate Training and Career Selection.

Objective. To evaluate scholarly deliverables from student-driven research and explore the impact on postgraduate training placement rates, pharmacy faculty appointments and lifetime publications. Methods. A retrospective analysis of Doctor of Pharmacy graduates who conducted student research between the academic years of 2002 and 2015 was performed. Data were collected on research participation, abstracts, presentations, postgraduate training, full-time faculty appointments, and publications. Results. Of 1229 graduates, 300 participated in research during pharmacy school. Fifty-six percent (n=167) submitted at least one abstract and 68 students (23%) published their research. Research participation was associated with a significantly higher likelihood of postgraduate training and specialty training. Research participation positively affected the likelihood of faculty appointment and lifetime publication rate. Conclusion. Students who engaged in elective research had significant scholarly deliverables, including peer-reviewed publications, and were more likely to successfully match in a postgraduate position and achieve full-time academic appointments.

The impact of dementia on antidiabetic drug use in Medicare beneficiaries with diabetes: findings post-Medicare part D.

AIM: The objectives of the study were to measure the utilization rates of antidiabetic drugs in diabetic patients with dementia and to assess the impact of dementia on antidiabetic drug use. MATERIALS & METHODS: This study was a pooled cross-sectional study of the Medicare Current Beneficiaries Survey from 2006 to 2010. RESULTS & CONCLUSION: Lower utilizations of biguanides, DPP-4 inhibitors and thiazolidinediones were observed in dementia patients. The likelihood of using antidiabetic drugs was about 30% (odds ratio: 0.69; 95% CI: 0.56-0.84) lower in dementia patients and 40% (odds ratio: 0.61; 95% CI: 0.44-0.84) lower in patients with Alzheimer's disease. Healthcare providers should be aware of underuse of antidiabetic drugs in patients with dementia.

The Midwifery Legacies Project: history, progress, and future directions.

The Midwifery Legacies Project, formerly known as the OnGoing Group, was founded as an annual greeting card outreach aimed at maintaining contact with midwives as they approached retirement and beyond. In 2009, the importance of documenting personal and professional stories of midwives arose out of a bequest by a midwife who was relatively unknown outside of the community she served. The result has been the evolution of a robust collection of stories, which are known as the 20th Century Midwife Story Collection. Between 2009 and 2014, more than 120 US midwives aged 65 years or older were interviewed by a midwife, a student midwife, or a professional filmmaker. Collectively, these midwives' stories offer an intimate snapshot of the social, political, and cultural influences that have shaped US midwifery during the past half century. Individually, the stories honor and recognize midwives' contributions to the profession and the women they have served. This article details the development, progress, and future directions of the Midwifery Legacies Project.

Nuclear transport of the serum response factor coactivator MRTF-A is downregulated at tensional homeostasis.

The serum response factor (SRF) coactivator myocardin-related transcription factor A (MAL/MKL1/MRTF-A), the nuclear transport and activity of which is regulated by monomeric actin, has been implicated in tension-based regulation of SRF-mediated transcriptional activity. However, the mechanisms involved remain unclear. We used fibroblasts grown within collagen matrices to explore whether MRTF-A transport is regulated by tissue tension. We show that MRTF-A nuclear accumulation following stimulation with serum, actin drugs or acute mechanical stress is prevented within mechanically loaded, anchored matrices at tensional homeostasis. This is accompanied by a higher G/F actin ratio, defective nuclear import and increased cofilin expression. We propose that tension regulates MRTF-A/SRF activity through cofilin-mediated modulation of actin dynamics.

P115 RhoGEF and microtubules decide the direction apoptotic cells extrude from an epithelium.

To preserve epithelial barrier function, dying cells are squeezed out of an epithelium by "apoptotic cell extrusion." Specifically, a cell destined for apoptosis signals its live neighboring epithelial cells to form and contract a ring of actin and myosin II that squeezes the dying cell out of the epithelial sheet. Although most apoptotic cells extrude apically, we find that some exit basally. Localization of actin and myosin IIA contraction dictates the extrusion direction: basal extrusion requires circumferential contraction of neighboring cells at their apices, whereas apical extrusion also requires downward contraction along the basolateral surfaces. To activate actin/myosin basolaterally, microtubules in neighboring cells reorient and target p115 RhoGEF to this site. Preventing microtubule reorientation restricts contraction to the apex, driving extrusion basally. Extrusion polarity has important implications for tumors where apoptosis is blocked but extrusion is not, as basal extrusion could enable these cells to initiate metastasis.

The molecular and functional phenotype of glomerular podocytes reveals key features of contractile smooth muscle cells.

The glomerular podocyte is a highly specialized cell, with the ability to ultrafilter blood and support glomerular capillary pressures. However, little is known about either the genetic programs leading to this functionality or the final phenotype. We approached this question utilizing a human conditionally immortalized cell line, which differentiates from a proliferating epithelial phenotype to a differentiated form. We profiled gene expression during several time points during differentiation and grouped the regulated genes into major functional categories. A novel category of genes that was upregulated during differentiation was of smooth muscle-related molecules. We further examined the smooth muscle phenotype and showed that podocytes consistently express the differentiated smooth muscle markers smoothelin and calponin and the specific transcription factor myocardin, both in vitro and in vivo. The contractile contribution of the podocyte to the glomerular capillary is controversial. We demonstrated using two novel techniques that podocytes contract vigorously in vitro when differentiated and in real time were able to demonstrate that angiotensin II treatment decreases monolayer resistance, morphologically correlating with enhanced contractility. We conclude that the mature podocyte in vitro possesses functional apparatus of contractile smooth muscle cells, with potential implications for its in vivo ability to regulate glomerular dynamic and permeability characteristics.

Disruption of target cell adhesion structures by the Yersinia effector YopH requires interaction with the substrate domain of p130Cas.

The docking protein p130Cas has, together with FAK, been found as a target of the Yersinia virulence effector YopH. YopH is a protein tyrosine phosphatase that is delivered into host cells via the bacterial type III secretion machinery, and the outcome of its activity is inhibition of host cell phagocytosis. In the present study using p130Cas-/- cells, and p130Cas-/- cells expressing variants of GFPp130Cas, we show that this docking protein, via its substrate domain, is responsible for subcellular targeting of YopH in eukaryotic cells. Since YopH inhibits phagocytosis, p130Cas was expected to be critical for signalling mediating bacterial internalization. However, p130Cas-/- cells did not exhibit reduced capacity to internalize Yersinia. On the other hand, when a dominant negative variant of p130Cas was expressed in these cells, the phagocytic capacity was severely impaired. Moreover, the p130Cas-/- cells displayed a marked reduced sensitivity towards YopH-mediated detachment compared to wild-type cells. Transfecting these cells with full-length p130Cas rendered cells hypersensitive to both mechanical and Yersinia-mediated detachment. This hypersensitivity was not seen upon transfection with the dominant negative substrate domain-deleted variant of p130Cas. This implicates p130Cas as a prominent regulator of cell adhesion, where its substrate-binding domain has a significant function.

Complementary therapy use by women's health clinic clients.

CONTEXT: While it is known that more women than men use complementary and alternative therapies, it is important to look at women who are pregnant or possibly receiving hormonal therapy, as side effects and consequences of these therapies may have a significant effect on their health status. OBJECTIVE: To assess women's knowledge, perceived effectiveness and use of 20 complementary and alternative therapies. DESIGN: Descriptive four-page questionnaire to obtain data on the use, reason for use, knowledge, perceived effectiveness, and sources of information of twenty complementary and alternative therapies. SETTING: Women's Health Center at a large Midwestern hospital. PARTICIPANTS: A convenience sample of 250 women waiting to be seen by either a nurse midwife or obstetrician/gynecologist at an outpatient clinic. RESULTS: Sixty-nine percent of the participants used one or more complementary therapy. The most frequently used therapies included prayer, vitamins, massage, diet, and aromatherapy. The best predictor of use of each therapy was the participant's knowledge of the therapy. Participants generally rated the efficacy of the therapies higher than their knowledge level. Frequently cited sources of information were popular media and family. The least common information sources were nurse-midwives, drug stores, Internet, and other professional healthcare providers. CONCLUSIONS: Women in this setting use complementary therapies at a rate greater than the general population. The participants obtained a great deal of their information about the therapies from popular press, media, friends, and family members rather than from licensed healthcare providers.

Myosin II-dependent cortical movement is required for centrosome separation and positioning during mitotic spindle assembly.

The role of myosin II in mitosis is generally thought to be restricted to cytokinesis. We present surprising new evidence that cortical myosin II is also required for spindle assembly in cells. Drug- or RNAi-mediated disruption of myosin II in cells interferes with normal spindle assembly and positioning. Time-lapse movies reveal that these treatments block the separation and positioning of duplicated centrosomes after nuclear envelope breakdown (NEBD), thereby preventing the migration of the microtubule asters to opposite sides of chromosomes. Immobilization of cortical movement with tetravalent lectins produces similar spindle defects to myosin II disruption and suggests that myosin II activity is required within the cortex. Latex beads bound to the cell surface move in a myosin II-dependent manner in the direction of the separating asters. We propose that after NEBD, completion of centrosome separation and positioning around chromosomes depends on astral microtubule connections to a moving cell cortex.

Microtubule-dependent regulation of Rho GTPases during internalisation of Yersinia pseudotuberculosis.

Internalisation of the human pathogen Yersinia pseudotuberculosis via interaction of bacterial invasin with host beta1 integrins depends on the actin cytoskeleton and involves Src family kinases, focal adhesion kinase, p130Crk-associated substrate, proline-rich tyrosine kinase 2, Rac, Arp 2/3 complex and WASP family members. We show here that Rho GTPases are regulated by the microtubule system during bacterial uptake. Interfering with microtubule organisation using nocodazole or paclitaxel suppressed uptake by HeLa cells. The nocodazole effect on microtubule depolymerisation was partially inhibited through overexpression of Rac, Cdc42, RhoG or RhoA and completely prevented by expression of Vav2. This suggests that microtubules influence Rho GTPases during invasin-mediated phagocytosis and in the absence of functional microtubules Vav2 can mimic their effect on one, or more, of the Rho family GTPases. Lastly, overexpression of p50 dynamitin partially inhibited bacterial uptake and this effect was also blocked by co-expression of Vav2, thus further implicating this guanine nucleotide exchange factor in activating Rho GTPases for internalisation during loss of microtubule function.

Resistance to phagocytosis by Yersinia.

Enteropathogenic species of the genus Yersinia penetrate the intestinal epithelium and then spread to the lymphatic system, where they proliferate extracellularly. At this location, most other bacteria are effectively ingested and destroyed by the resident phagocytes. Yersinia, on the other hand binds to receptors on the external surface of phagocytes, and from this location it blocks the capacity of these cells to exert their phagocytic function via different receptors. The mechanism behind the resistance to phagocytosis involves the essential virulence factor YopH, a protein tyrosine phosphatase that is translocated into interacting target cells via a type III secretion machinery. YopH disrupts peripheral focal complexes of host cells, seen as a rounding up of infected cells. The focal complex proteins that are dephosphorylated by YopH are focal adhesion kinase and Crk-associated substrate, the latter of which is a common substrate in both professional and non-professional phagocytes. In macrophages additional substrates have been found, the Fyn-binding/SLP-76-associated protein and SKAP-HOM. Phagocytosis is a rapid process that is activated when the bacterium interacts with the phagocyte. Consequently, the effect exerted by a microbe to block this process has to be rapid and precise. This review deals with the mechanisms involved in impeding uptake as well as with the role of the YopH substrates and focal complex structures in normal cell function.