Pancreatic Duct Glands Are Distinct Ductal Compartments That React to Chronic Injury and Mediate Shh-Induced Metaplasia

BACKGROUND & AIMS: Pancreatic intraepithelial neoplasia (PanIN) are pancreatic cancer precursor lesions of unclear origin and significance. PanIN aberrantly express sonic hedgehog (Shh), an initiator of pancreatic cancer, and gastrointestinal mucins. A majority of PanIN are thought to arise from ducts. We identified a novel ductal compartment that is gathered in gland-like outpouches (pancreatic duct glands [PDG]) of major ducts and characterized its role in injury and metaplasia. METHODS: The ductal system was analyzed in normal pancreata and chronic pancreatitis in humans and mice. Anatomy was assessed by serial hematoxylin and eosin sections and scanning electron microscopy of corrosion casts. Expression of mucins and developmental genes and proliferation were assessed by immunohistochemistry or real-time quantitative polymerase chain reaction. Effects of Shh on ductal cells were investigated by exposure to Shh in vitro and transgenic misexpression in vivo. RESULTS: Three-dimensional analysis revealed blind-ending outpouches of ducts in murine and human pancreata. These PDG are morphologically and molecularly distinct from normal ducts; even in normal pancreata they display PanIN and metaplastic features, such as expression of Shh and gastric mucins. They express other developmental genes, such as Pdx-1 and Hes-1. In injury, Shh is up-regulated along with gastric mucins. Expansion of the PDG compartment results in a mucinous metaplasia. Shh promotes this transformation in vitro and in vivo. CONCLUSIONS: PDG are distinct gland-like mucinous compartments with a distinct molecular signature. In response to injury, PDG undergo an Shh-mediated mucinous gastrointestinal metaplasia with PanIN-like features. PDG may provide a link between Shh, mucinous metaplasia, and neoplasia

Screening for Chronic Conditions Using a Patient Internet Portal: Recruitment for an Internet-based Primary Care Intervention

Background: Patient Internet portals have created new opportunities for assessment and management of chronic conditions. Objective: To conduct an online screening survey for a study recruitment using a secure patient Internet portal to identify primary care patients with untreated depression, chronic pain, or mobility difficulty before nonurgent office visits. Design: Internet-based screening survey for a randomized trial. Participants: Patients who were registered portal users who had scheduled primary care appointments. Approach: Electronic study invitations via the portal were sent to 4,047 patients with scheduled visits to 34 primary care physicians participating in the study. After clicking on a link in the study invitation, patients were consecutively shown the study description, consent form, and lastly, the screening survey to determine final eligibility for study participation. Results: Of the 2,113 (52%) patients who opened the study invitation, 1,001 consented online to join the study and 981 (98%) of these completed the screening survey. Of the respondents, 319 (33%) screened positive for 1 or more of the 3 conditions. Conclusions: The online screening survey conducted through the patient portal was effective in identifying patients with chronic conditions in advance of scheduled primary care visits for participation in an intervention study

Prospective study comparing skin impedance with EEG parameters during the induction of anaesthesia with fentanyl and etomidate

<p>Abstract</p> <p>Objective</p> <p>Sympathetic stimulation leads to a change in electrical skin impedance. So far it is unclear whether this effect can be used to measure the effects of anaesthetics during general anaesthesia. The aim of this prospective study is to determine the electrical skin impedance during induction of anaesthesia for coronary artery bypass surgery with fentanyl and etomidate.</p> <p>Methods</p> <p>The electrical skin impedance was measured with the help of an electro-sympathicograph (ESG). In 47 patients scheduled for elective cardiac surgery, anaesthesia was induced with intravenous fentanyl 10 μg/kg and etomidate 0.3 mg/kg. During induction, the ESG (Electrosympathicograph), BIS (Bispectral IndeX), BP (arterial blood pressure) and HR (heart rate) values of each patient were recorded every 20 seconds. The observation period from administration of fentanyl to intubation for surgery lasted 4 min.</p> <p>Results</p> <p>The ESG recorded significant changes in the electrical skin impedance after administration of fentanyl and etomidate(p < 0.05). During induction of anaesthesia, significant changes of BIS, HR and blood pressure were observed as well (p < 0.05).</p> <p>Conclusions</p> <p>The electrical skin impedance measurement may be used to monitor the effects of anesthetics during general anaesthesia.</p

Disability and the Immigrant Health Paradox: Gender and Timing of Migration

Although research has documented better health and longer life expectancy among the foreign-born relative to their U.S.-born counterparts, the U.S. Mexican-origin immigrant population is diverse and the healthy immigrant effect likely varies by key structural and demographic factors such as gender, migration history, and duration in the United States. Using a life course framework, we use data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly (H-EPESE 1993–2013) which includes Mexican-American individuals aged 65 and older to assess the heterogeneity in the immigrant health advantage by age of migration and gender. We find that age of migration is an important delineating factor for disability among both men and women. The healthy immigrant hypothesis is only observable among mid- and late-life migrant men for ADL disability. While among immigrant women, late-life migrants are more likely to have an IADL disability putting them at a health disadvantage. These findings illustrate that Mexican immigrants are not a homogeneous group and migrant health selectivity depends on both gender and when migrants arrived in the United States

The MOBILIZE Boston Study: Design and methods of a prospective cohort study of novel risk factors for falls in an older population

<p>Abstract</p> <p>Background</p> <p>Falls are the sixth leading cause of death in elderly people in the U.S. Despite progress in understanding risk factors for falls, many suspected risk factors have not been adequately studied. Putative risk factors for falls such as pain, reductions in cerebral blood flow, somatosensory deficits, and foot disorders are poorly understood, in part because they pose measurement challenges, particularly for large observational studies.</p> <p>Methods</p> <p>The MOBILIZE Boston Study (MBS), an NIA-funded Program Project, is a prospective cohort study of a unique set of risk factors for falls in seniors in the Boston area. Using a door-to-door population-based recruitment, we have enrolled 765 persons aged 70 and older. The baseline assessment was conducted in 2 segments: a 3-hour home interview followed within 4 weeks by a 3-hour clinic examination. Measures included pain, cerebral hemodynamics, and foot disorders as well as established fall risk factors. For the falls follow-up, participants return fall calendar postcards to the research center at the end of each month. Reports of falls are followed-up with a telephone interview to assess circumstances and consequences of each fall. A second assessment is performed 18 months following baseline.</p> <p>Results</p> <p>Of the 2382 who met all eligibility criteria at the door, 1616 (67.8%) agreed to participate and were referred to the research center for further screening. The primary reason for ineligibility was inability to communicate in English. Results from the first 600 participants showed that participants are largely representative of seniors in the Boston area in terms of age, sex, race and Hispanic ethnicity. The average age of study participants was 77.9 years (s.d. 5.5) and nearly two-thirds were women. The study cohort was 78% white and 17% black. Many participants (39%) reported having fallen at least once in the year before baseline.</p> <p>Conclusion</p> <p>Our results demonstrate the feasibility of conducting comprehensive assessments, including rigorous physiologic measurements, in a diverse population of older adults to study non-traditional risk factors for falls and disability. The MBS will provide an important new data resource for examining novel risk factors for falls and mobility problems in the older population.</p

Do social networks affect the use of residential aged care among older Australians?

Background: Older people's social networks with family and friends can affect residential aged care use. It remains unclear if there are differences in the effects of specific (with children, other relatives, friends and confidants) and total social networks upon use of low-level residential care and nursing homes. Methods: Data were drawn from the Australian Longitudinal Study of Ageing. Six waves of data from 1477 people aged ≥ 70 collected over nine years of follow-up were used. Multinomial logistic regressions of the effects of specific and total social networks on residential care use were carried out. Propensity scores were used in the analyses to adjust for differences in participant's health, demographic and lifestyle characteristics with respect to social networks. Results Higher scores for confidant networks were protective against nursing home use (odds ratio [OR] upper versus lower tertile of confidant networks = 0.50; 95%CI 0.33–0.75). Similarly, a significant effect of upper versus lower total network tertile on nursing home use was observed (OR = 0.62; 95%CI 0.43–0.90). Evidence of an effect of children networks on nursing home use was equivocal. Nursing home use was not predicted by other relatives or friends social networks. Use of lower-level residential care was unrelated to social networks of any type. Social networks of any type did not have a significant effect upon low-level residential care use. Discussion: Better confidant and total social networks predict nursing home use in a large cohort of older Australians. Policy needs to reflect the importance of these particular relationships in considering where older people want to live in the later years of life.Lynne C Giles, Gary FV Glonek, Mary A Luszcz and Gary R Andrew

Schools out : Adam Smith and pre-disciplinary international political economy

In this article, I argue that invocations of Adam Smith in international political economy (IPE) often reveal the influence therein of a disciplinary ontological disaggregation of economic and non-economic rationality, which I claim is obscured by the tendency to map its complex intellectual contours in terms of competing schools. I trace the origins of the disciplinary characterisation of Smith as the founder of IPE's liberal tradition to invocations of his thought by centrally important figures in the perceived Austrian, Chicago and German historical schools of economics, and reflect upon the significance to IPE of the reiteration of this portrayal by apparent members of its so-called American and British schools. I additionally contrast these interpretations to those put forward by scholars who seek to interpret IPE and Smith's contribution to it in pre-disciplinary terms, which I claim reflects a distinct ontology to that attributed to the British school of IPE with which their work is often associated. I therefore contend that reflection upon invocations of Smith's thought in IPE problematises the longstanding tendency to map its intellectual terrain in terms of competing schools, reveals that the disciplinary ontological consensus that informs this tendency impacts upon articulations of its core concerns and suggests that a pre-disciplinary approach offers an alternative lens through which such concerns might be more effectively framed

A model of management academics' intentions to influence values

Business schools face increased criticism for failing in the teaching of management studies to nurture their students’ values. Assuming that individual academics play an important role in shaping the value-related influence of business schools, I model management academics’ intentions to influence values. The suggested model encompasses academics’ economic and social values as internal variables, as well as perceived support for attempting to influence values and academic tenure as social and structural variables. A test with empirical data from 1,254 management academics worldwide reveals that perceived external support is most relevant for explaining intentions. Moreover, academics’ social values, but not their economic ones, contribute to an explanation of their intentions to influence values. The results reveal how important it is for academics to believe that their colleagues, higher education institutions, and other stakeholders support their value-related behavioral intentions