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Secondary outcomes included EGD findings and symptom response to dilation. RESULTS Thirty consecutive patients were included in the analyses. The most common presenting symptoms were nausea (66.7%), vomiting (60.0%) reflux (66.7%), and abdominal pain (54.8%). Twenty-two (73.3%) patients underwent UGIS prior to EGD. On diagnostic EGD, 27 (87.1%) patients were diagnosed with GSS. The sensitivity and NPV of UGIS to detect GSS was 30.0%, and 12.5%, respectively. All 6 patients with GSS on UGIS also had GSS on endoscopic evaluation (specificity = 100%, PPV = 100%). Twenty-six (86.6%) patients had resolution of symptoms with a mean 1.97 ± 1.13 dilations. CONCLUSION UGIS following SG has low NPV to evaluate for GSS. Independent of the UGIS findings, majority of patients found to have GSS on EGD had symptom improvement with dilations. The utility of UGIS is limited for diagnosing GSS and when suspicion for GSS is high, patients should be referred directly for EGD.BACKGROUND Unemployment has been reported to be associated with an increased risk of mortality. While most available studies focused on the effects of temporary unemployment on mortality, it remains unclear whether similar trends can be found in subjects who were never employed or are retirement. Therefore, this study examined the associations between temporary unemployment, never employed and retirement, integrating the risk of all-cause and cause-specific mortality in US adults. METHODS Data from the National Health Interview Survey from 2001 to 2013 Linked Mortality files through 31 December 2015 were used. A total of 282 364 participants aged 18 to 65 years were included. Their employment status was categorised into four groups employed, never employed, temporary unemployed and retired. RESULTS During the mean follow-up time of 8.2 years, 12 645 subjects died from a variety of causes. Compared with employed participants, temporary unemployed, never employed or retired participants faced an increased risk of mortality for all-cause (temporary unemployed HR 1.76, 95% CI 1.67 to 1.86; never employed HR 1.63, 95% CI 1.47 to 1.81; retired HR 1.27, 95% CI 1.17 to 1.37). Cause-specific mortality analysis showed that compared with employed participants, temporary unemployed or never employed participants faced a significantly increased risk of mortality from cancer, cardiovascular disease, chronic lower respiratory disease, diabetes and kidney disease. CONCLUSION This study showed that retired, temporary unemployed and never employed participants aged 18 to 65 years were strongly associated with higher mortality, indicating that both temporary and long-term unemployment are associated with a higher risk of mortality and adversely affect longevity. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Onametostat manufacturer Published by BMJ.BACKGROUND We used a relational social-class measure based on property ownership and managerial authority to analyse the longitudinal relationships between class, self-rated health (SRH) and mental illness. To our knowledge, this is the first study using a relational social-class measure to evaluate these relationships longitudinally. METHODS Using Panel Study of Income Dynamics data from 1984 to 2017, we first assigned respondents aged 25-64 to the not in the labour force (NILF), worker, manager, petit bourgeois (PB) or capitalist classes based on business ownership, managerial authority and employment status. Next, using Cox models, we estimated the confounder-adjusted associations between 2-year-lagged class and incidence of poor/fair SRH and serious mental illness. We also tested whether the associations varied by gender, whether they persisted after more-fully adjusting for traditional socioeconomic-status measures (education and income) and how they changed temporally. RESULTS We identified large inequities in poor/fair SRH. NILFs had the greatest hazard, followed by workers, PBs, managers and capitalists. We also identified large inequities in serious mental illness; NILFs and workers had the greatest hazard, while capitalists had the lowest. Class inequities in both outcomes lessened but remained considerable after confounder and socioeconomic-status adjustment, and we found some evidence that the class-SRH relationship varied by gender, as being NILF was more harmful among men than women. Additionally, class inequities in the outcomes decreased somewhat over time. CONCLUSION We identified substantial class inequities in SRH and mental illness. Our findings demonstrate the importance of using relational social-class measures to deepen understanding of health inequities' root causes. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Perineural invasion (PNI) is an ominous form of cancer progression along nerves associated with poor clinical outcome. Glial derived neurotrophic factor (GDNF) interacts with cancer cell RET receptors to enable PNI, but downstream events remain undefined. We demonstrate that GDNF leads to early activation of the GTPase Cdc42 in pancreatic cancer cells, but only delayed activation of RhoA and does not affect Rac1. Depletion of Cdc42 impairs pancreatic cancer cell chemotaxis towards GDNF and nerves. An siRNA library of guanine nucleotide exchange factors was screened to identify activators of Cdc42. ARHGEF7 (β-Pix) was required for Cdc42 activation and chemotaxis towards nerves, and also co-localizes with RET under GDNF stimulation. Cdc42 enables PNI in an in vitro dorsal root ganglia (DRG) co-culture model, and controls the directionality of migration but does not affect cell speed or cell viability. In contrast, Rac1 was necessary for cell speed but not directionality, while the RhoA was not necessary for either cell speed or directionality. Cdc42 was required for PNI in an in vivo murine sciatic nerve model. Depletion of Cdc42 significantly diminished the length of PNI, volume of PNI, and motor nerve paralysis resulting from PNI. Activated Cdc42 is expressed in human salivary ductal cancer cells invading nerves. These findings establish the GDNF-RET-β-Pix-Cdc42 pathway as a directional regulator of pancreatic cancer cell migration towards nerves, highlight the importance of directional migration in PNI, and offer novel targets for therapy. Implications The GTPase Cdc42 drives directional migration of pancreatic cancer cells towards nerves. Copyright ©2020, American Association for Cancer Research.

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