Long interspersed nuclear element-1 (L1) is a genetic element that mobilizes throughout the mammalian genome via retrotransposition and damages host DNA via mutational insertions, chromosomal rearrangements, and reprogramming of gene expression. The cellular mechanisms responsible for aberrant L1 expression during cancer pathogenesis are unclear. Previously, we have shown that L1 reactivation in several human cell lines is dependent upon the activation of aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor member of the PAS superfamily of proteins. We also showed that ectopic expression of L1 reprograms the HepG2 genome leading to epithelial-to-mesenchymal transition (EMT). Here we present evidence that reactivation of L1 and modulation of EMT in HepG2 cells by the AhR ligand benzo(a)pyrene (BaP) is effected through the canonical TGF-β1 signaling pathway. BaP increased TGF-β1 mRNA, SMAD2 phosphorylation and decreased expression of E-Cadherin. The functional relevance of these interactions and the involvement of TGFBR1/ALK5 and SMAD2/3 were confirmed by siRNA interference. Furthermore, expression of L1-encoded ORF1p was positively correlated with the activation of TGF-β1 signaling in human hepatocarcinoma samples at various stages of malignant progression. These results indicate that ligand-mediated AhR activation regulates L1 via canonical TGF-β1 signaling and raise important questions about the molecular etiology of human hepatocarcinomas.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.

Precise positioning of a plasmonic nanoparticle (NP) near a small dielectric surface is not only necessary for understanding gap-dependent interactions between a metal and dielectric but it is also a critical component in building ultrasensitive molecular rulers and force sensing devices. In this study we investigate the gap-dependent scattering of gold and silver NPs by controllably depositing them on an atomic force microscope (AFM) tip and monitoring their scattering within the evanescent field of a tin dioxide nanofiber waveguide. The enhanced distance-dependent scattering profiles due to plasmon-dielectric coupling effects show similar decays for both gold and silver NPs given the strong dependence of the coupling on the decaying power in the near-field. Experiments and simulations also demonstrate that the NPs attached to the AFM tips act as free NPs, eliminating optical interference typically observed from secondary dielectric substrates. With the ability to reproducibly place individual plasmonic NPs on an AFM tip, and optically monitor near-field plasmon-dielectric coupling effects, this approach allows a wide-variety of light-matter interactions studies to be carried out on other low-dimensional nanomaterials.

Background: Knowledge about tuberculosis (TB) is important for TB control, and China's national TB control guidelines emphasise TB health promotion. A 2010 national TB epidemiology survey showed that the general public had limited knowledge and awareness of TB. Objective: To assess the level of TB knowledge after 5 years of TB health promotion in Guizhou Province, one of the regions with the highest TB burden in China. Design and setting: A community-based, cross-sectional survey of 10 237 residents of Guizhou Province from June to August 2015. Multiple logistic regression models were used to examine factors associated with core TB knowledge and TB health education among respondents. Results: Overall, residents of Guizhou Province had inadequate knowledge of TB. The overall awareness of TB was 41.5%. Less than 30% of respondents were familiar with China's policy of free treatment for TB or knew that the disease could be cured. Factors associated with core TB knowledge included gender, age, ethnicity, education, occupation, region, and having received TB health education. Women, older adults, people employed in non-government institutions, and those living in counties with low TB burdens had little access to TB health education, whereas people with higher education levels had greater access. Respondents' sources of TB knowledge did not necessarily match their preferred channels for delivery of TB health education. Conclusions: Our findings indicate that TB health education should be further strengthened in China and other countries with a high TB burden. TB health education programmes require further formative and implementation research in order to improve programme effectiveness.

No description available.

Access to the bypassed portion of the stomach after Roux-en-Y gastric bypass remains a challenge. We present a case of 64-year-old woman who presented with gastric outlet obstruction. We used a novel endoscopic technique to access the bypassed stomach by creating a jejunogastrostomy using a specialized stent, which allowed the insertion of a pediatric gastroscope to examine the bypassed portion of the stomach. Stomach biopsies revealed poorly differentiated adenocarcinoma with signet cell features.

Background: Workforce and leadership development is imperative for the advancement of public health along the U.S./Mexico border. The Leaders across borders (LaB) program aims to train the public health and health-care workforce of the border region. The LaB is a 6-month intensive leadership development program, which offers training in various areas of public health. Program curriculum topics include: leadership, border health epidemiology, health diplomacy, border public policies, and conflict resolution. Methods: This article describes the LaB program evaluation outcomes across four LaB cohort graduates between 2010 and 2014. LaB graduates received an invitation to participate via email in an online questionnaire. Eighty-five percent (n = 34) of evaluation participants indicated an improvement in the level of binationality since participating in the LaB program. Identified themes in the evaluation results included increased binational collaborations and partnerships across multidisciplinary organizations that work towards improving the health status of border communities. Approximately 93% (n = 37) of the LaB samples were interested in participating in future binational projects while 80% (n = 32) indicated interest in the proposal of other binational initiatives. Participants expressed feelings of gratitude from employers who supported their participation and successful completion of LaB. Discussion: Programs such as LaB are important in providing professional development and education to a health-care workforce along the U.S./Mexico border that is dedicated to positively impacting the health outcomes of vulnerable populations residing in this region.

Background: Angiosarcomas are tumors of malignant endothelial origin that have a poor prognosis with a five-year survival of less than 40%. These tumors can be found in all age groups, but are more common in older patients; with the cutaneous form most common in older white men. Combined modality therapy including surgery and radiation appears to have a better outcome than each modality alone. When metastatic, agents such as liposomal doxorubicin, paclitaxel and ifosfamide have activity but it is short-lived and not curative. Immunotherapy targeting either the PD-1 receptor or PD-L1 ligand has recently been shown to have activity in multiple cancers including melanoma, renal, and non-small lung cancer. Although these agents have been used in sarcoma therapy, their ability to treat angiosarcoma has not been reported. Case presentation: Here we describe the case of a 63-year-old man who presented initially with angiosarcoma of the nose and received surgery for the primary. Over 4 years he had recurrent disease in the face and liver and was treated with nab-paclitaxel, surgery, and radioembolization, but continued to have progressive disease. His tumor was found to express PD-L1 and he received off- label pembrolizumab 2 mg/kg every 21 days for 13 cycles with marked shrinkage of his liver disease and no new facial lesions. Secondary to this therapy he developed hepatitis and has been treated with decreasing doses of prednisone. During the 8 months off therapy he has developed no new or progressive lesions. Conclusions: Although occasional responses to immunotherapy have been reported for sarcomas, this case report demonstrates that angiosarcoma can express PD-L1 and have a sustained response to PD-1 directed therapy.

Background: We evaluated the concept of whether liver failure patients with a superimposed kidney injury receiving a simultaneous liver and kidney transplant (SLKT) have similar outcomes compared to patients with liver failure without a kidney injury receiving a liver transplantation (LT) alone. Methods: Using data from the United Network of Organ Sharing (UNOS) database, patients were divided into five groups based on pre-transplant model for end-stage liver disease (MELD) scores and categorized as not having (serum creatinine (sCr) <= 1.5 mg/dL) or having (sCr > 1.5 mg/dL) renal dysfunction. Of 30,958 patients undergoing LT, 14,679 (47.5%) had renal dysfunction, and of those, 5,084 (16.4%) had dialysis. Results: Survival in those (liver failure with renal dysfunction) receiving SLKT was significantly worse (P < 0.001) as compared to those with sCr < 1.5 mg/dL (liver failure only). The highest mortality rate observed was 21% in the 36+ MELD group with renal dysfunction with or without SLKT. In high MELD recipients (MELD > 30) with renal dysfunction, presence of renal dysfunction affects the outcome and SLKT does not improve survival. In low MELD recipients (16 - 20), presence of renal dysfunction at the time of transplantation does affect post-transplant survival, but survival is improved with SLKT. Conclusions: SLKT improved 1-year survival only in low MELD (16 - 20) recipients but not in other groups. Performance of SLKT should be limited to patients where a benefit in survival and post-transplant outcomes can be demonstrated.

<div>From the mind</div><div>of a single, long vine,</div><div>one-hundred opening lives</div><div><br></div><div>(Chiyo-Ni translated by Jane Hirshfield and Mariko Aratani)<br></div>