"Okay, We Get It. You Vape": An Analysis of Geocoded Content, Context, and Sentiment regarding E-Cigarettes on Twitter.

The current study examined conversations on Twitter related to use and perceptions of e-cigarettes in the United States. We employed the Social Media Analytic and Research Testbed (SMART) dashboard, which was used to identify and download (via a public API) e-cigarette-related geocoded tweets. E-cigarette-related tweets were collected continuously using customized geo-targeted Twitter APIs. A total of 193,051 tweets were collected between October 2015 and February 2016. Of these tweets, a random sample of 973 geocoded tweets were selected and manually coded for information regarding source, context, and message characteristics. Our findings reveal that although over half of tweets were positive, a sizeable portion was negative or neutral. We also found that, among those tweets mentioning a stigma of e-cigarettes, most confirmed that a stigma does exist. Conversely, among tweets mentioning the harmfulness of e-cigarettes, most denied that e-cigarettes were a health hazard. These results suggest that current efforts have left the public with ambiguity regarding the potential dangers of e-cigarettes. Consequently, it is critical to communicate the public health stance on this issue to inform the public and provide counterarguments to the positive sentiments presently dominating conversations about e-cigarettes on social media. The lack of awareness and need to voice a public health position on e-cigarettes represents a vital opportunity to continue winning gains for tobacco control and prevention efforts through health communication interventions targeting e-cigarettes.

Cutaneous structural and biochemical correlates of foot complications in high-risk diabetes.

OBJECTIVE: Impairment of skin quality may contribute to diabetic foot ulceration (DFU). Our goal was to determine whether high-risk patients exhibited specific skin structural and metabolic deficits that could predispose to foot complications. RESEARCH DESIGN AND METHODS: A total of 46 patients comprising 9 diabetic control subjects, 16 with diabetic peripheral neuropathy (DPN) alone, and 21 with recurrent DFUs (including 9 with Charcot neuroarthropathy [CNA]) were recruited and compared with 14 nondiabetic control (NDC) subjects. DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI). Skin punch biopsies (3 mm) were performed on upper and lower leg skin for measurements of intraepidermal nerve fiber density (IENFD), structural analysis, type 1 procollagen abundance, tissue degrading matrix metalloproteinases (MMPs), and poly(ADP-ribose) (PAR) immunoreactivity. RESULTS: MNSI scores were comparable across DPN groups. IENFD was decreased by diabetes and DPN but did not differ between neuropathic groups. Skin structural deficit scores were elevated in all neuropathic subjects, particularly in the DFU group. Type 1 procollagen abundance was reduced in DFU subjects 387 ± 256 units (mean ± 1 SD) compared with NDC subjects (715 ± 100, P < 0.001). MMP-1 and MMP-2 were activated by diabetes. PAR immunoreactivity was increased in DFU (particularly in the CNA group; P < 0.01) compared with other DPN subjects. CONCLUSIONS: Increased PAR, reduced type 1 procollagen abundance, and impaired skin structure are associated with foot complications in diabetes. The potential of therapies that improve skin quality to reduce DFU needs to be investigated.

Effects of a synthetic retinoid on skin structure, matrix metalloproteinases, and procollagen in healthy and high-risk subjects with diabetes.

BACKGROUND: In diabetes, foot ulceration may result from increased skin fragility. Retinoids can reverse some diabetes-induced deficits of skin structure and function, but their clinical utility is limited by skin irritation. The effects of diabetes and MDI 301, a nonirritating synthetic retinoid, and retinoic acid have been evaluated on matrix metalloproteinases (MMPs), procollagen expression, and skin structure in skin biopsies from nondiabetic volunteers and diabetic subjects at risk of foot ulceration using organ culture techniques. METHODS: Zymography and enzyme-linked immunosorbent assay were utilized for analysis of MMP-1, -2, and -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) and immunohistochemistry for type I procollagen protein abundance. Collagen structure parameters were assessed in formalin-fixed, paraffin-embedded tissue sections. RESULTS: The % of active MMP-1 and -9 was higher and TIMP-1 abundance was lower in subjects with diabetes. Type 1 procollagen abundance was reduced and skin structural deficits were increased in diabetes. Three µM MDI 301 reduced active MMP-1 and -9 abundance by 29% (P < .05) and 40% (P < .05), respectively, and increased TIMP-1 by 45% (P = .07). MDI 301 increased type 1 procollagen abundance by 40% (P < .01) and completely corrected structural deficit scores. Two µM retinoic acid reduced MMP-1 but did not significantly affect skin structure. CONCLUSIONS: These data indicate that diabetic patients at risk of foot ulceration have deficits of skin structure and function. MDI 301 offers potential for repairing this skin damage complicating diabetes.

A novel use of a landmark to avoid injury of the anterior ethmoidal artery during endoscopic sinus surgery.

BACKGROUND: The aim of this study was to describe and correlate radiographically the anterior ethmoidal artery (AEA) to useful endoscopic surgical landmarks, such as the nasal beak (NB), nasal crest (NC), and axilla of the middle turbinate, because these are commonly encountered during endoscopic sinus surgery and skull base surgery. METHODS: A retrospective review and software analysis was performed by three independent observers. Measurements of distance and angulation from the AEA to the NC, NB, and axilla of the middle turbinate were performed. A total of 138 unique computed tomography (CT) scans performed at a university tertiary care center were evaluated. RESULTS: The average age of the patients whose scans were analyzed was 50.5 (range, 17-90 years) years of age. The gender distribution was 61 male and 89 female patients. After comparing the measurements to the three landmarks noted, it was determined that the NB had the most interpatient concordance and the least interobserver variability. The average distance between the NB and the AEA as it penetrates the lamina papyracea is 2.34 cm (variance, 0.07) at an angle of 45.21° from the Frankfurt horizontal line. CONCLUSION: The real advantage of this novel use of the NB as a landmark to identify the AEA is that it is easy to use, unobtrusive, and is not time-consuming. This relationship between the NB and the AEA is consistent across genders and ethnicities and is more valuable than others presented previously, which may be more variable.

Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer.

BACKGROUND: There is no established standard chemotherapy for patients with locally advanced or metastatic biliary tract cancer. We initially conducted a randomized, phase 2 study involving 86 patients to compare cisplatin plus gemcitabine with gemcitabine alone. After we found an improvement in progression-free survival, the trial was extended to the phase 3 trial reported here. METHODS: We randomly assigned 410 patients with locally advanced or metastatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer to receive either cisplatin (25 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter on days 1 and 8, every 3 weeks for eight cycles) or gemcitabine alone (1000 mg per square meter on days 1, 8, and 15, every 4 weeks for six cycles) for up to 24 weeks. The primary end point was overall survival. RESULTS: After a median follow-up of 8.2 months and 327 deaths, the median overall survival was 11.7 months among the 204 patients in the cisplatin-gemcitabine group and 8.1 months among the 206 patients in the gemcitabine group (hazard ratio, 0.64; 95% confidence interval, 0.52 to 0.80; P<0.001). The median progression-free survival was 8.0 months in the cisplatin-gemcitabine group and 5.0 months in the gemcitabine-only group (P<0.001). In addition, the rate of tumor control among patients in the cisplatin-gemcitabine group was significantly increased (81.4% vs. 71.8%, P=0.049). Adverse events were similar in the two groups, with the exception of more neutropenia in the cisplatin-gemcitabine group; the number of neutropenia-associated infections was similar in the two groups. CONCLUSIONS: As compared with gemcitabine alone, cisplatin plus gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity. Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer. (ClinicalTrials.gov number, NCT00262769.)

Overexpression of cellular iron import proteins is associated with malignant progression of esophageal adenocarcinoma.

PURPOSE: There is growing evidence that iron is important in esophageal adenocarcinoma, a cancer whose incidence is rising faster than any other in the Western world. However, how iron mediates carcinogenesis at the molecular level remains unclear. In this study, we investigated the expression of iron transport proteins involved in cellular iron import, export, and storage in the premalignant lesion Barrett's metaplasia and esophageal adenocarcinoma. EXPERIMENTAL DESIGN: Perls' staining was used to examine iron deposition in tissue. mRNA expression in samples of Barrett's metaplasia matched with esophageal adenocarcinoma and samples of Barrett's metaplasia without evidence of adenocarcinoma were examined by real-time PCR. Semiquantitative immunohistochemistry was used to examine cellular localization and protein levels. The effect of iron loading on cellular proliferation and iron transporter expression was determined in esophageal cell lines OE33 and SEG-1 using a bromodeoxyuridine assay and real-time PCR, respectively. RESULTS: In the progression of Barrett's metaplasia to adenocarcinoma, there was overexpression of divalent metal transporter 1 (DMT1), transferrin receptor 1, duodenal cytochrome b, ferroportin, and H-ferritin, and these changes were associated with increased iron deposition. Overexpression of DMT1 was further associated with metastatic adenocarcinoma. Iron loading OE33 and SEG-1 cells caused increased cellular proliferation, which was associated with increased H-ferritin and decreased transferrin receptor 1 and DMT1 expression. CONCLUSIONS: Progression to adenocarcinoma is associated with increased expression of iron import proteins. These events culminate in increased intracellular iron and cellular proliferation. This may represent a novel mechanism of esophageal carcinogenesis.

Snail family transcription factors are implicated in thyroid carcinogenesis.

E-Cadherin (CDH1) expression is reduced in thyroid carcinomas by primarily unknown mechanisms. In several tissues, SNAIL (SNAI1) and SLUG (SNAI2) induce epithelial-mesenchymal transition by altering target gene transcription, including CDH1 repression, but these transcription factors have not been studied in thyroid carcinoma. Recently, our group has provided direct evidence that ectopic SNAI1 expression induces epithelial and mesenchymal mouse tumors. SNAI1, SNAI2, and CDH1 expression were analyzed in thyroid-derived cell lines and samples of human follicular and papillary thyroid carcinoma by reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry. The effect of SNAI1 expression on CDH1 transcription was analyzed by reverse transcriptase-polymerase chain reaction and Western blotting in ori-3 cells. Thyroid carcinoma development was analyzed in CombitTA-Snail mice, in which SNAI1 levels are up-regulated. SNAI1 and SNAI2 were not expressed in cells derived from normal thyroid tissue, or in normal human thyroid samples, but were highly expressed in cell lines derived from thyroid carcinomas, in human thyroid carcinoma samples, and their metastases. SNAI1 expression in ori-3 cells repressed CDH1 transcription. Combi-TA mice developed papillary thyroid carcinomas, the incidence of which was increased by concomitant radiotherapy. In conclusion, SNAI1 and SNAI2 are ectopically expressed in thyroid carcinomas, and aberrant expression in mice is associated with papillary carcinoma development.

Slug regulates integrin expression and cell proliferation in human epidermal keratinocytes.

The human epidermis is a self-renewing epithelial tissue composed of several layers of keratinocytes. Within the epidermis there exists a complex array of cell adhesion structures, and many of the cellular events within the epidermis (differentiation, proliferation, and migration) require that these adhesion structures be remodeled. The link between cell adhesion, proliferation, and differentiation within the epidermis is well established, and in particular, there is strong evidence to link the process of terminal differentiation to integrin adhesion molecule expression and function. In this paper, we have analyzed the role of a transcriptional repressor called Slug in the regulation of adhesion molecule expression and function in epidermal keratinocytes. We report that activation of Slug, which is expressed predominantly in the basal layer of the epidermis, results in down-regulation of a number of cell adhesion molecules, including E-cadherin, and several integrins, including alpha3, beta1, and beta4. We demonstrate that Slug binds to the alpha3 promoter and that repression of alpha3 transcription by Slug is dependent on an E-box sequence within the promoter. This reduction in integrin expression is reflected in decreased cell adhesion to fibronectin and laminin-5. Despite the reduction in integrin expression and function, we do not observe any increase in differentiation. We do, however, find that activation of Slug results in a significant reduction in keratinocyte proliferation.

Beta-endorphin decreases fatigue and increases glucose uptake independently in normal and dystrophic mice.

beta-Endorphin and a C-terminal analogue have been shown to decrease muscle fatigue and increase glucose uptake in muscles of normal mice. In order to provide evidence whether these peptides might be useful in muscle-wasting conditions and whether the two actions of the peptides are interdependent, the effect of beta-endorphin on muscle fatigue and glucose uptake was studied using isolated hemidiaphragm preparations of dystrophic mice as well as normal mice. Muscle contractions were elicited by high-frequency stimulation of the phrenic nerve. Glucose uptake was measured using (nonmetabolizable) 2-deoxy-D-[1-(3)H]glucose. beta-Endorphin and the C-terminal analogue reduced fatigue in normal muscles of males but not females. Insulin had no effect in either sex. The peptides increased 2-deoxyglucose uptake in contracting and noncontracting muscles of normal males and females. beta-Endorphin reduced fatigue and increased deoxyglucose uptake in dystrophic muscles. The effect on fatigue was not due to increased glucose uptake, as the energy substrate present was pyruvate. Nerve stimulation released beta-endorphin immunoreactivity from intramuscular nerves of dystrophic mice. It is hypothesized that beta-endorphin released from motor nerves as well as from the pituitary could be responsible for improving muscle function during exercise. beta-Endorphin or analogues could have therapeutic use in muscle-wasting disease.

Upregulation of the pro-opiomelanocortin gene in motoneurones after acrylamide administration in mice.

Immunocytochemistry was used to demonstrate the presence of beta-endorphin and alpha-MSH, and in situ hybridisation was used to study the presence of pro-opiomelanocortin (POMC) mRNA, in spinal motoneurones, up to 8 days following the administration of a single dose of acrylamide in mice. The proportions of POMC-mRNA positive neurones, beta-endorphin-immunoreactive neurones and alpha-MSH-immunoreactive neurones were significantly increased in the treated animals compared to controls. It seems likely that upregulation of the POMC gene precedes acrylamide-induced neuropathy.

gamma delta T cells infiltrating sensory nerve biopsies from patients with inflammatory neuropathy.

Sensory nerve biopsy specimens from patients with Guillain Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and controls consisting of other neuropathies, were examined in order to characterise the nature and intensity of any inflammatory infiltrate. In order to establish whether gamma delta T cells were present in these infiltrates we examined the expression of alpha beta and gamma delta T cell receptors in the biopsy specimens from patients with inflammatory neuropathy. A section of each biopsy specimen was simultaneously cultured in order to attempt to establish T cell lines. T cell lines were established in 4 out of 7 patients with GBS of which 2 were gamma delta in phenotype. There was a significant correlation between the number of mononuclear cells detected by immunostaining within the biopsy specimens and the chance of successfully establishing a T cell line. Histological studies detected gamma delta T cell receptor in 2 out of the 7 patients with GBS, 14 out of the 20 with CIDP and in 5 out of the 13 controls (vasculitis 3, paraneoplastic 1, axonal neuropathy of uncertain cause 1). The presence of T cells of a gamma delta T cell receptor phenotype in nerve biopsy specimens from patients with inflammatory neuropathy is consistent with a possible pathogenetic role of a cellular immune response against non-protein antigens such as gangliosides.