Background The epithelial-mesenchymal transition (EMT) is critical in the development of invasive epithelial malignancies. EMT is accelerated by inflammation and results in decreased E-cadherin ...expression. Diet-induced obesity is an inflammatory state that accelerates pancreatic carcinogenesis; its effect on EMT and E-cadherin expression in the development of pancreatic ductal adenocarcinoma is unclear. Methods Conditional KrasG12D mice were fed a control diet or a high-fat, high-calorie diet for 3 or 9 months ( n = 10 each). Immunohistochemistry with anti-E-cadherin antibody was performed. E-cadherin expression was characterized by staining intensity, location, and proportion of positive cells. In vitro expression of E-cadherin and Slug in primary pancreatic intraepithelial neoplasia (PanIN) and cancer cells was determined by Western blot. Results The HFCD led to increased weight gain in both 3- (15.8 vs 5.6 g, P < .001) and 9-month (19.8 vs 12.9 g, P = .007) mice. No differences in E-cadherin expression among various stages of preinvasive PanIN lesions were found—regardless of age or diet. In invasive cancer, E-cadherin expression was aberrant, with loss of membranous staining and prominent cytoplasmic staining, associated with strong, cytoplasmic expression of β-catenin. In vitro expression of E-cadherin was greatest in primary PanIN cells, accompanied by absent Slug expression. Cancer cell lines demonstrated significantly decreased E-cadherin expression in the presence of upregulated Slug. Conclusion Despite increased pancreatic inflammation and accelerated carcinogenesis, the high-fat, high-calorie diet did not induce changes in E-cadherin expression in PanIN lesions of all stages. Invasive lesions demonstrated aberrant cytoplasmic E-cadherin staining. Loss of normal membranous localization may reflect a functional loss of E-cadherin.
This paper presents a unique perspective on enhancing the physicochemical mechanisms of two distinct highly sensitive nanostructured metal oxide micro hot plate gas sensors by utilizing an innovative ...multifrequency interrogation method. The two types of sensors evaluated here employ an identical silicon transducer geometry but with a different morphological structure of the sensitive film. While the first sensing film consists of self-ordered tungsten oxide nanodots, limiting the response kinetics of the sensor–chemical species pair only to the reaction phenomena occurring at the sensitive film surface, the second modality is a three-dimensional array of tungsten oxide nanotubes, which in turn involves both the diffusion and adsorption of the gas during its reaction kinetics with the sensitive film itself. By utilizing the proposed multifrequency interrogation methodology, we demonstrate that the optimal temperature modulation frequencies employed for the nanotubes-based sensors to selectively detect hydrogen, carbon monoxide, ethanol, and dimethyl methyl phosphonate (DMMP) are significantly higher than those utilized for the nanodot-based sensors. This finding helps understand better the amelioration in selectivity that temperature modulation of metal oxides brings about, and, most importantly, it sets the grounds for the nanoengineering of gas-sensitive films to better exploit their practical usage.
•Among medically insured patients, pharmacotherapy for alcohol use disorder is rare.•Patients who are male, younger, or have liver disease have lower odds of receipt.•Patients with comorbid cannabis ...use disorders have lower odds of receipt.•Psychiatry evaluation correlates with increased patient receipt.
Alcohol use disorder is a highly prevalent disease with multiple medications available for treatment. The overall prevalence of patients receiving pharmacotherapy is believed to be low and the characteristics and comorbidities that affect receipt are not well-established.
We created a dataset from Truven Health Analytics MarketScan Commercial Claims and Encounters Database of patients with an outpatient encounter for alcohol abuse or dependence in 2014. We subsequently identified patient characteristics, comorbid medical, psychiatric, or substance use disorders, as well as encounter provider specialties and, using multivariable logistic regression, assessed which variables correlated with increased or decreased receipt of pharmacotherapy for alcohol use disorder for this population.
In our dataset of 123,355 patients, patient receipt of pharmacotherapy for alcohol use disorder was 3.3 %, and 9.3 % when restricted to the former diagnosis of alcohol dependence only. Male sex, younger age, alcohol-related liver disease, and cannabis use disorders correlated with decreased receipt whereas comorbid major depressive disorders and anxiety disorders correlated with increased receipt. Compared to patients seen by psychiatrists, those seen by primary medical doctors had a lower odds of receiving pharmacotherapy.
Pharmacotherapy for alcohol use disorder is an underutilized treatment modality with a low prevalence of prescription in insured individuals. Patients with specific characteristics and comorbidities are less likely to receive this treatment and greater focus on these patients and in the primary care setting can allow for increased prescribing of these medications.
Introduction
Patients at increased risk of bleeding and recurrent VTE who develop venous thromboembolism (VTE) present challenges for clinical management. This study evaluated the effectiveness and ...safety of apixaban vs warfarin in patients with VTE who have risk factors for bleeding or recurrences.
Methods
Adult patients with VTE initiating apixaban or warfarin were identified from five claims databases. Stabilized inverse probability treatment weighting (IPTW) was used to balance characteristics between cohorts for the main analysis. Subgroup interaction analyses were conducted to evaluate treatment effects among patients with and without each of the conditions that increased the risk of bleeding (thrombocytopenia and history of bleed) or recurrent VTE (thrombophilia, chronic liver disease, and immune-mediated disorders).
Results
A total of 94,333 warfarin and 60,786 apixaban patients with VTE met selection criteria. After IPTW, all patient characteristics were balanced between cohorts. Apixaban (vs warfarin) patients were at lower risk of recurrent VTE (HR 95% confidence interval (CI) 0.72 0.67–0.78), major bleeding (MB) (HR 95% CI 0.70 0.64–0.76), and clinically relevant non-major (CRNM) bleeding (HR 95% CI 0.83 0.80–0.86). Subgroup analyses showed generally consistent findings with the overall analysis. For most subgroup analyses, there were no significant interactions between treatment and subgroup strata on VTE, MB and CRNM bleeding.
Conclusion
Patients with prescription fills for apixaban had lower risk of recurrent VTE, MB, and CRNM bleeding compared with warfarin patients. Treatment effects of apixaban vs warfarin were generally consistent across subgroups of patients at increased risk of bleeding/recurrences.
Indoor nonindustrial work environments were designated a priority research area through the nationwide stakeholder process that created the National Occupational Research Agenda. A multidisciplinary ...research team used member consensus and quantitative estimates, with extensive external review, to develop a specific research agenda. The team outlined the following priority research topics: building-influenced communicable respiratory infections, building-related asthma/allergic diseases, and nonspecific building-related symptoms; indoor environmental science; and methods for increasing implementation of healthful building practices. Available data suggest that improving building environments may result in health benefits for more than 15 million of the 89 million US indoor workers, with estimated economic benefits of $5 to $75 billion annually. Research on these topics, requiring new collaborations and resources, offers enormous potential health and economic returns.
Obesity increases the incidence of multiple types of cancer. Our previous work has shown that a high-fat, high-calorie diet (HFCD) leads to visceral obesity, pancreatic inflammation, and accelerated ...pancreatic neoplasia in KrasG12D (KC) mice. In this study, we aimed to investigate the effects of an HFCD on visceral adipose inflammation with emphasis on potential differences between distinct visceral adipose depots.
We examined the weight and visceral obesity in both wild-type and KC mice on either control diet (CD) or HFCD. After 3 months, mice were killed for histological examination. Multiplex assays were also performed to obtain cytokine profiles between different adipose depots.
Both wild-type and KC mice on an HFCD exhibited significantly increased inflammation in the visceral adipose tissue, particularly in the peripancreatic fat (PPF), compared with animals on a CD. This was associated with significantly increased inflammation in the pancreas. Cytokine profiles were different between visceral adipose depots and between mice on the HFCD and CD.
Our results clearly demonstrate that an HFCD leads to obesity and inflammation in the visceral adipose tissue, particularly the PPF. These data suggest that obesity-associated inflammation in PPF may accelerate pancreatic neoplasia in KC mice.
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