Sinonasal mucosal melanoma: Molecular profile and therapeutic implications from a series of 32 cases

BACKGROUND: Primary sinonasal mucosal melanomas are aggressive tumors with a poor clinical control by current treatments, raising the urgent need of novel strategies. METHODS: By fluorescence in situ hybridization (FISH), direct sequencing, and immunohistochemistry, we investigate the spectrum of molecular abnormalities in a cohort of 32 cases of primary sinonasal mucosal melanomas. RESULTS: We found that all primary sinonasal mucosal melanomas lack BRAF V600E mutation; in addition, they are characterized by somatic mutations of NRAS (22%) and KIT (12.5%), together with amplification of RREB1 (100%) and loss of MYB (76%). The large majority of cases showed KIT protein expression (96.9%). Among tumor suppressor genes, primary sinonasal mucosal melanomas showed loss of PTEN (48.1%) and p16/INK4a (55.2%). All tested cases showed expression of pAkt and pErk, suggesting a combined activation of PI3K/Akt and RAS-mitogen-activated protein kinase (MAPK) pathways. CONCLUSIONS: This molecular fingerprint strongly argues against the clinical efficacy of BRAF-inhibitors, but could candidate primary sinonasal mucosal melanomas to therapeutic strategies targeting RAS and KIT mutations or inhibiting PI3K-Akt-mTOR pathway

How to be SSB-free: Assessing the attitudes and readiness for a sugar sweetened beverage-free healthcare center in the Bronx, NY

In recent years, communities and institutions have sought new interventions intended to reduce sugar sweetened beverage (SSB) consumption among children. Among these interventions are “SSB-free zones,” where such beverages are not permitted to be consumed on the premises. Insufficient knowledge still exists, however, about the readiness for such restrictive SSB policies within health care institutions. Understanding attitudes toward SSB consumption among adults is necessary to guide an institution-wide policy, where staff and patients serve as role models for parents and their children. We conducted focus groups with health center patients and staff to determine perceptions surrounding health and SSB consumption and to better understand the support and readiness (or lack thereof) for an SSB-free zone intervention prior to its implementation. We found that contextual practices present challenges to breaking personal consumption habits, even if beverages are banned from the worksite. Nevertheless, participants expressed support for SSB-free zones, and recommended more education about the harmful effects of soda and energy drink consumption to help improve acceptability for the policy. We conclude that policies restricting onsite SSB consumption may be more effective when combined with educational information and expressions of understanding that this specific behavior change can be difficult

Equality, Trust and Universalism in Europe, Canada and the United States: Implications for Health Care Policy

A number of theoretical explanations seek to describe the factors that have led to the position of the United States as the last industrialized Western nation without a universal health care program. Theories focus on institutional arrangement, historic precedent, and the influence of the private sector and market forces. This study explores another factor: the role of underlying social values. The research examines differences in values among ten European countries, the United States and Canada, and analyzes the associations between the values that have been seen to contribute the individualism-collectivism dynamic in the United States. The hypothesis that equality and generalized trust are positively associated with universalism is only partially true. Equality is positively associated (B = .301, p \u3c .001), while generalized trust is negatively associated with universalism (B = -.052, p \u3c .001). Not only do Americans show lower levels of support for income equality and universalism than Europeans, but the effect of being American holds even after controlling for socio-demographic and religious variables (B = .044, p \u3c .01). When the model tests the association of equality and trust on universalism in each region, it explains approximately 17 percent of the variance of universalism for the United States, and approximately 13 percent in Europe and Canada

Sinonasal mucosal melanoma: Molecular profile and therapeutic implications from a series of 32 cases

BACKGROUND: Primary sinonasal mucosal melanomas are aggressive tumors with a poor clinical control by current treatments, raising the urgent need of novel strategies. METHODS: By fluorescence in situ hybridization (FISH), direct sequencing, and immunohistochemistry, we investigate the spectrum of molecular abnormalities in a cohort of 32 cases of primary sinonasal mucosal melanomas. RESULTS: We found that all primary sinonasal mucosal melanomas lack BRAF V600E mutation; in addition, they are characterized by somatic mutations of NRAS (22%) and KIT (12.5%), together with amplification of RREB1 (100%) and loss of MYB (76%). The large majority of cases showed KIT protein expression (96.9%). Among tumor suppressor genes, primary sinonasal mucosal melanomas showed loss of PTEN (48.1%) and p16/INK4a (55.2%). All tested cases showed expression of pAkt and pErk, suggesting a combined activation of PI3K/Akt and RAS-mitogen-activated protein kinase (MAPK) pathways. CONCLUSIONS: This molecular fingerprint strongly argues against the clinical efficacy of BRAF-inhibitors, but could candidate primary sinonasal mucosal melanomas to therapeutic strategies targeting RAS and KIT mutations or inhibiting PI3K-Akt-mTOR pathway

Renal impairment after liver transplantation - a pilot trial of calcineurin inhibitor-free vs. calcineurin inhibitor sparing immunosuppression in patients with mildly impaired renal function after liver transplantation

<p>Abstract</p> <p>Objectives</p> <p>Chronic kidney disease is frequent in patients after orthotopic liver transplantation (OLT) and has impact on survival. Patients receiving calcineurin inhibitors (CNI) are at increased risk to develop impaired renal function. Early CNI reduction and concomitant use of mycophenolat mofetil (MMF) has been shown to improve renal function.</p> <p>Methods</p> <p>The aim of this trial was to compare dose-reduced CNI/MMF versus CNI-free MMF/prednisone-based treatment in stable patients after OLT with respect to glomerular filtration rate (GFR). 21 patients [GFR 44.9 ± 9.9 mL/min/1.73 m²measured by 99m-Tc-DTPA-clearance, serum creatinine (SCr) 1.5 ± 0.42 mg/dL] were randomized either to exchange CNI for 10 mg prednisone (group 1; n = 8) or to receive CNI at 25% of the initial dose (group 2; n = 13) each in combination with 1000 mg MMF b.i.d.</p> <p>Results</p> <p>At month 12 mean SCr (-0.3 ± 0.4 mg/dL, p = 0.031) and GFR improved (8.6 ± 13.1 mL/min/1.73 m², p = 0.015) in group 2 but remained unchanged in group 1. Main side effects were gastroinstestinal symptoms (14.3%) and infections (4.8%). Two biopsy proven, steroid-responsive rejections occurred. In group 1 mean diastolic blood pressure (BP) increased by 11 ± 22 mmHg (p = 0.03).</p> <p>Conclusions</p> <p>Reduced dose CNI in combination with MMF but not CNI-free-immunosuppression leads to improvement of GFR in patients with moderately elevated SCr levels after OLT. Addition of steroids resulted in increased diastolic blood pressure presumably counterbalancing the benefits of CNI withdrawal on renal function.</p

Northeast Waste Management Enterprise (NEWME) 1996 annual/final report

The Northeast Waste Management Enterprise was created in response to Dr. Clyde Frank`s vision of a new partnership between research, industrial, and financial sectors, with the goal of speeding development and use (particularly at U.S. Department of Energy [DOE] facilities) of environmental remediation technologies. It was anticipated that this partnership would also strengthen the international competitiveness of the U.S. environmental industry. Brookhaven National Laboratory`s (BNL) response to Dr. Frank was a proposal to create the Northeast Waste Management Alliance, later renamed the Northeast Waste Management Enterprise (NEWME). Recognizing the need to supplement its own technical expertise with acumen in business, financial management, and venture capital development, BNL joined forces with the Long Island Research Institute (LIRI). Since its inception at the end of FY 1993, NEWME has achieved several significant accomplishments in pursuing its original business and strategic plans. However, its successes have been constrained by a fundamental mismatch between the time scales required for technology commercialization, and the immediate need for available environmental technologies of those involved with ongoing environmental remediations at DOE facilities

What Do Urban College Students Really Think about Health Insurance? A Qualitative Study

Objective: To determine barriers and opportunities to health insurance enrollment among an undergraduate students at a large urban university. Participants: Participants were 31 college students enrolled in 4-year and community colleges in the City University of New York (CUNY), and six health services and insurance enrollment specialists who facilitate and assist in the health insurance enrollment process for CUNY students. Methods: Focus groups were conducted with students and in-depth interviews with key informants in May 2017. Results: The research revealed important insights into how students perceive and value insurance and yielded recommendations for the university to improve enrollment of its students. Conclusions: Many colleges can increase student enrollment in health insurance by informing and educating students about the process. Improving enrollment processes can increase insurance rates and improve student population health

Countermarketing Alcohol and Unhealthy Food: An Effective Strategy for Preventing Noncommunicable Diseases? Lessons from Tobacco

Countermarketing campaigns use health communications to reduce the demand for unhealthy products by exposing motives and undermining marketing practices of producers. These campaigns can contribute to the prevention of noncommunicable diseases by denormalizing the marketing of tobacco, alcohol, and unhealthy food. By portraying these activities as outside the boundaries of civilized corporate behavior, countermarketing can reduce the demand for unhealthy products and lead to changes in industry marketing practices. Countermarketing blends consumer protection, media advocacy, and health education with the demand for corporate accountability. Countermarketing campaigns have been demonstrated to be an effective component of comprehensive tobacco control. This review describes commonelements of tobacco countermarketing such as describing adverse health consequences, appealing to negative emotions, highlighting industry manipulation of consumers, and engaging users in the design or implementation of campaigns. It then assesses the potential for using these elements to reduce consumption of alcohol and unhealthy foods

Imaging in situ breast carcinoma (with or without an invasive component) with technetium-99m pentavalent dimercaptosuccinic acid and technetium-99m 2-methoxy isobutyl isonitrile scintimammography

INTRODUCTION: The aim of the study was to retrospectively define specific features of the technetium-99m pentavalent dimercaptosuccinic acid ((99m)Tc-(V)DMSA) and technetium-99m 2-methoxy isobutyl isonitrile ((99m)Tc-Sestamibi [(99m)Tc-MIBI]) distribution in ductal breast carcinoma in situ and lobular breast carcinoma in situ (DCIS/LCIS), in relation to mammographic, histological and immunohistochemical parameters. MATERIALS AND METHODS: One hundred and two patients with suspicious palpation or mammographic findings were submitted preoperatively to scintimammography (a total of 72 patients with (99m)Tc-(V)DMSA and a total of 75 patients with (99m)Tc-Sestamibi, 45 patients receiving both radiotracers). Images were acquired at 10 min and 60 min, and were evaluated for a pattern of diffuse radiotracer accumulation. The tumor-to-background ratios were correlated (T-pair test) with mammographic, histological and immunohistochemical characteristics. RESULTS: Histology confirmed malignancy in 46/102 patients: 20/46 patients had DCIS/LCIS, with or without coexistent invasive lesions, and 26/46 patients had isolated invasive carcinomas. Diffuse (99m)Tc-(V)DMSA accumulation was noticed in 18/19 cases and (99m)Tc-Sestamibi in 6/13 DCIS/LCIS cases. Epithelial hyperplasia demonstrated a similar accumulation pattern. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value for each tracer were calculated. Solely for (99m)Tc-(V)DMSA, the tumor-to-background ratio was significantly higher at 60 min than at 10 min and the diffuse uptake was significantly associated with suspicious microcalcifications, with the cell proliferation index ≥ 40% and with c-erbB-2 ≥ 10%. CONCLUSION: (99m)Tc-(V)DMSA showed high sensitivity and (99m)Tc-Sestamibi showed high specificity in detecting in situ breast carcinoma ((99m)Tc-(V)DMSA especially in cases with increased cell proliferation), and these radiotracers could provide clinicians with preoperative information not always obtainable by mammography