MDM2 amplification in malignant Brenner tumors may play a role in progression to malignancy and aid in separation from urothelial and other ovarian carcinomas.

Malignant Brenner tumor (MBT) is diagnosed in the setting of invasive high-grade carcinoma with urothelial-like morphology and the presence of an adjacent benign Brenner tumor (BBT) or borderline Brenner tumor (BLBT). MDM2 amplification was recently detected by next-generation sequencing on a small number of MBTs, potentially significant for future targeted therapy. Experience is limited, however, and evaluation of widely available MDM2 immunohistochemistry (IHC) has not been performed to determine clinical utility. After confirming all diagnoses morphologically and immunohistochemically, we performed MDM2 IHC on 4 MBTs, 3 BLBTs, 26 BBTs, 142 high-grade serous carcinomas (HGSC), 6 ovarian endometrioid carcinomas (OEC) with urothelial-like morphology, and 49 high-grade urothelial carcinomas (HGUC). MDM2 IHC was considered positive with diffuse (>25%) nuclear reactivity; in cases of patchy staining (10-25% nuclear reactivity), MDM2 was considered equivocal. Positive staining in <10% of cells was considered negative. In cases with positive or equivocal staining, MDM2 amplification was evaluated by fluorescence in-situ hybridization (FISH). Three MBTs (75%) showed diffuse nuclear reactivity for MDM2 by IHC, a finding corroborated by amplification of MDM2 in all three cases. One MBT and 2 BLBTs showed equivocal MDM2 IHC, but all three were negative for MDM2 amplification. The final BLBT, as well as all BBTs, HGSC, OEC, and HGUC, were negative for MDM2. In conclusion, our limited cohort confirms MDM2 amplification in MBT and suggests that MDM2 IHC may have an influence in rare diagnostically challenging cases.

Challenges and opportunities to increasing fruit and vegetable distribution through the US charitable feeding network: increasing food systems recovery of edible fresh produce to build healthy food access.

This qualitative study describes opportunities and challenges to produce recovery identified by food banking executive leadership across the US (n = 33). Identified challenges included regional variation in fresh produce availability, long transportation times, and lack of refrigerated storage. Opportunities included high client demand for fresh produce, internal benchmarks for fresh produce distribution, and organizational partnerships to create regional sourcing and distribution efficiencies. This research indicates the need for cross-sector collaboration and planning efforts across the agricultural, health, and charitable feeding sectors in order to best recover and redistribute fresh produce.

Impact of an alternative chromosome 17 probe and the 2013 American Society of Clinical Oncology and College of American Pathologists guidelines on fluorescence in situ hybridization for the determination of HER2 gene amplification in breast cancer.

BACKGROUND: The dual-probe fluorescence in situ hybridization (FISH) assay for human epidermal growth factor receptor 2 (HER2) gene amplification in breast cancer provides an HER2:CEP17 (centromere enumeration probe for chromosome 17) ratio. Copy number alteration (CNA) in CEP17 may skew this ratio. The authors analyzed the impact of the 2013 American Society of Oncology/College of American Pathologists (ASCO/CAP) guidelines and an alternative chromosome 17 probe on HER2 status in tumor specimens with CEP17 CNA. METHODS: Specimens with CEP17 CNA (n = 310) were selected from 3048 tumor samples that were received from January 2013 to June 2015 for testing with the alternative chromosome 17 probe D17S122. Reclassification of HER2 status was assessed using the 2007 and 2013 ASCO/CAP guidelines. RESULTS: The alternative chromosome 17 probe reclassified 82 of 310 (26.5%) and 87 of 310 (28.1%) tumors using the 2007 and 2013 guidelines, respectively. Of the 41 of 310 tumors (13.2%) that were reclassified from nonamplified to amplified according to 2007 guidelines, 28 of 41 (68.3%) had an average HER2 copy number ≥4.0 and <6.0. The 39 of 310 tumors (12.6%) that were reclassified from equivocal to amplified according to 2013 guidelines had a mean HER2 copy number between ≥4.0 and <6.0. Most of these patients had stage I, hormone receptor-positive, lymph node-negative tumors, which is an unusual clinicopathologic profile for HER2-amplified tumors, and most received HER2-targeted therapy in addition to endocrine therapy. CONCLUSIONS: Reflex testing with an alternative chromosome 17 probe using the 2013 ASCO/CAP guidelines reclassified 28.1% of tumor samples that had CEP17 CNA, converting nearly one-half from equivocal to amplified. The benefit of HER2-targeted therapy in this patient population requires further study. Cancer 2017;123:2230-2239. © 2017 American Cancer Society.

Perinatal complications and aging indicators by midlife.

BACKGROUND: Perinatal complications predict increased risk for morbidity and early mortality. Evidence of perinatal programming of adult mortality raises the question of what mechanisms embed this long-term effect. We tested a hypothesis related to the theory of developmental origins of health and disease: that perinatal complications assessed at birth predict indicators of accelerated aging by midlife. METHODS: Perinatal complications, including both maternal and neonatal complications, were assessed in the Dunedin Multidisciplinary Health and Development Study cohort (N = 1037), a 38-year, prospective longitudinal study of a representative birth cohort. Two aging indicators were assessed at age 38 years, objectively by leukocyte telomere length (TL) and subjectively by perceived facial age. RESULTS: Perinatal complications predicted both leukocyte TL (ß = -0.101; 95% confidence interval, -0.169 to -0.033; P = .004) and perceived age (ß = 0.097; 95% confidence interval, 0.029 to 0.165; P = .005) by midlife. We repeated analyses with controls for measures of family history and social risk that could predispose to perinatal complications and accelerated aging, and for measures of poor health taken in between birth and the age-38 follow-up. These covariates attenuated, but did not fully explain the associations observed between perinatal complications and aging indicators. CONCLUSIONS: Our findings provide support for early-life developmental programming by linking newborns' perinatal complications to accelerated aging at midlife. We observed indications of accelerated aging "inside," as measured by leukocyte TL, an indicator of cellular aging, and "outside," as measured by perceived age, an indicator of declining tissue integrity. A better understanding of mechanisms underlying perinatal programming of adult aging is needed.

A Compilation of Metals and Trace Elements Extracted from Materials Relevant to Pharmaceutical Applications such as Packaging Systems and Devices.

Nearly 100 individual test articles, representative of materials used in pharmaceutical applications such as packaging and devices, were extracted under exaggerated conditions and the levels of 32 metals and trace elements (Ag, Al, As, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Ge, Li, Mg, Mn, Mo, Na, Ni, P, Pb, S, Sb, Se, Si, Sn, Sr, Ti, V, Zn, and Zr) were measured in the extracts. The extracting solvents included aqueous mixtures at low and high pH and an organic solvent mixture (40/60 ethanol water). The sealed vessel extractions were performed by placing an appropriate portion of the test articles and an appropriate volume of extracting solution in inert extraction vessels and exposing the extraction units (and associated extraction blanks) to defined conditions of temperature and duration. The levels of extracted target elements were measured by inductively coupled plasma atomic emission spectroscopy. The overall reporting threshold for most of the targeted elements was 0.05 µg/mL, which corresponds to 0.5 µg/g for the most commonly utilized extraction stoichiometry (1 g of material per 10 mL of extracting solvent). The targeted elements could be classified into four major groups depending on the frequency with which they were present in the over 250 extractions reported in this study. Thirteen elements (Ag, As, Be, Cd, Co, Ge, Li, Mo, Ni, Sn, Ti, V, and Zr) were not extracted in reportable quantities from any of the test articles under any of the extraction conditions. Eight additional elements (Bi, Cr, Cu, Mn, Pb, Sb, Se, and Sr) were rarely extracted from the test articles at reportable levels, and three other elements (Ba, Fe, and P) were infrequently extracted from the test articles at reportable levels. The remaining eight elements (Al, B, Ca, Mg, Na, S, Si, and Zn) were more frequently present in the extracts in reportable quantities. These general trends in accumulation behavior were compared to compiled lists of elements of concern as impurities in pharmaceutical products. LAY ABSTRACT: Nearly 100 individual test articles, representative of materials used in pharmaceutical applications such as packaging and devices, were extracted under exaggerated conditions, and the levels of thirty-two metals and trace elements (Ag, Al, As, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Ge, Li, Mg, Mn, Mo, Na, Ni, P, Pb, S, Sb, Se, Si, Sn, Sr, Ti, V, Zn, and Zr) were measured in the extracts. The targeted elements could be classified into four major groups depending on the frequency with which they were present in the extractions reported in this study: those elements that were not extracted in reportable quantities from any of the test articles under any of the extraction conditions, those elements that were rarely extracted from the test articles at reportable levels, those elements that were infrequently extracted from the test articles at reportable levels, and those elements that were more frequently present in the extracts in reportable quantities.

Using computer-based monitoring and intervention to prevent harmful combinations of antiretroviral drugs in the New York State AIDS Drug Assistance Program.

BACKGROUND: Despite the growing number of HIV-infected people and the acknowledged complexity of HIV therapy, there are no standard safeguards in the outpatient setting against dangerous antiretroviral (ARV) therapy combinations in the publicly financed arena. METHODS: Using quarterly pharmacy claims data from the New York State AIDS Drug Assistance Program, a three-phase approach was developed: The extent of contraindicated ARV combinations was ascertained; prescriber alerts were developed; and, finally, the reimbursement of contraindicated ARV combinations was blocked at pharmacy. ARV dosages, the number of ARV medications in a regimen, clinical adequacy of the regimen, medication claim denials, clinician adjudication, and subsequent clinician prescribing patterns were analyzed. RESULTS: For the 27-month study period (October 1, 2006-December 31, 2009), 112,383 ARV regimens involving 396,303 ARV medications for 25,463 unique recipients were individually analyzed. A total of 1,089 interventions occurred; denials and interventions increased per quarter from a baseline of 129 to 217 by the study's end. All contraindicated combinations referred for adjudication during the study were upheld. More than 88.3% (range, 87.1% to 89.9%) of regimens per quarter were consistent with effective ARV as promulgated by current guidelines. The targeted dissemination of ARV drug interaction safety alerts to previous prescribers of contraindicated combinations during the first year of the review curtailed the practice by 77.3%. CONCLUSION: A systems-level intervention can be used on a state level to reduce ARV contraindicated medication errors in the outpatient setting through a coordinated approach of prescriber clinical education and electronic pharmacy and billing systems and provides an effective safety and quality monitoring model.

What shall I be, what must I be: neural correlates of personal goal activation.

How is the brain engaged when people are thinking about their hopes, dreams, and obligations? Regulatory focus theory postulates two classes of personal goals and motivational systems for pursuing them. Ideal goals, such as hopes and aspirations, are pursued via the promotion system through "making good things happen." Ought goals, such as obligations or responsibilities, are pursued via the prevention system through "keeping bad things from happening." This study investigated the neural correlates of ideal and ought goal priming using an event-related fMRI design with rapid masked stimulus presentations. We exposed participants to their self-identified ideal and ought goals, yoked-control words and non-words. We also examined correlations between goal-related activation and measures of regulatory focus, behavioral activation/inhibition, and negative affect. Ideal priming led to activation in frontal and occipital regions as well as caudate and thalamus, whereas prevention goal priming was associated with activation in precuneus and posterior cingulate cortex. Individual differences in dysphoric/anxious affect and regulatory focus, but not differences in BAS/BIS strength, were predictive of differential activation in response to goal priming. The regions activated in response to ideal and ought goal priming broadly map onto the cortical midline network that has been shown to index processing of self-referential stimuli. Individual differences in regulatory focus and negative affect impact this network and appeared to influence the strength and accessibility of the promotion and prevention systems. The results support a fundamental distinction between promotion and prevention and extend our understanding of how personal goals influence behavior.

Height, body mass index, and ovarian cancer: a pooled analysis of 12 cohort studies.

BACKGROUND: Although many studies have investigated the association between anthropometry and ovarian cancer risk, results have been inconsistent. METHODS: The associations of height, body mass index (BMI), and ovarian cancer risk were examined in a pooled analysis of primary data from 12 prospective cohort studies from North America and Europe. The study population consisted of 531,583 women among whom 2,036 epithelial ovarian cancer cases were identified. To summarize associations, study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model. RESULTS: Women with height > or =1.70 m had a pooled multivariate RR of 1.38 [95% confidence interval (95% CI), 1.16-1.65] compared with those with height <1.60 m. For the same comparison, multivariate RRs were 1.79 (95% CI, 1.07-3.00) for premenopausal and 1.25 (95% CI, 1.04-1.49) for postmenopausal ovarian cancer (P(interaction) = 0.14). The multivariate RR for women with a BMI > or =30 kg/m(2) was 1.03 (95% CI, 0.86-1.22) compared with women with a BMI from 18.5 to 23 kg/m(2). For the same comparison, multivariate RRs were 1.72 (95% CI, 1.02-2.89) for premenopausal and 1.07 (95% CI, 0.87-1.33) for postmenopausal women (P(interaction) = 0.07). There was no statistically significant heterogeneity between studies with respect to height or BMI. BMI in early adulthood was not associated with ovarian cancer risk. CONCLUSION: Height was associated with an increased ovarian cancer risk, especially in premenopausal women. BMI was not associated with ovarian cancer risk in postmenopausal women but was positively associated with risk in premenopausal women.

Risk factors for infectious disease in corneal transplant screening.

PURPOSE: To identify potential medical and behavioral risk factors associated with infectious disease seropositivity in potential corneal donors using an extensive questionnaire completed by the next of kin. METHODS: Retrospective review of medical history and behavioral risk assessment questionnaire and microbiology data for potential corneal donors seropositive for hepatitis B, hepatitis C, human immunodeficiency virus, human T-cell leukemia virus and syphilis as compared to controls. RESULTS: Tobacco use, cigarette smoking, chest pain and heart disease are each associated with corneal donor seropositivity (P < 0.05). Vaccination in the last twelve months is inversely associated with infectious disease (P < 0.05). Statistically significant factors associated with hepatitis C positive donors include: cigarette use, illicit drug use, chest pain, cardiac medications, kidney stones and lung disease (P < 0.05). Factors most often associated with transmission of this disease panel (such as intravenous drug use, sexual contact with prostitutes and history of blood transfusion) are often not identified by the next of kin in the questionnaire. CONCLUSIONS: While there are questionnaire identified risk factors associated with seropositivity in this study, their clinical usefulness is unclear. Many factors crucial to the elimination of potentially infectious donor tissues are not identified in the posthumous history typically completed by next of kin. These questionnaires alone do not provide exclusion criteria for elimination of potentially infectious tissues from the donor pool.