Partial Gastric Resection for Symptomatic Anemia following Diagnosis of Merkel Cell Carcinoma (MCC) of the Skin with Gastric Metastasis.

Merkel Cell Carcinoma (MCC) is a rare dermatologic malignancy with significant morbidity and mortality associated with metastatic disease. In this case, we discuss and extremely rare presentation of MCC with metastasis to the stomach in a patient that presented with profound anemia. Unfortunately, mortality following diagnosis of MCC with gastric metastasis approaches 67% at 4 months based on available published reports. Due to its rarity and high rate of mortality, there is a lack of available research and literature to help guide treatment of this rare presentation of MCC. This case report presents a positive outcome associated with a partial gastrectomy for the treatment of symptomatic MCC with gastric metastasis and continued survival with persistently stable hemoglobin at 12 months. Key clinical message: Anemia may be a significant cause of the morbidity and mortality associated with MCC with gastric metastasis. Our case demonstrates a positive outcome associated with partial gastric resection and presents a possible treatment option for this rare disease process.

Evaluation of an Air Quality Health Index for Predicting the Mutagenicity of Simulated Atmospheres.

No study has evaluated the mutagenicity of atmospheres with a calculated air quality health index (AQHI). Thus, we generated in a UV-light-containing reaction chamber two simulated atmospheres (SAs) with similar AQHIs but different proportions of criteria pollutants and evaluated them for mutagenicity in three Salmonella strains at the air-agar interface. We continuously injected into the chamber gasoline, nitric oxide, and ammonium sulfate, as well as either α-pinene to produce SA-PM, which had a high concentration of particulate matter (PM): 119 ppb ozone (O3), 321 ppb NO2, and 1007 µg/m3 PM2.5; or isoprene to produce SA-O3, which had a high ozone (O3) concentration: 415 ppb O3, 633 ppb NO2, and 55 µg/m3 PM2.5. Neither PM2.5 extracts, NO2, or O3 alone, nor nonphoto-oxidized mixtures were mutagenic or cytotoxic. Both photo-oxidized atmospheres were largely direct-acting base-substitution mutagens with similar mutagenic potencies in TA100 and TA104. The mutagenic potencies [(revertants/h)/(mgC/m3)] of SA-PM (4.3 ± 0.4) and SA-O3 (9.5 ± 1.3) in TA100 were significantly different ( P < 0.0001), but the mutation spectra were not ( P = 0.16), being ∼54% C → T and ∼46% C → A. Thus, the AQHI may have some predictive value for the mutagenicity of the gas phase of air.

Editor's Highlight: Genetic Targets of Acute Toluene Inhalation in Drosophila melanogaster.

Interpretation and use of data from high-throughput assays for chemical toxicity require links between effects at molecular targets and adverse outcomes in whole animals. The well-characterized genome of Drosophila melanogaster provides a potential model system by which phenotypic responses to chemicals can be mapped to genes associated with those responses, which may in turn suggest adverse outcome pathways associated with those genes. To determine the utility of this approach, we used the Drosophila Genetics Reference Panel (DGRP), a collection of ∼200 homozygous lines of fruit flies whose genomes have been sequenced. We quantified toluene-induced suppression of motor activity in 123 lines of these flies during exposure to toluene, a volatile organic compound known to induce narcosis in mammals via its effects on neuronal ion channels. We then applied genome-wide association analyses on this effect of toluene using the DGRP web portal (http://dgrp2.gnets.ncsu.edu), which identified polymorphisms in candidate genes associated with the variation in response to toluene exposure. We tested ∼2 million variants and found 82 polymorphisms located in or near 66 candidate genes that were associated with phenotypic variation for sensitivity to toluene at P < 5 × 10-5, and human orthologs for 52 of these candidate Drosophila genes. None of these orthologs are known to be involved in canonical pathways for mammalian neuronal ion channels, including GABA, glutamate, dopamine, glycine, serotonin, and voltage sensitive calcium channels. Thus this analysis did not reveal a genetic signature consistent with processes previously shown to be involved in toluene-induced narcosis in mammals. The list of the human orthologs included Gene Ontology terms associated with signaling, nervous system development and embryonic morphogenesis; these orthologs may provide insight into potential new pathways that could mediate the narcotic effects of toluene.

A novel laser-induced fluorescence scheme for Ar-I in a plasma.

Here we describe a novel infrared laser-induced fluorescence scheme for the 1s2 state of Ar-I using an 841.052 nm (vacuum) Sacher tunable diode laser oscillator and compare it to an established 667.913 nm (vacuum) 1s4-pumping Ar-I LIF scheme using a master oscillator power amplifier laser [A. M. Keesee et al. Rev. Sci. Instrum. 75, 4091 (2004)]. The novel scheme exhibits a significantly greater signal-to-noise ratio for a given injected laser power than the established scheme. We argue that this is caused by less intense spontaneous Ar-I radiation near the LIF emission wavelength for the 1s2 scheme as compared to the 1s4 scheme. In addition we present an updated iodine cell spectrum around the 1s4 LIF scheme pump wavelength.

Intracystic Biopsy and Diagnosis of Intraductal Papillary Mucinous Neoplasm via SpyGlass Pancreatoscopy.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas carries a risk of malignancy ranging from 15%-60%, depending on certain high-risk features. Diagnostic efforts often include radiographic imaging with computed tomography, magnetic resonance imaging, magnetic resonance cholangiopancreatography, and endoscopic ultrasound. Once IPMN has been diagnosed, the proposed indications for cyst resection are based primarily on size, main duct involvement, symptoms, and the presence of mural nodules. Diagnostic difficulty still remains, however, in patients with small lesions and with normal carcinoembryonic antigen levels, so alternative endoscopic modalities are needed. CASE REPORT: We report a case of intracystic SpyGlass Direct Visualization System (Boston Scientific) evaluation and biopsy of an IPMN in a 74-year-old male patient who presented to our surgical clinic with a history of chronic pancreatitis and significant weight loss during the last 2½ years. CONCLUSION: In difficult diagnostic cases, SpyGlass pancreatoscopy can be quite useful because the device allows direct endoscopic visualization of the pancreaticobiliary ducts. Ductal pathology, including stones, strictures, and proliferative epithelial abnormalities, can be observed and even directly biopsied. Early experience in applying this technology to pancreatic cyst evaluation has indicated improved diagnostic accuracy.

Progress in assessing air pollutant risks from in vitro exposures: matching ozone dose and effect in human airway cells.

In vitro exposures to air pollutants could, in theory, facilitate a rapid and detailed assessment of molecular mechanisms of toxicity. However, it is difficult to ensure that the dose of a gaseous pollutant to cells in tissue culture is similar to that of the same cells during in vivo exposure of a living person. The goal of the present study was to compare the dose and effect of O3 in airway cells of humans exposed in vivo to that of human cells exposed in vitro. Ten subjects breathed labeled O3 ((18)O3, 0.3 ppm, 2 h) while exercising intermittently. Bronchial brush biopsies and lung lavage fluids were collected 1 h post exposure for in vivo data whereas in vitro data were obtained from primary cultures of human bronchial epithelial cells exposed to 0.25-1.0 ppm (18)O3 for 2 h. The O3 dose to the cells was defined as the level of (18)O incorporation and the O3 effect as the fold increase in expression of inflammatory marker genes (IL-8 and COX-2). Dose and effect in cells removed from in vivo exposed subjects were lower than in cells exposed to the same (18)O3 concentration in vitro suggesting upper airway O3 scrubbing in vivo. Cells collected by lavage as well as previous studies in monkeys show that cells deeper in the lung receive a higher O3 dose than cells in the bronchus. We conclude that the methods used herein show promise for replicating and comparing the in vivo dose and effect of O3 in an in vitro system.

Fate of pathologically bound oxygen resulting from inhalation of labeled ozone in rats.

Inhaled ozone (O3) reacts chemically with respiratory tract biomolecules where it forms covalently bound oxygen adducts. We investigated the fate of these adducts following inhalation exposure of rats to labeled ozone ((18)O3, 2 ppm, 6 hr or 5 ppm, 2 hr). Increased (18)O was detected in blood plasma at 7 hr post exposure and was continuously present in urine for 4 days. Total (18)O excreted was ~53% of the estimated amount of (18)O3 retained by the rats during (18)O3 exposure suggesting that only moderate recycling of the adduct material occurs. The time course of excretion, as well as properties of the excreted (18)O were determined to provide guidance to future searches for urinary oxidative stress markers. These results lend plausibility to published findings that O3 inhalation could exert influences outside the lung, such as enhancement of atherosclerotic plaques.

Biomarkers of Dose and Effect of Inhaled Ozone in Resting versus Exercising Human Subjects: Comparison with Resting Rats.

To determine the influence of exercise on pulmonary dose of inhaled pollutants, we compared biomarkers of inhaled ozone (O3) dose and toxic effect between exercise levels in humans, and between humans and rats. Resting human subjects were exposed to labeled O3 ((18)O3, 0.4 ppm, for 2 hours) and alveolar O3 dose measured as the concentration of excess (18)O in cells and extracellular material of nasal, bronchial, and bronchoalveolar lavage fluid (BALF). We related O3 dose to effects (changes in BALF protein, LDH, IL-6, and antioxidant substances) measurable in the BALF. A parallel study of resting subjects examined lung function (FEV1) changes following O3. Subjects exposed while resting had (18)O concentrations in BALF cells that were 1/5th of those of exercising subjects and directly proportional to the amount of O3 breathed during exposure. Quantitative measures of alveolar O3 dose and toxicity that were observed previously in exercising subjects were greatly reduced or non-observable in O3 exposed resting subjects. Resting rats and resting humans were found to have a similar alveolar O3 dose.

When a natural disaster occurs: lessons learned in meeting students' needs.

Across the nation, weather-related natural disasters-tropical storms, floods, tornadoes, and earthquakes-struck even areas where weather concerns are not paramount on the minds of most people. These natural disasters heightened awareness that all geographic areas are susceptible to aberrant weather conditions. The purpose of this article was to relate the lessons learned by one academic health center in meeting students' emergency preparedness and disaster recovery needs following a major hurricane in fall 2008. To gauge students' storm-related needs, a Hurricane Needs Survey (HNS) was conducted in spring 2009, 7 months after the hurricane. Students responded to 26 structured response items and 3 open-ended questions. Five hundred fifteen surveys were completed, constituting a response rate of 37.2%. Data were analyzed by creating frequencies to profile students' hurricane experiences. Results indicated that all students left the island under mandatory evacuation orders; most stayed with their families, and most experienced moderate material losses. For some students, the evacuation process and life after the storm contributed to ongoing problems, worries, and academic performance issues. Qualitative content analysis was used to derive themes from the students' narrative responses to the HNS open-ended questions about their perceptions of the extent to which the University of Texas Medical Branch met their needs. When students' hurricane response comments were analyzed, three major themes emerged: being prepared, needing to be connected, and returning to normalcy. The major lessons learned are that the emergency preparation of students requires greater specificity and that discussion about poststorm recovery expectations is essential. Following a natural disaster, students experience more distress than may be readily apparent.

Vascular and cardiac impairments in rats inhaling ozone and diesel exhaust particles.

BACKGROUND: Mechanisms of cardiovascular injuries from exposure to gas and particulate air pollutants are unknown. OBJECTIVE: We sought to determine whether episodic exposure of rats to ozone or diesel exhaust particles (DEP) causes differential cardiovascular impairments that are exacerbated by ozone plus DEP. METHODS AND RESULTS: Male Wistar Kyoto rats (10-12 weeks of age) were exposed to air, ozone (0.4 ppm), DEP (2.1 mg/m(3)), or ozone (0.38 ppm) + DEP (2.2 mg/m(3)) for 5 hr/day, 1 day/week for 16 weeks, or to air, ozone (0.51 or 1.0 ppm), or DEP (1.9 mg/m(3)) for 5 hr/day for 2 days. At the end of each exposure period, we examined pulmonary and cardiovascular biomarkers of injury. In the 16-week study, we observed mild pulmonary pathology in the ozone, DEP, and ozone + DEP exposure groups, a slight decrease in circulating lymphocytes in the ozone and DEP groups, and decreased platelets in the DEP group. After 16 weeks of exposure, mRNA biomarkers of oxidative stress (hemeoxygenase-1), thrombosis (tissue factor, plasminogen activator inhibitor-1, tissue plasminogen activator, and von Willebrand factor), vasoconstriction (endothelin-1, endothelin receptors A and B, endothelial NO synthase) and proteolysis [matrix metalloprotease (MMP)-2, MMP-3, and tissue inhibitor of matrix metalloprotease-2] were increased by DEP and/or ozone in the aorta, but not in the heart. Aortic LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) mRNA and protein increased after ozone exposure, and LOX-1 protein increased after exposure to ozone + DEP. RAGE (receptor for advanced glycation end products) mRNA increased in the ozone + DEP group. Exposure to ozone or DEP depleted cardiac mitochondrial phospholipid fatty acids (DEP > ozone). The combined effect of ozone and DEP exposure was less pronounced than exposure to either pollutant alone. Exposure to ozone or DEP for 2 days (acute) caused mild changes in the aorta. CONCLUSIONS: In animals exposed to ozone or DEP alone for 16 weeks, we observed elevated biomarkers of vascular impairments in the aorta, with the loss of phospholipid fatty acids in myocardial mitochondria. We conclude that there is a possible role of oxidized lipids and protein through LOX-1 and/or RAGE signaling.

Personal Background Preparation Survey for early identification of nursing students at risk for attrition.

During 2004 and 2005 orientations, all 187 and 188 new matriculates, respectively, in two southwestern U.S. nursing schools completed Personal Background and Preparation Surveys (PBPS) in the first predictive validity study of a diagnostic and prescriptive instrument for averting adverse academic status events (AASE) among nursing or health science professional students. One standard deviation increases in PBPS risks (p < 0.05) multiplied odds of first-year or second-year AASE by approximately 150%, controlling for school affiliation and underrepresented minority student (URMS) status. AASE odds one standard deviation above mean were 216% to 250% those one standard deviation below mean. Odds of first-year or second-year AASE for URMS one standard deviation above the 2004 PBPS mean were 587% those for non-URMS one standard deviation below mean. The PBPS consistently and significantly facilitated early identification of nursing students at risk for AASE, enabling proactive targeting of interventions for risk amelioration and AASE or attrition prevention.

Using the personal background preparation survey to identify health science professions students at risk for adverse academic events.

In the first predictive validity study of a diagnostic and prescriptive instrument for averting adverse academic status events (AASE) among multiple populations of diverse health science professions students, entering matriculates' personal background and preparation survey (PBPS) scores consistently significantly predicted 1st- or 2nd-year AASE. During 1st-year orientations, 441 entering matriculates in four southwestern schools from dental, medical, and nursing disciplines completed the 2004 PBPS. The following year during 1st-year orientations, 526 entering matriculates in five schools from dental, medical, nursing, and biomedical science disciplines completed the 2005 PBPS. The PBPS identifies and quantifies a student's noncognitive and cognitive academic performance risks. One standard deviation increments in PBPS risks consistently multiplied 1st- or 2nd-year AASE odds by approximately 140% (p < .05), controlling for underrepresented minority student (URMS) status and school affiliation. Odds of 2nd-year AASE for URMS one standard deviation above the 2004 PBPS mean reached 494% of odds for nonURMS at the mean. PBPS total risks, school affiliation, and URMS status together provided 70-76% correct predictions of 1st- or 2nd-year AASE. PBPS predictive validity did not differ significantly among dental, medical, nursing, or biomedical science schools, or URMS/nonURMS. PBPS sensitivity and specificity approached those for FDA-approved screening mammograms for breast cancer and PSA tests for prostate cancer. PBPS positive predictive values of 42-60% exceeded those for both. The diagnostic and prescriptive PBPS can facilitate proactive targeting of corrective interventions aimed at reducing AASE and attrition among health science education students at risk for academic difficulties.

Overproduction of abscisic acid in tomato increases transpiration efficiency and root hydraulic conductivity and influences leaf expansion.

Overexpression of genes that respond to drought stress is a seemingly attractive approach for improving drought resistance in crops. However, the consequences for both water-use efficiency and productivity must be considered if agronomic utility is sought. Here, we characterize two tomato (Solanum lycopersicum) lines (sp12 and sp5) that overexpress a gene encoding 9-cis-epoxycarotenoid dioxygenase, the enzyme that catalyzes a key rate-limiting step in abscisic acid (ABA) biosynthesis. Both lines contained more ABA than the wild type, with sp5 accumulating more than sp12. Both had higher transpiration efficiency because of their lower stomatal conductance, as demonstrated by increases in delta(13)C and delta(18)O, and also by gravimetric and gas-exchange methods. They also had greater root hydraulic conductivity. Under well-watered glasshouse conditions, mature sp5 plants were found to have a shoot biomass equal to the wild type despite their lower assimilation rate per unit leaf area. These plants also had longer petioles, larger leaf area, increased specific leaf area, and reduced leaf epinasty. When exposed to root-zone water deficits, line sp12 showed an increase in xylem ABA concentration and a reduction in stomatal conductance to the same final levels as the wild type, but from a different basal level. Indeed, the main difference between the high ABA plants and the wild type was their performance under well-watered conditions: the former conserved soil water by limiting maximum stomatal conductance per unit leaf area, but also, at least in the case of sp5, developed a canopy more suited to light interception, maximizing assimilation per plant, possibly due to improved turgor or suppression of epinasty.

A novel method of supplying nutrients permits predictable shoot growth and root : shoot ratios of pre-transplant bedding plants.

BACKGROUND AND AIMS: Growth of bedding plants, in small peat plugs, relies on nutrients in the irrigation solution. The object of the study was to find a way of modifying the nutrient supply so that good-quality seedlings can be grown rapidly and yet have the high root : shoot ratios essential for efficient transplanting. METHODS: A new procedure was devised in which the concentrations of nutrients in the irrigation solution were modified during growth according to changing plant demand, instead of maintaining the same concentrations throughout growth. The new procedure depends on published algorithms for the dependence of growth rate and optimal plant nutrient concentrations on shoot dry weight W(s) (g m(-2)), and on measuring evapotranspiration rates and shoot dry weights at weekly intervals. Pansy, Viola tricola 'Universal plus yellow' and petunia, Petunia hybrida 'Multiflora light salmon vein' were grown in four independent experiments with the expected optimum nutrient concentration and fractions of the optimum. Root and shoot weights were measured during growth. KEY RESULTS: For each level of nutrient supply W(s) increased with time (t) in days, according to the equation DeltaW(s)/Deltat=K(2)W(s)/(100+W(s)) in which the growth rate coefficient (K(2)) remained approximately constant throughout growth. The value of K(2) for the optimum treatment was defined by incoming radiation and temperature. The value of K(2) for each sub-optimum treatment relative to that for the optimum treatment was logarithmically related to the sub-optimal nutrient supply. Provided the aerial environment was optimal, R(sb)/R(o) approximately W(o)/W(sb) where R is the root : shoot ratio, W is the shoot dry weight, and sb and o indicate sub-optimum and optimum nutrient supplies, respectively. Sub-optimal nutrient concentrations also depressed shoot growth without appreciably affecting root growth when the aerial environment was non-limiting. CONCLUSION: The new procedure can predict the effects of nutrient supply, incoming radiation and temperature on the time course of shoot growth and the root : shoot ratio for a range of growing conditions.

Regulation and manipulation of ABA biosynthesis in roots.

Overexpression of 9-cis-epoxycarotenoid dioxygenase (NCED) is known to cause abscisic acid (ABA) accumulation in leaves, seeds and whole plants. Here we investigated the manipulation of ABA biosynthesis in roots. Roots from whole tomato plants that constitutively overexpress LeNCED1 had a higher ABA content than wild-type (WT) roots. This could be explained by enhanced in situ ABA biosynthesis, rather than import of ABA from the shoot, because root cultures also had higher ABA content, and because tetracycline (Tc)-induced LeNCED1 expression caused ABA accumulation in isolated tobacco roots. However, the Tc-induced expression led to greater accumulation of ABA in leaves than in roots. This demonstrates for the first time that NCED is rate-limiting in root tissues, but suggests that other steps were also restrictive to pathway flux, more so in roots than in leaves. Dehydration and NCED overexpression acted synergistically in enhancing ABA accumulation in tomato root cultures. One explanation is that xanthophyll synthesis was increased during root dehydration, and, in support of this, dehydration treatments increased beta-carotene hydroxylase mRNA levels. Whole plants overexpressing LeNCED1 exhibited greatly reduced stomatal conductance and grafting experiments from this study demonstrated that this was predominantly due to increased ABA biosynthesis in leaves rather than in roots. Genetic manipulation of both xanthophyll supply and epoxycarotenoid cleavage may be needed to enhance root ABA biosynthesis sufficiently to signal stomatal closure in the shoot.