Letteratura scientifica selezionata sul tema "Wu 49 o63 2002"

Chinese herbal medicine (CHM) has been commonly used for treating insomnia in Asian countries for centuries. The aim of this study was to conduct a large-scale pharmaco-epidemiologic study and evaluate the frequency and patterns of CHM use in treating insomnia. We obtained the traditional Chinese medicine (TCM) outpatient claims from the National Health Insurance in Taiwan for the year 2002. Patients with insomnia were identified from the diagnostic code of International Classification of Disease among claimed visiting files. Corresponding prescription files were analyzed, and an association rule was applied to evaluate the co-prescription of CHM. Results showed that there were 16 134 subjects who visited TCM clinics for insomnia in Taiwan during 2002 and received a total of 29 801 CHM prescriptions. Subjects between 40 and 49 years of age comprised the largest number of those treated (25.3%). In addition, female subjects used CHMs for insomnia more frequently than male subjects (female : male = 1.94 : 1). There was an average of 4.8 items prescribed in the form of either an individual Chinese herb or formula in a single CHM prescription for insomnia. Shou-wu-teng (Polygonum multiflorum) was the most commonly prescribed single Chinese herb, while Suan-zao-ren-tang was the most commonly prescribed Chinese herbal formula. According to the association rule, the most commonly prescribed CHM drug combination was Suan-zao-ren-tang plus Long-dan-xie-gan-tang, while the most commonly prescribed triple drug combination was Suan-zao-ren-tang,Albizia julibrissin, andP. multiflorum. Nevertheless, further clinical trials are needed to evaluate the efficacy and safety of these CHMs for treating insomnia.

The genus Armillaria (2) and Armillaria mellea sensu lato (3) have been reported previously from Hawaii. However, Armillaria species in Hawaii have not been previously identified by DNA sequences, compatibility tests, or other methods that distinguish currently recognized taxa. In August 2005, Armillaria rhizomorphs and mycelial bark fans were collected from two locations on the island of Hawaii. Stands in which isolates were collected showed moderate to heavy tree mortality and mycelial bark fans. Pairing tests (4) to determine vegetative compatibility groups revealed three Armillaria genets (HI-1, HI-7, and HI-9). Rhizomorphs of genet HI-1 were collected from both dead and healthy mature trees of the native 'Ohia Lehua (Metrosideros polymorpha) approximately 27 km west of Hilo, HI (approximately 19°40′49″N, 155°19′24″W, elevation 1,450 m). Rhizomorphs of HI-7 and HI-9 were collected, respectively, from dead/declining, mature, introduced Nepalese alder (Alnus nepalensis) and from an apparently healthy, mature, introduced Chinese banyan (Ficus microcarpa) in the Waipi'o Valley (approximately 20°03′29″N, 155°37′35″W, elevation 925 m). On the basis of somatic pairing tests and intergenic spacer-1 (IGS-1) nucleotide sequence identities of 99 to 100% with North American A. nabsnona (GenBank Accession No. AY509178), HI-1 (GenBank Accession No. DQ995356), HI-7 (GenBank Accession No. DQ995358), and HI-9 (GenBank Accession No. DQ995359) were identified as A. nabsnona, a pathogen of hardwoods (1). The IGS-1 sequences of A. nabsnona genets (HI-1, HI-7, and HI-9) had a greater similarity to North American collections of A. nabsnona than to the Asian A. nabsnona, even though the two introduced hosts originated from Asia. Phylogeographic studies could help determine the potential introduction and original source of A. nabsnona in Hawaii. Although A. nabsona was isolated from multiple hosts in declining stands, pathogenicity studies are needed to confirm whether this pathogen causes disease on diverse native and exotic tree species in Hawaii. References: (1) E. Allen et al. Pages 2–7 in: Common Tree Diseases of British Columbia. Natural Resources Canada. Canadian Forest Service, Victoria, BC, Canada, 1998. (2) D. E. Hemmes and D. E. Desjardin. Pages 129 and 153 in: Mushrooms of Hawaii. Ten Speed Press, Berkeley, CA, 2002. (3) F. F. Laemmlen and R. V. Bega. Plant Dis. Rep. 58:102, 1974. (4) Y. Wu et al. USDA Forest Service Tech. Rep. R2-58, 1996.

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Abstract Background: Between 54%-85% of pediatric patients (pts) with ALL can be cured by definitive chemotherapy protocols. HSCT may be considered for high-risk pts after induction therapy or for refractory/relapsed pts. However, HSCT is recognized as a highly specialized, costly and resource intensive procedure requiring ongoing care over months to years. HSCT is associated with significant life-threatening complications with transplant related mortality of 20-30% and acute/chronic graft vs. host disease and infections. The objective of this study was to assess the economic burden up to 5 years of pediatric pts with ALL who received HSCT from the US commercial payers' perspective. Method: Pediatric pts (<18 years old) with ALL (ICD-9 CM codes 204.0x) who underwent an allogeneic HSCT ([ICD-9 CM] procedure codes 41.02, 41.03, 41.05, 41.06, 41.08) in the US (2002-2013) were identified from two large administrative claims databases. Selected pts were continuously enrolled in their healthcare plan for ≥6 months before and ≥1 month after the index date (i.e., the date the first HSCT procedure was recorded). Age and gender as of the index date and total healthcare costs (direct medical costs and pharmacy costs) during the 6 months preceding the index date were reported. The economic burden associated with HSCT was described by assessing the healthcare resource utilization (HRU) and costs over the following study periods: between the index date and the HSCT hospitalization discharge date, during the first 100 days following the index date, and, during the first, second, third, fourth and fifth years following the index date. For each period, the analyses were conducted among pts with continuous healthcare plan enrollment for that entire period. Healthcare costs reported reflect the costs reimbursed by US private payers for a pediatric pt with ALL who underwent HSCT. Costs were adjusted for inflation (based on the consumer price index for medical components) and reported as 2014 US dollars (USD). Results: A total of 209 pediatric ALL pts were identified. Mean age was 10 years and 43.1% of pts were female. The median follow-up period after the index date was 1.3 years. During the 6 months prior to the index date, pts incurred average total healthcare costs of $287,001. The median duration of the initial hospitalization for the HSCT was 41 days (interquartile range 32-55). Over the five years following the index date, results showed substantial HRU and costs associated with the HSCT. The most intensive HRU and highest healthcare costs were observed within the first year following the index date; pts had an average of 49 days with outpatient (OP) visits, 29 days with OP laboratory services, and 68 inpatient (IP) days corresponding to 3.10 IP admissions (including the hospitalization for the first HSCT) and incurred mean total healthcare costs of $683,099 (median of $511,021) (Figure 1 and 2). Costs associated with the first HSCT hospitalization represented 62.4% of the total costs incurred during the first year. Although a decreasing trend was observed over time, HRU and costs remained high; 28.8% of pts had at least one IP admission at year 2, 19.6% at year 3, 20.0% at year 4, and 6.7% at year 5 (Figure 1). The number of days with OP visits and the number of days with laboratory services also remained high over time (Figure 1). The average total healthcare cost was $104,584 (median of $21,877) at year 2, $79,092 (median of $11,000) at year 3, $106,334 (median of $10,426) at year 4 and, and $38,291 (median of $10,082) at year 5 (Figure 2). Our results also showed high variation in healthcare costs across pediatric pts following the index date; 29.4% of the total costs (over the entire sample) in year 1 were incurred by the 10% pts with the highest costs. Starting from the second year, the 10% of pts with the highest costs accounted for 61.3 to 76.6% of the total costs for each year, suggesting that a small proportion of pts still incur very high costs several years after HSCT. Conclusions: Healthcare resource utilization and direct costs associated with allogeneic HSCT are substantial with the first year direct cost alone of $683,099 with substantial costs over the following years. Further studies are needed to understand the humanistic and financial burden of HSCT for pediatric pts and their caregivers. Figure 1. HRU after Index Date Figure 1. HRU after Index Date Figure 2. Total Healthcare Costs after Index Date Figure 2. Total Healthcare Costs after Index Date Disclosures Maziarz: Athersys: Consultancy, Patents & Royalties, Research Funding; Novartis: Consultancy. Guerin:GlaxoSmithKline, Janssen Scientific Affairs, Janssen-Ortho, Inc., Merck & Co., Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ogilvy Renault, Ortho-Clinical Diagnostics, Inc., Otsuka America Pharmaceutical, Inc.,: Consultancy, Other: Annie Guerin is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Pfizer Canada, Inc., RX&D, Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc., Takeda Global Research & Development Center, Inc., Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Annie Guerin is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; AbbVie Inc., Alcon Laboratories, Bayer Healthcare Pharmaceuticals, LLC, Celgene Corporation, Cempra Inc., Centocor Ortho Biotech, Cooley LLP, Cyberonics, Inc., DLA Piper, Eli Lilly & Company,Forest Laboratories, Inc., Genentech, Inc.,: Consultancy, Other: Annie Guerin is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Gauthier:AbbVie Inc., Celgene Corporation, Eli Lilly & Company, Genentech, Inc. ,GlaxoSmithKline, Janssen Scientific Affairs, LLC, Novartis Pharmaceuticals Corporation, Pfizer Canada, Inc., Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc.,: Consultancy, Other: Genevieve Gauthier is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Sunovion Pharmaceuticals Inc.,Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Genevieve Gauthier is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Heroux:AbbVie Inc., Alcon Laboratories, Celgene Corporation, Genentech, Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation, Shire Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc., Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Julie Heroux is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Zhdanava:AbbVie Inc., Genentech, Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation,Shire Pharmaceuticals Inc., Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Maryia Zhdanava is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Wu:Molecular Insight Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Ortho McNeil Pharmaceuticals, Inc., Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc.,: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Takeda Global Research & Development Center, Inc., Takeda Pharmaceuticals U.S.A., Inc., TAP Pharmaceutical Products, Inc., Vertex Pharmaceuticals Incorporated: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Janssen Pharmaceutica, Inc., Janssen Scientific Affairs, LLC, Lilly Research Laboratories, McNeil Consumer & Specialty Pharmaceuticals, MedImmune, LLC, Melinta Therapeutics, Inc., Millennium Pharmaceuticals, Inc.,: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Celgene Corporation, Centocor Ortho Biotech, Cephalon, Inc., ConvaTec Inc., Corus Pharma, Inc., Eli Lilly & Company, Eli Lilly & Company, Ethicon, Inc., Forest Laboratories, Inc., Genentech, Inc., GlaxoSmithKline, Janssen Global Services, LLC,: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; AbbVie Inc., Alcon Laboratory, Astellas Pharma Inc., Astellas Pharma US, Inc., AstraZeneca, Barger & Wolen LLP, Bayer Healthcare Pharmaceuticals, LLC, Biosense Webster, Inc., Blue Cross Blue Shield Association, Boehringer Ingelheim, Bristol-Myers Squibb C: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Thomas:Novartis: Employment. Chen:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership, Other: Lei Chen is an employee of and owns stocks/options of Novartis Pharmaceuticals Corporation, the sponsor of this study.

Background:N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and troponin I (TnI) are established cardiac biomarkers that predict cardiovascular events (CVEs) in the general population. While patients with psoriatic arthritis and psoriasis, collectively termed psoriatic disease (PsD), have an increased risk of developing CVEs, the use of these cardiac biomarkers to predict CV risk has not been investigated in this population.Objectives:We aimed to evaluate the association between these cardiac biomarkers and incident CVEs, and assess their predictive value beyond the Framingham Risk Score (FRS).Methods:A longitudinal cohort study was conducted in patients with PsD without prior history of CVEs. NT-proBNP and TnI concentrations were measured using automated clinical assays in the first available serum sample. The study outcome included any of the following CVEs occurring within the first 10 years of biomarker assessment: angina, myocardial infarction, transient ischemic attack, stroke, revascularization and CV death. Associations with incident CVEs were analyzed separately for each biomarker using Cox proportional hazards regression models first adjusted for age and sex, and subsequently for the FRS. The added value of cardiac biomarkers to improve predictive performance beyond the FRS was assessed using the area under the receiver operator characteristic curve (AUC), net reclassification index (NRI) and integrated discrimination index (IDI).Results:A total of 1000 patients with PsD were assessed between 2002 and 2019 (mean age 49 ± 12.8 years, 44.6% female) (Table 1). During a mean follow-up of 7.1 years, 64 patients developed incident CVEs. Both TnI (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) 1.12, 8.16) and NT-proBNP (HR 2.02; 95% CI 1.28, 3.18) predicted CVEs independently of the FRS (Figure 1). The association was stronger in males than females. Including all cardiac biomarkers and the FRS in a single model, NT-proBNP retained statistical significance (HR 1.91, 95% CI 1.23, 2.97), while TnI did not (HR 2.60, 95% CI 0.98, 6.87). When comparing the predictive performance of the base model (FRS alone, AUC 75.4) to the expanded models, there was no significant improvement in any of the predictive indices with the addition of TnI (AUC 73.5, p = 0.21; NRI 0.08, p = 0.67; IDI 0.005, p = 0.37), NT-proBNP (AUC 71.0, p = 0.35; NRI 0.20, p = 0.06; IDI 0.017, p = 0.10), or both TnI and NT-proBNP (AUC 70.0, p = 0.23; NRI 0.27, p = 0.05; IDI 0.021, p =0.05).Conclusion:In patients with PsD, elevated NT-proBNP and TnI predict incident CVEs independent of the FRS. We did not observe a significant improvement in the performance of the predictive model when combining these cardiac biomarkers with the FRS.References:[1]Eder L, Wu Y, Chandran V, et al. Incidence and predictors for cardiovascular events in patients with psoriatic arthritis. Ann Rheum Dis 2016;75(9):1680-6.Table 1.Baseline characteristics of the study population (n=1000)VariableMean ± SD / Frequency (%)PsA, no. (%)648 (64.8)PsC, no. (%)352 (35.2)Age (years)49 ± 12.8Male sex, no. (%)554 (55.4)Disease duration (years)20.2 ± 14.1Ethnicity, Caucasian (%)834 (83.4)Current smoker (%)164 (16.4)FRS (%)8.2 ± 8.6Diabetes77 (7.7)Hypertension274 (27.4)BMI (kg/m2)28.7 ± 5.9PASI4.1 ± 6.3Use of lipid-lowering medications (%)100 (10)Current use of DMARDs362 (36.2)Current use of Biologics214 (21.4)Current use of NSAIDs (daily use)265 (26.5)1 Applicable only to patients with PsA CVE, cardiovascular events; DMARD, disease-modifying antirheumatic drug; FRS, Framingham Risk Score; NSAID, non-steroidal anti-inflammatory drug; PASI, Psoriasis Area Severity Index; PsA, psoriatic arthritis; PsC, psoriasis without arthritisFigure 1.Hazard ratios of cardiac biomarker measures for incident cardiovascular events (n = 1000, 64 events). Error bars denote 95% confidence intervals. CI indicates confidence interval; CVEs, cardiovascular events; FRS, Framingham Risk Score; NT-proBNP, N-terminal pro-brain-type natriuretic peptide; TnI, troponin I.Acknowledgements:Keith Colaco is supported by the Enid Walker Estate, Women’s College Research Institute, Arthritis Society (TGP-19-0446), National Psoriasis Foundation (Early Career Grant) and the Edward Dunlop Foundation. Lihi Eder is supported by a Young Investigator Award from the Arthritis Society and an Early Researcher Award from the Ontario Ministry of Science and Innovation. The study was supported in part by a discovery grant from the National Psoriasis Foundation and an operating grant from the Arthritis Society (YIO-16-394).Disclosure of Interests:None declared.

Abstract Abstract 4274 Background: While iron overload is known to cause hepatic toxicity, the effect of iron chelation therapy on liver pathology is not well understood. Data evaluating liver fibrosis during iron chelation therapy are limited to small studies (eg, Wu SF et al. Hemoglobin 2006 [n=17], Berdoukas V et al. Hematol J 2005 [n=49], Wanless IR et al. Blood 2002 [n=56]). In order to address such effects in a more robust patient population, we assessed liver biopsy samples from β-thalassemia patients enrolled in two large clinical studies (Porter J et al. Blood 2005, Cappellini MD et al. Blood 2006) that evaluated the effects of deferasirox on iron burden for up to 5 years. Methods: Patients with β-thalassemia and transfusional hemosiderosis receiving ≥8 blood transfusions/year, with liver biopsy assessment (defined as having either liver iron concentration [LIC], Ishak grading or Ishak staging assessment), after at least 3 years of deferasirox treatment, were included. Deferasirox dose was 5–40 mg/kg/day based upon level of iron overload (Study 107, patients randomized to deferoxamine [DFO] or deferasirox for the first year; Study 108, patients received deferasirox only). Treatment response success was defined according to baseline (start of deferasirox dosing) and end-of-study (EOS) LIC measurements (Table). Histological total iron score (TIS) was derived from the iron load observed in hepatocytes (hepatocytic iron score [HIS] range, 0–12), sinusoidal cells (sinusoidal iron score [SIS] range, 0–4) and main structures of the portal tracts (portal iron score [PIS]). A heterogeneity factor (H = 1, 2 or 3) was then applied, based on the overall appearance of the tissue, to provide TIS, calculated as (HIS + SIS + PIS) × (H/3) [range 0–60]. Hepatocytic to total liver iron ratio was calculated as HIS/(HIS + SIS + PIS) (Deugnier Y et al. Gastroenterol 1992). Fibrosis staging was performed according to Ishak scale from 0 (no fibrosis) to 6 (cirrhosis, probable or definite). Liver inflammation was assessed according to the Ishak necroinflammatory grading system with an overall scoring range from 0–18 (Ishak K et al. J Hepatology 1995). Results: Of 770 patients enrolled in the deferasirox studies, 219 with histological biopsy data at baseline and at the end of at least 3 years of treatment with deferasirox were eligible for analyses. Mean LIC was 15.7 ± 9.9 mg Fe/g dw and median serum ferritin was 2069 ng/mL (range 273–11698) at the start of deferasirox treatment. After at least 3 years of treatment, overall LIC success response rate was 63.8% (n=134), and mean LIC decreased by 5.5 ± 10.6 to 10.1 ± 8.2 mg Fe/g dw. Mean absolute change in TIS and liver iron ratio were -8.2 ± 13.3 and -2.1 ± 27.3, respectively. The range of Ishak necroinflammatory scores at baseline was 0–8 with a mean of 2.0 (2.2 in patients who met success rate criteria [Group A], 1.6 in patients who did not meet the success rate criteria [Group B]). At EOS the necroinflammatory score improved to a mean of 0.8 overall, and in both subgroups, with a mean relative change of -66% (69% in Group A and -61% in Group B). Overall 83.3% (n=175) [85.8% (n=115) in Group A, 78.9% (n=60) in Group B] of patients experienced either stabilization or improvement in their Ishak fibrosis score. Ishak staging remained stable (change of -1, 0 or +1) in 55.7% (n=122) of patients. Fifty-nine patients (26.9%) had an improvement in Ishak grading by a score of ≥2. Similar improvements were observed between Group A (26.1%, n=35) and Group B (30.3%, n=23). Conclusions: This is the first study to assess the effect of iron chelation therapy on liver pathology in a large cohort of iron-overloaded patients with β-thalassemia. In addition to reducing total iron burden, deferasirox led to an improvement in pathological markers of iron overload-induced liver damage in the majority of patients; 83.3% showed stabilization or improvement in Ishak fibrosis staging as well as an overall improvement in necroinflammatory score. These effects were similar in both patients who met the LIC success rate criteria and those who did not, suggesting that the observed effects may be at least partly independent of the drug's chelation effect. These findings are important as stabilization or regression of hepatic fibrosis in the face of chronic insult may prevent progressive liver disease. Disclosures: Deugnier: Novartis: Honoraria. Dong:Novartis: Employment. Giannone:Novartis: Employment. Zhang:Novartis: Employment. Griffel:Novartis: Employment. Brissot:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Strawberry is one of the beloved fruits worldwide due to its exquisite flavor with highly nutritious compounds which give promising health benefits. [1] With dragging the great attention, efforts to monitor the quality of strawberries and strawberry derivatives are becoming significant to obtain better flavor and nutrition. 2,5-Dimethyl-4-hydroxy-3(2H)-furanone(furaneol) is one of the compounds which plays an important role in a flavor that can be naturally found in various fruits such as strawberry, pineapple, raspberry, and mango. Especially, furaneol composition is reported as a significant factor for maturity condition monitoring of strawberries due to the different amounts at the ripening stage. [2] Furaneol is also known to be an essential signature for controlling the food production process, verifying the food production origin, and regulating the quality of products. Currently, furaneol detection is conducted with time-consuming techniques, such as gas chromatography (GC) and high-performance liquid chromatography (HPLC). For example, Yuan et al. [3] showed the identification of furaneol with HPLC. Also, Buttery et al. [4], and Lopez et al. [5], used GC for the determination of furaneol in foods. Developing a real-time gas sensor for fast, cheap, stable, sensitive detection of furaneol is a significant challenge in the area of the food industry. Chemo-resistive gas sensors can be an attractive approach due to their miniaturization, simple operation, ease of fabrication, and low production cost. For utilizing resistive gas sensors, polyaniline (PANI) got great attention because of its environmental stability, simple synthesis, and ease of tailoring the surface charge characteristics by changing the dopants. However, PANI-based gas sensors are reactive to numerous gases which limits the selective detection of target gas molecules. Many compounds in strawberries may restrict the use of PANI-based sensors. [6] Molecular imprinting technology (MIT), which can create molecularly imprinted polymers (MIPs) obtaining specific binding sites for target molecules, is utilized to achieve selective gas sensing similar to biological antibodies. [7] The improved affinity not only provides selective detection but also enhances response to target gas molecules. In this study, a resistive gas sensor based on synthesized molecularly imprinted polymer and polyaniline is demonstrated for the detection of furaneol gas molecules for its operation in food packaging. Herein, we developed a unique method to synthesize molecularly imprinted polymer and polyaniline (MIP-PANI) nanocomposites with an interfacial polymerization technique. Aniline monomer is polymerized and oxidized simultaneously to tailor the surface charge characteristics forming polyaniline. Then, the molecularly imprinting process on polyaniline is conducted with methacrylic acid (MAA) as a functional monomer, ethylene glycol dimethacrylate (EGDMA) as a crosslinker, furaneol as a template, and benzoyl peroxide as a radical initiator. After the furaneol template was constructed, MIP-PANI presented a high affinity to furaneol target molecules and showed a high sensing response. Their response signals are enhanced tens of times compared to the pure PANI. Furthermore, selective detection of the target furaneol molecules was observed. This study may broaden the application of resistive gas sensors for selective and sensitive detection of volatile organic compounds in food industries. Reference [1] S. Afrin, M. Gasparrini, T.Y. Forbes-Hernandez, P. Reboredo-Rodriguez, B. Mezzetti, A. Varela-Lopez, F. Giampieri, M. Battino, Promising Health Benefits of the Strawberry: A Focus on Clinical Studies, J Agric Food Chem 64 (2016) 4435-4449. [2] C. Aubert, S. Baumann, H. Arguel, Optimization of the analysis of flavor volatile compounds by liquid-liquid microextraction (LLME). Application to the aroma analysis of melons, peaches, grapes, strawberries, and tomatoes, Journal of Agricultural and Food Chemistry 53 (2005) 8881-8895. [3] J.P. Yuan, F. Chen, Separation and identification of furanic compounds in fruit juices and drinks by high-performance liquid chromatography photodiode array detection, Journal of Agricultural and Food Chemistry 46 (1998) 1286-1291. [4] R.G. Buttery, G.R. Takeoka, M. Naim, H. Rabinowitch, Y. Nam, Analysis of furaneol in tomato using dynamic headspace sampling with sodium sulfate, Journal of Agricultural and Food Chemistry 49 (2001) 4349-4351. [5] R. Lopez, M. Aznar, J. Cacho, V. Ferreira, Determination of minor and trace volatile compounds in wine by solid-phase extraction and gas chromatography with mass spectrometric detection, Journal of Chromatography A 966 (2002) 167-177. [6] A.T. Oz, G. Baktemur, S.P. Kargi, E. Kafkas, Volatile Compounds of Strawberry Varieties, Chemistry of Natural Compounds 52 (2016) 507-509. [7] L. Chen, X. Wang, W. Lu, X. Wu, J. Li, Molecular imprinting: perspectives and applications, Chem Soc Rev 45 (2016) 2137-2211.

The paper presents research findings with 56 Roma children from Macedonia and Serbia between the ages of 3-6 years. The children’s knowledge of Romani as their mother tongue was assessed with a specially designed test. The test measures the children’s comprehension and production of different types of grammatical knowledge such as wh–questions, wh-complements, passive verbs, possessives, tense, aspect, the ability of the children to learn new nouns and new adjectives, and repetition of sentences. In addition, two pictured narratives about Theory of Mind were given to the children. The hypothesis of the authors was that knowledge of the complex grammatical categories by children will help them to understand better the Theory of Mind stories. The results show that Roma children by the age of 5 know most of the grammatical categories in their mother tongue and most of them understand Theory of Mind. References Bakalar, P. (2004). The IQ of Gypsies in Central Europe. 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Arsenic and Protein Expression: It might help to know the mechanism of As toxicity is described Introduction One of the largest public health problems at present is the drinking of water containing levels of Inorg-As that are known to be carcinogenic. The chronic ingestion of Inorg-As can results in skin cancer, urinary bladder cancer, lungs cancer, kidneys cancer, liver cancer, and cancer of other human organs 1-6. The molecular mechanisms of the carcinogenicity and toxicity of inorganic arsenic are not well understood 7–9. Many mechanisms of arsenic toxicity and carcinogenicity have been suggested 1, 7, 10 including chromosome abnormalities 11, oxidative stress 12, 13, altered growth factors 14, cell proliferation 15, altered DNA repair 16, altered DNA methylation patterns 17, inhibition of several key enzymes 18, gene amplification 19 etc. Some of these mechanisms result in alterations in protein expression. Proteomics is a powerful tool developed to enhance the study of complex biological system 20. This technique has been extensively employed to investigate the proteome response of cells to drugs and other diseases 21, 22. A proteome analysis of the Na-As (III) response in cultured lung cells found in vitro oxidative stress-induced apoptosis 23. In one of the study, hamsters were exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days and several protein spots were over expressed and several were under expressed in the livers and urinary bladders of hamsters (Fig.) 24, 25. Hamsters were exposed to sodium arsenite (173 mg As/L) in drinking water for 6 days. The control hamsters were given tap water. The spot pairs of (A) equally expressed, (B) overexpressed, and (C) under expressed proteins in the liver tissues were shown. The amount of the protein is proportional to the volume of the protein peak. Transgelin was down-regulated, and GST-pi was up-regulated in the urinary bladder tissues of hamsters. In the liver tissues ornithine aminotransferase (OAT) was up-regulated, and senescence marker protein 30 (SMP 30), and fatty acid binding protein (FABP) were down-regulated. Down-regulation of transgelin has been noted in the urinary bladders of rats having bladder outlet obstruction 26. Ras-dependent and Ras-independent mechanisms can cause the down regulation of transgelin in human breast and colon carcinoma cell lines and patient-derived tumor samples 27. The loss of transgelin expression has been found in prostate cancer cells 28 and in human colonic neoplasms 29. It has been suggested that the loss of transgelin expression may be an important early event in tumor progression and a diagnostic marker for cancer development 26-29. Figure. Three-dimentional simulation of over-and under expressed protein spots in the livers of hamsters using Decyder software. Over-expression of GST-pi has been found in colon cancer tissues 30. Strong expression of GST-pi also has been found in gastric cancer 31, malignant melanoma 32, lung cancer 33, breast cancer 34 and a range of other human tumors 35. GST-pi has been up-regulated in transitional cell carcinoma of human urinary bladder 36. OAT has a role in regulating mitotic cell division and it is required for proper spindle assembly in human cancer cell 37. Ornithine amino transferase knockdown in human cervical carcinoma and osteosarcoma cells by RNA interference blocks cell division and causes cell death 37. It has been suggested that ornithine amino transferase has a role in regulating mitotic cell division and it is required for proper spindle assembly in human cancer cells 37. SMP 30 expressed mostly in the liver. By stimulating membrane calcium-pump activity it protects cells against various injuries 38. High levels of saturated, branched chain fatty acids are deleterious to cells and resulting in lipid accumulation and cytotoxicity. FABP expression has protected the cells against branched chain saturated fatty acid 39. Proteomics would be a powerful tool to know the unknown cellular mechanisms of arsenic toxicity in humans. References. NRC (National Research Council). (2001). Arsenic in Drinking Water. Update to the 1999 Arsenic in Drinking Water Report. National Academy Press, Washington, DC. Chen, C. J., Chen, C. , Wu, M. M., Kuo, T. L. (1992). Cancer potential in liver, lung, bladder, and kidney due to ingested inorganic arsenic in drinking water. Br. J. Cancer 66, 888-892. Hopenhayn-Rich, C., M.L. Biggs, A. Fuchs, et al. 1996. Bladder cancer mortality with arsenic in drinking water in Argentina. Epidemiology 7: 117–124. International Agency for Research on Cancer. (1987). In IARC Monograph on the Evaluation of Carcinogenicity Risk to Humans. 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R., Carcinogenicity and co-carcinogenicity of sodium arsenite in p53+/- male mice. Toxicologist 2000, 54, 134. Li, J. H., Rossman, T. G., Mechanism of co-mutagenesis of sodium arsenite with N-methyl-N-nitrosourea. Bi Trace Elem. 1989, 21, 373-381. Zhao, C. Q., Young, M. R., Diwan, B. A., Coogan, T. P., et , Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression. Proc. Natl. Acad. Sci. USA 1997, 94, 10907-10912. Abernathy, C. O., Lui, Y. P., Longfellow, D., Aposhian, H. , et al., Arsenic: Health effects, mechanisms of actions and research issues. Environ. Health Perspect. 1999, 107, 593-597. Lee, T. C., Tanaka, N., Lamb, P. W., Gilmer, T. M., et al., Induction of gene amplification by arsenic. Science 1988, 241, 79-81. Lau, A. T., He, Q. Y., Chiu, J. F. (2003). Proteomic technology and its biomedical applications. Acta Biochim. Bioph Sin. 35, 965-975. Jungblut, P. 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Our studies have indicated that the relative concentration of Se or Hg to As in urine and blood positively correlates with percentage of inorganic arsenic (% Inorg-As) and percentage of monomethlyarsonic acid [% MMA (V)]. We also found a negative correlation with percentage of dimethylarsinic acid [% DMA (V)] and the ratio of % DMA (V) to % MMA (V). In another study, we found that a group of proteins were significantly over expressed and conversely other groups were under-expressed in tissues in Na-As (III) treated hamsters. Introduction.Inorganic arsenic (Inorg-As) in drinking water.One of the largest public health problems at present is the drinking of water containing levels of Inorg-As that are known to be carcinogenic. At least 200 million people globally are at risk of dying because of arsenic (As) in their drinking water1-3. The chronic ingestion of Inorg-As can results in skin cancer, bladder cancer, lung cancer, and cancer of other organs1-3. The maximum contamination level (MCL) of U.S. drinking water for arsenic is 10 ug/L. The arsenic related public health problem in the U.S. is not at present anywhere near that of India4, Bangladesh4, and other countries5. Metabolism and toxicity of Inorg-As and arsenic species.Inorg-As is metabolized in the body by alternating reduction of pentavalent arsenic to trivalent form by enzymes and addition of a methyl group from S-adenosylmethionine6, 7; it is excreted mainly in urine as DMA (V)8. Inorganic arsenate [Inorg-As (V)]is biotransformed to Inorg-As (III), MMA (V), MMA (III), DMA (V), and DMA (III)6(Fig. 1). Therefore, the study of the toxicology of Inorg-As (V) involves at least these six chemical forms of arsenic. Studies reported the presence of 3+ oxidation state arsenic biotransformants [MMA (III) and DMA (III)] in human urine9and in animal tissues10. The MMA (III) and DMA (III) are more toxic than other arsenicals11, 12. In particular MMA (III) is highly toxic11, 12. In increased % MMA in urine has been recognized in arsenic toxicity13. In addition, people with a small % MMA in urine show less retention of arsenic14. Thus, the higher prevalence of toxic effects with increased % MMA in urine could be attributed to the presence of toxic MMA (III) in the tissue. Previous studies also indicated that males are more susceptible to the As related skin effects than females13, 15. A study in the U.S population reported that females excreted a lower % Inorg-As as well as % MMA, and a higher % DMA than did males16. Abbreviation: SAM, S-adenosyl-L-methionine; SAHC, S-adenosyl-L-homocysteine. Differences in susceptibility to arsenic toxicity might be manifested by differences in arsenic metabolism among people. Several factors (for examples, genetic factors, sex, duration and dosage of exposure, nutritional and dietary factors, etc.) could be influence for biotransformation of Inorg-As,6, 17 and other unknown factors may also be involved. The interaction between As, Se, and Hg.The toxicity of one metal or metalloid can be dramatically modulated by the interaction with other toxic and essential elements18. Arsenic and Hg are toxic elements, and Se is required to maintain good health19. But Se is also toxic at high levels20. Recent reports point out the increased risk of squamous cell carcinoma and non-melanoma skin cancer in those treated with 200 ug/day of selenium (Nutritional Prevention of Cancer Trial in the United States)21. However, it is well known that As and Se as well as Se and Hg act as antagonists22. It was also reported that Inorg-As (III) influenced the interaction between selenite and methyl mercury23. A possible molecular link between As, Se, and Hg has been proposed by Korbas et al. (2008)24. The identifying complexes between the interaction of As and Se, Se and Hg as well as As, Se, and Hg in blood of rabbit are shown in Table 1. Influence of Se and Hg on the metabolism of Inorg-As.The studies have reported that Se supplementation decreased the As-induced toxicity25, 26. The concentrations of urinary Se expressed as ug/L were negatively correlated with urinary % Inorg-As and positively correlated with % DMA27. The study did not address the urinary creatinine adjustment27. Other researchers suggested that Se and Hg decreased As methylation28-31(Table 2). They also suggested that the synthesis of DMA from MMA might be more susceptible to inhibition by Se (IV)29 as well as by Hg (II)30,31 compared to the production of MMA from Inorg-As (III). The inhibitory effects of Se and Hg were concentration dependent28-31. The literature suggests that reduced methylation capacity with increased % MMA (V), decreased % DMA (V), or decreased ratios of % DMA to % MMA in urine is positively associated with various lesions32. Lesions include skin cancer and bladder cancer32. The results were obtained from inorganic arsenic exposed subjects32. Our concern involves the combination of low arsenic (As) and high selenium (Se) ingestion. This can inhibit methylation of arsenic to take it to a toxic level in the tissue. Dietary sources of Se and Hg.Global selenium (Se) source are vegetables in the diet. In the United States, meat and bread are the common source. Selenium deficiency in the US is rare. The US Food and Drug Administration (FDA) has found toxic levels of Se in dietary supplements, up to 200 times greater than the amount stated on the label33. The samples contained up to 40,800 ug Se per recommended serving. For the general population, the most important pathway of exposure to mercury (Hg) is ingestion of methyl mercury in foods. Fish (including tuna, a food commonly eaten by children), other seafood, and marine mammals contain the highest concentrations. The FDA has set a maximum permissible level of 1 ppm of methyl mercury in the seafood34. The people also exposed mercury via amalgams35. Proteomic study of Inorg-As (III) injury.Proteomics is a powerful tool developed to enhance the study of complex biological system36. This technique has been extensively employed to investigate the proteome response of cells to drugs and other diseases37, 38. A proteome analysis of the Na-As (III) response in cultured lung cells found in vitro oxidative stress-induced apoptosis39. However, to our knowledge, no in vivo proteomic study of Inorg-As (III) has yet been conducted to improve our understanding of the cellular proteome response to Inorg-As (III) except our preliminary study 40. Preliminary Studies: Results and DiscussionThe existing data (Fig. 1) from our laboratory and others show the complex nature of Inorg-As metabolism. For many years, the major way to study, arsenic (As) metabolism was to measure InorgAs (V), Inorg-As (III), MMA (V), and DMA (V) in urine of people chronically exposed to As in their drinking water. Our investigations demonstrated for the first time that MMA (III) and DMA (III) are found in human urine9. Also we have identified MMA (III) and DMA (III) in the tissues of mice and hamsters exposed to sodium arsenate [Na-As (V)]10, 41. Influence of Se as well as Hg on the As methyltransferase.We have reported that Se (IV) as well as mercuric chloride (HgCl2) inhibited As (III) methyltransferase and MMA (III) methyltransferase in rabbit liver cytosol. Mercuric chloride was found to be a more potent inhibitor of MMA (III) methyltransferase than As (III) methyltransferase30. These results suggested that Se and Hg decreased arsenic methylation. The inhibitory effects of Se and Hg were concentration dependent30. Influence of Se and Hg in urine and blood on the percentage of urinary As metabolites.Our human studies indicated that the ratios of the concentrations of Se or Hg to As in urine and blood were positively correlated with % Inorg-As and % MMA (V). But it negatively correlated with % DMA (V) and the ratios of % DMA (V) to % MMA (V) in urine of both males and females (unpublished data) (Table 3). These results confirmed that the inhibitory effects of Se as well as Hg for the methylation of Inorg-As in humans were concentration dependent. We also found that the concentrations of Se and Hg were negatively correlated with % Inorg-As and % MMA (V). Conversely it correlated positively with % DMA (V) and the ratios of % DMA (V) to % MMA (V) in urine of both sexes (unpublished data). These correlations were not statistically significant when urinary concentrations of Se and Hg were adjusted for urinary creatinine (Table 3). Interactions of As, Se, Hg and its relationship with methylation of arsenic are summarized in Figure 2. Sex difference distribution of arsenic species in urine.Our results indicate that females have more methylation capacity of arsenic as compared to males. In our human studies (n= 191) in Mexico, we found that females (n= 98) had lower % MMA (p<0.001) and higher % DMA (p=0.006) when compared to males (n= 93) (Fig. 3). The means ratio of % MMA (V) to % Inorg-As and % DMA (V) to %MMA (V) were also lower (p<0.05) and higher (p<0.001), respectively in females compared to males. The protein expression profiles in the tissues of hamsters exposed to Na-As (III).In our preliminary studies40, hamsters were exposed to Na-As (III) (173 pg/ml as As) in their drinking water for 6 days and control hamsters were given only the water used to make the solutions for the experimental animals. After DIGE (Two-dimensional differential in gel electrophoresis) and analysis by the DeCyder software, several protein spots were found to be over-expressed (red spot) and several were under expressed (green spot) as compared to control (Figs. 4a-c). Three proteins (one was over-expressed and two were under-expressed) of each tissue (liver and urinary bladder) were identified by LC-MS/MS (liquid chromatography-tandem mass spectrometry).DIGE in combination with LC-MS/MS is a powerful tool that may help cancer investigators to understand the molecular mechanisms of cancer progression due to Inorg-As. Propose a new researchThese results suggested that selenium (Se) as well as mercury (Hg) may influence the methylation of Inorg-As and this influence could be dependent on the concentration of Se, Hg and/or the sex of the animal. Our study also suggested that the identification and functional assignment of the expressed proteins in the tissues of Inorg-As (III) exposed animals will be useful for understanding and helping to formulate a theory dealing with the molecular events of arsenic toxicity and carcinogenicity.Therefore, it would be very useful if we could do a research study with combination of Inorg-arsenic, Se, and Hg. The new research protocol could be the following:For metabolic processing, hamsters provide a good animal model. For carcinogenesis, mouse model is well accepted. The aims of this project are: 1) To map the differential distributions of arsenic (As) metabolites/species in relation to selenium (Se) and mercury (Hg) levels in male and female hamsters and 2) To chart the protein expression profile and identify the defense proteins in mice and hamsters after As injury. Experimental hamsters (male or female) will include four groups. The first group will be treated with Na arseniteNa-As(III), the second group with Na-As (III) and Na-selenite (Na-Se (IV)], the third group with Na As (III) and methyl mercuric chloride (MeHgCl), and the final group with Na-As (III), Na-Se (IV), and MeHgci at different levels. Urine and tissue will be collected at different time periods and measured for As species using high performance liquid chromatography/inductively coupled plasma-mass spectrometry (HPLC/ICP-MS). For proteomics, mice (male and female) and hamsters (male and female) will be exposed to Na-As (III)at different levels in tap water, and control mice and hamsters will be given only the tap water. Tissue will be harvested at different time periods. TWO dimensional differential in gel electrophoresis (2D-DIGE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) will be employed to identify the expressed protein. In summary, we intend to extend our findings to: 1) Differential distribution of As metabolites in kidney, liver, lung, and urinary bladder of male and female hamsters exposed to Na-As (III), and combined with Na-As (III) and Na-Se (IV) and/or MeHgCl at different levels and different time periods, 2) Show the correlation of As species distribution in the tissue and urine for both male and female hamsters treated with and without Na-Se (IV) and/or MeHgCl, and 3) Show protein expression profile and identify the defense proteins in the tissues (liver, lung, and urinary bladder epithelium) in mice after arsenic injury. The significance of this study: The results of which have the following significances: (A) Since Inorg-As is a human carcinogen, understanding how its metabolism is influenced by environmental factors may help understand its toxicity and carcinogenicity, (B) The interactions between arsenic (As), selenium (Se), and mercury (Hg) are of practical significance because populations in various parts of the world are simultaneously exposed to Inorg-As & Se and/or MeHg, (C) These interactions may inhibit the biotransformation of Inorg-As (III) which could increase the amount and toxicity of Inorg-As (III) and MMA (III) in the tissues, (D) Determination of arsenic species profile in the tissues after ingestion of Inorg-As (III), Se (IV), and/or MeHg+ will help understand the tissue specific influence of Se and Hg on Inorg-As (III) metabolism, (E) Correlation of arsenic species between tissue and urine might help to understand the tissue burden of arsenic species when researchers just know the distribution of arsenic species in urine, (F) The identification of the defense proteins (over-expressed and under-expressed) in the tissues of the mouse may lead to understanding the mechanisms of inorganic arsenic injury in human. The Superfund Basic Research Program NIEHS Grant Number ES 04940 from the National Institute of Environmental Health Sciences supported this work. Additional support for the mass spectrometry analyses was provided by grants from NIWHS ES 06694, NCI CA 023074 and the BIO5 Institute of the University of Arizona. Acknowledge:The Authorwantsto dedicate this paper to the memory of Dr. H. VaskenAposhian and Dr. Mary M. Aposhian who collected urine and bloodsamples from Mexican population. The work was done under Prof. H. V. Aposhian sole supervision and with his great contribution. References NRC (National Research Council). Arsenic in Drinking Water. Update to the 1999 Arsenic in Drinking Water Report. National Academy Press, Washington, DC. 2001. Gomez-Caminero, A.; Howe, P.; Hughes, M.; Kenyon, ; Lewis, D. R.; Moore, J.; Mg, J.; Aitio, A.; Becking, G. Environmental Health Criteria 224. Arsenic and Arsenic Compounds (Second Edition). 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