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Effect of discounting on estimation of benefits determined by hepatitis C treatment

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World Journal of Gastroenterology 2012年第23期18卷 3032-3034页

作者： Andrea Messori valeria Fadda Dario Maratea Sabrina Trippoli Laboratorio SIFO di Farmacoeconomia Area Vasta Centro Toscana 59100 Prato Italy Dario Maratea Department of Pharmaceutical Sciences University of Firenze 50019 Sesto Fiorentino Italy

The combination of either boceprevir or telaprevir with ribavirin and interferon (triple therapy) has been shown to be more effective than ribavirin+interferon (dual therapy) for the treatment of genotype 1 hepatitis C. Since the benefit of these treatments takes place after years, simulation models are needed to predict long-term outcomes. In simulation models, the choice of different values of yearly discount rates (e.g., 6%, 3.5%, 2%, 1.5% or 0%) influences the results, but no studies have specifically addressed this issue. We examined this point by determining the long-term benefits under different conditions on the basis of standard modelling and using quality-adjusted life years (QALYs) to quantify the benefits. In our base case scenario, we compared the long-term benefit between patients given a treatment with a 40% sustained virologic response (SVR) (dual therapy) and patients given a treatment with a 70% SVR (triple therapy), and we then examined how these specific yearly discount rates influenced the incremental benefit. The gain between a 70% SVR and a 40% SVR decreased from 0.45 QA-LYs with a 0% discount rate to 0.22 QALYs with a 6% discount rate (ratio between the two values = 2.04).Testing the other discounting assumptions confirmed that the discount rate has a marked impact on the magnitude of the model-estimated incremental benefit. In conclusion, the results of our analysis can be helpful to better interpret cost-effectiveness studies evaluating new treatment for hepatitis C.

关键词： Boceprevir Telaprevir Cost-effectiveness Markov model Hepatitis C

Genotoxicity of gold nanoparticles functionalized with indolicidin towards Saccharomyces cerevisiae

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Journal of Environmental Sciences 2018年第4期30卷 138-145页

作者： Elisabetta de Alteriis Annarita Falanga Stefania Galdiero Marco Ouida valeria Maselli Emilia Galdiero Department of Biology University of Naples "Federico II" 80100 Naples Italy Department of Pharmacy University of Naples "Federico II" 80134 Naples Italy

The toxic effects of gold nanoparticles surface-functionalized with the antimicrobial peptide indolicidin（Au NPs-indolicidin） towards the yeast Saccharomyces cerevisiae, one of the major eukaryotic model organisms, have been evaluated. Growth and survival,genotoxicity, as measured by comet assay, and expression of the YCA1, an apoptosis indicating gene, following 72 hr exposure of yeast to Au NPs-indolicidin, and to Au NPs and indolicidin alone have been examined. The gold nanoparticles exerted toxicity with DNA damage, accompanied by reactive oxygen species production（ROS）, but they do not inhibit yeast growth and viability. Genotoxicity was less pronounced for surface-functionalized nanoparticles, showing that S. cerevisiae is quite resistant to the complex Au NPs-indolicidin.A progressive reduction of the genotoxic effect was observed along 72 hr exposure,presumably due to the activation of DNA repair mechanisms. These findings suggest the occurrence of a physiological protective response of S. cerevisiae towards nanoparticles,thereby providing useful information to the assessment of the environmental impact of metal nanoparticles.

关键词： Ecotoxicity Antimicrobial peptide Comet assay Yeast Nanoparticles Oxidative stress

Do pathological variables have prognostic significance in rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and surgery?

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World Journal of Gastroenterology 2017年第8期23卷 1412-1423页

作者： Luca Reggiani Bonetti Simona Lionti Federica Domati valeria Barresi Department of Laboratory Integrated Activities Anatomic Pathology and Legal Medicine Section of Pathology University of Modena and Reggio Emilia Department of Pathology in Evolutive Age and Adulthood "Gaetano Barresi" University of Messina

To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and *** regression grade (TRG) according to the Dworak system and yTNM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced (cTNM stage II and III) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival (DFS) and cancer specific survival (CSS) was analyzed by Kaplan Meier and Cox-regression ***+ status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response (low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified two-tiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The two-tiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic *** data suggest that caution should be applied in using a conservative approach in rectal carcinomas with cN+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma.

关键词： Rectal carcinoma Dworak Acellular mucin pools Downstaging Mucinous

Evidence for a con served microbiota across the different developmental stages of Plodia interpunctella

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Insect Science 2019年第3期26卷 466-478页

作者： valeria Mereghetti Bessem Chouaia Lidia Limonta Daria Patrizia Locatelli Matteo Montagna Dipartimento di Scienze Agrarie e Ambientali Universita degli Studi di Milano Milan Italy Dipartimento di Scienze per gli Alimenti la Nutrizione I'Ambiente Universita degli Studi di Milano Milan Italy

Diversity and composition of lepidopteran microbiotas are poorly investigated, especially across the different developmental stages. To improve this knowledge, we characterize the microbiota among different developmental stages of the Indian meal moth, Plodia interpunctella, which is considered one of the major pest of commodities world-wide. Using culture-independent approach based on Illumina 16S rRNA gene sequencing we characterized the microbiota of four developmental stages: eggs, first-, and last-instar larvae, and adult. A total of 1022 bacterial OTUs were obtained, showing a quite diversified microbiota associated to all the analyzed stages. The microbiotas associated with P. interpunctella resulted almost constant throughout the developmental stages, with approximately 77% of bacterial OTUs belonging to the phylum of Proteobacteria. The dominant bacterial genus is represented by Burkholderia (?64%), followed by Propionibacterium, Delftia, Pseudomonas, and Stenotrophomonas. A core bacterial community, composed of 139 OTUs, was detected in all the developmental stages, among which 112 OTUs were assigned to the genus Burkholderia. A phylogenetic reconstruction, based on the 16S rRNA, revealed that our Burkholderia OTUs clustered with Burkholderia cepacia complex, in the same group of those isolated from the hemipterans Gossyparia spuria and Acanthococcus aceris. The functional profiling, predicted on the base of the bacterial 16S rRNA, indicates differences in the metabolic pathways related to metabolism of amino acids between preimaginal and adult stages. We can hypothesize that bacteria may support the insect host during preimaginal stages.

关键词： Burkholderia Illumina sequencing Indian meal moth insect symbiosis Proteobacteria

Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2014年第39期20卷 14205-14218页

作者： Giuseppe Paradies valeria Paradies Francesca M Ruggiero Giuseppe Petrosillo Department of Biosciences Biotechnologies and Biopharmaceutics University of Bari 70126 Bari Italy Institute of Biomembranes and Bioenergetics National Research Council 70126 Bari Italy

Nonalcoholic fatty liver disease(NAFLD) is today considered the most common form of chronic liver disease, affecting a high proportion of the population worldwide. NAFLD encompasses a large spectrum of liver damage, ranging from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. Obesity, hyperglycemia, type 2 diabetes and hypertriglyceridemia are the most important risk factors. The pathogenesis of NAFLD and its progression to fibrosis and chronic liver disease is still unknown. Accumulating evidence indicates that mitochondrial dysfunction plays a key role in the physiopathology of NAFLD, although the mechanisms underlying this dysfunction are still unclear. Oxidative stress is considered an important factor in producing lethal hepatocyte injury associated with NAFLD. Mitochondrial respiratory chain is the main subcellular source of reactive oxygen species(ROS), which may damage mitochondrial proteins, lipids and mitochondrial DNA. Cardiolipin, a phospholipid located at the level of the inner mitochondrial membrane, plays an important role in several reactions and processes involved in mitochondrial bioenergetics as well as in mitochondrial dependent steps of apoptosis. This phospholipid is particularly susceptible to ROS attack. Cardiolipin peroxidation has been associated with mitochondrial dysfunction in multiple tissues in several physiopathological conditions, including NAFLD. In this review, we focus on the potential roles played by oxidative stress and cardiolipin alterations in mitochondrial dysfunction associated with NAFLD.

关键词： Oxidative stress Cardiolipin Mitochondrial bioenergetics Antioxidants Nonalcoholic fatty liver disease

Endoscopic ultrasound-guided fine-needle aspiration cytology in pancreaticobiliary carcinomas:diagnostic efficacy of cell-block immunocyto-chemistry

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Hepatobiliary & Pancreatic Diseases International 2015年第3期14卷 305-312页

作者： Antonio Ieni Paolo Todaro Stefano Francesco Crinò valeria Barresi Giovanni Tuccari Department of Human Pathology "Gaetano Barresi" Section of Pathological AnatomyAzienda Ospedaliera Universitaria "Policlinico G. Martino" University of Messina Department of Internal Medicine Digestive Endoscopy UnitAzienda Ospedaliera Universitaria "Policlinico G. Martino" University of Messina

BACKGROUND： Endoscopic ultrasound-guided fine-needle aspiration cytology was demonstrated to be a useful tool for the diagnosis and staging of pancreaticobiliary neoplastic le- sions. Nonetheless, the diagnostic value of this procedure may be limited by low cellularity of the specimen, contamination of intestinal cells and unfeasibility of ancillary immunocy- tochemical procedures. The present study was to evaluate its usefulness in the diagnosis of neoplastic lesions.

关键词： endoscopic ultrasound fine-needle aspiration cytology pancreas cell-block contaminant cells immunohistochemistry

Cumulative effects of volcanic ash on the food preferences of two Orthopteran species

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Insect Science 2017年第4期24卷 640-646页

作者： valeria Fern&ndez-Arhex Maria E. Amadio Octavio A. Bruzzone Instituto Nacional de Tecnologia Agropecuaria Estacion Experimental Agropecuaria-Bariloche CC277 A v Modesta Victoria 4450 (8400) San Carlos de Bariloche Argentina Lab ECO TONO-INIBIOMA Pie. Gutierrez 850 San Carlos de Bariloche Rio Negro Argentina Centro Cientifico Tecnologico - Consejo Nacional de Investigaciones Cientificas y Tocnicas (CCT-CONICET) Patagonia Norte. Av. de los Pioneros 2350 San Carlos de Bariloche Rio Negro Argentina

Inert dusts are an early form of insecticide which is still in use. One of the most common inert dusts is volcanic ash. In order to study the reaction ofrangeland grasshoppers, Dichroplus vittigerum （Acrididae） and a katydid, t]wgilis mendosensis （Phaneropteridae）, to the presence of volcanic ash in their food sources and how this reaction changed as a function of time, we conducted paired preference tests between clean leaves of their pre- ferred host plant and leaves exposed to volcanic ash of different grain size. The behavioral response was measured as the rating on the Thurstonian preference scale of leaves with ash in relation to clean leaves. The results showed that the avoidance of volcanic ash increased as a function of time in both species. Both species studied are occasionally exposed to vol- canic activity, and come from an area in which a volcanic eruption had recently occurred. As their populations did not decrease after the ash fall, we propose that some behavioral responses such as avoidance of places with ash, works as tolerance mechanism to inert dusts exposure.

关键词： Burgilis mendosensis Dichroplus vittigerum inert dust preference test thurstone scale

The relationship between morphology and flight in Drosophila:a study of two pairs of sibling species from a natural population

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Insect Science 2024年第3期31卷 885-900页

作者： Nicolás Flaibani Victoría Estefania Ortiz Juan JoséFanara valeria Paula Carreira Laboratorio de Evolucion Departamento de EcologiaGenética y Evolucion(DEGE)Facultad de Ciencias Exactas y Naturales(FCEN)Universidad de Buenos Aires(UBA)Instituto de GenéticaEcologia y Evolucion de Buenos Aires(IEGEBA)Consejo Nacional de Investigaciones Cientificasy Tecnicas(CONICET)-UBABuenos AiresArgentina

Insect flight is a complex trait involved in different behaviors,from the search for sexual partners,food,or breeding *** studies have postulated the adaptive advantages of certain morphological traits in relation to increased flight capacity,such as low values of wing loading or high values of wing:thorax ratio and wing-aspect ***,few studies have evaluated the relationship between variables related to flight and morphological traits in *** work aimed to study morphological traits in males and females of two pairs of sibling species:Drosophila buzzati Patterson and Wheeler-Drosophila koeferae Fontdevila and Wasserman,and Drosophila melanogaster Meigen-Drosophila simulans Sturtevant,and to analyze its relationship with *** detected the highest proportion of flight time in *** and *** compared to *** and ***,*** results also revealed sexual dimorphism,with males exhibiting a higher proportion of flight time than ***,we did not find a general pattern to explain the relationship between morphology and the proportion of flight time because associations varied depending upon the analyses(considering all groups together or each sex-species combination separately).Moreover,these associations explained a low percentage of variation,suggesting that other nonmorphological components related to flight,such as physiological variables,should be taken into *** work allowed us to show the variability and complexity of an aspect of flight,suggesting that the adaptive role of the morphological traits studied might have been overestimated.

关键词： morphological traits time in flight wing loading wing:thorax ratio wingaspect ratio wing second moment of area

Gastrointestinal and nutritional care in pediatric neuromuscular disorders

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World Journal of Clinical Pediatrics 2023年第4期12卷 197-204页

作者： valeria Dipasquale Rossella Morello Claudio Romano Department of Human Pathology in Adulthood and Childhood“G.Barresi” University Hospital“G.Martino”Messina 98124Italy

Neuromuscular diseases(NMDs)affect the development and growth of the neuromuscular system in *** pathology can occur anywhere along the neuromuscular pathway,from the brain to the nerves to the muscle *** diseases have a profound impact on the quality of life not only of children but also of their *** predominant manifestation in NMDs is hypotonia,which leads to muscle weakness and fatigue,reduced mobility,and decreased physical ***,multiple organ systems can be affected,with resulting orthopedic,cardiac,infectious,respiratory,and nutritional *** with NMD present an increased risk for several dietary and feeding difficulties because of their neuromuscular diagnosis,presentation,and *** problems include chronic gastrointestinal issues(constipation,dysphagia,gastroesophageal reflux,and diarrhea),dysphagia,malnutrition,and body composition *** a result,compared to the overall pediatric population,infants and children with NMD are more likely to be malnourished,ranging from failure to thrive to overweight or ***-specific guidelines vary in level of detail and recommendations for dietary ***,nutritional data available are sparse,with the exception of Duchenne muscular dystrophy,spinal muscular atrophy,and congenital muscular *** purpose of this review is to describe the spectrum of nutritional challenges in children with NMD and to summarize the main dietary and gastrointestinal recommendations for each neuromuscular disorder to provide guidance for daily clinical practice.

关键词： Neuromuscular disorders Diet Malnutrition Overweight Dysphagia Gastrointestinal dysmotility Gastrointestinal symptoms Tube feeding