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RET in breast cancer:pathogenic implications and mechanisms of drug resistance

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Cancer Drug Resistance 2019年第4期2卷 1136-1152页

作者： Cristiana Lo Nigro Marta Rusmini isabella Ceccherini Laboratory Department S.Croce&Carle Teaching HospitalCuneo 12100Italy U.O.C.Medical Genetics IRCCS Istituto Giannina GasliniGenoa 16147Italy

Initiation,progression,outcome and sensibility to therapies in breast cancer(BC),the most frequent cancer in women,are driven by somatic and germline *** the effectiveness of hormonal therapies is well-founded,it is prescribed for cancers which express steroid hormone receptors,such as estrogen receptor(ER).RET is a proto-oncogene encoding a transmembrane tyrosine kinase receptor that is activated by one of its four ligands(GDNF,neurturin,artemin or persephin)and one of its coreceptors(Gfrα1-4).Loss-of-function mutations in RET are responsible for Hirschsprung disease,while gain-of-function mutations for multiple endocrine neoplasia type *** addition,deregulation of its intracellular signaling,due to mutations,gene rearrangements,overexpression or transcriptional upregulation,can cause several neuroendocrine and epithelial *** BC,amplification of receptor tyrosine kinases,such as ERBB2,EGFR,IGFR and FGFR1,and/or their upregulation contribute to cancer initiation and *** can also have an important role in BC,but only in the subset of ER-positive(ER+)tumors,where it is found *** the RET pathway and shedding light on molecular basis of the resistance to hormone therapy may lead to new therapies in ER+BC,improving treatment outcome and preventing tumor-related ***,here,we review the state of the art of RET biology in BC and agents targeting RET tested in the clinical trials and discuss the specificity of the still available RET inhibitors and the molecular mechanisms underlying the BC resistance to endocrine therapy.

关键词： Breast cancer RET hormone resistance receptor tyrosine kinases inhibitors

Sexual Abuse and Mental Disorders:The Dark Side of Violence

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Journal of Forensic Science and Medicine 2023年第1期9卷 76-80页

作者： isabella Aquila Matteo Antonio Sacco Pietrantonio Ricci Department of Surgical and Medical Sciences Institute of Legal MedicineUniversity“Magna Graecia”of CatanzaroCatanzaroItaly

Rape and sexual violence occur in all social classes and *** most cases,the sexual offenders are known to the victim and the majority of rapes happen in intimate *** are particularly vulnerable to sexual abuse,in particular,the female *** sexual abuse of minors is defined as“any sexual activities that an adult carries on or with a person under the age of consent.”Literature evidence that the prevalence of any type of violence among women with disabilities varies between 26.0%and 90.0%,compared to nondisabled women,showing that people with disabilities have an increased risk of suffering physical and sexual *** with intellectual disabilities(ID)show a high risk of sexual *** World Health Organization presently defines mental retardation as“a significantly reduced ability to understand new or complex information and to learn and apply new skills(impaired intelligence).This results in a reduced ability to cope independently(impaired social functioning),and begins before adulthood,with a lasting effect on development.”The aim of this study is to investigate the correct identification of sexual abuse and severe mental retardation through the collaboration of a team of experts(forensic pathologist,psychiatrist,psychologist,gynecologist,pediatrician,and social worker).We present a case of a 12-year-old female child,who suffers from severe mental retardation and was the victim of rape by a 79-year-old *** study shows the difficulties in discovering episodes of sexual abuse among children affected by ID by evidencing the importance of adequate analysis through a multidisciplinary *** work focuses on the need to improve knowledge about medical and forensic investigations through proper protocols,for early recognition and appropriate management of these complicated cases.

关键词： Child abuse domestic violence and cultural context forensic interviewing mental health and violence sexual abuse

Endoscopic papillary balloon dilation for diffi cult common bile duct stones:Our experience

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World Journal of Clinical Cases 2013年第1期1卷 19-24页

作者： Maddalena Zippi isabella De Felici Roberta Pica Giampiero Traversa Giuseppe Occhigrossi Unit of Gastroenterology and Digestive Endoscopy Sandro Pertini Hospital 00157 Rome Italy

AIM: To evaluate the eff icacy and safety of endoscopic balloon dilation(EBD) performed for common bile duct(CBD) ***: From a computer database, we retrospectively analyzed the data relating to EBD performed in patients at the gastrointestinal unit of the Sandro Pertini Hospital of Rome(small center with low case volume) who underwent endoscopic retrograde cholangiopancreatography(ERCP) for CBD from January 1, 2010 to February 29, 2012. All patients had a proven diagnosis of CBD stones studied with echography, RMN cholangiography and, when necessary, with computed tomography of the abdomen(for example, in cases with pace-makers). Prophylactic therapies, with gabexate mesilate 24 h before the procedure and with an antibiotic(ceftriaxone 2 g) 1 h before, were administered in all patients. The duodenum was intubated with a side-viewing endoscope under deep sedation with intravenous midazolam and propofol. The patients were placed in the supine position in almost all cases. EBDof the ampulla was performed under endoscopic and f luoroscopic guidance with a balloon through the scope(Hercules, wireguided balloon, Cook Ireland Ltd. and CRE, Microvasive, Boston Scientific Co., Natick, MA, United States). RESULTS: A total of 14 patients(9 female, 5 male; mean age of 73 years; range 57-82 years) were enrolled in the study, in whom a total of 15 EBDs were performed. All patients underwent minor endoscopic sphincterotomy(ES) prior to the EBD. The size of balloon insuff lation depended on stone size and CBD dilation and this was performed until it reached 16 mm in diameter. EBD was performed under endoscopic and f luoroscopic guidance. The balloon was gradually f illed with diluted contrast agent and was maintained inf lated in position for 45 to 60 s before def lation and removal. The need for precutting the major papilla was 21.4%. In one patient(an 81-year-old), EBD was performed in a Billroth Ⅱ. Periampullary diverticula were found only in a 74-year-old female. T

关键词： Choledocholithiasis Endoscopic balloon dilation Endoscopic retrograde cholangiopancreatography Endoscopic sphincterotomy Mechanical lithotripsy

Comparison of reversed-phase enantioselective HPLC methods for determining the enantiomeric purity of (S)-omeprazole in the presence of its related substances

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Journal of Pharmaceutical Analysis 2016年第2期6卷 132-136页

作者： Bruno Gallinella Rosella Ferretti Leo Zanitti isabella Sestili Antonina Mosca Roberto Cirilli Istituto Superiore di Sanita Dipartimento del Farmaco Viale Regina Elena 299 1-00161 Rome Italy

A simple analytical high-performance liquid chromatography （HPLC） method was applied for the en- antiomeric excess determination of esomeprazole （（S）-OME）, the enantiopure active ingredient con- tained in drug products, in the presence of its potential organic impurities A-E. The enantioselective separation was accomplished on the immobilized-type Chiralpak ID-3 chiral stationary phase （CSP） under reversed-phase conditions. The results were evaluated and compared with those obtained by the official enantioselective method of European Pharmacopoeia used as the reference for checking the enantiomeric excess of （S）-OME. It has been established that the use of the Chiralpak ID-3 CSP allows the determination of the enantiomeric purity of （S）-OME without any interference coming from its chiral and achiral related substances. The analytical procedure of the drug regulatory agencies based on the AGP CSP suffered instead from poor specificity due to overlap of the peaks pertinent to the achiral impurity A and the chiral impurity （R）-OME （impurity F）.

关键词： Chiralpak ID-3 Enantiomers Enantioselective HPLC Impurities(S)-Omeprazole

Erratum to:Sub-gap defect density characterization of molybdenum oxide:An annealing study for solar cell applications

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Nano Research 2022年第8期15卷 7752-7753页

作者： Daniele Scirè Paul Procel Antonino Gulino Olindo isabella Miro Zeman Isodiana Crupi Department of Engineering University of PalermoPalermo 90128Italy Photovoltaic Materials and Devices group Delft University of TechnologyDelft 2628 CDthe Netherlands Department of Chemical Sciences University of CataniaCatania 95125Italy

Erratum to Nano Research 2020,13(12):3416–3424 https://***/10.1007/s12274-020-3029-9 Ref.[56]was unfortunately wrong,Instead of[56]Corless,R.M.;Gonnet,G.H.;Hare,D.E.G.;Jeffrey,D.J.;Knuth,*** the Lambert W ***.1996,5,329–*** should be changed to Biswas,R.K.;Khan,P.;Mukherjee,S.;Mukhopadhyay,A.K.;Ghosh,J.;Muraleedharan,*** of short range structure of amorphous Silica from PDF using Ag radiation in laboratory XRD system,RAMAN and *** 2018,488,1–9.

关键词： function. annealing molybdenum

Occurrence and patterns of nutritional traits and polycyclic aromatic hydrocarbons(PAHs)in sea cucumber(Holothuria poli)tissues:benefits and risk for human health

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Food Quality and Safety 2022年第2期6卷 287-309页

作者： Francesca Biandolino isabella Parlapiano Lucia Spada Antonella Di Leo Maria Calo Giovanni Fanelli Ermelinda Prato Santina Giandomenico CNR-IRSA National Research CouncilWater Research Institute--Via Roma 3TarantoItaly

Objectives:The paper evaluates the benefit and risk for human health associated with consumption of sea cucumber Holothuria poli(*** from Italian coasts(Central Mediterranean Sea).Materials and Methods:Body wall(BW),internal tunic(ITu),muscle bands(MBs),alimentary canal(AC),gonad(Gd),and respiratory tree(RT)of *** were analyzed for proximate ***,amino acids(AAs),fatty acids(FAs)and polycyclic aromatic hydrocar bons(PAHs)were determined with high-performance liquid chromatography coupled with ultraviolet-visible spectroscopy(UPLC UV/Vis),gas chromatography-flame ionization detector(GC-FID)and gas chromatography mass spectrometry(GC-MS),***:Differences in the contents of total amino acids(TAAs)occurred based on tissue and sex,with AC and MB of female and Gd of male showing higher contents(range 47.8-60.2 g/kg we weight(ww)).Glycine and glutamic acid were the most *** fatty acid(PUFA)was the major class of FAs and arachidonic acid and eicosapentenoic acid(EPA)were the predominant PUFA.n-3 PUFA showed higher content in Gd,AC,and RT,indicating higher quality.A favorable n-3/n-6 in the range of 1.04-1.67 was *** showed values ranging from 23 to 207μg/kg ww with the highest levels in Gd and AC tissues and the lower in ***[alpyrene,the most toxic compound,was detected in all tissues,of both sexes,at levels of 1.5-18μg/kg ***:All tissues of ***,although with differences among them,are valuable food and can contribute for a healthy *** cancer risk(CR)values for Gd and AC tissues were above the considerable CR threshold of one in 10000 established by the United States Environmental Protection Agency(USEPA)for high ingestion rate of this seafood.

关键词： Holothuria poli,nutitional quality polycyclic aromatic hydrocarbons risk assessment estimated weekly intake cancer risk

Sex and stress modulate pupal defense response in tobacco hornworm

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Current Zoology 2023年第5期69卷 592-599页

作者： Sukhman Singh Sakshi Watts Ishveen Kaur isabella Rodriguez Jessica Ayala Dariela Rodriguez Elian Martin Rupesh Kariyat Department of Entomology The Pennsylvania State UniversityState CollegePA 16802USA Department of Biology The University of Texas Rio Grande ValleyEdinburgTX 78539USA School of Earth Environmental and Marine Sciences The University of Texas Rio Grande ValleyEdinburgTX 78539USA Department of Entomology and Plant Pathology University of ArkansasFayettevilleAR 72701USA

In insects,larval and adult defenses against predators have been well ***,pupal(also known as resting stage)defenses have been overlooked and not examined *** some pupa possess antipredator strategies such as hairs,spines,cryptic coloration,and exudation of chemicals,few studies have tested these responses and the factors affecting ***,we investigated the behavioral responses in tobacco hornworm Manduca sexta that pupates in soil by introducing an external stimulus using vibrations from an electric toothbrush to mimic *** observed that *** made violent wriggling(twitching),followed by pulsating movements in response to the vibrational *** examination showed that these twitches and pulsating events occurred more frequently and for longer periods of time in male pupa and were dependent on the magnitude of the stress(high and low frequency).However,when we estimated the angular force exerted by pupa using radian and angular momentum of twitches,it was found to be independent of pupal sex.A follow-up experiment on possible cascading effects of stress exposure on eclosion success revealed that low-and high-frequency stress exposure didn’t cause any of the common defects in eclosed *** study clearly demonstrates that the so-called defenseless pupal stage uses a wide range of measurable defense behaviors that can actively defend against predators and should be examined further-linking observed behavior with underlying mechanisms.

关键词： hornworm predation pupal defenses pupal sex twitching

Impact of technology use in type 2 diabetes distress:A systematic review

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World Journal of Diabetes 2020年第10期11卷 459-467页

作者： Patricia Vieira Renata Kobayasi Filomena Pereira isabella Martins Zaia Sandra Umeda Sasaki Department of Health Iron SaúdeAlcabideche 2649-517Portugal Department of Internal Medicine University of Sao PauloSao Paulo 05410-020Brazil School of Psychology and Science of Education University of PortoPorto 4200-465Portugal Medical School UNICID Sao Paulo 03071-000Brazil

BACKGROUND Diabetes distress is an important factor in treatment outcomes and results in poor behavioral and biological *** has been used in management programs of diabetes to improve communication between patients and health care providers and to promote education about the disease and its psychological aspects,which can impact the self-efficacy of the ***,the true impact of technological approaches on the management of type 2 diabetes distress remains *** To investigate the effectiveness of technology interventions on the management of type 2 diabetes *** Studies published from 2014 to 2019 were searched in five databases:MEDLINE,PubMed,Library and Information Science Source,Academic Search Ultimate and *** Boolean logic search terms were:(1)T2Diabetes;(2)diabetes distress;and(3)technology OR mobile OR phone OR application OR *** also systematically searched the reference lists of the included studies and relevant *** controlled trials with technology interventions,type 2 diabetes patients and diabetes distress as the outcome were *** Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was *** Of the 88 studies selected,nine full articles met the inclusion criteria and were subjected to final careful *** the JADAD scale,one article was classified as having poor quality and eight as having good *** out of nine articles showed that technology interventions had a positive impact on diabetes distress scale scores when compared with the initial *** the six articles,five showed a greater reduction in the diabetes distress scores from control ***-based interventions had good results when users received personalized feedback and routine caregiver support and *** Technology interventions can contribute positively to the management of type 2 diabetes distress,especially with a tailored appro

关键词： Technology Type 2 diabetes Diabetes distress Healthcare Systematic review

No evidence of circulating autoantibodies against osteoprotegerin in patients with celiac disease

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World Journal of Gastroenterology 2012年第14期18卷 1622-1627页

作者： Tiziana Larussa Evelina Suraci Immacolata Nazionale isabella Leone Tiziana Montalcini Ludovico Abenavoli Maria Imeneo Arturo Pujia Francesco Luzza Department of Health Science University of Catanzaro "Magna Graecia"88100 CatanzaroItaly Department of Medical and Surgical Science University of Catanzaro "Magna Graecia"88100 CatanzaroItaly

AIM:To investigate risk factors for low bone mineral density(BMD) in celiac disease(CD) patients,focusing on circulating autoantibodies against osteoprotegerin(OPG).METHODS:Seventy asymptomatic CD adult patients on gluten-free diet(GFD) and harbouring persistent negative CD-related serology were *** risk factors for osteoporosis(e.g.,age,sex,menopausal status,history of fractures,smoke,and body mass index) were checked and BMD was assessed by dual energy X ray *** calcium and parathyroid hormone(PTH) levels were ***-eight patients underwent repeat duodenal *** samples from a selected sub-group of 30 patients,who were also typed for human leukocyte antigen(HLA) DQ2 and DQ8 haplotype,were incubatedwith homodimeric recombinant human OPG and tested by western blotting with an anti-OPG antibody after ***:Despite persistent negative CD-related serology and strict adherence to GFD,49 out of the 70(74%) patients displayed low *** these patients,13(24%) showed osteoporosis and 36(76%) *** the exception of age,conventional risk factors for osteoporosis did not differ between patients with normal and low *** serum calcium and PTH levels were normal in all *** mucosa healing was found in 31(82%) out of 38 patients who underwent repeat duodenal biopsy with 20(64%) still displaying low *** remaining 7 patients had an incomplete normalization of duodenal mucosa with 6(84%) showing low *** evidence of circulating antibodies against OPG was found in the serum of 30 celiac patients who were tested for,independent of BMD,duodenal histology,and HLA ***:If any,the role of circulating autoantibodies against OPG in the pathogenesis of bone derangement in patients with CD is not a major one.

关键词： Celiac disease Osteoprotegerin Bone mineral density Gluten-free diet Osteoporosis Osteopenia