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Physicians’perspectives on adverse drug reactions in pediatric routine care:a survey

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World Journal of Pediatrics 2022年第1期18卷 50-58页

作者： martina P.Neininger Sarah Jeschke Lisa M.Kiesel Thilo Bertsche Astrid Bertsche Clinical Pharmacy Institute of PharmacyMedical FacultyLeipzig University and Drug Safety CenterLeipzig University and University HospitalBruederstrasse 3204103 LeipzigGermany University Hospital for Children and Adolescents NeuropediatricsErnst-Heydemann-Str.818057 RostockGermany

Background Children and adolescents are at particular risk for adverse drug reactions(ADRs).We investigated physicians’perceptions on ADRs in pediatric routine *** In this exploratory study from April to November 2020,we invited physicians treating pediatric patients across Germany to complete an online questionnaire consisting mainly of closed *** Completion rate was 98%(127/129).Of all participants,23%(29/127)stated they were not able to estimate how many of their pediatric patients experienced ADRs during drug *** remaining physicians estimated that 7.5%(median;Q25/Q753%/20%)of their pediatric patients were afected by *** counseling on ADRs,61%(77/127)stated they do not ask regularly the extent to which parents want to be *** total,26%(33/127)stated they avoid counseling on ADRs concerning commonly used approved therapies,whereas only 4%(5/127)did so concerning of-label use(P<0.001).Altogether,16%(20/127)stated they rather prescribe new medicines as they hope for better efectiveness;72%(91/127)said they are cautious about doing so owing to yet unknown *** all respondents,46%(58/127)stated they do not report ADRs to the *** the black triangle symbol,a European pharmacovigilance measure,11%(14/127)stated they knew it and 6%(7/127)stated they reported any suspected ADR for drugs with that *** Physicians’perspectives on ADRs were ambivalent:ADRs infuenced their parent counseling and drug prescribing;yet,they struggled to estimate the impact of ADRs on their patients and were not aware of specifc pharmacovigilance measures.

关键词： Adverse drug reactions Pediatrics Physicians Routine care Spontaneous reporting

From Neglecting to Including Cultivar-Specific Per Se Temperature Responses:Extending the Concept of Thermal Time in Field Crops

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Plant Phenomics 2024年第3期6卷 547-562页

作者： Lukas Roth martina Binder Norbert Kirchgessner Flavian Tschurr Steven Yates Andreas Hund Lukas Kronenberg Achim Walter ETH Zurich Institute of Agricultural SciencesUniversitätstrasse 28092 ZürichSwitzerland John Innes Centre Crop GeneticsNorwich NR47UHUnited Kingdom

Predicting plant development,a longstanding goal in plant physiology,involves 2 interwoven components:continuous growth and the progression of growth stages(phenology).Current models for winter wheat and soybean assume species-level growth responses to *** challenge this assumption,suggesting that cultivar-specific temperature responses substantially affect *** investigate,we collected field-based growth and phenology data in winter wheat and soybean over multiple *** used diverse models,from linear to neural networks,to assess growth responses to temperature at various trait and covariate ***-specific nonlinear models best explained phenology-related cultivar-environment *** cultivar-specific models,additional relations to other stressors than temperature were *** availability of the presented field phenotyping tools allows incorporating cultivar-specific temperature response functions in future plant physiology studies,which will deepen our understanding of key factors that influence plant ***,this work has implications for crop breeding and cultivation under adverse climatic conditions.

关键词： temperature specific concept crops field time from cultivar extending including

;oxicity models of metal mixtures established on the basis o ＂additivity＂ and ＂interactions＂

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Frontiers of Environmental Science & Engineering 2017年第2期11卷 11-23页

作者： Yang Liu martina G. Vijver Bo Pan Willie J. G. M. Peijnenburg Faculty of Environmental Science and Engineering Kunming University of Science and Technology Kunming 650500 China Institute of Environmental Sciences (CML) Leiden University Leiden 2300 RA The Netherlands National Institute of Public Health and the Environment (RIVM) Center for Safety of Substances and Products Bilthoven 3720 BA The Netherlands

Observed effects of metal mixtures on animals and plants often differ from the estimates, which are commonly calculated by adding up the biological responses of individual metals. This difference from additivity is commonly referred to as being a consequence of specific interactions between metals. The science of how to quantify metal interactions and whether to include them in risk assessment models is in its infancy. This review summarizes the existing predictive tools for evaluating the combined toxicity of metals present in mixtures and indicates the advantages and disadvantages of each method. We intend to provide eco-toxicologists with background information on how to make good use of the tools and how to advance the methods for assessing toxicity of metal mixtures, It is concluded that statistically significant deviations from additivity are not necessarily biologically relevant. Incorporation of interactions between metals in a model does not on forehand mean that the model is more accurate than a model developed based on additivity only. It is recommended to first use a relatively simple method for effect prediction of uninvestigated metal mixtures. To improve the reliability of toxicity modeling for metal mixtures, further efforts should focus on balancing the relationship between the significance of statistics and the biological meaning, and unraveling the toxicity mechanisms of metals and their mixtures.

关键词： Metal Mixtures Toxicity Additivity Modeling Interactions

Cell-mediated immune resistance in cancer

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Cancer Drug Resistance 2020年第2期3卷 232-251页

作者： Yuhao Wang Emily Hays martina Rama Benjamin Bonavida Department of Microbiology Immunologyand Molecular GeneticsDavid Geffen School of MedicineThe University of CaliforniaLos AngelesLos AngelesCA 90025-1747USA

The genetic and epigenetic aberrations that underlie immune resistance lead to tumors that are refractory to clinically established and experimental immunotherapies,including monoclonal antibodies and T cell-based *** various forms of cytotoxic T cells to small molecule inhibitors that revamp the tumor microenvironment,these therapies have demonstrated notable responses in cancer models and a resistant subset of cancer patients,used both alone and in ***,even current approaches,such as those targeting checkpoint molecules,tumor ligands,and involving gene-related therapies,present a challenge in non-responding *** this perspective,we discuss the most common mechanisms of immune resistance,including tumor heterogeneity,tumor ligand and major histocompatibility complex modulation,anti-apoptotic pathways,checkpoint inhibitory ligands,immunosuppressive cells and factors in the tumor microenvironment,and activation-induced cell *** addition,we discuss the strategies designed to circumvent these resistance pathways to showcase the potential of emerging technologies in battling the rise of resistance.

关键词： Immune system immune resistance survival pathways heterogeneity cancer T cells checkpoint inhibitors tumor microenvironment

Patient-derived organoids for therapy personalization in inflammatory bowel diseases

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World Journal of Gastroenterology 2022年第24期28卷 2636-2653页

作者： Marianna Lucafò Antonella Muzzo martina Marcuzzi Lorenzo Giorio Giuliana Decorti Gabriele Stocco Advanced Translational Diagnostics Laboratory Institute for Maternal and Child Health-IRCCS“Burlo Garofolo”Trieste 34137Italy Department of Medicine Surgery and Health SciencesUniversity of TriesteTrieste 34127Italy Department of Life Sciences University of TriesteTrieste 34127Italy

Inflammatory bowel diseases(IBDs)are chronic inflammatory disorders of the intestinal tract that have emerged as a growing problem in industrialized *** of IBD pathogenesis is still incomplete,and the most widely-accepted interpretation considers genetic factors,environmental stimuli,uncontrolled immune responses and altered intestinal microbiota composition as determinants of IBD,leading to dysfunction of the intestinal epithelial *** vitro models commonly used to study the intestinal barrier do not fully reflect the proper intestinal *** important innovation is represented by organoids,3D in vitro cell structures derived from stem cells that can self-organize into functional organ-specific *** may be generated from induced pluripotent stem cells or adult intestinal stem cells of IBD patients and therefore retain their genetic and transcriptomic *** models are powerful pharmacological tools to better understand IBD pathogenesis,to study the mechanisms of action on the epithelial barrier of drugs already used in the treatment of IBD,and to evaluate novel target-directed molecules which could improve therapeutic *** aim of this review is to illustrate the potential use of organoids for therapy personalization by focusing on the most significant advances in IBD research achieved through the use of adult stem cells-derived intestinal organoids.

关键词： Inflammatory bowel disease Organoids Intestinal epithelium 3D cell cultures Personalized medicine

Anesthesia of a patient with congenital cataract,facial dysmorphism,and neuropathy syndrome for posterior scoliosis:A case report

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World Journal of Clinical Cases 2022年第13期10卷 4207-4213页

作者： Jan Hudec martina Kosinova Tereza Prokopova Milan Filipovic Martin Repko Petr Stourac Department of Anesthesiology and Intensive Care Medicine University Hospital BrnoMedical Faculty of Masaryk UniversityBrno 62500Czech Republic Department of Simulation Medicine Medical Faculty of Masaryk UniversityBrno 62500Czech Republic Department of Pediatric Anesthesiology and Intensive Care Medicine University Hospital BrnoMedical Faculty of Masaryk UniversityBrno 62500Czech Republic Department of Orthopedic Surgery University Hospital BrnoMedical Faculty of Masaryk UniversityBrno 62500Czech Republic

BACKGROUND Congenital cataract,facial dysmorphism,and neuropathy(CCFDN)syndrome is an extremely rare multiorgan *** include congenital cataracts,facial deformation,extremity deformities,and demyelinating *** syndrome is associated with increased risk during anesthesia including rhabdomyolysis or epileptic *** is a lack of published information about difficult airways in these *** airways during intubation represent one of the most dreaded anesthesia complications:A"can not intubate,can not oxygenate"*** herein is the first described successful endotracheal intubation of a CCFDN syndrome *** SUMMARY We report the anesthetic management of a 13-year-old girl with CCFDN syndrome scheduled for posterior neuromuscular scoliosis correction *** patient suffered from extensive progressive neuromuscular scoliosis with a Cobb angle of 83°.Her limitations included neuropathy and a scoliotic *** condition negatively impacted her quality of *** case reflects the potential anesthetic complications for posterior scoliosis correction and CCFDN *** challenge for our anesthetic team was the limited amount of data about anesthetic management of this *** total,one case report without any data about endotracheal intubation of patients with this condition was *** intubation in our case was *** focus of our case was the prevention of possible complications associated with this syndrome,including rhabdomyolysis and *** can be triggered by some types of anesthetic agents like suxamethonium or volatile anesthetics,especially in patients with certain types of *** Adequate understanding of the anesthetic management of CCFDN syndrome can reduce perioperative complications and improve patient outcome after surgery.

关键词： CCFDN syndrome Neuromuscular scoliosis Anesthetic management Total intravenous anesthesia Endotracheal intubation Case report

Therapeutic potential of glial cell line-derived neurotrophic factor and cell reprogramming for hippocampal-related neurological disorders

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Neural Regeneration Research 2022年第3期17卷 469-476页

作者： Priscila Chiavellini martina Canatelli-Mallat Marianne Lehmann Rodolfo G.Goya Gustavo R.Morel Biochemistry Research Institute of La Plata(INIBIOLP)-Histology and Embryology B School of Medical SciencesNational University of La Plata(UNLP)La PlataBuenos AiresArgentina

Hippocampus serves as a pivotal role in cognitive and emotional processes,as well as in the regulation of the hypothalamus-pituitary *** is known to undergo mild neurodegenerative changes during normal aging and severe atrophy in Alzheimer's ***,dysregulation in the hippocampal function leads to epilepsy and mood *** the first section,we summarized the most salient knowledge on the role of glial cell-line-derived neurotrophic factor and its receptors focused on aging,cognition and neurodegenerative and hippocampal-related neurological diseases mentioned *** the second section,we reviewed the therapeutic approaches,particularly gene therapy,using glial cell-line-derived neurotrophic factor or its gene,as a key molecule in the development of neurological *** the third section,we pointed at the potential of regenerative medicine,as an emerging and less explored strategy for the treatment of hippocampal *** briefly reviewed the use of partial reprogramming to restore brain functions,non-neuronal cell reprogramming to generate neural stem cells,and neural progenitor cells as source-specific neuronal types to be implanted in animal models of specific neurodegenerative disorders.

关键词： aging Alzheimer's disease cell reprogramming epilepsy gene therapy glial cell line-derived neurotrophic factor hippocampus major depression

A case of nontraumatic subperiosteal orbital hemorrhage following vomiting in pregnancy

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International Journal of Ophthalmology(English edition) 2020年第10期13卷 1675-1677页

作者： martina Liovic Sandra Sekelj Zeljka Janjetovic Zeljka Vukovic Arar Department of Ophthalmology General Hospital"Dr.Josip Bencevic"Slavonski Brod 35000Croatia

Dear Editor,We present a rare case of nontraumatic subperiosteal orbital hemorrhage(NTSOH)associated with the increase of intracranial venous *** orbital hemorrhage is a rare condition in ophthalmology,most commonly c... 详细信息

关键词： traumatic hemorrhage pregnancy

Effect of the position of the corneal lamella on the frequency of its detachment

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International Journal of Ophthalmology(English edition) 2022年第12期15卷 1940-1943页

作者： Pavel Studeny Magdalena Netukova martina Nemcokova Yun-Min Klimesova Deli Krizova Department of Ophthalmology University Hospital Kralovske Vinohrady and 3rd Faculty of MedicineCharles UniversityPrague 10034Czech Republic Eye Clinic SomichKarlovy Vary 36006Czech Republic

AIM:To determine the influence of gaps[places where neither the donor's nor the recipient's Descemet's membrane(DM)is present]and overlaps(places where the recipient's DM is covered by the donor's DM)on the frequency of postoperative detachment of DM endothelial keratoplasty(DMEK)***:Totally 64 eyes of 64 patients with Fuchs'endothelial dystrophy or bullous keratopathy indicated for DMEK were randomly divided in two *** diameter of the implanted DMEK lamella was the same in both groups(8 mm),but we changed the diameter of the removed recipient *** the first group(32 eyes),the circular area was approximately 8.5 mm(gaps);in the second group(32 eyes),the diameter was 7.5 mm(overlaps).Postoperatively we noted all cases of detachment visible on the slit lamp and these cases we indicated for *** also measured the uncorrected distance visual acuity(UDVA)as well as corrected distance visual acuity(CDVA)in decimal and postoperative endothelial cell density(ECD).The minimum follow-up time was ***:The number of rebubbling procedures in the entire group of patients was 13,i.e.,20.3%,with 6 eyes(18.7%)in the gap group,and 7 eyes(21.9%)in the overlap *** replacement(re-DMEK)was required in 3(gap group)and 2 patients(overlap group),*** dif ference between the groups was statistically *** UDVA was 0.54±0.21 in the gap group and 0.58±0.24 in the overlap *** CDVA was 0.74±0.22 and 0.80±0.16,*** was 1920±491 and 2149±570 cells/*** small differences between both groups were not statistically ***:We do not notice any difference in the group of patients with overlaps or gaps of *** presence of small areas of gaps or overlaps does not affect the frequency of detachment of the DMEK lamellae.

关键词： centrally positioned Descemet graft Descemet graf t detachment Descemet membrane endothelial keratoplasty posterior lamellar keratoplasty recovery of corneal transparency