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5-Fluorouracil dose escalation generated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential

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Oncology Research 2024年第6期32卷 1047-1061页

作者： kimberly FENECH ISAAC MICALLEF BYRON BARON Centre for Molecular Medicine and Biobanking University of MaltaMsidaMSD 2080Malta Department of Tumor Genetics and Biology Graduate School of Medical SciencesFaculty of Life SciencesKumamoto UniversityKumamoto860-8556Japan

Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be les

关键词： Chemoresistance Epithelial-to-mesenchymal transition Protein methylation Protein methyltransferases

The Role of Impulsivity and Addiction in Gambling Behaviors: How Applied Neuroscience Research Can Help in the Monitoring and Management of Mental Health Issues

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Open Journal of Medical Psychology 2024年第1期13卷 11-24页

作者： Yingzhen Jia kimberly Rose Clark College of Arts and Sciences Boston University Boston MA USA Department of Psychological and Brain Sciences Dartmouth College Hanover NH USA

One in five Americans experience symptoms associated with at least one mental health disorder every year. These include behavioral addictions, which have long been overlooked despite their similar neural bases with substance addictions. Gambling addiction, a type of behavioral addiction, deserves particular attention given the significant negative effects, this addiction has on financial and interpersonal health. The purpose of this paper is to review the available literature concerning the behavioral and neural processes involved in gambling addiction, including: the anticipation of reward, the role of dopamine, and the neural substrates of the decision-making processes involved in gambling addiction. Market research has also identified solutions that integrate applied neuroscience and self-tracking systems to monitor and manage mental health issues associated with gambling addiction. The authors then propose a gambling treatment-focused mobile app solution that addresses outstanding issues with a special design aimed at reversing plasticity in order to relieve the effects of gambling addiction. .

关键词： Applied Neuroscience Gambling Addiction Mental Health Management

护理专业国际学生短期访学教育项目的设计与实施

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International Journal of Nursing Sciences 2024年第1期11卷 83-90页

作者： Ubolrat Piamjariyakul Saima Shafique Dana L.Friend kimberly A.Adams Wiyakarn Sanghuachang Trisha M.Petitte Stephanie Young School of Nursing West Virginia UniversityMorgantownWVUSA Boromarajonani College of Nursing Saraburi SaraburiThailand

目的旨在描述制定及评估一项短期留学生研究和教育项目。方法研究分为项目制定与实施及评价2部分。根据1名国际学生的短期访学需求,护理学院的全球护理项目协调员和首席导师共同确定项目基本内容和团队成员。该项目学习活动考虑了该国... 详细信息

目的旨在描述制定及评估一项短期留学生研究和教育项目。方法研究分为项目制定与实施及评价2部分。根据1名国际学生的短期访学需求,护理学院的全球护理项目协调员和首席导师共同确定项目基本内容和团队成员。该项目学习活动考虑了该国际学生对老年人和居家临终关怀的兴趣,包括4项内容:.开展研究工作,参与教学活动,参与临床实践活动,以及特殊活动和专业发展培训课程。在为期6个月的访学结束时,对参与此次教学活动的教师、研究生及留学生进行访谈和简短问卷调查。结果通过访谈了解到3个方面的内容:通过参与该项目中获得的经验(增强了教育和研究的多样性,获得了新的全球医疗保健知识,对文化意识的自我反思和促进);项目实施的障碍和挑战(签证申请过程,英语语言障碍,缺乏公共交通设施,时间安排冲突);克服这些障碍和挑战的策略(在课程中增加文化多样性信息;与其他同学一起学习英语;使用不同的沟通技巧;在签证申请过程中与大学全球事务办公室持续合作;提供互动体验)。所有项目参与者都对该项目表示非常满意(4.67±0.50),认为对他们在科研、教学和临床实践方面的护理技能有很大影响(4.67±0.50)。结论此次项目的参与者均获得了相关经验,可用于今后的教学指导活动。国际护理专业学生需要得到帮助才能更好地适应访学环境,教师必须具有文化敏感性,了解学生的学习需求,并倡导营造适合学生学习的环境。

关键词：评价国际学生护理教育课程

A Case Report: Emergency Management of a Pregnant Trauma Patient—An Anesthesiologist’s Perspective and Role

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Open Journal of Anesthesiology 2024年第2期14卷 25-39页

作者： Kalpana Tyagaraj Candice Ibarra kimberly Moy Nina Luksanapol Gianna Torre Raymond Powers Anuj Bapodra Maimonides Medical Center New York USA

Trauma is the leading cause of death for all women of childbearing age. Motor vehicle accidents account for almost two-thirds of all maternal non-obstetric, trauma-related deaths, while falls and domestic violence comprise a large percentage of the rest. The leading causes of obstetric trauma are motor vehicle accidents, falls, assaults, and gunshots, and ensuing injuries are classified as blunt abdominal trauma, pelvic fractures, or penetrating trauma . The causes are different with different life styles and different socio-economic and cultural background. Pregnant trauma victims tend to be younger, less severely injured, and more likely African American or of Hispanic descent compared with nonpregnant victims of trauma. Drugs and alcohol are a factor in about 20 percent of maternal trauma. With pregnancy comes the challenge and responsibility of caring for two patients at once, the mother and the fetus. In general, providing optimal maternal care is the best strategy to optimize fetal survival. Decision-making including the condition of the mother, gestational age, status of the fetus, and interventions are based on these key factors. Many providers are involved in the care of the pregnant patient: at the trauma scene, in the emergency department, and in the operating room. The anesthesiologist plays a key role in the care and management of the pregnant trauma patient. All anesthesiologists have ample training in obstetric anesthesia during their residency and frequently cover obstetric units in hospitals where pregnant patients are cared for. On the other hand, most nonobstetric physicians have little obstetric exposure and may be uncomfortable caring for the pregnant patient because of unfamiliarity with the physiologic changes of pregnancy or the evaluation of fetal well-being. This is not only a source of stress for other trauma providers, but can put maternal well-being at risk. Non-obstetric physicians may hesitate to order necessary diagnostic and therapeutic interventions for fear of doing the “wrong t

关键词： Obstetric Anesthesiology Ob Trauma Maternal and Fetal Resuscitation

Diabetes as a consequence of acute pancreatitis

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世界胃肠病学杂志:英文版 2023年第31期29卷 4736-4743页

作者： Ericka Charley Brett Dinner kimberly Pham Neil Vyas Department of Gastroenterology Creighton University-St.Joseph’s Hospital and Medical Center PhoenixAZ 85013United States Department of Internal Medicine Creighton University St.Joseph’s Hospital and Medical CenterPhoenixAZ 85013United States Department of Gastroenterology Creighton University St.Joseph’s Hospital and Medical CenterPhoenixAZ 85013United States

Diabetes is a highly prevalent disease that was initially simplified into three major types:Type 1,type 2 and gestational diabetes.With the global rise in incidence of acute pancreatitis(AP),a lesser-known type of diabetes referred to as diabetes of the exocrine pancreas(DEP)is becoming more recognized.However,there is a poor understanding of the inherent relationship between diabetes and AP.There is established data about certain diseases affecting the exocrine function of the pancreas which can lead to diabetes.More specifically,there are well established guidelines for diagnosis and management of DEP caused be chronic pancreatitis.Conversely,the sequelae of AP leading to diabetes has limited recognition and data.The purpose of this review is to provide a comprehensive summary of the prevalence,epidemiology,pathophysiology and future research aims of APrelated diabetes.In addition,we propose a screening and diagnostic algorithm to aid clinicians in providing better care for their patients.

关键词： Acute pancreatitis Type 3c diabetes Diabetes of the exocrine pancreas Sequelae of acute pancreatitis Screening and diagnostic algorithm

Exploring the role of interleukin-27 as a regulator of neuronal survival in central nervous system diseases

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Neural Regeneration Research 2022年第10期17卷 2149-2152页

作者： Andrea N.Nortey kimberly N.Garces Abigail S.Hackam Bascom Palmer Eye Institute University of Miami Miller School of MedicineMiamiFLUSA

Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection,cell stress,neuronal disease,and tumors.Recent studies in various tissues indicate that interleukin-27 has complex activating and inhibitory properties in innate and acquired immunity.The availability of recombinant interleukin-27 protein and mice with genetic deletions of interleukin-27,its receptors and signaling mediators have helped define the role of interleukin-27 in neurodegenerative diseases.Interleukin-27 has been well-characterized as an important regulator of T cell activation and differentiation that enhances or suppresses T cell responses in autoimmune conditions in the central nervous system.Evidence is also accumulating that interleukin-27 has neuroprotective activities in the retina and brain.Interleukin-27 is secreted from and binds to infiltrating microglia,macrophage,astrocytes,and even neurons and it promotes neuronal survival by regulating pro-and anti-inflammatory cytokines,neuroinflammatory pathways,oxidative stress,apoptosis,autophagy,and epigenetic modifications.However,interleukin-27 can have the opposite effect and induce inflammation and cell death in certain situations.In this review,we describe the current understanding of regulatory activities of interleukin-27 on cell survival and inflammation and discuss its mechanisms of action in the brain,spinal cord,and retina.We also review evidence for and against the therapeutic potential of interleukin-27 for dampening harmful neuroinflammatory responses in central nervous system diseases.

关键词： central nervous system cytokine inflammatory interleukin-27 neuroprotection retina

Otologic and vestibular symptoms in COVID-19:A scoping review

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2022年第4期8卷 287-296页

作者： kimberly Mae C.Ong Teresa Luisa G.Cruz Philippine National Ear Institute National Institutes of HealthUniversity of the Philippines ManilaManilaPhilippines College of Medicine University of the Philippines ManilaManilaPhilippines Department of Otorhinolaryngology University of the Philippines-Philippine General HospitalManilaPhilippines

Background:Otologic and vestibular symptoms have been seen in patients confirmed to have COVID-19 disease.Further discussion of these symptoms may provide insight into short-and long-term management for these patients.Objective:The aim of this review was to describe the otologic and vestibular symptoms that present in patients with COVID-19.The primary outcomes of this review were onset,duration and clinical outcomes of these symptoms.Sources of Evidence:Pub Med,APAMed Central,Herdin,CINAHL,Scopus,Springer Link,ProQuest Coronavirus Research Database,and Google Scholar were searched for the articles to be included.Eligibility Criteria:Studies included were those involving adult patients diagnosed with COVID-19 who experienced hearing loss,ear pain,ear discharge,otitis media,vertigo,or tinnitus.Studies were eligible for inclusion if there was a description of the otologic dysfunction,specifically onset,duration,or clinical outcomes.Results:The majority of patients who experienced hearing loss(68%),tinnitus(88%),vertigo/dizziness(30%),ear pain(8%),and discharge(100%)did so within a month of experiencing the typical symptoms of COVID-19.A majority also experienced complete resolution of their symptoms within 2 weeks.Standard treatment for COVID-19 was usually provided but when specific diagnoses are made for these symptoms(e.g.,sudden sensorineural hearing loss,otitis media,vestibular neuritis),they are treated in the same manner as one would for non-COVID-19 cases,in addition to the management for COVID-19.In certain cases,there may be a need for additional work-up to rule out other causes.Conclusions:Otologic and vestibular symptoms were present in COVID-19 patients,majority as part of the systemic nature of the disease.The onset,duration,and course were consistent with the natural history of a systemic viral infection.COVID-19 should be considered in any patient with a new-onset hearing loss,tinnitus,or vertigo/dizziness,even in the absence of infectious or respiratory symptoms.

关键词： COVID-19 dizziness hearing loss tinnitus vertigo

Evaluation of adenosine triphosphate bioluminescence-based system in rooms occupied by patients with methicillin resistant Staphylococcus

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Infectious Medicine 2022年第3期1卷 217-220页

作者： Anna Montgomery kimberly Hammer Dubert Guerrero Tze Shien Lo Department of Research San Francisco VA Medical CenterSan FranciscoCAUSA Department of Medicine University of California San FranciscoSan FranciscoCAUSA Department of Medicine University of North Dakota School of Medicine and Health SciencesGrand ForksNDUSA Department of Infection Prevention Fargo VA Healthcare SystemFargoNDUSA Department of Infection Prevention Sanford HealthFargoNDUSA

Background:Adenosine triphosphate(ATP)-based monitoring systems can detect the amount of organic matter that remains on hospital surfaces after cleaning.We evaluated an ATP-based monitoring system in assessing con-tamination of high touched objects in rooms occupied by patients on methicillin resistant S.aureus precautions.Methods:We compared the ATP to standard aerobic cultures as well as to gloved hand culture to predict risk of healthcare-worker hand contamination.Results:More than a third of high touch object surfaces were measured unclean with ATP yet only reflects about 5%chance of contaminating healthcare-workers’hands.Conclusions:Our study emphasizes the shortcomings of using the ATP system even in pathogen specific environ-ment such as surfaces in methicillin resistant S.aureus rooms.

关键词： Environment Healthcare-associated infections Hand hygiene Infection prevention Infection control MRS

Genetics-inspired data-driven approaches explain and predict crop performance fluctuations attributed to changing climatic conditions

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Molecular Plant 2022年第2期15卷 203-206页

作者： Xianran Li Tingting Guo Guihua Bai Zhiwu Zhang Deven See Juliet Marshall kimberly A.Garland-Campbell Jianming Yu USDA Agricultural Research ServiceWheat HealthGeneticsand Quality Research UnitPullmanWA 99164USA Department of Agronomy Iowa State UniversityAmesIA 50011USA USDA Agricultural Research ServiceHard Winter Wheat Genetics Research UnitManhattanKS 66506USA Department of Crop and Soil Sciences Washington State UniversityPullmanWA 99164USA Department of Plant Sciences University of Idaho Research and ExtensionIdaho FallsID 83402USA

Dear Editor,Genetics-focused approaches have been widely used to uncover major genetic variants associated with performance variation.Selecting,manipulating,and editing genetic variants significantly improve crop performance.Meanwhile,the genetic component explains a portion of performance variation,and the environ-mental component contributes to the remaining,often large,portion(Laidig et al.,2017;Bonecke et al.,2020;Li et al.,2021).To ensure superior and robust performance,elite varieties are extensively tested across multiple years and locations.These extensive performance records,coupled with climatic profiles,could be leveraged to understand climate's impact on agriculture through approaches parallel to quantitative genetics approaches(Figure 1A).

关键词： performance attributed Figure