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Effect of Androstenedione on Adipogenesis in Murine C3H10T1/2 Mesenchymal Cells

Open Journal of Endocrine and Metabolic Diseases 2015年第2期5卷 9-18页

作者： Pandurangan Ramaraj Jorge N. Artaza Indrani Sinha-Hikim Wayne E. Taylor Department of Biochemistry Kirksville College of Osteopathic Medicine A.T. Still University of Health Sciences Kirksville MO USA Division of Endocrinology Charles R. Drew University of Medicine and Science Los Angeles CA USA Department of Health and Life Sciences Charles R. Drew University of Medicine and Science Los Angeles CA USA

Clinical trials of weak androgen androstenedione (AD) administered at a high concentration, showed an increase in muscle mass in men like strong androgens testosterone (T) and dihydrotestosterone (DHT), but did not show any inhibitory effect on fat mass unlike strong androgens. This observation prompted us to check the in-vitro effect of AD on adipogenesis using mouse mesenchymal multipotent cells (C3H10T1/2), which can differentiate into both myoblasts and adipocytes. Results indicated that AD inhibited adipogenesis at 10 nM, 100 nM and 1 μM concentrations, but not at 10 μM concentration. AD did not inhibit adipogenesis at 10 μM concentration and also did not inhibitmyogenesis at 10 μM concentration. Addition of bicalutamide, an androgen receptor (AR) antagonist decreased myogenesis and increased adipogenesis, indicating that the effect of AD was mediated through AR. Another weak androgen dehydroepiandrosterone (DHEA) also showed the same pattern of adipogenesis in 10T1/2 cells. AD also showed a similar pattern of adipogenesis in 3T3-L1 preadipocyte cells. Thus, the in-vitro results of AD on adipogenesis correlated with the in-vivo results of AD on fat-mass from clinical trials and suggested a possible difference in biological action between weak androgens (AD, DHEA) and strong androgens (T, DHT) on adipogenesis. Since the biological action of AD was mediated through AR, this physiological difference onadipogenesis could be due to the nature (partial agonist/antagonist) of AD binding to AR.

关键词： Androstenedione Adipogenesis Myogenesis Androgen Receptor Bicalutamide

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An Assessment of the Social, Cultural, and Economical Barriers to Option B+Retention and Their Solutions in Malawi: A Review

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World Journal of AIDS 2021年第1期11卷 15-24页

作者： Jamie Yoon David S. Chung Michelle Kim Kunmin Kim Sang Heon Lee Tae Youn Kim Hark Joon Lee Seog In Moon Jooheon Park Paul S. Chung Thomas Nyirenda School of Medical Boston University Boston USA Edward Via college of osteopathic medicine Blacksburg USA School of medicine University of Virginia Charlottesville USA Youth with Talents Fairfax USA Department of Art & Science Biology Johns Hopkins University Baltimore USA Clinical Research Education and Management Service Lilongwe Malawi

Malawi has one of the highest rates of HIV prevalence in the world, and accounts for 4% of the total number of people living in sub-Saharan Africa with HIV. Approximately one million people in Malawi were living with HIV in 2016, with 24,000 HIV-related deaths. The Option B+ program, first implemented in Malawi, aimed to initiate ART for all pregnant women, regardless of their CD4 cell count or disease stage. This study serves to analyze and assess the effectiveness of Option B+ retention, in relation to the facilitation of how various social and cultural barriers were handled. A literature review of 29 publications was conducted. Careful evaluation of various studies indicates that although there is a myriad of reasons explaining low levels of retention, the women who were at the highest risk for low retention were young pregnant women who were treated on the same day of HIV-diagnosis. Solutions focused around women and their partners or communities showed promising evidence of success in increasing adherence, as these strategies likely provided women reliable social and emotional support to address major barriers to retention such as a lack of support from male partners, ineffective education from healthcare workers, or stigma towards their HIV disclosure statue.

关键词： HIV Option B+ Malawi Retention CHTC PMTCT

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The Evolving Nature of Hepatic Abscess:A Review

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Journal of Clinical and Translational Hepatology 2016年第2期4卷 158-168页

作者： Marianna G.Mavilia Marco Molina George Y.Wu University of New England college of osteopathic medicine BiddefordMEUSA Department of Radiology UCONN HealthFarmingtonCTUSA Department of medicine Division of Gastroenterology-HepatologyUCONN HealthFarmingtonCTUSA

Hepatic abscess (HA) remains a serious and often difficult to diagnose *** can be divided into three main categories based on the underlying conditions:infectious,malignant,and *** abscesses include those secondary to direct extension from local infection,systemic bacteremia,and intra-abdominal infections that seed the portal ***,over the years,the etiologies and risks factors for HA have continued to *** recognition is important for instituting effective management and obtaining good outcomes.

关键词： Liver abscess Liver neoplasms Iatrogenic disease Risk factors

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Trauma Activation and Substance Use in an Urban Trauma Center

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Surgical Science 2021年第3期12卷 53-66页

作者： Derek Titus Areta Kowal-Vern John Porter Marc R. Matthews Philomene Spadafore Sydney Vail college of osteopathic medicine of the Pacific-Northwest Lebanon USA Department of Research Valleywise Health Medical Center Phoenix USA Arizona Burn Center Valleywise Health Medical Center Phoenix USA Department of Physical medicine & Rehabilitation Valleywise Health Medical Center Phoenix USA Department of Surgery Valleywise Health Medical Center Phoenix USA

Background: Alcohol and drug screens in trauma patients are endorsed by the American college of Surgeons Committee on Trauma. The objective was to determine the characteristics and frequency of alcohol and poly-drug combinations in patients triaged by Trauma Team Activation (TTA) codes. Methods: A retrospective study of a Level I hospital trauma registry was initiated with 14,972 patients of whom 7028 (47%) were Substance Users (SU). There were 10,369 TTA patients: 5396 (52%) were SU, and 4603 (31%) non-TTA patients, of whom 1632 (35.5%) were SU. Inclusion criteria were: age ≥14 years old, blood alcohol level and Urine Drug Screen (UDS) documentation, Injury Severity Score (ISS), TTA code, hospital charges and Length of Hospitalization (LOS). Statistical analyses were performed with one-way ANOVA, Maximum Likelihood chi squared, and Mann-Whitney U tests. Results: The median ISS was 5 for both groups. TTA patients were younger than non-TTA patients (median 33 years versus 41 years). Mortality was significantly higher for TTA (4.7%) than for non-TTA (0.7%) patients. From 2010-2013 to 2014-2018, all substance users had a significant decrease in alcohol only use (58.0% to 42.0%) with an increase in single drug (42.0% to 58.0%) and poly-drug use (36.9% to 63.1%), p Conclusions: By trauma activation code designation, the TTA group had most of the positive alcohol and drug screens in this study. Since the change in mandated opioid prescription practices in 2014, this study showed increased poly-drug use (two to six-drug combinations) in urban trauma patients between 2014-2018. Op

关键词： Drugs Alcohol Trauma

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Colo-renal fistula:An unusual cause of hematochezia

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World Journal of Gastrointestinal Pathophysiology 2010年第3期1卷 106-108页

作者： John D Wysocki Virendra Joshi John W Eiser Naveed Gil Tulane University School of medicine Lake Erie college of osteopathic medicine

A 76 year old woman with bloody stools and symp-tomatic anemia presented to the Emergency Department approximately 2 wk after computed tomography (CT)-guided cryoablation to a 4.5 cm renal cell car-cinoma on her left posterior kidney. The patient was initially prepped for a colonoscopy to view possible causes of lower gastrointestinal bleeding. However, the patient had a CT with PO contrast that revealed a variation of a renoalimentary fistula. The patient was subsequently brought to the operating room, and it was discovered that a colo-renal fistula had formed, with transmural perforation of the posterior descending colon. A left nephrectomy, left colectomy with colostomy and Hartmann's pouch was performed.

关键词： Colo-renal fistula Renocolic fistula Hema- tochezia Cryoablation Alimentary fistula

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Clinical significance of anti-nucleocapsid-IgG sero-positivity in SARS-CoV-2 infection in hospitalized patients in North Dakota

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World Journal of Clinical Infectious Diseases 2022年第2期12卷 50-60页

作者： Bakir Dzananovic Mark Williamson Casmiar Nwaigwe Chittaranjan Routray Department of medicine Idaho College of Osteopathic MedicineMeridianID 83642United States Department of Biostatistics Epidemiology and Research Design CoreUniversity of North DakotaGrand ForksND 58202United States Department of Internal medicine University of North Dakota School of Medicine and Health SciencesMinotND 58701United States Family medicine University of North Dakota School of Medicine and Health SciencesMinotND 58701United States Department of Internal medicine Trinity HealthMinotND 58701United States

BACKGROUND During the peak of the coronavirus diseases 2019(COVID-19)pandemic,clinicians actively studied the utility of various epidemiologic-clinical parameters to determine the prognosis for patients hospitalized with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** IgG antibody level,DDimer,C-reactive protein and neutrophil to lymphocyte ratio,*** studied to assess their association with the clinical course in hospitalized patients and predict who may be at increased risk for poor clinical ***,the influence of SARS-CoV-2-anti-nucleocapsid-IgG antibody(IgG-N)sero-positivity on the clinical outcome of patients with COVID-19 is largely *** To study the influence of SARS-CoV-2 anti-nucleocapsid-IgG seropositivity on clinical course and diseases severity in hospitalized COVID-19 *** We conducted a retrospective study of adults admitted to a tertiary care community hospital in North Dakota with *** patients had severeCOVID-19 disease or worse and so required supplemental oxygen on *** were serologically tested for SARS-CoV-2-anti-nuceocapsid-IgG(IgG-N).The IgG-N positive group were 26 patients and the IgG-N negative group had 33 *** groups received similar treatment for COVID-19 as approved by our healthcare system from Day 1 of admission until discharge or *** parameters for monitoring the patients’clinical course included the following:Length of hospitalization(LOS),use of high flow nasal canula(HFNC),use of noninvasive bilevel positive pressure ventilation(BiPAP),admission into the intensive care unit,need for mechanical ventilation(VENT);and the patient outcome/discharge or *** variables included were age,gender and body-mass-index,and duration of symptoms before *** each variable,the outcome was modeled as a function of SARS-CoV-2-IgG-N status(positive or negative)using a generalized linear *** LOS-days,a negative binomial dist

关键词： COVID-19 SARS-CoV-2 IgG-N Anti-nucleocapsid IgG Cytokines

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GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis

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Translational Neurodegeneration 2018年第1期7卷 322-345页

作者： William R.Swindell Krzysztof Bojanowski Mark S.Kindy Raymond M.W.Chau Dorothy Ko Heritage college of osteopathic medicine Ohio UniversityAthensOHUSA Sunny BioDiscovery IncSanta PaulaCAUSA Department of Pharmaceutical Sciences College of PharmacyUniversity of South FloridaTampaFLUSA James A.Haley VAMC TampaFLUSA Genervon Biopharmaceuticals LLC PasadenaCAUSA

Background:Amyotrophic lateral sclerosis(ALS)is currently an incurable disease without highly effective pharmacological *** peptide drug GM604(GM6 or Alirinetide)was developed as a candidate ALS therapy,which has demonstrated safety and good drug-like properties with a favorable pharmacokinetic ***6 is hypothesized to bolster neuron survival through the multi-target regulation of developmental pathways,but mechanisms of action are not fully ***:This study used RNA-seq to evaluate transcriptome responses in SH-SY5Y neuroblastoma cells following GM6 treatment(6,24 and 48 h).Results:We identified 2867 protein-coding genes with expression significantly altered by GM6(FDR<0.10).Early(6 h)responses included up-regulation of Notch and hedgehog signaling components,with increased expression of developmental genes mediating neurogenesis and axon *** GM6 treatment(24 and 48 h)altered the expression of genes contributing to cell adhesion and the extracellular ***6 further down-regulated the expression of genes associated with mitochondria,inflammatory responses,mRNA processing and chromatin ***6-increased genes were located near GC-rich motifs interacting with C2H2 zinc finger transcription factors,whereas GM6-decreased genes were located near AT-rich motifs associated with helix-turn-helix homeodomain *** motifs interacted with a diverse network of transcription factors encoded by GM6-regulated genes(STAT3,HOXD11,HES7,GLI1).We identified 77 ALS-associated genes with expression significantly altered by GM6 treatment(FDR<0.10),which were known to function in neurogenesis,axon guidance and the intrinsic apoptosis ***:Our findings support the hypothesis that GM6 acts through developmental-stage pathways to influence neuron *** expression responses were consistent with neurotrophic effects,ECM modulation,and activation of the Notch and hedgehog neurodevelopmental *** multif

关键词： Alzheimer’s disease Amyotrophic lateral sclerosis Extracellular matrix,Hedgehog Huntington’s disease Neurodegenerative disease Notch,Parkinson’s disease RNA-seq Transcriptome

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Unilateral 6-OHDA <i>th-fgfr1</i>(<i>tk-</i>) mouse model supports the role of FGFs in Parkinson’s disease and the effects of nicotine and L-DOPA on spontaneous motor impairments

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Health 2012年第11期4卷 1178-1190页

作者： Aaron Kucinski Scott Wersinger Ewa K. Stachowiak Milen Radell Renae Hesse Thomas Corso Matthew Parry Merouane Bencherif Kristen Jordan Sharon Letchworth Michal K. Stachowiak Department of Biochemistry and Neuroscience Lake Erie College of Osteopathic Medicine Erie USA Department of Pathology and Anatomical Sciences State University of New York Buffalo USA Department of Pathology and Anatomical Sciences State University of New York Buffalo USA Targacept Inc. Winston-Salem USA

In the developing and adult brain, neurotrophic growth factors support the growth and protec tion of dopaminergic neuronal systems. Recently, links between impaired neurotrophin support of dopamine (DA) neurons has been described in Parkinson’s Disease (PD). Fibro- blast growth factor (FGF) has a unique association with DA neurons in that FGF signaling is vitally important for the development and protection of adult DA neurons. We assessed the role of substantia nigra (SN)-expressed FGFs in the nigrostriatal dopaminergic system using a transgenic mouse, th-fgfr1(tk-). In these mice, generated by expression of dominant negative FGFR1(TK-) from the tyrosine hydroxylase (TH) gene promoter, reduced FGF signaling results in smaller and less dense adult nigrostriatal DA neurons, similar to what is observed in PD. With unilateral 6-hydroxydopamine (6-OHDA) lesions, th-fgfr1(tk-) mice exhibited extensive unilateral nigrostriatal damage with robust spontaneous (non-drug induced) asymmetrical turning and a decreased latency to remain on the accelerating rotarod. L-DOPA remains the gold standard for PD therapy despite debilitating hyperkinetic and dyskinetic side effects. The nicotinic acetylcholine system has recently been targeted as an alternative system to combat PD motor symptoms. Nicotine effectively stimulates dopaminergic transmission in the nigrostriatal pathway and mediates movement. Using unilaterally lesioned th-fgfr1(tk-) mice, long term (11 day) oral administration of nicotine increased spontaneous bidirectional turning and increased the latency before falling from the accelerating rotarod. In a separate analysis, L-DOPA treatment reversed directionality of rotation and further deepened motor discoordination, suggesting activation of hypersensitive postsynaptic DA receptors in the denervated striata. These results in a transgenic model of PD provide insights into the cellular mechanisms underlying L-DOPA and nicotinic therapies and offer further evidence of nicot

关键词： Parkinson’s Disease Fibroblast Growth Factor (FGF) Signaling Transgenic Mouse Nicotine L-DOPA

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The COVID-19 Outbreak in South Korea: Lessons to Be Learned

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Advances in Infectious Diseases 2022年第2期12卷 298-311页

作者： Hark Joon Lee Richard Kang Michelle Kim Justin Kong Woo Jun Shim Kunmin Kim Paul S. Chung Lewis Katz School of medicine Temple University Philadelphia USA School of medicine Virginia Commonwealth University Richmond USA Youth With Talents Fairfax USA Edward Via college of osteopathic medicine Blacksburg USA Department of Biology Washington University St. Louis USA Bachelor of Science in Biology California Institute of Technology Pasadena USA Department of Chemistry and Biochemistry University of California San Diego USA

The Coronavirus 2019 (COVID-19) is a novel type of coronavirus-related disease that has over 4 million confirmed cases worldwide as of May 13th, 2020. With over 200 countries impacted by the pandemic, many countries have taken drastic measures such as temporary closure of international borders. The purpose of this thesis is to examine the South Korean response to COVID-19 and the keys to successful containment of the disease. Real time analysis was performed on data provided by the Centers for Disease Control (CDC). Comparisons of disease containment among countries with the highest confirmed cases were normalized for population size differences by taking the proportion of confirmed cases to population size. We further compared the disease outbreak in Seoul, a very urban environment, to the whole country of South Korea, to compare public health in urban and rural environments. We found that the efficient partnership between the private sector and the state led to rapid development in testing kits, which was integral to the South Korean response to COVID-19. In addition, the South Koreans’ community spirit, approval of government-led interventions, and societal norm of wearing masks were also efficient social responses to the spreading disease. In this paper, we navigate the impacts of a universal healthcare system and its ability to battle infectious diseases and the efficacy of various governmental actions in response to a public health crisis.

关键词： Infectious Diseases Respiratory Viral Infections Public Health Disease Prevention

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Secondary angiodysplasia-associated gastrointestinal bleeding in end-stage renal disease: Results from the nationwide inpatient sample

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World Journal of Gastrointestinal Endoscopy 2019年第10期11卷 504-514页

作者： Tooba Tariq Patrick Karabon Furqan B Irfan Sachin Goyal Matthew Masaru Mayeda Austin Parsons Stephanie Judd Murray Ehrinpreis Department of Internal medicine Western Michigan University Homer Stryker M.D.School of MedicineKalamazooMI 49008United States Oakland University William Beaumont School of medicine Oakland UniversityDetroitMI 48309United States college of osteopathic medicine Michigan State UniversityEast LansingMI 48824United States 不详 Department of Internal medicine Division of GastroenterologyJohn D Dingell VA Medical CenterDetroitMI 48201United States

BACKGROUND Chronic kidney disease is associated with angiodysplasia of gastrointestinal tract leading to increased risk of gastrointestinal *** To determine the nationwide prevalence,trends,predictors and resource utilization of angiodysplasia-associated gastrointestinal bleeding in end-stage renal disease *** The Nationwide Inpatient Sample database from 2009 to 2014,was utilized to conduct a retrospective study on patients with angiodysplasia associatedgastrointestinal bleeding and end-stage renal *** with endstage renal disease were included in the Nationwide Inpatient Sample database and a subset of hospitalizations with end-stage renal disease and angiodysplasiaassociated gastrointestinal bleeding were identified with International Classification of Diseases,9th revision,Clinical Modification codes for both endstage renal disease(585.6)and angiodysplasia(569.85,537.83).RESULTS The prevalence of angiodysplasia-associated gastrointestinal bleeding was 0.45%(n=24709)among all end-stage renal disease patients(n=5505252)that were *** analysis indicated that the following were significant factors associated with higher odds of angiodysplasia associated-gastrointestinal bleeding in end-stage renal disease patients:an increasing trend from 2009-2014(P<0.01),increasing age(P<0.0001);African American race(P=0.0206);increasing Charlson-Deyo Comorbidity Index(P<0.01);hypertension(P<0.0001);and tobacco use(P<0.0001).Diabetes mellitus(P<0.0001)was associated with lower odds of angiodysplasia associated-gastrointestinal bleeding in end-stage renal disease *** comparison with urban teaching hospitals,rural and urban nonteaching hospitals were associated with decreased odds of angiodysplasia associated-gastrointestinal *** Angiodysplasia-associated gastrointestinal bleeding in end-stage renal disease patients showed an increasing trend from *** age,African American

关键词： Angiodysplasia Renal Gastrointestinal Hemorrhage

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