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Influence of biological sex and exercise on murine cardiac metabolism

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Journal of Sport and Health Science 2022年第4期11卷 479-494页

作者： Kyle Fulghum Helen E.Collins steven P.Jones Bradford g.Hill Diabetes and Obesity Center Department of MedicineDivision of Environmental MedicineChristina Lee Brown Envirome InstituteUniversity of LouisvilleLouisvilleKY 40202USA Department of Physiology University of LouisvilleLouisvilleKY 40202USA

Although the structural and functional effects of exercise on the heart are well established,the metabolic changes that occur in the heart during and after exercise remain *** this study,we used metabolomics to assess time-dependent changes in the murine cardiac metabolome following 1 session of treadmill *** the exercise bout,we also recorded blood lactate,glucose,and ketone body levels and measured cardiac mitochondrial *** both male and female mice,moderate-and high-intensity exercise acutely increased blood lactate *** both sexes,low-and moderate-intensity exercise augmented circulating 3-hydroxybutryrate levels immediately after the exercise bout;however,only in female mice did high-intensity exercise increase 3-hydroxybutyrate levels,with significant increases occurring 1 h after the exercise *** metabolomics analyses of sedentary female and male hearts suggest considerable sex-dependent differences in basal cardiac metabolite levels,with female hearts characterized by higher levels of pantothenate,pyridoxamine,homoarginine,tryptophan,and several glycerophospholipid and sphingomyelin species and lower levels of numerous metabolites,including acetyl coenzyme A,glucuronate,gulonate,hydroxyproline,prolyl-hydroxyproline,carnosine,anserine,and carnitinylated and glycinated species,as compared with male *** after a bout of treadmill exercise,both male and female hearts had higher levels of corticosterone;however,female mice showed more extensive exercise-induced changes in the cardiac metabolome,characterized by significant,time-dependent changes in amino acids(e.g.,serine,alanine,tyrosine,tryptophan,branched-chain amino acids)and the ketone body *** from experiments using isolated cardiac mitochondria suggest that high-intensity treadmill exercise does not acutely affect respiration or mitochondrial coupling;however,female cardiac mitochondria demonstrate generally higher adenosi

关键词： Ketone bodies Metabolomics Mitochondria Physical activity Sex difference

SEgMENTATION AND CORRELATION OF OPTICAL COHERENCE TOMOgRAPHY AND X-RAY IMAgES FOR BREAST CANCER DIAgNOSTICS

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Journal of Innovative Optical Health Sciences 2013年第2期6卷 71-81页

作者： JONATHAN g.SUN steven g.ADIE ERIC J.CHANEY STEPHEN A.BOPPART Beckman Institute for Advanced Science and Technology 405 North Mathews Avenue UrbanaIllinois 61801USA Department of Bioengineering Beckman Institute for Advanced Science and Technology 405 North Mathews Avenue UrbanaIllinois 61801USA Departments of Electrical and Computer Engineering and Internal Medicine University of Illinois at Urbana-Champaign UrbanaIllinoisUSA

Pre-operative X ray mammography and int raoperative X-ray specimen radiography are routinely used to identify breast cancer *** advances in optical coherence tomography(OCT)have enabled its 1use for the intraoperative assessment of surgical margins during breast cancer *** each modality offers distinct contrast of normal and pathological features,there is an essential need to correlate image based features between the two modalities to take adv antage of the diagnostic capabilities of each *** compare OCT to X-ray images of resected human breast tissue and correlate different tissue features between modalities for future use in real-tine intraoperative OCT imaging.X ray imaging(specimen radiography)is currently used during surgical breast cancer procedures to verify tumor margins,but cannot image tissue in *** has the potential to solve this problem by providing intrao-perative imaging of the resected specimen as well as the in situ tumor *** and micro-CT(X-ray)images are automatically segmented using different computational approaches,and quantitatively compared to determine the ability of these algorithms to automat ically differentiate regions of adipose tissue from ***,two-dimensional(2D)and three-dimensional(3D)results are *** correlations,combined with real-time intraoperative OCT,have the potential to identify possible regions of tumor within breast tissue which correlate to tumor regions identified previously on X-ray imaging(mammography or specimen radiography).

关键词： Optical imaging mammography specimen radiography segmentation breast cancer intraoperative imaging

c-Met signaling in the development of tumorigenesis and chemoresistance: Potential applications in pancreatic cancer

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World Journal of gastroenterology 2014年第26期20卷 8458-8470页

作者： Daniel Delitto Eva Vertes-george steven J Hughes Kevin E Behrns Jose g Trevino Department of Surgery University of Florida-Gainesville Department of Pathology University of Florida-Gainesville

Pancreatic ductal adenocarcinoma is the 4th leading cause of cancer deaths in the United States. The majority of patients are candidates only for palliative chemotherapy, which has proven largely ineffective in halting tumor progression. One proposed mechanism of chemoresistance involves signaling via the mesenchymal-epithelial transition factor protein (MET), a previously established pathway critical to cell proliferation and migration. Here, we review the literature to characterize the role of MET in the development of tumorigenesis, metastasis and chemoresistance, highlighting the potential of MET as a therapeutic target in pancreatic cancer. In this review, we characterize the role of c-Met in the development of tumorigenesis, metastasis and chemoresistance, highlighting the potential of c-Met as a therapeutic target in pancreatic cancer.

关键词： Pancreatic adenocarcinoma c-Met Chemoresistance Receptor tyrosine kinase

Colonic ulcerations may predict steroid-refractory course in patients with ipilimumab-mediated enterocolitis

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World Journal of gastroenterology 2017年第11期23卷 2023-2028页

作者： Animesh Jain Evan J Lipson William H Sharfman steven R Brant Mark g Lazarev Division of gastroenterology and Hepatology Department of Internal MedicineUniversity of North Carolina Chapel Hill Department of Oncology Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center Division of gastroenterology and Hepatology Department of Internal MedicineJohns Hopkins University School of Medicine

AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line *** We retrospectively reviewed all patients at our centerwith metastatic melanoma who were treated with ipilimumab between March 2011 and May 2014. All patients received a standard regimen of intravenous ipilimumab 3 mg/kg every 3 wk for four doses or until therapy was stopped due to toxicity or disease progression. Basic demographic and clinical data were collected on all patients. For patients who developed grade 2 or worse diarrhea(increase of 4 bowel movements per day), additional data were collected regarding details of gastrointestinal symptoms, endoscopic findings and treatment course. Descriptive statistics were *** A total of 114 patients were treated with ipilimumab during the study period and all were included. Sixteen patients(14%) developed ≥ grade 2 diarrhea. All patients were treated with high-dose corticosteroids(1-2 mg/kg prednisone daily or equivalent). Nine of 16 patients(56%) had ongoing diarrhea despite highdose steroids. Steroid-refractory patients received one dose of intravenous infliximab at 5 mg/kg, and all but one had brisk resolution of diarrhea. Fourteen of the patients underwent either colonoscopy or sigmoidoscopy with variable endoscopic findings, ranging from mild erythema to colonic ulcers. Among 8 patients with ulcers demonstrated by sigmoidoscopy or colonoscopy, 7 patients(88%) developed steroidrefractory symptoms requiring infliximab. With a median follow-up of 264 d, no major adverse events associated with prednisone or infliximab were *** In patients with ipilimumab-mediated enterocolitis, the presence of colonic ulcers on endoscopy was associated with a steroid-refractory course.

关键词： Ipilimumab Melanoma Enterocolitis Colitis Infliximab Corticosteroid Colonic ulcer

Hemoglobin Adducts as Biomarkers of Exposure to and metabolic Activation of Carcinogenic Tobacco-Specific Nitrosamines

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Biomedical and Environmental Sciences 1991年第1期4卷 93-103页

作者： STEPHEN S.HECHT steven g.CARMELLA SHARON E.MURPHY Dana Road American Health Foundation ValhallaDana Road American Health Foundation ValhallaDana Road American Health Foundation Valhalla New York 10595New York 10595 New York 10595

The carcinogenic tobacco-specific nitrosamines N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) form hemoglobin adducts in laboratory animals and humans. These adducts release 4-hydroxy-l-(3-pyridyl)-l-butanone (HPB) upon mild base hydrolysis. HPB released from human hemoglobin can be quantified by gas chromatography-mass spectrometry. It is the only available biochemical marker for determination of exposure to, and metabolic activation of, carcinogens present only in tobacco. Levels of HPB were highest in snuff-dippers, followed by smokers and nonsmokers. Large interindividual variations in adduct levels were observed. The relationship between HPB levels in globin and DNA of rats treated with NNK has been investigated in order to aid in interpretation of the data from humans. These studies have provided the initial database for understanding the metabolic activation of tobacco-specific nitrosamines in humans.

关键词： Hemoglobin Adducts as Biomarkers of Exposure to and metabolic Activation of Carcinogenic Tobacco-Specific Nitrosamines

Cytomegalovirus retinitis in the highly active anti-retroviral therapy era

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Annals of Eye Science 2022年第1期7卷 42-50页

作者： Ifeoma N.Ude steven Yeh Jessica g.Shantha Morehouse School of Medicine AtlantaGAUSA Francis I.Proctor Foundation University of CaliforniaSan FranciscoCAUSA Truhlsen Eye Institute University of Nebraska Medical CenterOmahaNEUSA

Cytomegalovirus(CMV)retinitis is an opportunistic infection that has traditionally affected those who have HIV/AIDS or immunosuppressed *** retinitis previously infected one-third of AIDS patients in the pre-highly active antiretroviral therapy(HAART)era,but since HAART,Western countries have seen an 80%decrease in the incidence of the *** recently,CMV retinitis has been reported in patients who are immunosuppressed,often due to chemotherapy or immunomodulatory *** diagnosis of CMV retinitis is often suspected based on clinical findings,with polymerase chain reaction for confirmation of CMV,especially in atypical *** active antiretroviral therapy and anti-CMV medications(systemic or local)remain the mainstay of ***,for those who are not responsive to HAART,CMV retinitis remains a challenge,and can still lead to significant vision ***,a regimen of anti-CMV medications can sometimes lead to viral resistance or organ *** such as immune recovery retinitis and rhegmatogenous retinal detachments continue to threaten the vision of patients who develop CMV *** complications can arise following initiation of treatment or if patients show disease *** vision screening for CMV retinitis in immunosuppressed patients at-risk is necessary for early detection and treatment.

关键词： Cytomegalovirus(CMV) retinitis highly active antiretroviral therapy(HAART)

Recent advances in the management of hyponatremia in cancer patients

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Journal of Cancer Metastasis and Treatment 2019年第10期4卷 21-32页

作者： Maryam I.Khan steven g.Waguespack Intekhab Ahmed Division of Endocrinology Diabetes and MetabolismJefferson HealthVoorheesNJ 08043USA Department of Endocrine Neoplasia and Hormonal disorders University of Texas M.D.Anderson Cancer CenterHoustonTX 77030USA Division of Endocrinology Diabetes and MetabolismJefferson HealthPhiladelphiaPA 19107USA.

Hyponatremia is the most frequently encountered electrolyte disorder in cancer patients and is usually multifactorial in its *** this review,we discuss the predisposing factors,pathophysiology,clinical symptomatology,and currently available diagnostic and therapeutic options for the management of *** addition to paraneoplastic syndromes,concurrent chemotherapy and comorbidities predispose oncology patients to the risk of *** symptoms and signs can be subtle and the prompt evaluation and initiation of treatment is of paramount importance to prevent neurocognitive and other *** syndrome of inappropriate antidiuresis(SIAD)is the most common cause of hyponatremia,and the use of serum and urine parameters that distinguish SIAD from other etiologies is *** treatment is preferred depending on the underlying cause and severity of *** treatment of hyponatremia is reviewed and the importance of avoiding rapid overcorrection of the sodium level to reduce the risk of osmotic demyelination syndrome is *** receptor antagonists(vaptans)offer a direct approach to the management of euvolemic and hypervolemic hyponatremia,but the indications for their use and long-term safety need to be *** treatment of hyponatremia is likely to reduce complications and improve survival in cancer patients.

关键词： Hyponatremia electrolyte abnormalities dysnatremias cancer

Introduction to IEEE 802.3av 10gbit/s Ethernet Passive Optical Networks(10g EPON)

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China Communications 2009年第4期6卷 136-147页

作者： steven Scott gorshe Jeff Mandin ICs for Optical Transmission and Access Systems United States Transmission Access and Optical Systems Technical Committee United States PMC-Sierra's Fiber-to-the-Home Business Unit United States

In the competitive broadband access environment, providing access to"triple play"services(voice, video, and high-speed data) is an important way for both telephone and CATV network providers to increase their *** Optical Networks(PONs) are a cost-effective, flexible, and future-proof medium for providing triple play *** 1 gbit/s IEEE 802.3ah Ethernet PON(EPON) and ITU-T g.984 2.5 gbit/ s PON(gPON) are currently being deployed for triple play service ***, high definition switched digital video service such as IPTV will require more *** paper provides a tutorial overview of the IEEE 802.3av 10gbit/s Ethernet PON(10g EPON) standard, including the ways in which it differs from EPON.

关键词： IEEE 以太网计算机网络电子邮件

Natural history,clinical characteristics,outcomes,and long-term follow-up of pain-free chronic pancreatitis

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gastroenterology Report 2023年第1期11卷 309-315页

作者： Awais Ahmed Ishani Shah Rachel Bocchino steven D.Freedman Darshan J.Kothari Sunil g.Sheth Department of Medicine Division of GastroenterologyBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Department of Medicine Division of Internal MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Department of Medicine Division of GastroenterologyDuke UniversityDurhamNCUSA

Background:Chronic pancreatitis(CP)is characterized by chronic abdominal pain and functional ***,a small subset of patients with prior acute pancreatitis(AP)and/or underlying risk factors for developing CP may be pain-free at diagnosis and may have a different clinical *** aimed to compare the clinical characteristics,outcomes,and healthcare utilization between CP patients with and without ***:Reviewed patients with established CP were followed in our Pancreas Center between January 2016 and April *** without risk factors for developing CP and/or without AP prior to their diagnosis and only with incidental radiologic features of CP were excluded,so as tominimize confounding factors of pancreatopathy unrelated to *** were divided into painful and pain-free groups to analyze differences in demographics,outcomes,and healthcare ***:Of 368 CP patients,49(13.3%)were pain-free at diagnosis and had remained so for>9 *** were no significant differences in body mass index,race,sex,or co-morbidities between the two ***-free patients were older at diagnosis(53.9 vs 45.7,P=0.004)and had less recurrent AP(RAP)(43.8%vs 72.5%,Pgery(0.0%vs 15.0%,P=0.059),and therapeutic interventions(0.0%vs 16.4%,P=0.005)for ***:We described a unique subset of patients with underlying risk factors for CP and/or prior AP who were painfree at *** were older at diagnosis,had less EPI and RAP,and overall favorable outcomes with minimal resource utilization.

关键词： chronic pancreatitis pain-free pancreatic insufficiency diabetes