tbuckley/cabot-search huggingface dataset:
Pharmacological inhibition of apical sodium‐dependent bile acid transporter changes bile composition and blocks progression of sclerosing cholangitis in multidrug resistance 2 knockout mice
Authors: Alexander G. Miethke, Wujuan Zhang, Julia Simmons, Amy E. Taylor, Tiffany Shi, Shiva Kumar Shanmukhappa, Rebekah Karns, Shana White, Anil G. Jegga, Celine S. Lages, Stephenson Nkinin, Bradley T. Keller, Kenneth D.R. Setchell
Journal: Hepatology (2015)

Deficiency of multidrug resistance 2 (mdr2), a canalicular phospholipid floppase, leads to excretion of low-phospholipid "toxic" bile causing progressive cholestasis. We hypothesize that pharmacological inhibition of the ileal, apical sodium-dependent bile acid transporter (ASBT), blocks progression of sclerosing cholangitis in mdr2(-/-) mice. Thirty-day-old, female mdr2(-/-) mice were fed high-fat chow containing 0.006% SC-435, a minimally absorbed, potent inhibitor of ASBT, providing, on average, 11 mg/kg/day of compound. Bile acids (BAs) and phospholipids were measured by mass spectrometry. Compared with untreated mdr2(-/-) mice, SC-435 treatment for 14 days increased fecal BA excretion by 8-fold, lowered total BA concentration in liver by 65%, reduced total BA and individual hydrophobic BA concentrations in serum by >98%, and decreased plasma alanine aminotransferase, total bilirubin, and serum alkaline phosphatase levels by 86%, 93%, and 55%, respectively. Liver histology of sclerosing cholangitis improved, and extent of fibrosis decreased concomitant with reduction of hepatic profibrogenic gene expression. Biliary BA concentrations significantly decreased and phospholipids remained low and unchanged with treatment. The phosphatidylcholine (PC)/BA ratio in treated mice corrected toward a ratio of 0.28 found in wild-type mice, indicating decreased bile toxicity. Hepatic RNA sequencing studies revealed up-regulation of putative anti-inflammatory and antifibrogenic genes, including Ppara and Igf1, and down-regulation of several proinflammatory genes, including Ccl2 and Lcn2, implicated in leukocyte recruitment. Flow cytometric analysis revealed significant reduction of frequencies of hepatic CD11b(+) F4/80(+) Kupffer cells and CD11b(+) Gr1(+) neutrophils, accompanied by expansion of anti-inflammatory Ly6C(-) monocytes in treated mdr2(-/-) mice.Inhibition of ASBT reduces BA pool size and retention of hydrophobic BA, favorably alters the biliary PC/BA ratio, profoundly changes the hepatic transcriptome, attenuates recruitment of leukocytes, and abrogates progression of murine sclerosing cholangitis.
Severity of symptoms in chronically institutionalized geriatric schizophrenic patients
Authors: M Davidson, P D Harvey, P Powchik, M Parrella, L White, H Y Knobler, M F Losonczy, R S Keefe, S Katz, E Frecska
Journal: American Journal of Psychiatry (1995)

The goal of this study was to characterize the symptoms of geriatric, chronically ill, institutionalized schizophrenic patients and investigate age-related differences in schizophrenic symptoms and cognitive performance from early adulthood to late senescence.The Positive and Negative Syndrome Scale and the Mini-Mental State examination were used to assess the schizophrenic symptoms and cognitive performance, respectively, of 393 institutionalized schizophrenic patients stratified into seven groups designated by 10-year age intervals from 25 years to over 85 years.In the comparisons of the seven age groups, significant differences between groups in positive and negative subscale scores on the Positive and Negative Syndrome Scale and in Mini-Mental State scores were revealed. Significant correlations between Mini-Mental State scores and Positive and Negative Syndrome Scale negative symptom scores, but not positive symptom scores, were found for all age groups, except for the youngest patients studied. Current treatment with neuroleptics and prior treatment with ECT, insulin coma, or leukotomy could not account for the poor cognitive performance of the older schizophrenic patients.The older schizophrenic patients continued to experience psychotic and nonpsychotic symptoms in senescence. Their positive symptoms were moderately less severe and their negative symptoms and cognitive impairment were significantly more severe than those of the younger patients. Somatic treatment appeared not to be responsible for the severe cognitive impairment and negative symptoms of the older patients. These data are relevant to chronically hospitalized geriatric schizophrenic patients but not necessarily to all geriatric schizophrenic patients.
Abstract 13365: Fasting Glucose Positively Predicts Word Memory Performance in Older Men
Authors: Beatrice A Golomb, Alexis K Bui
Journal: Circulation (2014)

Background:  Higher glucose, in the prediabetic range, is viewed as health-adverse. However, glucose is a pivotal substrate for energy production. Mitochondrial function (so, cell energy) declines exponentially with age. Some evidence suggests glucose rise may be in part adaptive, preserving cell energy and function. Glucose is particularly important to brain function: Though ~2% of body weight, the brain uses ~50% of the glucose.   Goal:  To assess the cross-sectional relation of serum glucose to word memory performance in older adults.   Method:  726 adults (432 male) age >50 were the over-50 screenees for a broadly sampling statin trial. Participants had no diagnosed diabetes, CVD or cancer, fasting glucose ≤142mg/dL, and LDL 115-190mg/dL. Word memory was assessed by “Recurrent words” test (RecWd): In a series of presented words, subjects designated if the word on a card was new or presented previously, scoring #correct responses. Regression assessed prediction of RecWd by fasting serum glucose, in a range of adjustment models (Table). Covariates assessed included age, sex, diet-variables linked in this sample to RecWd, exercise, mood, and metabolic factors (Table legend).   Result:  Mean RecWd was 86±7.5 (85±7.6 in men). Higher fasting glucose predicted better RecWd performance in this over-50 sample, driven by findings in men. In men, each 7.7mg/dL higher glucose was linked to an expected one more word correctly designated (fully adjusted model). No other predictor approached similar significance.   Discussion:  Prior evidence linked glucose rise in older age to protection against fatigue. These findings add to evidence suggesting glucose rise as age advances may serve adaptive functions - here, linked to better memory performance.   Conclusion:  Higher fasting glucose, in the assessed range (
Abstract 13220: The Efficiency of 1.5T Non-Contrast Single Breath Hold Whole Heart MR Coronary Angiography by 32-Channel Cardiac Coil
Authors: Hiroyuki Fukuya, Masayoshi Okada, Hiroyuki Ohnishi, Hiroko Yamamoto, Michiyo Su
Journal: Circulation (2011)

Background:  Non-contrast 1.5T whole heart MR coronary angiography (WH-MRCA) has a potential as ultimate non-invasive screening method for coronary artery disease (CAD). However, WH-MRCA scan needs long time under breath holding and conventional scan is usually performed under respiratory gating. Recently developed 32-channel cardiac coil can reduce scan time to half and single breath hold (SBH) WH-MRCA can finish within 30 seconds, approximately. We prospectively evaluated an availability of SBH WH-MRCA using this coil.   Method:  We successively performed SBH and free breath (FB) WH-MRCA in 72 new patients (38 males, 34 females, 58.9±12.5 y.o.). Scan time was recorded and two independent investigators scored image quality (4: fine, 3: good, 2: acceptable, 1: poor). We defined case that main coronary artery segment (AHA segment RCA#1-3, LMT#5, LAD#6-7 and LCx#11,13) is well-visualized as success. We compared images of SBH WH-MRCA with FB WH-MRCA.   Result:  Scan time of SBH was 31.6±5.3 seconds and significantly shorter than FB (270.3±131.8 seconds; p   Conclusion:  SBH WH-MRCA by 32ch-cardiac coil can dramatically reduce scan time with maintenance of main coronary artery visualization. SBH can contribute performance of MRCA even in cases of poor respiratory synchronization. In conclusion, this method can recognize an availability of convenient screening method for CAD.
The Application of the Haddon Matrix to Public Health Readiness and Response Planning
Authors: Daniel J. Barnett, Ran D. Balicer, David Blodgett, Ayanna L. Fews, Cindy L. Parker, Jonathan M. Links
Journal: Environmental Health Perspectives (2005)

State and local health departments continue to face unprecedented challenges in preparing for, recognizing, and responding to threats to the public's health. The attacks of 11 September 2001 and the ensuing anthrax mailings of 2001 highlighted the public health readiness and response hurdles posed by intentionally caused injury and illness. At the same time, recent natural disasters have highlighted the need for comparable public health readiness and response capabilities. Public health readiness and response activities can be conceptualized similarly for intentional attacks, natural disasters, and human-caused accidents. Consistent with this view, the federal government has adopted the all-hazards response model as its fundamental paradigm. Adoption of this paradigm provides powerful improvements in efficiency and efficacy, because it reduces the need to create a complex family of situation-specific preparedness and response activities. However, in practice, public health preparedness requires additional models and tools to provide a framework to better understand and prioritize emergency readiness and response needs, as well as to facilitate solutions; this is particularly true at the local health department level. Here, we propose to extend the use of the Haddon matrix--a conceptual model used for more than two decades in injury prevention and response strategies--for this purpose.
Confirmed moisture damage and risk of asthma from birth to age 6 years
Authors: Juha Pekkanen, Anne M. Karvonen, Matti Korppi, Jon Genuneit, Anne Hyvärinen
Journal: European Respiratory Journal (2012)

Introduction : Few cohort studies are available on the association between moisture damage, confirmed by technical inspection, and risk of new asthma.   Aim : To study the association between confirmed moisture damage at the age of 5 months on average and risk of asthma by the age of 6 years.   Methods : Building inspection was performed by building engineers in the homes of 394 children, and the children were followed up with repeated questionnaires from birth to the age of 6 years. Current asthma was defined as doctor diagnoses of asthma ever and either current asthma medication or wheezing symptoms at the age of 6 years. Odds ratios (OR) were adjusted for potential confounders using discrete time hazard model and GEE.   Results : Severe moisture damage in the kitchen (OR 2.80, 95%CI 1.02-7.64) or in the child9s bedroom (OR 3.65, 95%CI 1.00-13.28) and visible mold in the child9s bedroom (OR 4.02, 95%CI 1.58-10.21) increased the incidence of doctor diagnosed asthma ever in life (n=60). Similar associations were observed with current asthma (n=33) and with wheezing apart from cold. Weaker associations were observed with moisture damage in the main living areas. No consistent associations were observed with moisture damage in the bathrooms or in other interior spaces of the house. There was some suggestion that the associations were weaker during the latter part of the follow-up.   Conclusions : The results are consistent with our earlier report over the first 1.5 years of life (Karvonen et al. 2009). The results support earlier conclusions that moisture damage not only increases the risk of respiratory symptoms, but is also associated with increased risk of developing new asthma.
Mediterranean Diet, Retinopathy, Nephropathy, and Microvascular Diabetes Complications: A Post Hoc Analysis of a Randomized Trial
Authors: Andrés Díaz-López, Nancy Babio, Miguel A. Martínez-González, Dolores Corella, Antonio J. Amor, Montse Fitó, Ramon Estruch, Fernando Arós, Enrique Gómez-Gracia, Miquel Fiol, José Lapetra, Lluís Serra-Majem, Josep Basora, F. Javier Basterra-Gortari, Vicente Zanon-Moreno, Miguel Ángel Muñoz, Jordi Salas-Salvadó
Journal: Diabetes Care (2015)

To date no clinical trials have evaluated the role of dietary patterns on the incidence of microvascular diabetes complications. We hypothesized that a nutritional intervention based on the Mediterranean diet (MedDiet) would have greater protective effect on diabetic retinopathy and nephropathy than a low-fat control diet.This was a post hoc analysis of a cohort of patients with type 2 diabetes participating in the PREvención con DIeta MEDiterránea (PREDIMED) study, a multicenter randomized nutritional intervention trial conducted in a population at high cardiovascular risk. Individuals with type 2 diabetes who were free of microvascular complications at enrollment (n = 3,614, aged 55-80 years) were randomly assigned to one of three dietary interventions: MedDiet supplemented with extravirgin olive oil (MedDiet+EVOO), MedDiet supplemented with mixed nuts (MedDiet+Nuts), or a low-fat control diet. Two independent outcomes were considered: new onset of diabetic retinopathy and nephropathy. Hazard ratios (HRs) were calculated using multivariable-adjusted Cox regression.During a median follow-up of 6.0 years, we identified 74 new cases of retinopathy and 168 of nephropathy. Compared with the control diet, multivariable-adjusted HRs for diabetic retinopathy were 0.56 (95% CI 0.32-0.97) for the MedDiet+EVOO and 0.63 (0.35-1.11) for the MedDiet+Nuts. No between-group differences were found for nephropathy. When the yearly updated information on adherence to the MedDiet was considered, the HR for retinopathy in the highest versus the lowest quintile was 0.34 (0.13-0.89; P = 0.001 for trend). No significant associations were found for nephropathy.A MedDiet enriched with EVOO may protect against diabetic retinopathy but not diabetic nephropathy.
The ADA and the Supreme Court
Authors: Samuel R. Bagenstos
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium
Authors: L Tune, S Carr, E Hoag, T Cooper
Journal: American Journal of Psychiatry (1992)

Anticholinergic effects of the 25 drugs most commonly prescribed for the elderly were measured by radioreceptor assay. Fourteen had detectable anticholinergic drug levels; 10 of these had levels that have been associated with impairments in memory and attention in normal elderly subjects. These data indicate that patients taking multiple medications may be at increased risk for side effects from psychotropic drugs, most of which have anticholinergic effects.
Abstract 2757: Development of New Electrocardiographic Strain Pattern is Associated With an Increased Risk of Cardiovascular Morbidity and Mortality During Antihypertensive Treatment: The LIFE Study
Authors: Peter M Okin, Lasse Oikarinen, Matti Viitasalo, Lauri Toivonen, Sverre E Kjeldsen, Markku S Nieminen, Jonathan M Edelman, Bjorn Dahlof, Richard B Devereux
Journal: Circulation (2006)
Abstract 16955: The Direct Renin Inhibitor Aliskiren Improves Vascular Remodeling in Transgenic Rats Harboring Human Renin and Angiotensinogen Genes
Authors: Carmine Savoia, Emanuele Arrabito, Rosa Parente, Luigi Zezza, Lidia Sada, Luca Madaro, Carmine Nicoletti, Dominik D Muller, Massimo Volpe
Journal: Circulation (2011)

The renin inhibitor aliskiren (ALK) reduces blood pressure and improves cardio-renal organ damage in hypertensive double transgenic rats (dTGRs) which express both human renin and angiotensinogen. Little is known about the effect of ALK on hypertension-related vascular structural alterations of resistance arteries. We tested the hypothesis that chronic treatment with ALK improves vascular remodeling of resistance arteriesin in dTGR. dTGRs (5 weeks old) were treated with ALK (3 mg/kg/day, n=5) or ramipril (RAM, 1 mg/kg/day, n=5) for 14 days and compared with age-matched untreated dTGRs. Blood pressure (BP) was measured by tail-cuff method. Resistance arteries media-to-lumen ratio (M/L) was evaluated on mesenteric arteries as pressurized preparations. The expression of AT1 receptor, AT2 receptor, eNOS and the NADPH subunit gp91phox was evaluated in aorta by immunoblotting. The reactive oxygen species (ROS) production was evaluated in aorta by Dihydroethidium (DHE) staining. BP was similarly reduced in both ALK-treated and RAM-treated rats compared to untreated dTGRs (167±1.18 mmHg and 169.4±1.5 mmHg vs 196.8 ±3.9 mmHg, respectively P&lt;0.05; reduction of -15% and -14%; P&lt;0.05). M/L was equally reduced in ALK-treated and RAM-treated rats compared to untreated rats (6.3±0.5 % and 6.4±0.2 % vs 9.8±.04%, respectively; P&lt;0.05). AT1 and AT2 receptor expression was similar in all the groups. eNOS expression was increased only in ALK-treated rats (+41.3±6.3 % vs untreated dTGRs, p&lt;0.05). gp91phox was slightly reduced in both ALK-and RAM-treated dTGRs. Both ALK and RAM similarly reduced ROS production in dTGRs compared to untreated rats (14.7±0.2 AU and 13.9±0.3 AU vs 18.1±0.9 AU, respectively; p&lt;0.05). In conclusion equieffective antihypertensive dose of ALK or RAM improved oxidative stress and reduced M/L of mesenteric arteries. Only ALK increased the eNOS bioavailability. Hence, in dTGRs renin inhibition compares favorably to ACE inhibition in improving vascular remodeling.
Treatment outcome in recurrent major depression: a post hoc comparison of elderly ("young old") and midlife patients
Authors: C F Reynolds, E Frank, D J Kupfer, M E Thase, J M Perel, S Mazumdar, P R Houck
Journal: American Journal of Psychiatry (1996)

The authors compared response rates, the temporal course of response to acute treatment, and relapse rates during continuation treatment of elderly and midlife patients with recurrent major depression.They analyzed results from two separate controlled studies of maintenance therapies for recurrent major depression, in which 148 elderly patients (mean age = 67.9 years) and 214 midlife patients (mean age = 38.5 years) were treated in open acute and continuation therapy with a combination of interpersonal psychotherapy and a tricyclic antidepressant (nortriptyline for the elderly, imipramine for the midlife patients). In an intent-to-treat analysis, remission rates during acute treatment and relapse rates during continuation treatment were examined. Random regression analysis of weekly Hamilton depression scale ratings was used to compare the temporal course of response.During acute-phase therapy, 78.4% (N = 116) of the elderly patients and 69.6% (N = 149) of the midlife patients had remissions. The midlife patients had a faster reduction of Hamilton depression ratings. Following stabilization, 15.5% of the elderly patients and 6.7% of the midlife patients relapsed. Ultimately, 66.2% of the late-life patients and 57.0% of the midlife patients recovered fully.Older patients appear to benefit as much as, but perhaps more slowly then, midlife patients from treatment of major depression. Continuation treatment should be vigorous and closely monitored, given the apparently higher relapse rates among the elderly. These conclusions should be viewed as preliminary because of the post hoc nature of the analysis reported here.
Neural crest–derived SEMA3C activates endothelial NRP1 for cardiac outflow tract septation
Authors: Alice Plein, Amélie Calmont, Alessandro Fantin, Laura Denti, Naomi A. Anderson, Peter J. Scambler, Christiana Ruhrberg
Journal: Journal of Clinical Investigation (2015)

In mammals, the outflow tract (OFT) of the developing heart septates into the base of the pulmonary artery and aorta to guide deoxygenated right ventricular blood into the lungs and oxygenated left ventricular blood into the systemic circulation. Accordingly, defective OFT septation is a life-threatening condition that can occur in both syndromic and nonsyndromic congenital heart disease. Even though studies of genetic mouse models have previously revealed a requirement for VEGF-A, the class 3 semaphorin SEMA3C, and their shared receptor neuropilin 1 (NRP1) in OFT development, the precise mechanism by which these proteins orchestrate OFT septation is not yet understood. Here, we have analyzed a complementary set of ligand-specific and tissue-specific mouse mutants to show that neural crest-derived SEMA3C activates NRP1 in the OFT endothelium. Explant assays combined with gene-expression studies and lineage tracing further demonstrated that this signaling pathway promotes an endothelial-to-mesenchymal transition that supplies cells to the endocardial cushions and repositions cardiac neural crest cells (NCCs) within the OFT, 2 processes that are essential for septal bridge formation. These findings elucidate a mechanism by which NCCs cooperate with endothelial cells in the developing OFT to enable the postnatal separation of the pulmonary and systemic circulation.
Abstract 3014: Identification of the NDP kinase critical for DNA repair
Authors: Ning Tsao, Yu-Jyun Deng, Zee-Fen Chang, Wei Zhang
Journal: Cancer Research (2015)

Abstract Introduction and Purpose: Cellular supply of deoxynucleoside triphosphates (dNTPs) is crucial for DNA replication and repair. It is known that ribonucleotide reductase (RNR), a rate-limiting enzyme for dNTP synthesis, is required for DNA repair. The catalytic function of RNR produces dNDPs. There are eight isoforms of NDP kinase that catalyzes the subsequent step for dNTP formation in human cells. In this study, we aim to identify the isoform of NDP kinase required for DNA repair. Preliminary results: By RNA interference experiments, we identified NME3, one isoform of the nucleoside diphosphate kinases, critical for DNA repair. It has been shown that RNR forms a complex with Tip60, a histone acetyltransferase, by which RNR is recruited to DNA damage sites for repair. In this study, we found that NME3 directly interacts with Tip60. The effect of knockdown of NME3 on DNA repair was rescued by re-expression of wild-type but not the mutant type defective in Tip60 interaction. Overexpression of NME3 was able to facilitate DNA repair, which was intervened by disrupting the interaction of NME3 with Tip60. Moreover, exogenous addition of deoxynucleosides facilitates NME3-mediated DNA repair. Conclusion: Among 8 isoforms of NDP kinase, NME3 is identified to be critical for DNA repair, indicating its potential as a target for developing chemosensitization agent. Citation Format: Ning Tsao, Yu-Jyun Deng, Zee-Fen Chang, Wei Zhang. Identification of the NDP kinase critical for DNA repair. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3014. doi:10.1158/1538-7445.AM2015-3014