tbuckley/cabot-search huggingface dataset:
Resilience to Loss and Potential Trauma
Authors: George A. Bonanno, Maren Westphal, Anthony D. Mancini
Journal: Annual Review of Clinical Psychology (2011)

Initial research on loss and potentially traumatic events (PTEs) has been dominated by either a psychopathological approach emphasizing individual dysfunction or an event approach emphasizing average differences between exposed and nonexposed groups. We consider the limitations of these approaches and review more recent research that has focused on the heterogeneity of outcomes following aversive events. Using both traditional analytic tools and sophisticated latent trajectory modeling, this research has identified a set of prototypical outcome patterns. Typically, the most common outcome following PTEs is a stable trajectory of healthy functioning or resilience. We review research showing that resilience is not the result of a few dominant factors, but rather that there are multiple independent predictors of resilient outcomes. Finally, we critically evaluate the question of whether resilience-building interventions can actually make people more resilient, and we close with suggestions for future research on resilience.
Smallpox vaccine–induced antibodies are necessary and sufficient for protection against monkeypox virus
Authors: Yvette Edghill-Smith, Hana Golding, Jody Manischewitz, Lisa R King, Dorothy Scott, Mike Bray, Aysegul Nalca, Jay W Hooper, Chris A Whitehouse, Joern E Schmitz, Keith A Reimann, Genoveffa Franchini
Journal: Nature Medicine (2005)
A Decrease in Glucose Variability Does Not Reduce Cardiovascular Event Rates in Type 2 Diabetic Patients After Acute Myocardial Infarction
Authors: Sarah E. Siegelaar, Lisa Kerr, Scott J. Jacober, J. Hans Devries
Journal: Diabetes Care (2011)

OBJECTIVE To assess the effect of intraday glucose variability (GV) on cardiovascular outcomes in a reanalysis of Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (HEART2D) study data. RESEARCH DESIGN AND METHODS Type 2 diabetic patients after acute myocardial infarction were randomized to an insulin treatment strategy targeting postprandial (PRANDIAL; n = 557) or fasting/interprandial (BASAL; n = 558) hyperglycemia. GV was calculated as mean amplitude of glycemic excursions (MAGE), mean absolute glucose (MAG) change, and SD. RESULTS The PRANDIAL strategy resulted in an 18% lower MAG than BASAL (mean [SEM] difference 0.09 [0.04] mmol/L/h, P = 0.02). In addition, MAGE and SD were lower in the PRANDIAL group, however, not significantly. HbA1c levels and cardiovascular event rates were comparable between groups. CONCLUSIONS A PRANDIAL strategy demonstrated lower intraday GV vs. a BASAL strategy with similar overall glycemic control but did not result in a reduction in cardiovascular outcomes. This does not support the hypothesis that targeting GV would be beneficial in reducing subsequent secondary cardiovascular events.
Role of organic osmolytes in myelinolysis. A topographic study in rats after rapid correction of hyponatremia.
Authors: Y H Lien
Journal: Journal of Clinical Investigation (1995)

Organic osmolytes have been implicated in the pathogenesis of myelinolysis because some of them are accumulated slowly during correction of chronic hyponatremia. I investigated whether there was a topographic correlation between demyelinative lesions and the regional changes of organic osmolytes after rapid correction of chronic hyponatremia. In normal female Sprague-Dawley rats, concentrations of glutamate, glutamine, taurine, and betaine were highest in the cerebral cortex and decreased toward the brain stem. Conversely, glycine level was highest in the brainstem, and decreased toward the cortex. Myoinositol, glycerophosphorylcholine, glycerophosphorylethanolamine, and creatine were distributed more evenly. In chronic hyponatremic rats (plasma Na 110 +/- 4 meq/liter), organic osmolytes decreased globally with the total loss ranging from 13 (medulla) to 24 (cerebellum) mmol/kg H2O. After rapid correction with intraperitoneal injection of hypertonic saline, the recovery of the loss of organic osmolytes was 48% in the cerebral cortex, cerebellum, and medulla oblongata, 44% in pons, but only 17% in midbrain and 36% in striatum. Histopathology of the brain was examined in nine rats 2-7 d after correction of hyponatremia. Large demyelinative lesions were seen persistently in the midbrain and striatum, and smaller lesions in cerebrum, cerebellum, and pons were found less frequently. This is the first report of regional distribution of brain organic osmolytes. After rapid correction of chronic hyponatremia, a topographic correlation between demyelination lesions and delayed accumulation of organic osmolytes exists.
THE NATURE OF THE SO-CALLED RHEUMATOID ARTHRITIS AND OSTEO-ARTHRITIS: Summary of an Investigation into the Pathological Changes, with a Plea for a Scientific Classification
Authors: A. G. T. Fisher
Journal: BMJ (1923)

THE chronic forms of arthritis known in this country by the somewhat unscientific names " rheumatoid aithritis " and " osteo-arthritis " are among the commonest of all human ailments, and probably cause a greater loss of pro- ductive energy to the community than d-isease of any other system.It is true that the disease rarely, if ever, causes the death of the patient, but it often occurs in the com- paratively young and active, to whom the resulting crippledom is a. grave hardship.It is proposed in this paper to resist the temptation to discuss clinlical aspects and treat- melnt, and to review briefly certain aspects of the problem.
Release of doxorubicin in sweat: first step to induce the palmar-plantar erythrodysesthesia syndrome?
Authors: U. Jacobi, E. Waibler, P. Schulze, J. Sehouli, G. Oskay-Özcelik, T. Schmook, W. Sterry, J. Lademann
Journal: Annals of Oncology (2005)
Fetal nuchal translucency scan and early prenatal diagnosis of chromosomal abnormalities by rapid aneuploidy screening: observational study
Authors: Lyn S Chitty, Karl O Kagan, Francisca S Molina, Jonathan J Waters, Kypros H Nicolaides
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To investigate an approach for the analysis of samples obtained in screening for trisomy 21 that retains the advantages of quantitative fluorescent polymerase chain reaction (qf-PCR) over full karyotyping and maximises the detection of clinically significant abnormalities. <b>Design</b> Observational study. <b>Setting</b> Tertiary referral centre. <b>Subjects</b> 17 446 pregnancies, from which chorionic villous samples had been taken after assessment of risk for trisomy 21 by measurement of fetal nuchal translucency (NT) thickness at 11 to 13<sup>+6</sup> weeks of gestation. <b>Interventions</b> Analysis of chorionic villous samples by full karyotyping and by qf-PCR for chromosomes 13, 18, 21 X and Y. <b>Main outcome measure</b> Detection of clinically significant chromosomal abnormalities. <b>Results</b> The fetal karyotype was normal in 15 548 (89.1%) cases and abnormal in 1898 (10.9%) cases, including 1722 with a likely clinically significant adverse outcome. Karyotyping all cases would lead to the diagnosis of all clinically significant abnormalities, and a policy of relying entirely on qf-PCR would lead to the diagnosis of 97.9% of abnormalities. An alternative strategy whereby qf-PCR is the main method of analysis and full karyotyping is reserved for those cases with a minimum fetal NT thickness of 4 mm would require full karyotyping in 10.1% of the cases, would identify 99.0% of the significant abnormalities, and would cost 60% less than full karyotyping for all. <b>Conclusions</b> In the diagnosis of chromosomal abnormalities after first trimester screening for trisomy 21, a policy of qf-PCR for all samples and karyotyping only if the fetal NT thickness is increased would reduce the economic costs, provide rapid delivery of results, and identify 99% of the clinically significant chromosomal abnormalities.
Association of Serum Concentration of TNFR1 With All-Cause Mortality in Patients With Type 2 Diabetes and Chronic Kidney Disease: Follow-up of the SURDIAGENE Cohort
Authors: Pierre-Jean Saulnier, Elise Gand, Stéphanie Ragot, Grégory Ducrocq, Jean-Michel Halimi, Charlotte Hulin-Delmotte, Pierre Llaty, David Montaigne, Vincent Rigalleau, Ronan Roussel, Gilberto Velho, Philippe Sosner, Philippe Zaoui, Samy Hadjadj
Journal: Diabetes Care (2014)

Renal dysfunction is a key risk factor for all-cause mortality in patients with type 2 diabetes (T2D). Circulating tumor necrosis factor receptor 1 (TNFR1) was recently suggested as a strong biomarker for end-stage renal failure in T2D. However, its relevance regarding all-cause death has yet to be conclusively established. We aimed to assess the prognostic value of serum TNFR1 concentration for all-cause death in T2D and diabetic kidney disease (DKD) from the SURDIAGENE (Survie, Diabete de type 2 et Genetique) study.A total of 522 T2D patients with DKD (estimated glomerular filtration rate [eGFR] <60 and/or urinary albumin-to-creatinine ratio [uACR] >30 mg/mmol) were followed for a median duration of 48 months, and 196 deaths occurred.Incidence rate (95% CI) for death increased as quartiles of TNFR1 concentration increased (first quartile: 4.7% patient-years [3.0-6.3%]; second quartile: 7.7% [5.4-10.0%]; third quartile: 9.3% [6.7-11.9%]; fourth quartile: 15.9% [12.2-19.5%]). In multivariate analysis taking age, diabetes duration, HbA1c, uACR, and eGFR into account, compared with the first quartile, patients from the fourth quartile had an adjusted hazard ratio for death of 2.98 (95% CI 1.70-5.23). The integrated discrimination improvement index was statistically significant when adding TNFR1 concentration to the UK Prospective Diabetes Study outcome equation (P = 0.031).TNFR1 is a strong prognostic factor for all-cause mortality in T2D with renal dysfunction, and its clinical utility is suggested in addition to established risk factors for all-cause mortality.
Acute liver failure: What is it?
Authors: Kama A. Wlodzimirow, Saeid Eslami, Ameen Abu-Hanna, Martin Nieuwoudt, Robert A.F.M. Chamuleau
Journal: Hepatology (2011)

Quantitative synthesis of prognostic research findings in acute liver failure (ALF) requires uniformity in the definition of this disease. We wish to assess the variability and explicitness of the used ALF definitions in studies focusing on evaluating indicators of ALF outcome. We included studies published in HEPATOLOGY in the last decade that report original data from a clinical trial or observational study on adult patients with ALF and of which one of the main objectives was evaluating prognostic indicators for prediction of outcome, including adverse outcome. Out of eight included studies, seven used five different ALF definitions (Table 1), and one did not report an explicit definition. The differences in the ALF definitions can be characterized by four main components: (1) presence of hepatic encephalopathy with or without its grade of severity (reported in all studies, two of which reported its grade); (2) the interval between onset of disease and occurrence of hepatic encephalopathy (reported in six studies, three of which reported 26 weeks, two of which reported 8 weeks, and one of which reported 4 weeks); (3) presence of coagulopathy with or without its threshold value (reported in five studies, one of which operationalized it by international normalized ratio [INR], four of which operationalized it by prothrombin time or INR; four studies presented thresholds); and (4) presence of preexisting liver disease (reported in five studies). Some studies mentioned other elements in the definition, such as jaundice (one study) and asterixis, hyperbilirubinemia, or hypoglycemia (one study). We found a large variation in the definition of ALF in eight studies in one decade in one journal. Although the exact implications of the differences in ALF definitions on performance of prognostic markers remain unknown, these differences hinder such quantitative analysis. There is room for improvement in the reporting of ALF definitions, and there is a need for a uniform accepted definition of ALF in future studies to evaluate prognostic indicators. Kama A. Wlodzimirow*, Saeid Eslami*, Ameen Abu-Hanna*, Martin Nieuwoudt , Robert A.F.M. Chamuleau , * Department of Medical Informatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, South African DST/NRF Centre of Excellence in Epidemiological Modelling and Analysis, Stellenbosch, South Africa, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Cardiometabolic Risk in Patients With First-Episode Schizophrenia Spectrum Disorders
Authors: Christoph U. Correll, Delbert G. Robinson, Nina R. Schooler, Mary F. Brunette, Kim T. Mueser, Robert A. Rosenheck, Patricia Marcy, Jean Addington, Sue E. Estroff, James Robinson, David L. Penn, Susan Azrin, Amy Goldstein, Joanne Severe, Robert Heinssen, John M. Kane
Journal: JAMA Psychiatry (2014)

The fact that individuals with schizophrenia have high cardiovascular morbidity and mortality is well established. However, risk status and moderators or mediators in the earliest stages of illness are less clear.To assess cardiometabolic risk in first-episode schizophrenia spectrum disorders (FES) and its relationship to illness duration, antipsychotic treatment duration and type, sex, and race/ethnicity.Baseline results of the Recovery After an Initial Schizophrenia Episode (RAISE) study, collected between July 22, 2010, and July 5, 2012, from 34 community mental health facilities without major research, teaching, or clinical FES programs. Patients were aged 15 to 40 years, had research-confirmed diagnoses of FES, and had less than 6 months of lifetime antipsychotic treatment.Prebaseline antipsychotic treatment was based on the community clinician's and/or patient's decision.Body composition and fasting lipid, glucose, and insulin parameters.In 394 of 404 patients with cardiometabolic data (mean [SD] age, 23.6 [5.0] years; mean [SD] lifetime antipsychotic treatment, 47.3 [46.1] days), 48.3% were obese or overweight, 50.8% smoked, 56.5% had dyslipidemia, 39.9% had prehypertension, 10.0% had hypertension, and 13.2% had metabolic syndrome. Prediabetes (glucose based, 4.0%; hemoglobin A1c based, 15.4%) and diabetes (glucose based, 3.0%; hemoglobin A1c based, 2.9%) were less frequent. Total psychiatric illness duration correlated significantly with higher body mass index, fat mass, fat percentage, and waist circumference (all P<.01) but not elevated metabolic parameters (except triglycerides to HDL-C ratio [P=.04]). Conversely, antipsychotic treatment duration correlated significantly with higher non-HDL-C, triglycerides, and triglycerides to HDL-C ratio and lower HDL-C and systolic blood pressure (all P≤.01). In multivariable analyses, olanzapine was significantly associated with higher triglycerides, insulin, and insulin resistance, whereas quetiapine fumarate was associated with significantly higher triglycerides to HDL-C ratio (all P≤.02).In patients with FES, cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy lifestyle, and antipsychotic medications, which interact with each other. Prevention of and early interventions for psychiatric illness and treatment with lower-risk agents, routine antipsychotic adverse effect monitoring, and smoking cessation interventions are needed from the earliest illness phases.
Caudate Nucleus Volumes and Genetic Determinants of Homocysteine Metabolism in the Prediction of Psychomotor Speed in Older Persons With Depression
Authors: Sharon Naismith, Ian Hickie, Philip B. Ward, Keelin Turner, Elizabeth Scott, Craig Little, Philip Mitchell, Kay Wilhelm, Gordon Parker
Journal: American Journal of Psychiatry (2002)

The authors sought to determine whether caudate nucleus volumes or specific genotypes predict psychomotor slowing in older persons with depression.Forty-seven persons with depression (mean age=51.8 years, SD=12.4) and 20 healthy volunteers (mean age=56.1 years, SD=9.8) underwent clinical assessments, a neuropsychological test of psychomotor speed (part A of the Trail Making Test), high-resolution magnetic resonance imaging scans, and genotyping for the apolipoprotein E epsilon4 allele and a mutation of the methylenetetrahydrofolate reductase enzyme.Multivariate analyses revealed that psychomotor speed was uniquely predicted by age, a diagnosis of depression, right caudate nucleus volume, and mutation of the methylenetetrahydrofolate reductase enzyme.Psychomotor slowing, a key clinical and cognitive phenomenon in older persons with depression, is predicted by reduced caudate nucleus volumes and genetic determinants of homocysteine metabolism.
Effect of side chain length on bile acid conjugation: Glucuronidation, sulfation and coenzyme a formation of nor-bile acids and their natural C24 homologs by human and rat liver fractions
Authors: Robert B. Kirkpatrick, Mitchell D. Green, Lee R. Hagey, Alan F. Hofmann, Thomas R. Tephly
Journal: Hepatology (1988)

The effect of side chain length on bile acid conjugation by human and rat liver fractions was examined. The rate of conjugation with glucuronic acid, sulfate and coenzyme A of several natural (C 24 ) bile acids was compared with that of their corresponding nor-bile acids. The rate of coenzyme A ester formation by nor-bile acids was much lower than that of the natural bile acids. In human liver microsomes, the rate of coenzyme A formation was &lt;8% of the rate for the corresponding C 24 bile acid. Rat liver microsomes formed the coenzyme A ester of nor-bile acids &lt;20% of the rate of their corresponding C 24 homologs. Glucuronidation rates were greater than sulfation rates in both species. With human liver microsomes, nor-bile acids were glucuronidated more rapidly than their corresponding C 24 homologs, whereas with rat liver microsomes the reverse was true. Purified 3α-OH androgen UDP-glucuronyltransferase catalyzed the glucuronidation of both nor-bile acids and bile acids. Human liver cytosol sulfated nor-bile acids more slowly than the corresponding bile acids. Rat liver cytosol, however, sulfated nor-bile acids more rapidly than the corresponding bile acids. The highest rate was seen with lithocholylglycine. The results indicate that the novel biotransformation of nor-bile acids seen in vivo —sulfation and glucuronidation rather than amidation—is most likely explained as a consequent of defective amidation, to which the rate of coenzyme A formation contributes. Thus, side chain and nuclear structures as well as species differences in conjugating enzyme activity are determinants of the pattern of bile acid biotransformation by the mammalian liver.
Combined Proteomics and Pathways Analysis of Collecting Duct Reveals a Protein Regulatory Network Activated in Vasopressin Escape
Authors: Ewout J. Hoorn, Jason D. Hoffert, Mark A. Knepper
Journal: Journal of the American Society of Nephrology (2005)

Low sensitivity is characteristic of many proteomics methods. Presented here is an approach that combines proteomics based on difference gel electrophoresis (DIGE) with bioinformatic pathways analysis to identify both abundant and relatively nonabundant proteins in inner medullary collecting duct (IMCD) altered in abundance during escape from vasopressin-induced antidiuresis. Rats received the vasopressin analog dDAVP by osmotic minipump plus either a daily water load (vasopressin escape) or only enough water to replace losses (control). Immunoblotting confirmed the hallmark of vasopressin escape, a decrease in aquaporin-2, and demonstrated a decrease in the abundance of the urea transporter UT-A3. DIGE identified 22 mostly high-abundance proteins regulated during vasopressin escape. These proteins were analyzed using pathways analysis software to reveal protein clusters incorporating the proteins identified by DIGE. A single dominant cluster emerged that included many relatively low-abundance proteins (abundances too low for DIGE identification), including several transcription factors. Immunoblotting confirmed a decrease in total and phosphorylated c-myc, a decrease in c-fos, and increases in c-jun and p53. Furthermore, immunoblotting confirmed hypothesized changes in other proteins in the proposed network: Increases in c-src, receptor for activated C kinase 1, calreticulin, and caspase 3 and decreases in steroid receptor co-activator 1, Grp78/BiP, and annexin A4. This combined approach proved capable of uncovering regulatory proteins that are altered in response to a specific physiologic perturbation without being detected directly by DIGE. The results demonstrate a dominant protein regulatory network in IMCD cells that is altered in association with vasopressin escape, providing a new framework for further studies of signaling in IMCD.
Retinol Inhibits the Growth of <i>All-Trans</i>-Retinoic Acid–Sensitive and <i>All-Trans</i>-Retinoic Acid–Resistant Colon Cancer Cells through a Retinoic Acid Receptor–Independent Mechanism
Authors: Eun Young Park, Alice Dillard, Elizabeth A. Williams, Erik T. Wilder, M. Reese Pepper, Michelle A. Lane
Journal: Cancer Research (2005)

Abstract Retinol (vitamin A) is thought to exert its effects through the actions of its metabolite, all-trans-retinoic acid (ATRA), on gene transcription mediated by retinoic acid receptors (RAR) and retinoic acid response elements (RARE). However, retinoic acid resistance limits the chemotherapeutic potential of ATRA. We examined the ability of retinol to inhibit the growth of ATRA-sensitive (HCT-15) and ATRA-resistant (HCT-116, SW620, and WiDR) human colon cancer cell lines. Retinol inhibited cell growth in a dose-responsive manner. Retinol was not metabolized to ATRA or any bioactive retinoid in two of the cell lines examined. HCT-116 and WiDR cells converted a small amount of retinol to ATRA; however, this amount of ATRA was unable to inhibit cell growth. To show that retinol was not inducing RARE-mediated transcription, each cell line was transfected with pRARE-chloramphenicol acetyltransferase (CAT) and treated with ATRA and retinol. Although treatment with ATRA increased CAT activity 5-fold in ATRA-sensitive cells, retinol treatment did not increase CAT activity in any cell line examined. To show that growth inhibition due to retinol was ATRA, RAR, and RARE independent, a pan-RAR antagonist was used to block RAR signaling. Retinol-induced growth inhibition was not alleviated by the RAR antagonist in any cell line, but the antagonist alleviated ATRA-induced growth inhibition of HCT-15 cells. Retinol did not induce apoptosis, differentiation or necrosis, but affected cell cycle progression. Our data show that retinol acts through a novel, RAR-independent mechanism to inhibit colon cancer cell growth.