tbuckley/cabot-search huggingface dataset:
Neuroimaging Evidence for a Role of Neural Social Stress Processing in Ethnic Minority–Associated Environmental Risk
Authors: Ceren Akdeniz, Heike Tost, Fabian Streit, Leila Haddad, Stefan Wüst, Axel Schäfer, Michael Schneider, Marcella Rietschel, Peter Kirsch, Andreas Meyer-Lindenberg
Journal: JAMA Psychiatry (2014)

Relative risk for the brain disorder schizophrenia is more than doubled in ethnic minorities, an effect that is evident across countries and linked to socially relevant cues such as skin color, making ethnic minority status a well-established social environmental risk factor. Pathoepidemiological models propose a role for chronic social stress and perceived discrimination for mental health risk in ethnic minorities, but the neurobiology is unexplored.To study neural social stress processing, using functional magnetic resonance imaging, and associations with perceived discrimination in ethnic minority individuals.Cross-sectional design in a university setting using 3 validated paradigms to challenge neural social stress processing and, to probe for specificity, emotional and cognitive brain functions. Healthy participants included those with German lineage (n = 40) and those of ethnic minority (n = 40) from different ethnic backgrounds matched for sociodemographic, psychological, and task performance characteristics. Control comparisons examined stress processing with matched ethnic background of investigators (23 Turkish vs 23 German participants) and basic emotional and cognitive tasks (24 Turkish vs 24 German participants).Blood oxygenation level-dependent response, functional connectivity, and psychological and physiological measures.There were significant increases in heart rate (P < .001), subjective emotional response (self-related emotions, P < .001; subjective anxiety, P = .006), and salivary cortisol level (P = .004) during functional magnetic resonance imaging stress induction. Ethnic minority individuals had significantly higher perceived chronic stress levels (P = .02) as well as increased activation (family-wise error-corrected [FWE] P = .005, region of interest corrected) and increased functional connectivity (PFWE = .01, region of interest corrected) of perigenual anterior cingulate cortex (ACC). The effects were specific to stress and not explained by a social distance effect. Ethnic minority individuals had significant correlations between perceived group discrimination and activation in perigenual ACC (PFWE = .001, region of interest corrected) and ventral striatum (PFWE = .02, whole brain corrected) and mediation of the relationship between perceived discrimination and perigenual ACC-dorsal ACC connectivity by chronic stress (P < .05).Epidemiologists proposed a causal role of social-evaluative stress, but the neural processes that could mediate this susceptibility effect were unknown. Our data demonstrate the potential of investigating associations from epidemiology with neuroimaging, suggest brain effects of social marginalization, and highlight a neural system in which environmental and genetic risk factors for mental illness may converge.
Left ventricular diastolic dysfunction is linked to severity of obstructive sleep apnoea
Authors: J-P. Baguet, G. Barone-Rochette, P. Lévy, E. Vautrin, H. Pierre, O. Ormezzano, J-L. Pépin
Journal: European Respiratory Journal (2010)

Obstructive sleep apnoea (OSA) has been linked to increased cardiovascular risk. The present study examined the relationships between respiratory parameters and left ventricular abnormalities in OSA. 150 newly diagnosed OSA patients without any known cardiovascular disease were included in the study (mean± sd age 49±11 yrs, body mass index 27.1±3.3 kg·m −2 , respiratory disturbance index 41±18 h −1 ). Haemodynamic, biological, respiratory, cardiac and arterial parameters were assessed at inclusion. 34 (22.7%) patients had a grade 1 left ventricular diastolic dysfunction. Patients with an abnormal diastole were older (p&lt;0.001) and 81% of them were hypertensive. The only respiratory parameter independently associated with the peak flow velocity in early diastole/peak flow velocity at atrial contraction ratio was mean nocturnal oxygen saturation. 17 (13%) patients had left ventricular hypertrophy. A multivariate analysis showed that clinic systolic blood pressure and mean nocturnal oxygen saturation were independently associated with left ventricular hypertrophy. In a logistic regression model, age ≥58 yrs (OR 3.29, 95% CI 1.78–5.64) and mean nocturnal oxygen saturation &lt;92% (OR 2.76, 95% CI 1.45–4.91) were associated with left ventricular diastolic dysfunction. Our findings demonstrate that left ventricular diastolic dysfunction frequently occurs in patients with OSA and that it is related to the severity of oxygen desaturation.
Effect of Interaction of the Hypothalamus and the Carotid Sinus Mechanoreceptor System on Renal Hemodynamics in the Anesthetized Dog
Authors: Roger J. Bagshow, Masahiko lizuko, Lysle H. Peterson
Journal: Circulation Research (1971)

The purpose of this investigation was to show how the operating characteristics of the reflex having carotid sinus pressure as an input and renal pressure and flow as an output are modified by graded stimulation of the posterior hypothalamus. Consequently, the effects of graded stimulation of the posterior hypothalamus on renal hemodynamics were investigated in the anesthetized dog. The carotid sinuses were isolated and subjected to controlled pulsatile pressures. In general, discrete stimulation of the hypothalamus caused a frequency-dependent increase in renal impedance, and stimulation of the carotid sinus caused a decrease. Concomitant stimulation of the hypothalamus and the carotid sinuses had a significant, nonalgebraic effect on the d-c impedance (renal resistance) but no effect on renal impedance at high frequencies. Hypothalamic stimulation modified the sensitivity of renal resistance to carotid sinus pressure. This reflex sensitivity to hypothalamic stimulation passed through a single maximum. The estimated characteristic renal impedance varied inversely with carotid sinus pressure due to active vasomotor changes in renal vascular mechanical properties, rather than to passive effects of concomitant blood pressure changes.
Gut Microbiota of the Tick Vector Ixodes scapularis Modulate Colonization of the Lyme Disease Spirochete
Authors: Sukanya Narasimhan, Nallakkandi Rajeevan, Lei Liu, Yang O. Zhao, Julia Heisig, Jingyi Pan, Rebecca Eppler-Epstein, Kathleen DePonte, Durland Fish, Erol Fikrig
Journal: Cell Host & Microbe (2014)
Power Spectral Analysis of Heart Rate Variability During the 100-g Oral Glucose Tolerance Test in Pregnant Women
Authors: Amir Weissman, Lior Lowenstein, Amir Peleg, Israel Thaler, Etan Z. Zimmer
Journal: Diabetes Care (2006)

The aims of the present study were to 1) evaluate autonomic function during the oral glucose tolerance test (OGTT) in pregnant women and 2) investigate whether gestational diabetes mellitus (GDM) modifies autonomic control of heart rate variability.We prospectively studied 27 pregnant women (15 without GDM, 12 with GDM) during a 100-g OGTT. The maternal electrocardiogram was recorded before and 60 min after glucose ingestion, when peak glucose levels are expected. The time and frequency domains of maternal cardiac intervals were analyzed.There was a significant decrease in the high-frequency (HF) band in both groups after the ingestion of glucose. The normalized low-frequency (LF) band significantly increased and the normalized HF band significantly decreased after glucose ingestion. The LF-to-HF ratio was significantly higher in the group with GDM at baseline and significantly increased in both groups after glucose ingestion. A regression analysis revealed a significant decrease in the HF band with increasing blood glucose levels.Acute elevation of blood glucose levels during the OGTT caused substantial autonomic alterations, including sympathetic activation and parasympathetic withdrawal. Both arms of the autonomic system were affected during the test, thus lending support to the concept that these changes are centrally integrated. The autonomic changes were less pronounced in women with GDM compared with in normal control subjects, suggesting that chronic hyperglycemia and hyperinsulinemia may alter modulation of the autonomic nervous system.
Physical and physiological profiles of Malaysian dragon boat rowers.
Authors: R Singh, H J Singh, R G Sirisinghe
Journal: British Journal of Sports Medicine (1995)

Maximal oxygen consumption (VO2max) and maximal workload attained (WLmax) were determined in 28 Malaysian dragon boat rowers who were exercised to exhaustion on an arm ergometer. Mean VO2max was 2.75 l min-1 at a mean WLmax of 195.5 W. Anaerobic endurance power of the arms, determined by cranking at 100 RPM at a workload of 400 W and the time taken to maintain the cadence until it fell to 75 RPM, was 34.9(+/- 2.3) s. Leg performance, as determined by standing long jump and vertical jump, was 140.0(+/- 4.5) kg m and 100.3(+/- 3.1) kg m s-1 respectively. Right hand grip strength was significantly (p < 0.001) greater than the left hand. Percentage body fat of the rowers was 11.8(+/- 0.6)%. These values represent the first measurements of their kind performed on dragon boat rowers in Malaysia.
Approximating Model Probabilities in Bayesian Information Criterion and Decision-Theoretic Approaches to Model Selection in Phylogenetics
Authors: J. Evans, J. Sullivan
Journal: Molecular Biology and Evolution (2010)

A priori selection of models for use in phylogeny estimation from molecular sequence data is increasingly important as the number and complexity of available models increases. The Bayesian information criterion (BIC) and the derivative decision-theoretic (DT) approaches rely on a conservative approximation to estimate the posterior probability of a given model. Here, we extended the DT method by using reversible jump Markov chain Monte Carlo approaches to directly estimate model probabilities for an extended candidate pool of all 406 special cases of the general time reversible + Γ family. We analyzed 250 diverse data sets in order to evaluate the effectiveness of the BIC approximation for model selection under the BIC and DT approaches. Model choice under DT differed between the BIC approximation and direct estimation methods for 45% of the data sets (113/250), and differing model choice resulted in significantly different sets of trees in the posterior distributions for 26% of the data sets (64/250). The model with the lowest BIC score differed from the model with the highest posterior probability in 30% of the data sets (76/250). When the data indicate a clear model preference, the BIC approximation works well enough to result in the same model selection as with directly estimated model probabilities, but a substantial proportion of biological data sets lack this characteristic, which leads to selection of underparametrized models.
Hepatic Injury in the Toxic Epidemic Syndrome Caused by Ingestion of Adulterated Cooking Oil (Spain, 1981)
Authors: JosÉ A. Solis-Herruzo, Gregorio Castellano, Francisco Colina, Juan Diego Morillas, Maria Teresamuñoz-Yagüe, Maria Del Carmen Coca, Dusko Jelavic
Journal: Hepatology (1984)

We describe the clinico-pathological characteristics of hepatic injury associated with the toxic-epidemic syndrome caused by the consumption of adulterated rapeseed oil. Of 842 toxic-epidemic syndrome patients admitted to our hospital between May, 1981, and January, 1982, 24.1% showed signs of liver involvement which was more frequent in women and in the fourth decade of life. No statistical significance was found in relation to alcohol consumption, treatment with potentially hepatotoxic antibiotics, or adult respiratory distress syndrome. Most (91.6%) patients with hepatic injury were asymptomatic; jaundice or abdominal pain was rarely noted. One patient died of acute liver failure following Budd-Chiari syndrome. Serum gamma-glutamyl transpeptidase activity was raised in all cases, alkaline phosphatase in 94.6%, and less frequently lactate dehydrogenase (80%), SGPT (84.7%), and SGOT (76%). Serum total bilirubin was usually normal (89.2%). The histologic lesion was similar to drug-induced cholestatic hepatitis. Lamellar inclusions, canalicular injury, giant mitochondria, and hyperplasia of the smooth endoplasmic reticulum were seen by electron microscopy. Ultrastructural signs of cholestasis were common (78.9%). The pathogenesis of this lesion is unknown; however, because of similarities with chlorpromazine-induced cholestatic hepatitis, we suggest that a combination of hypersensitivity and intrinsic hepatoxicity is a possible mechanism.
A randomised tandem colonoscopy trial of narrow band imaging versus white light examination to compare neoplasia miss rates
Authors: T Kaltenbach, S Friedland, R Soetikno
Journal: Gut (2008)

<h3>Objective:</h3> Colonoscopy, the "gold standard" screening test for colorectal cancer (CRC), has known diagnostic limitations. Advances in endoscope technology have focused on improving mucosal visualisation. In addition to increased angle of view and resolution features, recent colonoscopes have non-white-light optics, such as narrow band imaging (NBI), to enhance image contrast. We aimed to study the neoplasia diagnostic characteristics of NBI, by comparing the neoplasm miss rate when the colonoscopy was performed under NBI versus white light (WL). <h3>Design:</h3> Randomised controlled trial. <h3>Setting:</h3> US Veterans hospital. <h3>Patients:</h3> Elective colonoscopy adults. <h3>Intervention:</h3> We randomly assigned patients to undergo a colonoscopic examination using NBI or WL. All patients underwent a second examination using WL, as the reference standard. <h3>Main outcome measures:</h3> The primary end point was the difference in the neoplasm miss rate, and secondary outcome was the neoplasm detection rate. <h3>Results:</h3> In 276 tandem colonoscopy patients, there was no significant difference of miss or detection rates between NBI or WL colonoscopy techniques. Of the 135 patients in the NBI group, 17 patients (12.6%; 95% confidence interval (CI) 7.5 to 19.4%) had a missed neoplasm, as compared with 17 of the 141 patients (12.1%; 95% CI 7.2 to 18.6%) in the WL group, with a miss rate risk difference of 0.5% (95% CI −7.2 to 8.3). 130 patients (47%) had at least one neoplasm. Missed lesions with NBI showed similar characteristics to those missed with WL. All missed neoplasms were tubular adenomas, the majority (78%) was ⩽5 mm and none were larger than 1 cm (one-sided 95% CI up to 1%). Nonpolypoid lesions represented 35% (13/37) of missed neoplasms. <h3>Interpretation:</h3> NBI did not improve the colorectal neoplasm miss rate compared to WL; the miss rate for advanced adenomas was less than 1% and for all adenomas was 12%. The neoplasm detection rates were similar high using NBI or WL; almost a half the study patients had at least one adenoma. <h3>Clinicaltrials.gov identifier:</h3> NCT00628147
Surgery for carotid artery stenosis: Patients with critical stenoses should be admitted to stroke prevention units
Authors: Chris Imray, Kyle Pattinson
Journal: BMJ (2004)

EDITOR—While shopping in Florida, a man found a booth offering carotid duplex scans for a modest fee. He had a family history of cerebrovascular disease, so he decided to be scanned for peace of mind. Unfortunately, a critical internal carotid stenosis was found.

He returned to his hotel somewhat perturbed, only to be …
Inactivation of BRCA1 and BRCA2 in Ovarian Cancer
Authors: J. L. Hilton
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Although BRCA1 and BRCA2 play important roles in hereditary ovarian cancers, the extent of their role in sporadic ovarian cancers and their mechanisms of inactivation are not yet well understood. Our goal was to characterize BRCA2 mutations and mRNA expression in a group of ovarian tumors previously evaluated for BRCA1 mutations and mRNA expression. Methods: The tumors of 92 unrelated women with "ovarian" cancer (i.e., ovarian, peritoneal, or fallopian tube cancer) were screened for BRCA2 null mutations using a protein truncation test. Methylation-specific polymerase chain reaction (PCR) was used to examine the BRCA2 promoter for hypermethylation in tumors that did not express BRCA2 mRNA. All statistical tests were two-sided. Results: Nine tumors had a germline (n = 5) or somatic (n = 4) BRCA2 mutation; each was associated with loss of heterozygosity. All of the somatic (1445delC, E880X, 4286del8, and 5783delT) and one of the germline (5984ins4) mutations were unique to this study. One tumor had somatic mutations in both BRCA1 and BRCA2. Two tumors are, to our knowledge, the first cases of germline BRCA2-associated peritoneal cancer. Twelve additional tumors lacked detectable BRCA2 mRNA, but the BRCA2 promoter was hypermethylated in only one of them, suggesting that other mechanisms effect transcriptional silencing of BRCA2. Tumors lacking BRCA1 mRNA were more likely to lack BRCA2 mRNA than tumors expressing BRCA1 mRNA (P<.001). Overall, 82% (95% confidence interval [CI] = 74% to 90%) of the tumors contained alterations in BRCA1, BRCA2, or both genes. Of 41 informative tumors with some alteration in BRCA2, 36 also had an alteration in BRCA1. The frequency, but not the mechanism, of BRCA1 or BRCA2 dysfunction in ovarian cancer was independent of family history. Conclusions: Multiple mechanisms cause nearly universal dysfunction of BRCA1 and/or BRCA2 in hereditary and sporadic ovarian carcinoma. Ovarian cancers with BRCA2 dysfunction often have simultaneous BRCA1 dysfunction.
Mammalian target of rapamycin and its downstream signalling components are activated in psoriatic skin
Authors: C. Buerger, B. Malisiewicz, A. Eiser, K. Hardt, W.H. Boehncke
Journal: British Journal of Dermatology (2013)

Mammalian target of rapamycin (mTOR) signalling integrates signals leading to cellular growth, proliferation and differentiation. Disturbance of this tightly regulated interplay leads to malignancies, as reflected by altered mTOR signalling in epidermal tumours. As psoriatic keratinocytes also show features of perturbed cell growth and differentiation, the question arises as to whether mTOR signalling also plays a role in the pathogenesis of psoriasis.To investigate the activation status of mTOR signalling components in psoriasis.Biopsies from lesional and nonlesional skin of patients with psoriasis (n = 10), as well as samples from healthy donors (n = 3), were analysed by immunohistochemistry and Western blot, utilizing antibodies detecting phosphorylated mTOR, phospho-S6 kinase and phospho-S6 ribosomal protein.We found mTOR and its downstream signalling molecule, the ribosomal protein S6, to be activated in lesional psoriatic skin. While mTOR is activated throughout the whole epidermis, with particularly strong activation in the basal layer, S6 is active in suprabasal layers of differentiating keratinocytes.Altogether these results suggest a role for mTOR signalling in the epidermal changes leading to the psoriatic phenotype. mTOR inhibition might be a mode of action to explore in developing innovative antipsoriatic drugs.
Analysis of Phase II Studies on Targeted Agents and Subsequent Phase III Trials: What Are the Predictors for Success?
Authors: John K. Chan, Stefanie M. Ueda, Valerie E. Sugiyama, Christopher D. Stave, Jacob Y. Shin, Bradley J. Monk, Branimir I. Sikic, Kathryn Osann, Daniel S. Kapp
Journal: Journal of Clinical Oncology (2008)

To identify the characteristics of phase II studies that predict for subsequent "positive" phase III trials (those that reached the proposed primary end points of study or those wherein the study drug was superior to the standard regimen investigating targeted agents in advanced tumors.We identified all phase III clinical trials of targeted therapies against advanced cancers published from 1985 to 2005. Characteristics of the preceding phase II studies were reviewed to identify predictive factors for success of the subsequent phase III trial. Data were analyzed using the chi(2) test and logistic regression models.Of 351 phase II studies, 167 (47.6%) subsequent phase III trials were positive and 184 (52.4%) negative. Phase II studies from multiple rather than single institutions were more likely to precede a successful trial (60.4% v 39.4%; P < .001). Positive phase II results were more likely to lead to a successful phase III trial (50.8% v 22.5%; P = .003). The percentage of successful trials from pharmaceutical companies was significantly higher compared with academic, cooperative groups, and research institutes (89.5% v 44.2%, 45.2%, and 46.3%, respectively; P = .002). On multivariate analysis, these factors and shorter time interval between publication of phase II results and III study publication were independent predictive factors for a positive phase III trial.In phase II studies of targeted agents, multiple- versus single-institution participation, positive phase II trial, pharmaceutical company-based trials, and shorter time period between publication of phase II to phase III trial were independent predictive factors of success in a phase III trial. Investigators should be cognizant of these factors in phase II studies before designing phase III trials.
Loss of PI3Kγ Enhances cAMP-Dependent MMP Remodeling of the Myocardial N-Cadherin Adhesion Complexes and Extracellular Matrix in Response to Early Biomechanical Stress
Authors: Danny Guo, Zamaneh Kassiri, Ratnadeep Basu, Fung L. Chow, Vijay Kandalam, Federico Damilano, Wenbin Liang, Seigo Izumo, Emilio Hirsch, Josef M. Penninger, Peter H. Backx, Gavin Y. Oudit
Journal: Circulation Research (2010)

Mechanotransduction and the response to biomechanical stress is a fundamental response in heart disease. Loss of phosphoinositide 3-kinase (PI3K)γ, the isoform linked to G protein-coupled receptor signaling, results in increased myocardial contractility, but the response to pressure overload is controversial.To characterize molecular and cellular responses of the PI3Kγ knockout (KO) mice to biomechanical stress.In response to pressure overload, PI3KγKO mice deteriorated at an accelerated rate compared with wild-type mice despite increased basal myocardial contractility. These functional responses were associated with compromised phosphorylation of Akt and GSK-3α. In contrast, isolated single cardiomyocytes from banded PI3KγKO mice maintained their hypercontractility, suggesting compromised interaction with the extracellular matrix as the primary defect in the banded PI3KγKO mice. β-Adrenergic stimulation increased cAMP levels with increased phosphorylation of CREB, leading to increased expression of cAMP-responsive matrix metalloproteinases (MMPs), MMP2, MT1-MMP, and MMP13 in cardiomyocytes and cardiofibroblasts. Loss of PI3Kγ resulted in increased cAMP levels with increased expression of MMP2, MT1-MMP, and MMP13 and increased MMP2 activation and collagenase activity in response to biomechanical stress. Selective loss of N-cadherin from the adhesion complexes in the PI3KγKO mice resulted in reduced cell adhesion. The β-blocker propranolol prevented the upregulation of MMPs, whereas MMP inhibition prevented the adverse remodeling with both therapies, preventing the functional deterioration in banded PI3KγKO mice. In banded wild-type mice, long-term propranolol prevented the adverse remodeling and systolic dysfunction with preservation of the N-cadherin levels.The enhanced propensity to develop heart failure in the PI3KγKO mice is attributable to a cAMP-dependent upregulation of MMP expression and activity and disorganization of the N-cadherin/β-catenin cell adhesion complex. β-Blocker therapy prevents these changes thereby providing a novel mechanism of action for these drugs.