tbuckley/cabot-search huggingface dataset:
Obesity and the lung: 2 {middle dot} Obesity and sleep-disordered breathing
Authors: F Crummy, A J Piper, M T Naughton
Journal: Thorax (2008)

<h3>Objective</h3> A nomogram for predicting the risk of mental health problems was established in a population of factory workers and miners, in order to quickly calculate the probability of a worker suffering from mental health problems. <h3>Methods</h3> A cross-sectional survey of 7500 factory workers and miners in Urumqi was conducted by means of an electronic questionnaire using cluster sampling method. Participants were randomly assigned to the training group (70%) and the validation group (30%). Questionnaire-based survey was conducted to collect information. A least absolute shrinkage and selection operator (LASSO) regression model was used to screen the predictors related to the risk of mental health problems of the training group. Multivariate logistic regression analysis was applied to construct the prediction model. Calibration plots and receiver operating characteristic-derived area under the curve (AUC) were used for model validation. Decision curve analysis was applied to calculate the net benefit of the screening model. <h3>Results</h3> A total of 7118 participants met the inclusion criteria and the data were randomly divided into a training group (n=4955) and a validation group (n=2163) in a ratio of 3:1. A total of 23 characteristics were included in this study and LASSO regression selected 12 characteristics such as education, professional title, age, Chinese Maslach Burnout Inventory, effort–reward imbalance, asbestos dust, hypertension, diabetes, working hours per day, working years, marital status and work schedule as predictors for the construction of the nomogram. In the validation group, the Brier score was 0.176, the calibration slope was 0.970 and the calibration curve of nomogram showed a good fit. The AUC of training group and verification group were 0.785 and 0.784, respectively. <h3>Conclusion</h3> The nomogram combining these 12 characteristics can be used to predict the risk of suffering mental health problems, providing a useful tool for quickly and accurately screening the risk of mental health problems.
Targeting Inflammation-Induced Obesity and Metabolic Diseases by Curcumin and Other Nutraceuticals
Authors: Bharat B. Aggarwal
Journal: Annual Review of Nutrition (2010)

Extensive research within the past two decades has revealed that obesity, a major risk factor for type 2 diabetes, atherosclerosis, cancer, and other chronic diseases, is a proinflammatory disease. Several spices have been shown to exhibit activity against obesity through antioxidant and anti-inflammatory mechanisms. Among them, curcumin, a yellow pigment derived from the spice turmeric (an essential component of curry powder), has been investigated most extensively as a treatment for obesity and obesity-related metabolic diseases. Curcumin directly interacts with adipocytes, pancreatic cells, hepatic stellate cells, macrophages, and muscle cells. There, it suppresses the proinflammatory transcription factors nuclear factor-kappa B, signal transducer and activators of transcription-3, and Wnt/beta-catenin, and it activates peroxisome proliferator-activated receptor-gamma and Nrf2 cell-signaling pathways, thus leading to the downregulation of adipokines, including tumor necrosis factor, interleukin-6, resistin, leptin, and monocyte chemotactic protein-1, and the upregulation of adiponectin and other gene products. These curcumin-induced alterations reverse insulin resistance, hyperglycemia, hyperlipidemia, and other symptoms linked to obesity. Other structurally homologous nutraceuticals, derived from red chili, cinnamon, cloves, black pepper, and ginger, also exhibit effects against obesity and insulin resistance.
Loss of selective endothelial cell vasoactive functions caused by hypercholesterolemia in pig coronary arteries.
Authors: R A Cohen, K M Zitnay, C C Haudenschild, L D Cunningham
Journal: Circulation Research (1988)

The influence of hypercholesterolemia on the reactivity of coronary arteries was investigated after feeding a high-cholesterol diet to pigs for 9 weeks. After this duration of hypercholesterolemia, the fatty or intimal proliferative changes of atherosclerosis were not yet evident in the coronary arteries by light or electron microscopy. Changes in isometric tension were compared in isolated ring segments of coronary arteries from normal and hypercholesterolemic animals. The endothelium failed to inhibit contractions caused by 5-hydroxytryptamine in coronary arteries from hypercholesterolemic animals, but it did so in normal vessels. In contracted arteries, endothelium-dependent relaxations caused by 5-hydroxytryptamine and substance P were reduced by hypercholesterolemia. In contrast, endothelium-dependent relaxations mediated by norepinephrine acting at alpha 2-adrenoceptors and those caused by the calcium ionophore A23187 were unaffected. Endothelium-independent beta-adrenergic relaxations caused by norepinephrine, as well as those caused by nitroprusside, and papaverine also were unaffected by hypercholesterolemia. The loss of selective endothelial cell receptor-mediated relaxation suggests that it is not the ability of the coronary artery endothelium to elaborate vasodilators, but the initiation of the coronary artery endothelial cell response to 5-hydroxytryptamine and substance P that is affected by hypercholesterolemia. Thus, during hypercholesterolemia, selective endothelial cell dysfunction giving rise to abnormal coronary artery reactivity precedes the onset of coronary artery atherosclerosis.
Subclinical atherosclerosis, airflow obstruction and emphysema: the MESA Lung Study
Authors: R.G. Barr, F.S. Ahmed, J.J. Carr, E.A. Hoffman, R. Jiang, S.M. Kawut, K. Watson
Journal: European Respiratory Journal (2011)

Airflow obstruction is an independent risk factor for cardiovascular events in the general population. The affected vascular bed and contribution of emphysema to cardiovascular risk are unclear. We examined whether an obstructive pattern of spirometry and quantitatively defined emphysema were associated with subclinical atherosclerosis in the carotid, peripheral and coronary circulations. The Multi-Ethnic Study of Atherosclerosis recruited participants aged 45–84 yrs without clinical cardiovascular disease. Spirometry, carotid intima-media thickness (IMT), ankle-brachial index (ABI) and coronary artery calcium (CAC) were measured using standard protocols. Percentage of emphysema-like lung was measured in the lung windows of cardiac computed tomography scans among 3,642 participants. Multiple linear regression was used to adjust for cardiac risk factors, including C-reactive protein. Decrements in forced expiratory volume in 1 s (FEV 1 ) and FEV 1 /forced vital capacity ratio were associated with greater internal carotid IMT, particularly among smokers (p=0.03 and p&lt;0.001, respectively) whereas percentage emphysema was associated with reduced ABI regardless of smoking history (p=0.004). CAC was associated with neither lung function (prevalence ratio for the presence of CAC in severe airflow obstruction 0.99, 95% CI 0.91–1.07) nor percentage emphysema. An obstructive pattern of spirometry and emphysema were associated distinctly and independently with subclinical atherosclerosis in the carotid arteries and peripheral circulation, respectively, and were not independently related to CAC.
Pyoderma gangrenosum: a report of 44 cases with follow-up
Authors: P. VON DEN DRIESCH
Journal: British Journal of Dermatology (1997)

Results of a study of 44 patients with pyoderma gangrenosum(PG) are presented. Each patient was diagnosed using standardized diagnostic criteria and followed up systematically. Thirty patients were women and 14 men. Their mean age was 50 years (range 11–80). Twenty patients had idiopathic and 14 parainflammatory occurrences (e.g. ulcerative colitis. Crohn's disease), whereas in 10 patients an associated haemoproliferative disease or neoplasia was noted. Whereas idiopathic and parainflammatory PG was found predominantly in women, the association with haemoproliferative diseases occurred more often in men. The lower legs and feet represented the typical predilection sites. Fifty-two per cent of patients had one lesion. 37% had up to five, and 11% had more than five lesions. Histologically, lymphocytic and/or leucocytoclastic vasculitis was present in 73% of the biopsy specimens obtained from the borders of the lesions. Long-term follow-up (n=42. median follow-up 26.5 months) revealed that eight patients had dies, in six cases due to the PG and/or the underlying diseases. Of the remaining 34 patients, 44% are in complete remission without further treatment, whereas continuing therapy is needed in 56%. No difference between idiopathic and parainflammatory PG was demonstrable in the follow-up and in no patient with idiopathic PG was a possibly related disease diagnosed in the follow-up. These data suggest that PG should be considered to be an independent disease and not a purely cutaneous complication in most patients.
Anti-CD4 abrogates rejection and reestablishes long-term tolerance to syngeneic newborn hearts grafted in mice chronically infected with Trypanosoma cruzi.
Authors: R R dos Santos, M A Rossi, J L Laus, J S Silva, W Savino, J Mengel
Journal: The Journal of Experimental Medicine (1992)

The contribution of autoimmunity in the genesis of chronic Chagas' heart pathology is not clear. In the present study, we show that: (a) BALB/c mice chronically infected with Trypanosoma cruzi reject syngeneic newborn hearts; (b) in vivo treatment with anti-CD4 but not anti-CD8 monoclonal antibodies (mAbs) abrogates rejection; (c) CD4+ T cells from chronically infected mice proliferate in vitro to syngeneic myocardium antigens and induce heart graft destruction when injected in situ; (d) anti-CD4 treatment of chronically infected mice establishes long-term tolerance to syngeneic heart grafts; and (e) the state of tolerance is related to in vitro and in vivo unresponsiveness of the CD4+ T cells. These findings allow us to suggest that autoimmunity is the major mechanism implicated in the rejection of syngeneic heart tissues grafted into the pinna of the ear of mice chronically infected with T. cruzi. The similarity of the lesions to those found in humans suggests that autoimmunity is involved in the pathogenesis of chagasic cardiomyopathy in humans. Moreover, this could imply therapeutic strategies by reestablishing long-term tissue-specific tolerance with anti-CD4 mAb treatment, mediating anergy, or deleting the responder CD4+ T cells to heart tissue antigens.
On a Case of Recovery from Organic Brain-Disease
Authors: J. H. Jackson
Journal: BMJ (1880)

THE case I have to bring before this society is one of great practical interest as regards both diagnosis and treatment.In one sense, it must be unsatisfactory, as there is no completion by necropsy.I do not ask anyone to believe that there is or has been local gross organic disease.We learn from the case, however, that a patient may recover from an exceedingly grave symptomatic condition which is often fatal, and such an one as usually does depend on local organic disease.Besides, although inconmplete in one way, the case is complete in another, in the very pleasant way of recovery-temporary recovery, at all'events.I speak of local gross organic disease.I add the adjective gross, as I do not believe that there is such a thing as a symptom inde- pendent of organic change, although of course I admit that the changes may be slight and recoverable, or that they may be undiscoverable post morent.I read a heading giving the most important symptoms of the case, mentioning some which may not be part of the ailment for which she was treated, and also certain symptoms conspicuous by their absence.The notes of the case were taken by Dr. J.
Effect of Cinnamon on Glucose Control and Lipid Parameters
Authors: William L. Baker, Gabriela Gutierrez-Williams, C. Michael White, Jeffrey Kluger, Craig I. Coleman
Journal: Diabetes Care (2007)

To perform a meta-analysis of randomized controlled trials of cinnamon to better characterize its impact on glucose and plasma lipids.A systematic literature search through July 2007 was conducted to identify randomized placebo-controlled trials of cinnamon that reported data on A1C, fasting blood glucose (FBG), or lipid parameters. The mean change in each study end point from baseline was treated as a continuous variable, and the weighted mean difference was calculated as the difference between the mean value in the treatment and control groups. A random-effects model was used.Five prospective randomized controlled trials (n = 282) were identified. Upon meta-analysis, the use of cinnamon did not significantly alter A1C, FBG, or lipid parameters. Subgroup and sensitivity analyses did not significantly change the results.Cinnamon does not appear to improve A1C, FBG, or lipid parameters in patients with type 1 or type 2 diabetes.
Reverse transcription in the eukaryotic genome: retroviruses, pararetroviruses, retrotransposons, and retrotranscripts.
Authors: H M Temin
Journal: Molecular Biology and Evolution (1985)

Recent studies indicate that greater than 10% of the human and mouse genome appears to consist of integrated DNA copies of RNA molecules. These sequences include retroviruses, retrovirus-like DNAs, retrotransposons, and retrotranscripts and represent more than 500,000 separate integration events. The nature of the enzymes used for the reverse transcription from RNA to DNA and for integration of the DNA copies into chromosomal DNA is unknown. A major evolutionary effect of these integrations would have been mutation. Thus, present-day organisms are those that survived this mutational load.
Critical care as part of respiratory medicine training in the UK
Authors: H Pattani, S Wharton, N Hart, A T Jones
Journal: Thorax (2006)

white pepper used in the factory, with stimulation indices of 311%, 244% and 2459%, respectively.The LST were negative for curry powder and ground pepper used in another curry sauce factory.LST using blood samples from three healthy volunteers and the three substrates were negative.We therefore concluded that the patient's lung disease was associated with the spices used in his factory and we advised him not to return to work.Prednisolone and azathioprine were administered but both drugs were discontinued owing to the occurrence of bilateral pneumothoraces which were surgically treated.Although the consolidations on the HRCT scan did not recur after his isolation from the factory, the subpleural cystic lesions-thought to be caused by a check valve mechanism with bronchiolar constriction-increased in size and number and post-inflammatory pleural thickening progressed (fig 1B).Fourteen months after onset of the disease the patient died from ventilatory insufficiency with hypercapnia.Although fungi or bacilli in the spices may have induced the lung disease 4 and further investigation is needed to determine the exact elements responsible, we wish to draw attention to the possibility of this type of lung disease.Progressive pulmonary cysts and respiratory failure may happen even after avoidance of pathogenic antigens, as found in pigeon breeder's lung, 5 and early diagnosis is necessary to improve its prognosis.
Novel mechanisms of protection against acetaminophen hepatotoxicity in mice by glutathione and N-acetylcysteine
Authors: Chieko Saito, Claudia Zwingmann, Hartmut Jaeschke
Journal: Hepatology (2009)

Acetaminophen (APAP) overdose is a major cause of acute liver failure. The glutathione (GSH) precursor N-acetylcysteine (NAC) is used to treat patients with APAP overdose for up to 48 hours. Although it is well established that early treatment with NAC can improve the scavenging of the reactive metabolite N-acetyl-p-benzoquinone imine, protective mechanisms at later times remain unclear. To address this issue, fasted C3Heb/FeJ mice were treated with 300 mg/kg APAP and then received intravenously 0.65 mmol/kg GSH or NAC at 1.5 hours after APAP. The animals were sacrificed at 6 hours. APAP alone caused severe liver injury with peroxynitrite formation and DNA fragmentation, all of which was attenuated by both treatments. However, GSH (−82%) was more effective than NAC (−46%) in preventing liver injury. Using nuclear magnetic resonance spectroscopy to measure tissue adenosine triphosphate (ATP) levels and the substrate flux through the mitochondrial Krebs cycle, it was observed that the reduced liver injury correlated with accelerated recovery of mitochondrial GSH content, maintenance of ATP levels, and an increased substrate supply for the mitochondrial Krebs cycle compared with APAP alone. NAC treatment was less effective in recovering ATP and mitochondrial GSH levels and showed reduced substrate flux through the Krebs cycle compared with GSH. However, increasing the dose of NAC improved the protective effect similar to GSH, suggesting that the amino acids not used for GSH synthesis were used as mitochondrial energy substrates. Conclusion: Delayed treatment with GSH and NAC protect against APAP overdose by dual mechanisms—that is, by enhancing hepatic and mitochondrial GSH levels (scavenging of reactive oxygen and peroxynitrite)—and by supporting the mitochondrial energy metabolism. (HEPATOLOGY 2009.)
Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation
Authors: Cristiana Guiducci, Gary Ott, Jean H. Chan, Emily Damon, Carlo Calacsan, Tracy Matray, Kyung-Dall Lee, Robert L. Coffman, Franck J. Barrat
Journal: The Journal of Experimental Medicine (2006)

Human plasmacytoid dendritic cells (PDCs) can produce interferon (IFN)-alpha and/or mature and participate in the adaptive immune response. Three classes of CpG oligonucleotide ligands for Toll-like receptor (TLR)9 can be distinguished by different sequence motifs and different abilities to stimulate IFN-alpha production and maturation of PDCs. We show that the nature of the PDC response is determined by the higher order structure and endosomal location of the CpG oligonucleotide. Activation of TLR9 by the multimeric CpG-A occurs in transferrin receptor (TfR)-positive endosomes and leads exclusively to IFN-alpha production, whereas monomeric CpG-B oligonucleotides localize to lysosome-associated membrane protein (LAMP)-1-positive endosomes and promote maturation of PDCs. However, CpG-B, when complexed into microparticles, localizes in TfR-positive endosomes and induces IFN-alpha from PDCs, whereas monomeric forms of CpG-A localize to LAMP-1-positive endosomes accompanied by the loss of IFN-alpha production and a gain in PDC maturation activity. CpG-C sequences, which induce both IFN-alpha and maturation of PDCs, are distributed in both type of endosomes. Encapsulation of CpG-C in liposomes stable above pH 5.75 completely abrogated the IFN-alpha response while increasing PDC maturation. This establishes that the primary determinant of TLR9 signaling is not valency but endosomal location and demonstrates a strict compartmentalization of the biological response to TLR9 activation in PDCs.
DNA Flow Cytometry in Early Breast Cancer: A Step in the Right Direction
Authors: C. K. Osborne
Journal: JNCI Journal of the National Cancer Institute (1989)

Dramatic changes occurred in the management of patients with primary breast cancer (stages I-DIa) after physicians recognized that many such patients already had established, clinically occult micrometastases by the time of initial diagnosis. Trials of adjuvant, systemic, cytotoxic chemotherapy or endocrine therapy were initiated by investigators in an attempt to eradicate these micrometastases and improve survival. Long-term results of many of these trials are now available, and they conclusively demonstrate a moderate therapeutic advantage for the addition of systemic therapy compared with that for local therapy alone (7). In patients with positive axillary lymph nodes, who have a relatively high rate of relapse, approximately one-third of the early deaths in premenopausal patients can be avoided or delayed by optimal combination chemotherapy. Similarly, about one-fifth of early deaths of postmenopausal patients are avoided or delayed by the administration of tamoxifen. Although follow-up time is much shorter, a similar pattern of results is now emerging from studies in patients with negative axillary lymph nodes (2-5).
A hereditary spastic paraplegia mutation in kinesin-1A/KIF5A disrupts neurofilament transport
Authors: Lina Wang, Anthony Brown
Journal: Molecular Neurodegeneration (2010)

Hereditary spastic paraplegias are a group of neurological disorders characterized by progressive distal degeneration of the longest ascending and descending axons in the spinal cord, leading to lower limb spasticity and weakness. One of the dominantly inherited forms of this disease (spastic gait type 10, or SPG10) is caused by point mutations in kinesin-1A (also known as KIF5A), which is thought to be an anterograde motor for neurofilaments. We investigated the effect of an SPG10 mutation in kinesin-1A (N256S-kinesin-1A) on neurofilament transport in cultured mouse cortical neurons using live-cell fluorescent imaging. N256S-kinesin-1A decreased both anterograde and retrograde neurofilament transport flux by decreasing the frequency of anterograde and retrograde movements. Anterograde velocity was not affected, whereas retrograde velocity actually increased. These data reveal subtle complexities to the functional interdependence of the anterograde and retrograde neurofilament motors and they also raise the possibility that anterograde and retrograde neurofilament transport may be disrupted in patients with SPG10.
Instructive Nanofiber Scaffolds with VEGF Create a Microenvironment for Arteriogenesis and Cardiac Repair
Authors: Yi-Dong Lin, Chwan-Yau Luo, Yu-Ning Hu, Ming-Long Yeh, Ying-Chang Hsueh, Min-Yao Chang, Da-Ching Tsai, Jieh-Neng Wang, Ming-Jer Tang, Erika I. H. Wei, Matthew L. Springer, Patrick C. H. Hsieh
Journal: Science Translational Medicine (2012)

An intramyocardial microenvironment was created using nanofibers and VEGF for endogenous cardiac repair after infarction.