tbuckley/cabot-search huggingface dataset:
Burnout in psychiatrists, general practitioners and surgeons
Authors: BOJANA PEJUSKOVIC, DUSICA LECIC-TOSEVSKI, STEFAN PRIEBE
Journal: World Psychiatry (2011)

Burnout is a serious consequence of chronic exposure to work-related stressors. Three key dimensions of this response are emotional exhaustion, feelings of cynicism and detachment, as well as a sense of lack of personal accomplishment and ineffectiveness. According to research reports, 40–60% of general practitioners 1 and 46–93% of emergency physicians suffer from burnout 2. It has been suggested that some health workers are more prone to the burnout syndrome than others. In particular, it has been reported that psychiatrists may be more vulnerable to experiencing burnout than other physicians and surgeons 3. We compared the level of burnout among 160 physicians (70 general practitioners working in public health centers, and 50 psychiatrists and 40 surgeons employed at university clinics). The assessment was carried out by the Maslach Burnout Inventory. The total burnout score was moderate in all three examined groups. However, there were significant differences between the groups in the dimensions of burnout. General practitioners had a higher score for emotional exhaustion than the other two groups (F=5.546, df=156, pmeno0.01). Surgeons had the highest depersonalization (F=15.314, df=156, pmeno0.01) and the lowest personal accomplishment score (F=16.079, df=156, pmeno0.01). Psychiatrists had the lowest and surgeons the highest total burnout score. Physicians with greater daily number of patients were more prone to emotional exhaustion but had higher sense of personal accomplishment. Older physicians with more years of practice and greater daily numbers of patients were less prone to depersonalization. There was no statistically significant gender difference on the total burnout score, but emotional exhaustion was higher in women (t=-3.460, pmeno;0.01) and lack of personal accomplishment in men (t=-2.132, pmeno0.05). These findings, which in general are in line with previous reports concerning correlates of burnout in the medical profession, do not confirm that psychiatrists are at higher risk for burnout than other physicians. Although the sample size was small and the design cross-sectional, this study may be of interest, because the perception that psychiatry is a particularly distressing medical specialty may contribute to the current decline in recruitment of young doctors into the profession 4,5,6,7. It has been brought to our attention that in Table 4 of the paper “Metabolic syndrome in people with schizophrenia: a review”, by de Hert et al, published in the February 2009 issue of World Psychiatry, there was a factual error: in the study by Saddichha et al, listed in the table, the number of patients was 99 instead of 433, and the prevalence of metabolic syndrome was 18.2% instead of 34.0%.
A Review of the Treatment of Cardiospasm
Authors: K. Lawrance, J. H. Shoesmith
Journal: Thorax (1959)

In 1948 Wooler reported the results of treatment in 47 patients with cardiospasm; he concluded that the treatment of choice was with the Negus hydrostatic dilator and, if this failed, Heller's operation. In 1950 Allison brought the total to 76 patients and recommended using the Negus dilator in all but three groups of patients, namely, (1) small children, (2) those not cured by the Negus dilator, and (3) those in whom the oesophagus had become so dilated and tortuous that the cardia could not be reached through the oesophagus. It is our intention to extend these reports and describe the results in 137 patients with cardiospasm who have been treated at Leeds. Many different procedures have from time to time been advocated in the treatment of cardiospasm. Most of these were recently reviewed by Acheson and Hadley (1958), who found that the only procedures to have withstood the test of time were dilatation of the cardia through the oesophagoscope, usually with a Negus dilator, and cardiomyotomy, first described by Heller (1914). However, no definite conclusions appear to have been reached as to which of these two procedures is the more desirable, and, in fact, there has been a reluctance to use Heller's operation. Olsen, Harrington, Moersch, and Andersen (1951) reported 601 cases treated by the Negus dilator, but in 1958 Ellis, Olsen, Holman, and Code rather cautiously reported their results in 55 patients treated by Heller's operation; a similar cautious attitude can be detected in the report of 22 cases by Hawthorne and Nemir (1953) and that of Acheson and Hadley (1958) in 35 patients. By reviewing both the results of treatment and the trend of treatment in this series, it is intended to demonstrate a choice between the two procedures and dispel some of the doubts about Heller's operation. MATERIAL.-One hundred and fifty-nine patients are listed in the records with a diagnosis of cardiospasm, and 22 of these were rejected because of doubt about the diagnosis or incomplete documentation, leaving a total of 137. These patients were seen between 1939 and August, 1956; 74 were women and 63 were men. The age distribution (as recorded when the patient was first seen) is shown in Fig. 1. The high incidence in the fifth and sixth decades was noted by Allison and is an expression of the time that many patients are prepared to tolerate symptoms.
Do We Still Need Pioglitazone for the Treatment of Type 2 Diabetes? A risk-benefit critique in 2013
Authors: Guntram Schernthaner, Craig J. Currie, Gerit-Holger Schernthaner
Journal: Diabetes Care (2013)

Type 2 diabetes mellitus (T2DM) is a serious, chronic, and progressive disease that is rapidly increasing in prevalence. The disease now affects >10% of adults in some developed countries, increasing most in Asia. People with T2DM are two to four times more likely to develop a serious cardiovascular (CV) outcome compared with those without diabetes. The majority of patients with T2DM are insulin resistant and have associated metabolic abnormalities that are themselves significant CV risk factors. It is believed that most of this increased risk is caused by lipid abnormalities, hypertension, chronic vascular inflammation, and a proatherothrombotic state. The glycemia-related contribution is evidently lower: a long-term observational study over 18 years from Finland showed that an increase of 1% in HbA1c increased the risk of CV disease (CVD) mortality by 53% in type 1 diabetic patients but by only 7.5% in T2DM patients (1). Based on these observational data, it would be expected that a lowering of HbA1c of 1–2% would not dramatically change the absolute risk for death in people with T2DM.

### Effects of pioglitazone on CV risk factors and biomarkers

Pioglitazone is known to improve insulin sensitivity, glycemic control, dyslipidemia, hypertension, and microalbuminuria in patients with T2DM. Pioglitazone decreases fasting and postprandial plasma glucose levels by improving the sensitivity of hepatic and peripheral (muscle) tissue to insulin. A large randomized controlled trial (RCT) showed that both pioglitazone and metformin reduced HbA1c by 1.5% from baseline (2). In contrast to the more commonly prescribed sulfonylureas, pioglitazone showed a significantly better durability of diabetes control in patients with T2DM (3). Similarly, pioglitazone was superior to the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin in reducing HbA1c levels in drug-naive patients (4). Pioglitazone also provides effective (lowering HbA1c by 0.5–1.5%) and durable glycemic control in combination with other oral antidiabetes drugs as well in combination with insulin …
Paclitaxel (Taxol®): A success story with valuable lessons for natural product drug discovery and development
Authors: Gordon M. Cragg
Journal: Medicinal Research Reviews (1998)

The discovery and development of paclitaxel, which covered a time span of some 30 years, has provided some important lessons for those involved in natural product drug discovery and development. These include the adoption of novel screens as they become available, the elucidation of mechanisms of action, and addressing the supply issue at an early stage of development. These issues, as applied to paclitaxel, are illustrated. The development of the NCI human cancer cell line screen, and its application to mechanistic studies through use of COMPARE analyses, are discussed, as is the production of the marine-derived anticancer agent, bryostatin 1, which provides another illustration of a successful approach to solving a supply issue. The history of the development of paclitaxel also illustrates the importance of multidisciplinary collaboration, and the various mechanisms used by the NCI Developmental Therapeutics Program for promoting such collaboration are presented. © 1998 John Wiley & Sons, Inc. Med Res Rev, 18, No. 5, 315–331, 1998.
Cardioprotection by the TSPO ligand 4′-chlorodiazepam is associated with inhibition of mitochondrial accumulation of cholesterol at reperfusion
Authors: Stéphanie Paradis, Valerio Leoni, Claudio Caccia, Alain Berdeaux, Didier Morin
Journal: Cardiovascular Research (2013)

AimsThe translocator protein (TSPO) is located on the outer mitochondrial membrane where it is responsible for the uptake of cholesterol into mitochondria of steroidogenic organs. TSPO is also present in the heart where its role remains uncertain. We recently showed that TSPO ligands reduced infarct size and improved mitochondrial functions after ischaemia–reperfusion. This study, thus, sought to determine whether cholesterol could play a role in the cardioprotective effect of TSPO ligands.
Predicting genes for orphan metabolic activities using phylogenetic profiles.
Authors: Lifeng Chen, Dennis Vitkup
Journal: Genome biology (2006)

Abstract Homology-based methods fail to assign genes to many metabolic activities present in sequenced organisms. To suggest genes for these orphan activities we developed a novel method that efficiently combines local structure of a metabolic network with phylogenetic profiles. We validated our method using known metabolic genes in Saccharomyces cerevisiae and Escherichia coli . We show that our method should be easily transferable to other organisms, and that it is robust to errors in incomplete metabolic networks.
CpG Immunostimulatory Oligodeoxynucleotide 1826 Enhances Antitumor Effect of Interleukin 12 Gene-Modified Tumor Vaccine in a Melanoma Model in Mice
Authors: Tomasz Switaj, Ahmad Jalili, Anna B. Jakubowska, Nadzieja Drela, Magdalena Stoksik, Dominika Nowis, Grzegorz Basak, Jakub Golab, Piotr J. Wysocki, Andrzej Mackiewicz, Agata Sasor, Koryna Socha, Marek Jakóbisiak, Witold Lasek
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The effectiveness of interleukin (IL)-12-secreting tumor vaccines in the treatment of mouse tumors could be enhanced by concurrent application of cytokines and costimulatory molecules. We investigated the therapeutic potential of IL-12 gene-transduced melanoma vaccine in combination with CpG immunostimulatory oligodeoxynucleotide (ODN) 1826, an adjuvant known to favor development of Th1-biased immune response, in a B78-H1 (B78) melanoma model in mice. Experimental Design: Mice injected with B78 melanoma cells were treated with irradiated IL-12 gene-transduced B78 cells [B78/IL-12(X)] and/or ODN 1826. Mechanisms responsible for the antitumor effects of the treatment were investigated using fluorescence-activated cell sorter analysis, a standard 51Cr releasing assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and ELISA. Results: Single injection of B78/IL-12(X) cells had no effect on tumor growth, whereas seven consecutive daily injections of ODN 1826 markedly inhibited tumor progression with occasional curative effects. When used in combination, B78/IL-12(X) cells and ODN 1826 caused additional tumor growth reduction and eradication of tumors in 62% of treated mice. The combined treatment activated local inflammatory response against tumor but also induced systemic antitumor immunity. In vitro studies have shown that when used together, B78/IL-12(X) cells and ODN 1826 induced a potent Th1 response and suggested the role of IFN-γ in activation of the host immune response. The antitumor effects in double-treated mice were accompanied by the development of cytotoxic effectors in the spleen and activation of macrophages. Conclusions: The results provided the evidence that the combination of IL-12 gene-modified melanoma vaccine and ODN 1826 induces synergistically systemic and local antitumor immunity.
Multilevel Analysis in Public Health Research
Authors: Ana V. Diez-Roux
Journal: Annual Review of Public Health (2000)

▪ Abstract Over the past few years there has been growing interest in considering factors defined at multiple levels in public health research. Multilevel analysis has emerged as one analytical strategy that may partly address this need, by allowing the simultaneous examination of group-level and individual-level factors. This paper reviews the rationale for using multilevel analysis in public health research, summarizes the statistical methodology, and highlights some of the research questions that have been addressed using these methods. The advantages and disadvantages of multi level analysis compared with standard methods are reviewed. The use of multilevel analysis raises theoretical and methodological issues related to the theoretical model being tested, the conceptual distinction between group and individual-level variables, the ability to differentiate “independent” effects, the reciprocal relationships between factors at different levels, and the increased complexity that these models imply. The potentialities and limitations of multilevel analysis, within the broader context of understanding the role of factors defined at multiple levels in shaping health outcomes, are discussed.
A Subtype of Markedly Abrupt Onset With Absolute Insulin Deficiency in Idiopathic Type 1 Diabetes in Japanese Children
Authors: Tatsuhiko Urakami, Makio Nakagawa, Shigeo Morimoto, Shigeki Kubota, Misao Owada, Kensuke Harada
Journal: Diabetes Care (2002)

Idiopathic type 1 diabetes, by definition, has no known etiology. Although only a minority of type 1 diabetic patients fall into this category, it is reported that the majority are of African or Asian descent. Individuals with this form of diabetes are considered to present heterogeneous clinical manifestations (1). Imagawa et al. (2) reported a new subtype of type 1 diabetes characterized by fulminant onset, absolute insulin deficiency, and absence of β-cell autoimmunity in Japanese adults. We reported similar cases of idiopathic …
Glomerulosclerosis and Tubulointerstitial Fibrosis are Attenuated with 17β-Estradiol in the Aging Dahl Salt Sensitive Rat
Authors: Christine Maric, Kathryn Sandberg, Carmen Hinojosa-Laborde
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. This study examined the effects of estrogen deficiency by ovariectomy (OVX) and 17β-estradiol (E<sub>2</sub>) replacement (OVX+E<sub>2</sub>) on glomerulosclerosis and tubulointerstitial fibrosis and the mechanisms contributing to these changes, including expression of collagen type IV and laminin, transforming growth factor-β (TGF-β), and activity of matrix metalloproteinases (MMP) in the kidneys of young (4 mo [4M]) and aged (12 mo [12M]) Dahl salt-sensitive (DSS) rats maintained on a low-salt (0.1% NaCl) diet. While normal renal morphology was observed in the 4M rats in all treatment groups, moderate to severe glomerulosclerosis (glomerulosclerotic index [GSI]: 4M, 0.22 ± 0.09 <i>versus</i> 12M, 1.43 ± 0.17; <i>P</i> &lt; 0.001) and cortical tubulointerstitial fibrosis (CTIFI: 4M, 0 <i>versus</i> 12M, 57.1 ± 4.9; <i>P</i> &lt; 0.01) was observed in the 12M rats. The severity of glomerulosclerosis and cortical tubulointerstitial fibrosis in the 12M group was augmented with OVX (GSI, 3.27 ± 0.34; CTIFI, 74.4 ± 9.2; <i>P</i> &lt; 0.01 <i>versus</i> Intact at 12M) and attenuated with E<sub>2</sub> replacement ([GSI], 1.09 ± 0.09; CTIFI, 49.2 ± 6.8). In the 12M animals, OVX was also associated with increased deposition and expression of laminin (Intact, 228.1 ± 6.7; OVX, 277.4 ± 9.6 AU; <i>P</i> &lt; 0.01), increased expression of TGF-β (Intact, 85.0 ± 23.0; OVX, 178.0 ± 20.5 AU; <i>P</i> &lt; 0.001), and decreased activity of cortical MMP-9 (Intact, 3.8 ± 0.8; OVX, 2.4 ± 0.6 AUC; <i>P</i> &lt; 0.01). E<sub>2</sub> replacement opposed these effects (laminin, 229.9 ± 6.2 AU; TGF-β, 101.3 ± 25.2 AU; MMP-9, 5.2 ± 0.2 AUC). The severity of the disease in the 12M rats correlated with a modest decrease in creatinine clearance (Intact, 0.26 ± 0.01; OVX, 0.22 ± 0.01; OVX+E<sub>2</sub>, 0.28 ± 0.01 mg/min per 100 g) and increase in BUN (Intact, 20.3 ± 2.1; OVX, 32.6 ± 5.1; OVX+E<sub>2</sub>, 24.3 ± 2.4 mg/dl). The authors conclude that E<sub>2</sub> is renoprotective in the aging DSS rat by attenuating glomerulosclerosis and tubulointerstitial fibrosis.
Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial
Authors: P J K Pearson
Journal: Thorax (2004)

<b>Background:</b> Increased dietary vitamin E intake is associated with a reduced incidence of asthma, and combinations of antioxidant supplements including vitamin E are effective in reducing ozone induced bronchoconstriction. A study was undertaken to investigate the effect of supplementation with vitamin E for 6 weeks on bronchial hyperresponsiveness in atopic adults with asthma. <b>Methods:</b> 72 participants from a clinical trial register of adults with asthma were randomised to receive 500 mg natural vitamin E or matched placebo for 6 weeks in a placebo controlled, double blind parallel group clinical trial. Inclusion criteria included age 18–60 years, maintenance treatment of at least one dose of inhaled corticosteroid per day, a positive skin prick test to one of three common allergens, and bronchial hyperresponsiveness to methacholine (defined as a dose provoking a 20% fall in forced expiratory volume in 1 second (FEV<sub>1</sub>) (PD<sub>20</sub>) of 12.25 μmol). Secondary outcomes were FEV<sub>1</sub>, forced vital capacity, mean morning and evening peak flow, symptom scores, bronchodilator use, and serum immunoglobulin E levels. <b>Results:</b> In the primary intention to treat analysis the change in PD<sub>20</sub> was similar in the vitamin E and placebo groups with a mean difference of +0.25 doubling doses of methacholine (95% confidence interval −0.67 to +1.16 greater with vitamin E). There was no effect of vitamin E supplementation on any other measure of asthma control, either in the intention to treat or per protocol analysis. There was also no effect of vitamin E supplementation on serum immunoglobulin levels. <b>Conclusion:</b> Dietary supplementation with vitamin E adds no benefit to current standard treatment in adults with mild to moderate asthma.
A novel MyD-1 (SIRP-1α) signaling pathway that inhibits LPS-induced TNFα production by monocytes
Authors: Rosemary E. Smith, Vanshree Patel, Sandra D. Seatter, Maureen R. Deehan, Marion H. Brown, Gareth P. Brooke, Helen S. Goodridge, Christopher J. Howard, Kevin P. Rigley, William Harnett, Margaret M. Harnett
Journal: Blood (2003)
Excessive formation of hydroxyl radicals and aldehydic lipid peroxidation products in cultured skin fibroblasts from patients with complex I deficiency.
Authors: X Luo, S Pitkänen, S Kassovska-Bratinova, B H Robinson, D C Lehotay
Journal: Journal of Clinical Investigation (1997)

Previous studies suggest oxygen free radicals' involvement in the etiology of cardiomyopathy with cataracts. To investigate the role of free radicals in the pathogenesis of the cardiomyopathy with cataracts and complex I deficiency, fibroblasts from patients were assessed for hydroxyl radical formation and aldehydic lipid peroxidation products with and without redox active agents that increase free radicals. The rate of hydroxyl radical formation in patient cells was increased over 2-10-fold under basal conditions, and up to 20-fold after menadione or doxorubicin treatment compared with normal cells. We also found an overproduction of aldehydes in patient cells both under basal conditions and after treatment. Both hydroxyl radicals and toxic aldehydes such as hexanal, 4-hydroxynon-2-enal, and malondialdehyde were elevated in cells from patients with three types of complex I deficiency. In contrast, acyloins, the less toxic conjugated products of pyruvate and saturated aldehydes, were lower in the patient cells. Our data provide direct evidence for the first time that complex I deficiency is associated with excessive production of hydroxyl radicals and lipid peroxidation. The resultant damage may contribute to the early onset of cardiomyopathy and cataracts and death in early infancy in affected patients with this disease.
Pseudogenization of the Umami Taste Receptor Gene Tas1r1 in the Giant Panda Coincided with its Dietary Switch to Bamboo
Authors: H. Zhao, J.-R. Yang, H. Xu, J. Zhang
Journal: Molecular Biology and Evolution (2010)

Although it belongs to the order Carnivora, the giant panda is a vegetarian with 99% of its diet being bamboo. The draft genome sequence of the giant panda shows that its umami taste receptor gene Tas1r1 is a pseudogene, prompting the proposal that the loss of the umami perception explains why the giant panda is herbivorous. To test this hypothesis, we sequenced all six exons of Tas1r1 in another individual of the giant panda and five other carnivores. We found that the open reading frame (ORF) of Tas1r1 is intact in all these carnivores except the giant panda. The rate ratio (ω) of nonsynonymous to synonymous substitutions in Tas1r1 is significantly higher for the giant panda lineage than for other carnivore lineages. Based on the ω change and the observed number of ORF-disrupting substitutions, we estimated that the functional constraint on the giant panda Tas1r1 was relaxed ∼ 4.2 Ma, with its 95% confidence interval between 1.3 and 10 Ma. Our estimate matches the approximate date of the giant panda's dietary switch inferred from fossil records. It is probable that the giant panda's decreased reliance on meat resulted in the dispensability of the umami taste, leading to Tas1r1 pseudogenization, which in turn reinforced its herbivorous life style because of the diminished attraction of returning to meat eating in the absence of Tas1r1. Nonetheless, additional factors are likely involved because herbivores such as cow and horse still retain an intact Tas1r1.
QUANTITATIVE STUDIES ON TUMOR ENHANCEMENT IN MICE
Authors: Pablo Rubinstein, Francine Decary, Edwin W. Streun
Journal: The Journal of Experimental Medicine (1974)

The concentration of specific alloantibody in purified mouse immunoglobulin preparations was determined. When passively transferred in adequate doses, IgM, IgG1, and IgG2 antibodies all induced tumor enhancement in allogeneic hosts. IgM and IgG2 antibodies in high concentration led to inhibition of tumor growth. IgM and either IgG1 or IgG2 had additive effects on tumor enhancement. IgG1, but not IgG2, suppressed the inhibitory effect of IgM in high concentration.