tbuckley/cabot-search huggingface dataset:
The Effects of n-3 Long-Chain Polyunsaturated Fatty Acid Supplementation on Biomarkers of Kidney Injury in Adults With Diabetes
Authors: Edgar R. Miller, Stephen P. Juraschek, Cheryl A. Anderson, Eliseo Guallar, Karen Henoch-Ryugo, Jeanne Charleston, Sharon Turban, Michael R. Bennett, Lawrence J. Appel
Journal: Diabetes Care (2012)

OBJECTIVE Long-chain n-3 polyunsaturated fatty acid (n-3 PUFA) supplements may have renoprotective effects in patients with diabetes, but previous trials have been inconsistent. We performed a randomized controlled trial of n-3 PUFA supplementation on urine albumin excretion and markers of kidney injury in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted a randomized, placebo-controlled, two-period crossover trial to test the effects of 4 g/day of n-3 PUFA supplementation on markers of glomerular filtration and kidney injury in adults with adult-onset diabetes and greater than or equal to trace amounts of proteinuria. Each period lasted 6 weeks and was separated by a 2-week washout. The main outcome was urine albumin excretion and, secondarily, markers of kidney injury (kidney injury molecule-1, N-acetyl β-d-glucosaminidase [NAG], neutrophil gelatinase-associated lipocalin [NGAL], and liver fatty acid–binding protein [LFABP]), serum markers of kidney function (cystatin C, β2-microglobulin, and creatinine), and estimated glomerular filtration rate (eGFR). RESULTS Of the 31 participants, 29 finished both periods. A total of 55% were male, and 61% were African American; mean age was 67 years. At baseline, mean BMI was 31.6 kg/m2, median eGFR was 76.9 mL/min/1.73 m2, and median 24-h urine albumin excretion was 161 mg/day. Compared with placebo, n-3 PUFA had nonsignificant effects on urine albumin excretion (−7.2%; 95% CI −20.6 to 8.5; P = 0.35) and significant effects on urine NGAL excretion (−16% [−29.1 to −0.5%]; P = 0.04). There was no effect on serum markers of kidney function or eGFR. In subgroup analyses, there were significant decreases in 24-h urinary excretion of albumin, NGAL, LFABP, and NAG among participants taking medications that block the renin-angiotensin-aldosterone system (RAAS). CONCLUSIONS These results suggest a potential effect of n-3 PUFA supplementation on markers of kidney injury in patients with diabetes and early evidence of kidney disease. In the context of prior studies, these results provide a strong rationale for long-term trials of n-3 PUFA on chronic kidney disease progression.
Biology and Clinical Relevance of the Micropthalmia Family of Transcription Factors in Human Cancer
Authors: Rizwan Haq, David E. Fisher
Journal: Journal of Clinical Oncology (2011)

Members of the micropthalmia (MiT) family of transcription factors (MITF, TFE3, TFEB, and TFEC) are physiologic regulators of cell growth, differentiation, and survival in several tissue types. Because their dysregulation can lead to melanoma, renal cell carcinoma, and some sarcomas, understanding why these genes are co-opted in carcinogenesis may be of general utility. Here we describe the structure of the MiT family of proteins, the ways in which they are aberrantly activated, and the molecular mechanisms by which they promote oncogenesis. We discuss how meaningful understanding of these mechanisms can be used to elucidate the oncogenic process. Because the expression of these proteins is essential for initiating and maintaining the oncogenic state in some cancer types, we propose ways that they can be exploited to prevent, diagnose, and rationally treat these malignancies.
Natural capsaicinoids improve swallow response in older patients with oropharyngeal dysphagia
Authors: Laia Rofes, Viridiana Arreola, Alberto Martin, Pere Clavé
Journal: Gut (2012)

<h3>Objective</h3> There is no pharmacological treatment for oropharyngeal dysphagia (OD). The aim of this study was to compare the therapeutic effect of stimulation of oropharyngeal transient receptor potential vanilloid type 1 (TRPV1) with that of thickeners in older patients with OD. <h3>Design</h3> A clinical videofluoroscopic non-randomised study was performed to assess the signs of safety and efficacy of swallow and the swallow response in (1) 33 patients with OD (75.94±1.88 years) while swallowing 5, 10 and 20 ml of liquid (20.4 mPa.s), nectar (274.4 mPa.s), and pudding (3930 mPa.s) boluses; (2) 33 patients with OD (73.94±2.23 years) while swallowing 5, 10 and 20 ml nectar boluses, and two series of nectar boluses with 150 μM capsaicinoids and (3) 8 older controls (76.88±1.51 years) while swallowing 5, 10 and 20 ml nectar boluses. <h3>Results</h3> Increasing bolus viscosity reduced the prevalence of laryngeal penetrations by 72.03% (p<i>&lt;</i>0.05), increased pharyngeal residue by 41.37% (p<i>&lt;</i>0.05), delayed the upper esophageal sphincter opening time and the larynx movement and did not affect the laryngeal vestibule closure time and maximal hyoid displacement. Treatment with capsaicinoids reduced both, penetrations by 50.% (p<i>&lt;</i>0.05) and pharyngeal residue by 50.% (p<i>&lt;</i>0.05), and shortened the time of laryngeal vestibule closure (p<i>&lt;</i>0.001), upper esophageal sphincter opening (p<i>&lt;</i>0.05) and maximal hyoid and laryngeal displacement. <h3>Conclusion</h3> Stimulation of TRPV1 by capsaicinoids strongly improved safety and efficacy of swallow and shortened the swallow response in older patients with OD. Stimulation of TRPV1 might become a pharmacologic strategy to treat OD.
Onions and blood fibrinolysis.
Authors: I S Menon
Journal: BMJ (1970)

hysteria or to altered xnedical perception in the community.Their erroneous conclusions about this illness may impair future inves- tigations of similar outbreaks.It is apparent that the authors failed to do their homework, and demonstrated a surprising lack of information about the principles of epidemiology and of psychia- try.Had they reviewed the literature on the
Balance in psychological research: The dual process perspective
Authors: Keith E. Stanovich
Journal: Behavioral and Brain Sciences (2004)

Krueger &amp; Funder (K&amp;F) are right that various imbalances characterize social psychology, but I question whether they are characteristic of psychology or cognitive science as a whole. Dual-process theories, popular in the latter fields, emphasize both processing biases and the adaptiveness of human cognition in a more balanced manner.
Serum Insulin-Like Growth Factor-1 Levels Predict Outcomes of Patients with Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy
Authors: Yu-Yun Shao, Chien-Chung Huang, Shiou-Der Lin, Chih-Hung Hsu, Ann-Lii Cheng
Journal: Clinical Cancer Research (2012)

Patients with liver cirrhosis or hepatocellular carcinoma (HCC) have decreased serum insulin-like growth factor (IGF)-1 levels. We evaluated whether IGF-1 levels were associated with the outcomes of patients with advanced HCC treated with systemic antiangiogenic therapy.The study was based on patients with advanced HCC who were enrolled in two clinical trials evaluating first-line combination antiangiogenic therapy. Serum samples were collected before treatment and four to six weeks after the start of treatment. The levels of IGF-1, IGF-2, and IGF-binding protein-3 (IGFBP3) were analyzed for their associations with treatment outcomes.A total of 83 patients were included in the study. Patients who had high (≥the median level) baseline IGF-1 levels had significantly higher disease control rate (DCR) than patients who had low (<the median level) levels (71% vs. 39%, P = 0.003). The levels of posttreatment IGF-1, and pre- or posttreatment IGF-2 and IGFBP3 were not associated with DCR. Patients with high baseline IGF-1 levels, compared with patients with low levels, had significantly longer progression-free survival (PFS; median, 4.3 vs. 1.9 months, P = 0.014) and overall survival (OS; median, 10.7 vs. 3.9 months, P = 0.009). The high baseline IGF-1 level remains an independent factor associated with favorable PFS and OS in multivariate analysis.High pretreatment IGF-1 levels were associated with better DCR, PFS, and OS of patients who received antiangiogenic therapy for advanced HCC. This finding warrants validation in large studies.
The Economic Analysis of Prevention in Mental Health Programs
Authors: Cathrine Mihalopoulos, Theo Vos, Jane Pirkis, Rob Carter
Journal: Annual Review of Clinical Psychology (2011)

This article introduces the role economics can play in deciding whether programs designed to prevent mental disorders, which carry large disease and economic burdens, are a worthwhile use of limited healthcare resources. Fortunately, preventive interventions for mental disorders exist; however, which interventions should be financed is a common issue facing decision makers, and economic evaluation can provide answers. Unfortunately, existing economic evaluations of preventive interventions have limited applicability to local healthcare contexts. An approach to priority setting largely based on economic techniques-Assessing Cost-Effectiveness (ACE)-has been developed and used in Australia to answer questions regarding the economic credentials of competing interventions. Eleven preventive interventions for mental disorders and suicide, mostly psychological in nature, have been evaluated using this approach, with many meeting the criteria of good value for money. Interventions targeting the prevention of suicide, adult and childhood depression, childhood anxiety, and early psychosis have particular merit.
Suppression of Tumor Lymphangiogenesis and Lymph Node Metastasis by Blocking Vascular Endothelial Growth Factor Receptor 3 Signaling
Authors: Y. He, K.-i. Kozaki, T. Karpanen, K. Koshikawa, S. Yla-Herttuala, T. Takahashi, K. Alitalo
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Vascular endothelial growth factor C (VEGF-C) stimulates tumor lymphangiogenesis (i.e., formation of lymphatic vessels) and metastasis to regional lymph nodes by interacting with VEGF receptor 3 (VEGFR-3). We sought to determine whether inhibiting VEGFR-3 signaling, and thus tumor lymphangiogenesis, would inhibit tumor metastasis. Methods: We used the highly metastatic human lung cancer cell line NCI-H460-LNM35 (LNM35) and its parental line NCI-H460-N15 (N15) with low metastatic capacity. We inserted genes by transfection and established a stable N15 cell line secreting VEGF-C and a LNM35 cell line secreting the soluble fusion protein VEGF receptor 3-immunoglobulin (VEGFR-3-Ig, which binds VEGF-C and inhibits VEGFR-3 signaling). Control lines were transfected with mock vectors. Tumor cells were implanted subcutaneously into severe combined immunodeficient mice (n = 6 in each group), and tumors and metastases were examined 6 weeks later. In another approach, recombinant adenoviruses expressing VEGFR-3-Ig (AdR3-Ig) or β-galactosidase (AdLacZ) were injected intravenously into LNM35 tumor-bearing mice (n = 14 and 7, respectively). Results: LNM35 cells expressed higher levels of VEGF-C RNA and protein than did N15 cells. Xenograft mock vector-transfected LNM35 tumors showed more intratumoral lymphatic vessels (15.3 vessels per grid; 95% confidence interval [CI] = 13.3 to 17.4) and more metastases in draining lymph nodes (12 of 12) than VEGFR-3-Ig-transfected LNM35 tumors (4.1 vessels per grid; 95% CI = 3.4 to 4.7; P<.001, two-sided t test; and four lymph nodes with metastases of 12 lymph nodes examined). Lymph node metastasis was also inhibited in AdR3-Ig-treated mice (AdR3-Ig = 0 of 28 lymph nodes; AdLacZ = 11 of 14 lymph nodes). However, metastasis to the lungs occurred in all mice, suggesting that LNM35 cells can also spread via other mechanisms. N15 tumors overexpressing VEGF-C contained more lymphatic vessels than vector-transfected tumors but did not have increased metastatic ability. Conclusions: Lymph node metastasis appears to be regulated by additional factors besides VEGF-C. Inhibition of VEGFR-3 signaling can suppress tumor lymphangiogenesis and metastasis to regional lymph nodes but not to lungs.
Effects of angiotensin II and arginine vasopressin on F-actin content of cultured mesangial cells.
Authors: P C Singhal, N Franki, N Gibbons, R M Hays
Journal: Journal of the American Society of Nephrology (1992)

The actin cytoskeleton of mesangial cells (MC) plays an important role in the contractile response to agonists as well as in the endocytosis of macromolecules. A quantitative study of the F-actin content of MC by the rhodamine-phalloidin binding assay was carried out. Angiotensin II (ANG II) (10(-6) M) significantly increased the F-actin content of MC by 30 min and at later time periods, with increases ranging from 31 to 46%. Arginine vasopressin (10(-8) M) produced a transient decrease of F-actin content of MC at 30 s but then significantly enhanced the F-actin content at later time periods. There was no change in total actin and protein content of MC at 30 min in the presence of either agent. Thus, the increase in F-actin is related to a shift in the G- to F-actin ratio and not to the synthesis of new F-actin. Because the incubation of MC with 1 (5-isoquinolinylsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, did not attenuate the ANG II-induced increase in the F-actin content of MC, the shift does not appear to be mediated by the activation of protein kinase C. The removal of external calcium did not prevent the increase in F-actin. Dibutyryl cAMP (5 x 10(-4) M), a smooth muscle cell and MC relaxant, did not alter the F-actin content in MC, and 10(-5) M cytochalasin B significantly lowered F-actin content.(ABSTRACT TRUNCATED AT 250 WORDS)
Class Restriction of Cephalosporin Use to Control Total Cephalosporin Resistance in Nosocomial &lt;EMPH TYPE="ITAL"&gt;Klebsiella&lt;/EMPH&gt;
Authors: James J. Rahal
Journal: JAMA (1998)

Context.-Resistance to most or all cephalosporin antibiotics in Klebsiella species has developed in many European and North American hospitals during the past 2 decades.Objective.-Todetermine if restriction of use of the cephalosporin class of antibiotics would reduce the incidence of patient infection or colonization by cephalosporin-resistant Klebsiella.Design.-A before-after comparative 2-year trial.Setting.-A 500-bed, university-affiliated community hospital in Queens, NY.Patients.-Alladult medical and surgical hospital inpatients.Intervention.-Anew antibiotic guideline excluded the use of cephalosporins except for pediatric infection, single-dose surgical prophylaxis, acute bacterial meningitis, spontaneous bacterial peritonitis, and outpatient gonococcal infection.All other cephalosporin use required prior approval by the infectious disease section.Main Outcome Measure.-Incidence of patient infection or colonization by ceftazidime-resistant Klebsiella during 1995 (control period) compared with 1996 (intervention period).Results.-An 80.1% reduction in hospital-wide cephalosporin use occurred in 1996 compared with 1995.This was accompanied by a 44.0%reduction in the incidence of ceftazidime-resistant Klebsiella infection and colonization throughout the medical center (PϽ.01), a 70.9% reduction within all intensive care units (PϽ.001), and an 87.5% reduction within the surgical intensive care unit (PϽ.001).A concomitant 68.7% increase in the incidence of imipenem-resistant Pseudomonas aeruginosa occurred throughout the medical center (PϽ.01).All such isolates ex- cept one were susceptible to other antibiotics.Conclusion.-Extensive cephalosporin class restriction significantly reduced nosocomial, plasmid-mediated, cephalosporin-resistant Klebsiella infection and colonization.This occurred at the price of increased imipenem resistance in P aeruginosa, which remained susceptible to other agents.Thus, an overall reduction in multiply-resistant pathogens was achieved within 1 year.
Integration of microRNA changes in vivo identifies novel molecular features of muscle insulin resistance in type 2 diabetes
Authors: Iain J Gallagher, Camilla Scheele, Pernille Keller, Anders R Nielsen, Judit Remenyi, Christian P Fischer, Karim Roder, John Babraj, Claes Wahlestedt, Gyorgy Hutvagner, Bente K Pedersen, James A Timmons
Journal: Genome Medicine (2010)

Skeletal muscle insulin resistance (IR) is considered a critical component of type II diabetes, yet to date IR has evaded characterization at the global gene expression level in humans. MicroRNAs (miRNAs) are considered fine-scale rheostats of protein-coding gene product abundance. The relative importance and mode of action of miRNAs in human complex diseases remains to be fully elucidated. We produce a global map of coding and non-coding RNAs in human muscle IR with the aim of identifying novel disease biomarkers. We profiled >47,000 mRNA sequences and >500 human miRNAs using gene-chips and 118 subjects (n = 71 patients versus n = 47 controls). A tissue-specific gene-ranking system was developed to stratify thousands of miRNA target-genes, removing false positives, yielding a weighted inhibitor score, which integrated the net impact of both up- and down-regulated miRNAs. Both informatic and protein detection validation was used to verify the predictions of in vivo changes. The muscle mRNA transcriptome is invariant with respect to insulin or glucose homeostasis. In contrast, a third of miRNAs detected in muscle were altered in disease (n = 62), many changing prior to the onset of clinical diabetes. The novel ranking metric identified six canonical pathways with proven links to metabolic disease while the control data demonstrated no enrichment. The Benjamini-Hochberg adjusted Gene Ontology profile of the highest ranked targets was metabolic (P < 7.4 × 10-8), post-translational modification (P < 9.7 × 10-5) and developmental (P < 1.3 × 10-6) processes. Protein profiling of six development-related genes validated the predictions. Brain-derived neurotrophic factor protein was detectable only in muscle satellite cells and was increased in diabetes patients compared with controls, consistent with the observation that global miRNA changes were opposite from those found during myogenic differentiation. We provide evidence that IR in humans may be related to coordinated changes in multiple microRNAs, which act to target relevant signaling pathways. It would appear that miRNAs can produce marked changes in target protein abundance in vivo by working in a combinatorial manner. Thus, miRNA detection represents a new molecular biomarker strategy for insulin resistance, where micrograms of patient material is needed to monitor efficacy during drug or life-style interventions.
Effect of increasing doses of mannitol on mucus clearance in patients with bronchiectasis
Authors: E. Daviskas, S. D. Anderson, S. Eberl, I. H. Young
Journal: European Respiratory Journal (2007)

Bronchiectasis is characterised by hypersecretion and impaired clearance of mucus. A 400-mg dose of inhaled mannitol improves mucus clearance however, the effect of other doses is unknown. A total of 14 patients, aged 63.3±5.7 yrs, were studied on five visits. Mucus clearance at baseline and with mannitol (160, 320 and 480 mg) was measured using technetium-99m-sulphur colloid and imaging with a gamma camera over 45 min, followed by a further 30 min involving 100 voluntary coughs. A control study assessed the effect of cough provoked by mannitol during the intervention. Whole right lung clearance over 45 min was 4.7±1.2 and 10.6±2.6% on baseline and control days, respectively, and increased to 16.7±4.2, 22.8±4.2 and 31±4.7% with 160, 320 and 480 mg mannitol, respectively. Clearance over 45 min with 480 mg mannitol was greater than clearance with 320 and 160 mg. Total clearance over 75 min, after mannitol administration and voluntary coughs, was 36.1±5.5, 40.9±5.6 and 46.0±5.2% with 160, 320 and 480 mg mannitol, respectively, all significantly different from baseline (24.1±6.0%) and control (13.1±3.0%). Total clearance over 75 min with 480 mg mannitol was greater compared with 160 mg. In conclusion, mucus clearance increases with increasing doses of mannitol and can be further increased by cough in patients with bronchiectasis.
Telomere Shortening Reduces Regenerative Capacity after Acute Kidney Injury
Authors: Jens H. Westhoff, Carolin Schildhorn, Christoph Jacobi, Meike Hömme, Andrea Hartner, Heidi Braun, Christine Kryzer, Chunfang Wang, Thomas von Zglinicki, Bettina Kränzlin, Norbert Gretz, Anette Melk
Journal: Journal of the American Society of Nephrology (2009)

Telomeres of most somatic cells progressively shorten, compromising the regenerative capacity of human tissues during aging and chronic diseases and after acute injury. Whether telomere shortening reduces renal regeneration after acute injury is unknown. Here, renal ischemia-reperfusion injury led to greater impairment of renal function and increased acute and chronic histopathologic damage in fourth-generation telomerase-deficient mice compared with both wild-type and first-generation telomerase-deficient mice. Critically short telomeres, increased expression of the cell-cycle inhibitor p21, and more apoptotic renal cells accompanied the pronounced damage in fourth-generation telomerase-deficient mice. These mice also demonstrated significantly reduced proliferative capacity in tubular, glomerular, and interstitial cells. These data suggest that critical telomere shortening in the kidney leads to increased senescence and apoptosis, thereby limiting regenerative capacity in response to injury.
Periostin is a novel therapeutic target that predicts and regulates glioma malignancy
Authors: Andrei M. Mikheev, Svetlana A. Mikheeva, Andrew D. Trister, Mari J. Tokita, Samuel N. Emerson, Carolina A. Parada, Donald E. Born, Barbara Carnemolla, Sam Frankel, Deok-Ho Kim, Rob G. Oxford, Yoshito Kosai, Kathleen R. Tozer-Fink, Thomas C. Manning, John R. Silber, Robert C. Rostomily
Journal: Neuro-Oncology (2014)

Periostin is a secreted matricellular protein critical for epithelial-mesenchymal transition and carcinoma metastasis. In glioblastoma, it is highly upregulated compared with normal brain, and existing reports indicate potential prognostic and functional importance in glioma. However, the clinical implications of periostin expression and function related to its therapeutic potential have not been fully explored. Periostin expression levels and patterns were examined in human glioma cells and tissues by quantitative real-time PCR and immunohistochemistry and correlated with glioma grade, type, recurrence, and survival. Functional assays determined the impact of altering periostin expression and function on cell invasion, migration, adhesion, and glioma stem cell activity and tumorigenicity. The prognostic and functional relevance of periostin and its associated genes were analyzed using the TCGA and REMBRANDT databases and paired recurrent glioma samples. Periostin expression levels correlated directly with tumor grade and recurrence, and inversely with survival, in all grades of adult human glioma. Stromal deposition of periostin was detected only in grade IV gliomas. Secreted periostin promoted glioma cell invasion and adhesion, and periostin knockdown markedly impaired survival of xenografted glioma stem cells. Interactions with αvβ3 and αvβ5 integrins promoted adhesion and migration, and periostin abrogated cytotoxicity of the αvβ3/β5 specific inhibitor cilengitide. Periostin-associated gene signatures, predominated by matrix and secreted proteins, corresponded to patient prognosis and functional motifs related to increased malignancy. Periostin is a robust marker of glioma malignancy and potential tumor recurrence. Abrogation of glioma stem cell tumorigenicity after periostin inhibition provides support for exploring the therapeutic impact of targeting periostin.
Considerations for a WHO European strategy on health-care-associated infection, surveillance, and control
Authors: Didier Pittet, Benedetta Allegranzi, Hugo Sax, Luigi Bertinato, Ercole Concia, Barry Cookson, Jacques Fabry, Hervé Richet, Pauline Philip, Robert C Spencer, Bernardus WK Ganter, Stefano Lazzari
Journal: The Lancet Infectious Diseases (2005)