tbuckley/cabot-search huggingface dataset:
Electrical and Mechanical Strategies to Enable Cardiac Repair and Regeneration
Authors: Hung Cao, Bong Jin Kang, Chia-An Lee, K. Kirk Shung, Tzung K. Hsiai
Journal: IEEE Reviews in Biomedical Engineering (2015)

Inadequate replacement of lost ventricular myocardium from myocardial infarction leads to heart failure. Investigating the regenerative capacity of mammalian hearts represents an emerging direction for tissue engineering and cell-based therapy. Recent advances in stem cells hold promise to restore cardiac functions. However, embryonic or induced pluripotent stem cell-derived cardiomyocytes lack functional phenotypes of the native myocardium, and transplanted tissues are not fully integrated for synchronized electrical and mechanical coupling with the host. In this context, this review highlights the mechanical and electrical strategies to promote cardiomyocyte maturation and integration, and to assess the functional phenotypes of regenerating myocardium. Simultaneous microelectrocardiogram and high-frequency ultrasound techniques will also be introduced to assess electrical and mechanical coupling for small animal models of heart regeneration.
Response to a behavioural treatment, biofeedback, in constipated patients is associated with improved gut transit and autonomic innervation
Authors: A V Emmanuel, M A Kamm
Journal: Gut (2001)

BACKGROUND Although behavioural treatment (biofeedback) successfully treats the pelvic floor abnormalities in patients with idiopathic constipation, many patients also normalise their impaired bowel frequency. We postulated that a response may be associated with altered cerebral outflow via extrinsic autonomic nerves to the gut. We investigated whether treatment changes extrinsic innervation, using mucosal laser Doppler flowmetry, whether autonomic changes are gut specific, and whether it changes gut transit. MATERIALS AND METHODS Forty nine patients (44 female, mean age 39 years) with idiopathic constipation were studied before and after biofeedback treatment (mean five sessions). Rectal mucosal blood flow was measured by laser Doppler flowmetry to assess direct extrinsic gut nerve autonomic activity. To assess general autonomic activity, RR (interval between successive R waves on the electrocardiogram) variability, Valsalva ratio, orthostatic adjustment ratio, and phase II:IV blood pressure ratio (II:IV) of the Valsalva manoeuvre were measured. All autonomic tests were compared with those of 26 healthy volunteers (19 female, mean age 37 years). RESULTS Twenty nine of 49 patients were symptomatically improved. Treatment reduced those with ⩽3 bowel actions per week (27 v 9, pre v post), need to strain (26 v 9), and laxative or suppository use (34 v 9). Biofeedback reduced retained markers by 32% in those with slow transit and by 20% in those with normal transit. Twenty two had slow transit before treatment—14 felt symptomatic improvement of whom 13 developed normal transit. There was a significantly greater increase in rectal mucosal blood flow in patients who subjectively improved compared with those who did not (29% v 7%; p&lt;0.03) and in those with improved bowel frequency (33% v 9%, increased v unchanged bowel frequency; p&lt;0.05). Thirty five patients had abnormal RR variability and 33 an abnormal Valsalva ratio; one had an abnormal orthostatic adjustment ratio and one an abnormal II:IV ratio. None of the general cardiorespiratory autonomic reflexes was changed by treatment. CONCLUSIONS Biofeedback treatment affects more than the pelvic floor. Successful outcome after biofeedback treatment is associated with improved activity of the direct cerebral innervation to the gut and improved gut transit. This effect is gut specific; cardiovascular autonomic reflexes were not altered.
Granulocyte colony-stimulating factor (G-CSF) accelerates reendothelialization and reduces neointimal formation after vascular injury in mice
Authors: T YOSHIOKA, M TAKAHASHI, Y SHIBA, C SUZUKI, H MORIMOTO, A IZAWA, H ISE, U IKEDA
Journal: Cardiovascular Research (2006)

Objective Neointimal formation following percutaneous coronary intervention (PCI), termed restenosis, limits therapeutic revascularization. Since reendothelialization is one of the determinant factors for the development of neointimal formation, we examined the effects of granulocyte colony-stimulating factor (G-CSF) on reendothelialization and neointimal formation after vascular injury in mice.
Individual identity and freedom of choice in the context of environmental and economic conditions
Authors: Roy F. Baumeister, Jina Park, Sarah E. Ainsworth
Journal: Behavioral and Brain Sciences (2013)

Abstract Van de Vliert's findings fit nicely with our recent arguments implying that (1) differentiated selfhood is partly motivated by requirements of cultural groups, and (2) free will mainly exists within culture. Some cultural groups promote individual freedom, whereas others constrict it so as to maintain elites' power and privilege. Thus, freedom is, to a great extent, a creation of culture.
Therapeutic use exemption
Authors: J Dvorak, D Kirkendall, M Vouillamoz
Journal: British Journal of Sports Medicine (2006)

Football players who have either physical symptoms or disease after injury may need to be treated with specific medicines that are on the list of prohibited substances. Therapeutic use exemption may be granted to such players, in accordance with strictly defined criteria-these are presented in this article. Procedures of how to request for an abbreviated or a standard therapeutic use exemption are explained, and data on therapeutic use exemptions (UEFA and FIFA, 2004 and 2005) are also presented.
Effect of temperature on lung function and symptoms in chronic obstructive pulmonary disease
Authors: G.C. Donaldson, T. Seemungal, D.j Jeffries, J.a Wedzicha
Journal: European Respiratory Journal (1999)

The present study investigated whether falls in environmental temperature increase morbidity from chronic obstructive pulmonary disease (COPD). Daily lung function and symptom data were collected over 12 months from 76 COPD patients living in East London and related to outdoor and bedroom temperature. Questionnaires were administered which asked primarily about the nature of night-time heating. A fall in outdoor or bedroom temperature was associated with increased frequency of exacerbation, and decline in lung function, irrespective of whether periods of exacerbation were excluded. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) fell markedly by a median of 45 mL (95% percentile range: -113-229 mL) and 74 mL (-454-991 mL), respectively, between the warmest and coolest week of the study. The questionnaire revealed that 10% had bedrooms &lt;13 degrees C for 25% of the year, possibly because only 21% heated their bedrooms and 48% kept their windows open in November. Temperature-related reduction in lung function, and increase in exacerbations may contribute to the high level of cold-related morbidity from chronic obstructive pulmonary disease.
The Toxicology of Mercury — Current Exposures and Clinical Manifestations
Authors: Thomas W. Clarkson, Laszlo Magos, Gary J. Myers
Journal: New England Journal of Medicine (2003)

Mercury poisoning still occurs as a result of accidental and occupational exposure. For the general population, however, the main concern is the possible adverse effect of exposure to mercury through fish consumption and the receipt of dental amalgams and thimerosal, a preservative used in vaccines. This review summarizes both the facts and the controversies surrounding exposure to methyl mercury, mercury vapor, and the ethyl mercury in thimerosal.
Urokinase type plasminogen activator receptor expression in colorectal neoplasms
Authors: S Suzuki, Y Hayashi, Y Wang, T Nakamura, Y Morita, K Kawasaki, K Ohta, N Aoyama, S R Kim, H Itoh, Y Kuroda, W F Doe
Journal: Gut (1998)

Background —The urokinase type plasminogen activator receptor (uPAR) may play a critical role in cancer invasion and metastasis. Aims —To study the involvement of uPAR in colorectal carcinogenesis. Methods —The cellular expression and localisation of uPAR were investigated in colorectal adenomas and invasive carcinomas by in situ hybridisation, immunohistochemistry, and northern and western blot analyses. Results —uPAR mRNA expression was found mainly in the cytoplasm of dysplastic epithelial cells of 30% of adenomas with mild (19%), moderate (21%), and severe (47%) dysplasia, and in that of carcinomatous cells of 85% of invasive carcinomas: Dukes’ stages A (72%), B (93%), and C (91%). Some stromal cells in the adjacent neoplastic epithelium were faintly positive. Immunoreactivity for uPAR was detected in dysplastic epithelial cells of 14% of adenomas and in carcinomatous cells of 49% of invasive carcinomas. uPAR mRNA and protein concentrations were significantly higher in severe than in mild or moderate dysplasia (p&lt;0.05); they were notably higher in Dukes’ stage A than in severe dysplasia (p&lt;0.05), and significantly higher in Dukes’ stage B than in stage A (p&lt;0.05), but those in stage B were not different from those in stage C or in metastatic colorectal carcinomas of the liver. Conclusions —Colorectal adenoma uPAR, expressed essentially in dysplastic epithelial cells, was upregulated with increasing severity of atypia, and increased notably during the critical transition from severe dysplasic adenoma to invasive carcinoma. These findings implicate uPAR expression in the invasive and metastatic processes of colorectal cancer.
Frequency of the cholesteryl ester storage disease common<i>LIPA</i>E8SJM mutation (c.894G&gt;A) in various racial and ethnic groups
Authors: Stuart A. Scott, Benny Liu, Irina Nazarenko, Suparna Martis, Julia Kozlitina, Yao Yang, Charina Ramirez, Yumi Kasai, Tommy Hyatt, Inga Peter, Robert J. Desnick
Journal: Hepatology (2013)

Cholesteryl ester storage disease (CESD) and Wolman disease are autosomal recessive later-onset and severe infantile disorders, respectively, which result from the deficient activity of lysosomal acid lipase (LAL). LAL is encoded by LIPA (10q23.31) and the most common mutation associated with CESD is an exon 8 splice junction mutation (c.894G>A; E8SJM), which expresses only ∼3%-5% of normally spliced LAL. However, the frequency of c.894G>A is unknown in most populations. To estimate the prevalence of CESD in different populations, the frequencies of the c.894G>A mutation were determined in 10,000 LIPA alleles from healthy African-American, Asian, Caucasian, Hispanic, and Ashkenazi Jewish individuals from the greater New York metropolitan area and 6,578 LIPA alleles from African-American, Caucasian, and Hispanic subjects enrolled in the Dallas Heart Study. The combined c.894G>A allele frequencies from the two cohorts ranged from 0.0005 (Asian) to 0.0017 (Caucasian and Hispanic), which translated to carrier frequencies of 1 in 1,000 to ∼1 in 300, respectively. No African-American heterozygotes were detected. Additionally, by surveying the available literature, c.894G>A was estimated to account for 60% (95% confidence interval [CI]: 51%-69%) of reported mutations among multiethnic CESD patients. Using this estimate, the predicted prevalence of CESD in the Caucasian and Hispanic populations is ∼0.8 per 100,000 (∼1 in 130,000; 95% CI: ∼1 in 90,000 to 1 in 170,000).These data indicate that CESD may be underdiagnosed in the general Caucasian and Hispanic populations, which is important since clinical trials of enzyme replacement therapy for LAL deficiency are currently being developed. Moreover, future studies on CESD prevalence in African and Asian populations may require full-gene LIPA sequencing to determine heterozygote frequencies, since c.894G>A is not common in these racial groups.
Expression and catalytic activity of the tyrosine phosphatase PTP1C is severely impaired in motheaten and viable motheaten mice.
Authors: M Kozlowski, I Mlinaric-Rascan, G S Feng, R Shen, T Pawson, K A Siminovitch
Journal: The Journal of Experimental Medicine (1993)

Mutations in the gene encoding the phosphotyrosine phosphatase PTP1C, a cytoplasmic protein containing a COOH-terminal catalytic and two NH2-terminal Src homology 2 (SH2) domains, have been identified in motheaten (me) and viable motheaten (mev) mice and are associated with severe hemopoietic dysregulation. The me mutation is predicted to result in termination of the PTP1C polypeptide within the first SH2 domain, whereas the mev mutation creates an insertion or deletion in the phosphatase domain. No PTP1C RNA or protein could be detected in the hemopoietic tissues of me mice, nor could PTP1C phosphotyrosine phosphatase activity be isolated from cells homozygous for the me mutation. In contrast, mice homozygous for the less severe mev mutation expressed levels of full-length PTP1C protein comparable to those detected in wild type mice and the SH2 domains of mev PTP1C bound normally to phosphotyrosine-containing ligands in vitro. Nevertheless, the mev mutation induced a marked reduction in PTP1C activity. These observations provide strong evidence that the motheaten phenotypic results from loss-of-function mutations in the PTP1C gene and imply a critical role for PTP1C in the regulation of hemopoietic differentiation and immune function.
Hepatitis B Vaccines—to Switch or Not to Switch
Authors: F. Blaine Hollinger
Journal: JAMA (1987)

With the recent licensure of a hepatitis B vaccine prepared in yeast by recombinant DNA technology (Recombivax-HB), a new era in vaccine development has emerged. The vaccine it is designed to compete with—Heptavax-B—is also a uniquely formulated product in that it is prepared from the plasma of humans chronically infected with hepatitis B. Several placebo-controlled, randomized, double-blind trials have clearly documented that the plasma-derived vaccine is highly effective in preventing hepatitis B in high-risk groups.<sup>1-3</sup> Shortly after the licensure of Heptavax-B in 1981 and its general availability in July 1982, the discovery of the acquired immunodeficiency syndrome (AIDS) among male homosexuals threatened the success of this product, since some of the hepatitis B surface antigen (HBsAg)-positive plasma donors were members of this high-risk group. Intensive epidemiologic, virological, and serological evaluations were launched, which eventually found no evidence for the transmission of AIDS to recipients of the plasma-derived HBsAg vaccine.
Extracorporeal therapy requirements for patients with acute renal failure.
Authors: W R Clark, B A Mueller, M A Kraus, W L Macias
Journal: Journal of the American Society of Nephrology (1997)

Renal replacement therapy (RRT) requirements for critically ill patients with acute renal failure (ARF) depend on numerous factors, including the degree of hypercatabolism, patient size, and desired level of metabolic control. However, the current practice at many institutions is to prescribe generally similar amounts of RRT to ARF patients essentially without regard for the above factors. In this study, a computer-based model designed to permit individualized RRT prescription to ARF patients was developed. The critical input parameter is the desired level of metabolic control, which is the time-averaged BUN (BUNa) or steady-state BUN (BUNs) for intermittent hemodialysis (IHD) or continuous RRT (CRRT), respectively. The basis for the model was a group of 20 patients who received uninterrupted CRRT for at least 5 days. In these patients, the normalized protein catabolic rate (nPCR) increased linearly (r = 0.974) from 1.55 +/- 0.14 g/kg per day (mean +/- SEM) on day 1 to 1.95 +/- 0.15 g/kg per day on day 6. The daily urea generation rate (G), determined from the above linear relationship, was utilized to produce BUN versus time curves by the direct quantification method for simulated patients of varying dry weights (50 to 100 kg) who received variable CRRT urea clearances (500 to 2000 ml/h). Steady-state BUN versus time profiles for the same simulated patient population treated with IHD regimens (K = 180 ml/min, T = 4 h) of variable frequency were generated by use of a variable-volume, single-pool kinetic model. From these profiles, regression lines of required IHD frequency (per week) versus patient weight for desired BUNa values of 60, 80, and 100 mg/dl were obtained. Regression lines of required CRRT urea K (ml/h) versus patient weight for desired BUNs values of 60, 80, and 100 mg/dl were also generated. For the attainment of intensive IHD metabolic control (BUNa = 60 mg/dl) at steady state, a required treatment frequency of 4.4 dialyses per week is predicted for a 50-kg patient. However, the model predicts that the same degree of metabolic control cannot be achieved even with daily IHD therapy in patients > or = 90 kg. On the other hand, for the attainment of intensive CRRT metabolic control (BUNs = 60 mg/dl), required urea clearance rates of approximately 900 ml/h and 1900 ml/h are predicted for 50- and 100-kg patients, respectively. This model suggests that, for many patients, rigorous azotemia control equivalent to that readily attainable with most CRRT can only be achieved with intensive IHD regimens. Following prospective clinical validation, this methodology may be a useful RRT prescription tool for critically ill ARF patients.
J. Watkins "An Introduction to Mechanics of Human Movement"
Authors: J. Atha
Journal: British Journal of Sports Medicine (1984)

Egyptian children.Furthermore, schistosomiasis is still a serious problem among Egyptians (Lehman et al, 1973).The extent of the interaction of this parasitic infection and the nutritional status of these growing children is undocumented.Perhaps the lower fitness scores for the girls above the age of 12 in this study may be attributed to the custom in many Islamic societies of withdrawing young women into domestic surroundings and away from vigorous participation in sports activities.
Non–Small-Cell Lung Cancer in Elderly Patients: A Discussion of Treatment Options
Authors: Ajeet Gajra, Aminah Jatoi
Journal: Journal of Clinical Oncology (2014)

Lung cancer is a disease of the elderly. In older patients, the management of a malignancy as complex and potentially as lethal as lung cancer is challenging. Despite the fact that a large proportion of patients with non–small-cell lung cancer are elderly, information remains scant on how best to treat these patients. The goal of this review is to discuss the published literature and to provide guidance on how to treat elderly patients within three broad stages: (1) metastatic cancer, (2) early-stage cancer after surgery, and (3) locally advanced inoperable cancer. Because decisions on how and when to prescribe systemic treatment can be particularly difficult, this review focuses heavily on chemotherapy-related treatment decisions with some discussion of emerging data on the use of the comprehensive geriatric assessment.
Targeted Deletion of PTEN in Smooth Muscle Cells Results in Vascular Remodeling and Recruitment of Progenitor Cells Through Induction of Stromal Cell–Derived Factor-1α
Authors: Raphael A. Nemenoff, Peter A. Simpson, Seth B. Furgeson, Nihal Kaplan-Albuquerque, Joseph Crossno, Pamela J. Garl, James Cooper, Mary C.M. Weiser-Evans
Journal: Circulation Research (2008)

We previously showed that changes in vascular smooth muscle cell (SMC) PTEN/Akt signaling following vascular injury are associated with increased SMC proliferation and neointima formation. In this report, we used a genetic model to deplete PTEN specifically in SMCs by crossing PTEN(LoxP/LoxP) mice to mice expressing Cre recombinase under the control of the SM22alpha promoter. PTEN was downregulated with increases in phosphorylated Akt in major vessels, hearts, and lungs of mutant mice. SMC PTEN depletion promoted widespread medial SMC hyperplasia, vascular remodeling, and histopathology consistent with pulmonary hypertension. Increased vascular deposition of the chemokine stromal cell-derived factor (SDF)-1alpha and medial and intimal cells coexpressing SM-alpha-actin and CXCR4, the SDF-1alpha receptor, was detected in SMC PTEN-depleted mice. PTEN deficiency in cultured aortic SMCs induced autocrine growth through increased production of SDF-1alpha. Blocking SDF-1alpha attenuated autocrine growth and blocked growth of control SMCs induced by conditioned media from PTEN-deficient SMCs. In addition, SMC PTEN deficiency enhanced progenitor cell migration toward SMCs through increased SDF-1alpha production. SDF-1alpha production by other cell types is regulated by the transcription factor hypoxia-inducible factor (HIF)-1alpha. We found SMC nuclear HIF-1alpha expression in PTEN-depleted mice and increased nuclear HIF-1alpha in PTEN-deficient SMCs. Small interfering RNA-mediated downregulation of HIF-1alpha reversed SDF-1alpha induction by PTEN depletion and inhibition of phosphatidylinositol 3-kinase signaling blocked HIF-1alpha and SDF-1alpha upregulation induced by PTEN depletion. Our data show that SMC PTEN inactivation establishes an autocrine growth loop and increases progenitor cell recruitment through a HIF-1alpha-mediated SDF-1alpha/CXCR4 axis, thus identifying PTEN as a target for the inhibition of pathological vascular remodeling.
Mitogen-Activated Protein Kinase Activation in Lung Adenocarcinoma: A Comparative Study between Ever Smokers and Never Smokers
Authors: Giannis Mountzios, David Planchard, Benjamin Besse, Pierre Validire, Philippe Girard, Christine Devisme, Meletios-Athanasios Dimopoulos, Jean-Charles Soria, Pierre Fouret
Journal: Clinical Cancer Research (2008)

Abstract Purpose: There are major differences affecting genes in adenocarcinomas in ever and never smokers. However, data on whether mitogen-activated protein kinase (MAPK) activation state differs according to smoking status are limited. Experimental Design: Expression of activated extracellular signal–regulated kinases, c-Jun NH2-terminal kinases, and P38 enzymes (pP38) were evaluated by means of immunohistochemistry in 188 chemonaïve patients with surgically resected lung adenocarcinoma. Cell viability of the lung adenocarcinoma cell line HCC827 was studied after treatment with cisplatin or the P38 MAPK inhibitor SB 203580. Results: Thirty-seven of 44 never smokers [84%; 95% confidence intervals (95% CI), 70-92%] expressed high pP38 levels compared with 45 of 104 ever smokers (43%; 95% CI, 34-53%; P &amp;lt; 0.0001). The proportion of never smokers expressing high c-Jun NH2-terminal kinase levels (72%; 95% CI, 57-83%) was greater than that of ever smokers (53%; 95% CI, 44-62%; P = 0.03). The proportion of ever smokers expressing high extracellular signal–regulated kinase levels (51%; 95% CI, 42-59%) was similar to that of never smokers (57%; 95% CI, 42-71%; P = 0.47). Never smokers were 10.5 times (95% CI, 3.5-31.5) more likely to express high pP38 levels after adjustment for variables linked to smoking status, including age, sex, and histologic subtype. None of the activated MAPKs predicted for overall survival. Cell viability of HCC827 was significantly reduced after exposure to SB203580 alone or when combined with cisplatin. Conclusions: Life-long nonsmoking is associated with high activated P38 levels in patients with lung adenocarcinoma. Activated P38 can contribute to the viability of adenocarcinoma cells in never smokers, but is not predictive for overall survival.
Comparison of Double Kissing Crush Versus Culotte Stenting for Unprotected Distal Left Main Bifurcation Lesions
Authors: Shao-Liang Chen, Bo Xu, Ya-Ling Han, Imad Sheiban, Jun-Jie Zhang, Fei Ye, Tak W. Kwan, Chitprapai Paiboon, Yu-Jie Zhou, Shu-Zheng Lv, George D. Dangas, Ya-Wei Xu, Shang-Yu Wen, Lang Hong, Rui-Yan Zhang, Hai-Chang Wang, Tie-Ming Jiang, Yan Wang, Fang Chen, Zu-Yi Yuan, Wei-Min Li, Martin B. Leon
Journal: Journal of the American College of Cardiology (2013)