Miracle-dz/UniFAR-FTUs huggingface dataset:
EFFECT OF HEPARIN

The long-term administration of the synthetic heparin substitutes dextran sulphate and laminarin sulphate to rabbits, guinea-pigs and rats induces osteoporosis and fractures (Adams, Thorpe & Glynn, 1958; Hint & Richter, 1958; Ellis, 1965). Heparin is relatively nontoxic in this respect, although mild degrees of osteoporosis and occasional fractures are produced if large enough doses are used in guinea-pigs (Ellis, 1965). Griffith, Nichols, Asher & Flanagan (1965) and Jaffe & Willis (1965) have recently reported osteoporosis and fractures in patients treated with heparin for prolonged periods. The precise mechanisms involved are unknown although it is thought the excess of natural or synthetic sulphated polysaccharide might inhibit ossification by competition with the naturally occurring sulphated polysaccharide in cartilage and bone. Chang, Witschi & Ponseti (1955) have shown that the addition of lathyrogenic factor, /3-aminopropionitrile, to the water in which amphibians are kept interferes with normal limb development during metamorphosis and with the regeneration of limbs following amputation. Their observations suggested that the effects of heparin and various synthetic substitutes might be conveniently studied using a similar technique. It is also known that a number of substances introduced into the yolk-sac or on to the chorioallantoic membrane of the developing chick embryo interfere with normal skeletal growth, for example insulin (Landauer, 1945, 1947a, b), P-aminopropionitrile (Chang et al., 1955) and cortisone (Karnofsky, Ridgway & Patterson, 1951), and it was therefore also decided to study the effect of dextran sulphate on the developing chick embryo.
Sensitizing Regimens of MDMA (Ecstasy) Elicit Enduring and Differential Structural Alterations in the Brain Motive Circuit of the Rat

Repeated, intermittent exposure to the psychomotor stimulants amphetamine and cocaine induces a progressive and enduring augmentation of their locomotor-activating effects, known as behavioral sensitization, which is accompanied by similarly stable adaptations in the dendritic structure of cortico-striatal neurons. We examined whether repeated exposure to the increasingly abused amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) also results in long-lasting behavioral and morphological changes in mesocortical (medial prefrontal cortex) and ventral striatal (nucleus accumbens) neurons. Rats received 2 daily injections of either 5.0 mg/kg (±)-MDMA or saline vehicle, ~6 hr apart, for 3 consecutive days, followed by 4 drug-free days for a total of 3 weeks. Following a 4-week drug-free period, MDMA-pretreated rats displayed behavioral sensitization, as well as large increases in spine density and the number of multiple-headed spines on medium spiny neurons in core and shell subregions of nucleus accumbens. In medial prefrontal cortex, the prelimbic subregion showed increased spine density on distal dendrites of layer V pyramidal neurons, while the anterior cingulate subregion showed a change in the distribution of dendritic material instead. Collectively, our results show that long-lasting locomotor sensitization to MDMA is accompanied by reorganization of synaptic connectivity in limbic-cortico-striatal circuitry. The differential plasticity in cortical subregions, moreover, suggests that drug-induced structural changes are not homogeneous and may be specific to the circuitry underlying long-term changes in drug-seeking and drug-taking behavior. *Please Address Correspondence to: George V. Rebec, Department of Psychological and Brain Sciences and Program in Neuroscience, Indiana University, 1101 East 10th Street, Bloomington, IN 47405-7007, TEL: 812-855-4832, FAX: 812-855-4520, Email: E-mail: rebec@indiana.edu. Section Editor: Dr. Geoffrey Schoenbaum Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Neuroscience. Author manuscript; available in PMC 2010 May 5. Published in final edited form as: Neuroscience. 2009 May 5; 160(2): 264–274. doi:10.1016/j.neuroscience. 2009.02. 025. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript
Post-Shock Mesenteric Lymph Induces Endothelial NF-κB Activation

Background—Post-hemorrhagic shock mesenteric lymph (PSML) has been shown to activate pulmonary endothelial cells, and cause lung injury. Although multiple mediators may be involved, most of these effects are mediated by NF-κB activation. Degradation of the inhibitor of kappa B (IκB) is a key regulatory step in the activation of NF-κB. We therefore hypothesized that PSML would cause IκB degradation with subsequent NF-κB phosphorylation and nuclear translocation. Methods—Mesenteric lymph was collected from male rats before shock and each hour after shock for up to 3 hours. (n=5) Buffer (control), buffer + 10% (v/v) lymph, or buffer + TNF (10ng/ml) was incubated with human pulmonary endothelial cells for 30 minutes and then lysed. Immunoblots of lysates were probed for IκB and phospho-p65. Immunohistochemistry was performed on cells grown on glass slides, and then treated as above with the 3rd PSML sample. Cells were fixed and then probed for p65. Statistical analysis was performed with student’s t-test and analysis of variance with significance set at p< 0.05. Results—Western blots of cell lysates for IκB demonstrated a steady decrease in total IκB with each lymph sample. Phosphorylation of NF-κB, p65 component, steadily increased with each PSML sample, with a maximum reached during the 3rd PSML sample, which also significantly increased translocation of NF-κB to the nucleus. Conclusion—Post-shock mesenteric lymph bioactivity is mediated by pathways which involved IκB degradation. These pathways offer novel targets for clinical intervention to prevent the distal organ injury caused by postinjury hemorrhagic shock.
DELIVERING HIGH QUALITY CARE IN THE 1990'S AND BEYOND

Cultural factors play a critical role in the practice of medicine. Culture is a body of beliefs and customs that define a group of people as being connected and that determines their identity. To a large degree, health care systems are cultural constructs, and beliefs about health and disease are culturally determined. As physicians, we subscribe to the biomedical model of health and disease and use the scientific method to understand our world. We are guided by a code of ethics that has at its foundation the Hippocratic Oath. However, this country has a culturally diverse patient population. Some share the biomedical model, but many do not. Delivering care of high quality demands that we acknowledge these cultural differences and adapt our practices appropriately. The idea of marrying the culture ofmedicine with the patient's culture to shape a therapeutic relationship is not new to medicine. However, doing so is increasingly challenging as our society becomes more diverse and our science and clinical practice become more complex. Moreover, all of medicine is now practiced in an environment of increasing accountability that increases our professional duty to assure that physicians are competent to practice. Just as each physician must be competent to perform a physical exam, today's society demands that the physician be culturally competent. In other words, physicians must understand how cultural diversity affects therapeutic outcomes. Cultural competence, as we are defining the term, has three components: population-specific health-related beliefs, epidemiology, and population-specific treatment outcomes. These three components could form the basis for quality indicators that measure the cultural competence of providers. Ensuring high-quality of health care for the twenty-first century requires that we establish guidelines for cultural competence just as we have established guidelines for cardiac catheterization, organ transplantation and fetal surgery.
PULMONARY PERSPECTIVE Systems Biology and Clinical Practice in Respiratory Medicine The Twain Shall Meet

Respiratory diseases are highly complex, being driven by host–environment interactions and manifested by inflammatory, structural, and functional abnormalities that vary over time. Traditional reductionist approaches have contributed vastly to our knowledge of biological systems in health and disease to date; however, they are insufficient to provide an understanding of the behavior of the system as a whole. In this Pulmonary Perspective, we discuss systems biology approaches, especially but not limited to the study of the lung as a complex system. Such integrative approaches take into account the large number of dynamic subunits and their interactions found in biological systems. Borrowing methods from physics and mathematics, it is possible to study the collective behavior of these systems over time and in a multidimensional manner. We first examine the physiological basis for complexity in the respiratory system and its implications for disease. We then expand on the potential applications of systems biology methods to study complex systems, within the context of diagnosis and monitoring of respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD), and critical illness. We summarize the significant advances made in recent years using systems approaches for disease phenotyping, applied to data ranging from themolecular to clinical level, obtained from large-scale asthma and COPD networks. We describe new studies using temporal complexity patterns to characterize asthma and COPD and predict exacerbations as well as predict adverse outcomes in critical care. We highlight new methods that are emerging with this approach and discuss remaining questions that merit greater attention in the field.
FAK Potentiates Rac1 Activation and Localization to Matrix Adhesion Sites: A Role for PIX□V

FAK, a cytoplasmic protein tyrosine kinase, is activated and localized to focal adhesions upon cell attachment to extracellular matrix. FAK null cells spread poorly and exhibit altered focal adhesion turnover. Rac1 is a member of the Rho-family GTPases that promotes membrane ruffling, leading edge extension, and cell spreading. We investigated the activation and subcellular location of Rac1 in FAK null and FAK reexpressing fibroblasts. FAK reexpressers had a more robust pattern of Rac1 activation after cell adhesion to fibronectin than the FAK null cells. Translocation of Rac1 to focal adhesions was observed in FAK reexpressers, but seldom in FAK null cells. Experiments with constitutively active L61Rac1 and dominant negative N17Rac1 indicated that the activation state of Rac1 regulated its localization to focal adhesions. We demonstrated that FAK tyrosinephosphorylated PIX and thereby increased its binding to Rac1. In addition, PIX facilitated the targeting of activated Rac1 to focal adhesions and the efficiency of cell spreading. These data indicate that FAK has a role in the activation and focal adhesion translocation of Rac1 through the tyrosine phosphorylation of PIX.
Deficiency Syndrome

SHEILA TAUBE, PhD MICHAEL GOLDBERG, PhD Dr. Goldberg as Associate Director for Program Planning and Evaluation, Office of the NIH Director. Anthony S. Fauci, MD, Chief of the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, reviewed this paper and provided the figure that accompanies it. Tearsheet requests to Dr. Sheila Taube, National Cancer Institute, Rm. IOA1 1, Westwood Bldg. , 5333 Westbard Ave., Bethesda, Md. 20205.
Myofibrillar protein turnover

The turnover of 3-methylhistidine (NT-methylhistidine) and in some cases actin, myosin heavy chain and aldolase in skeletal muscle was measured in a number of experiments in growing and adult rats in the fed and overnight-starved states. In growing fed rats in three separate experiments, measurements of the methylation rate of protein-bound 3-methylhistidine by either [14C]or [3H]-methyl-labelled S-adenosylmethionine show that 3-methylhistidine synthesis is slower than the overall rate of protein synthesis indicated by ['4C]tyrosine incorporation. Values ranged from 36 to 51%. However, in one experiment with rapidly growing young fed rats, acute measurements over 1h showed that 3-methylhistidine synthesis could be increased to the same rate as the overall rate. After overnight starvation in these rats, the steady-state synthesis rate of 3-methylhistidine was 38.8% of the overall rate. This was a similar value to that in adult non-growing rats, in which measurements of the relative labelling of 3-methylhistidine and histidine after a single injection of ['4C]histidine indicated that 3-methylhistidine synthesis was 37% of the overall rate in the fed or overnight-starved state. According to measurements of actin, myosin heavy-chain and aldolase synthesis in the overnight-starved state with young rats, with a variety of precursors, slow turnover of 3-methylhistidine results from the specific slow turnover of actin, since turnover rates of myosin heavy chain, mixed protein and aldolase were 2.5, 3 and 3.4 times faster respectively. However, in the fed state synthesis rates of actin were increased disproportionately to give similar rates for all proteins. These results show that (a) 3-methylhistidine turnover in muscle is less than half the overall rate in both young and adult rats, (b) slow 3-methylhistidine turnover reflects the specifically slow turnover of actin compared with myosin heavy chain and other muscle proteins, and (c) during growth the synthesis rate of actin is particularly sensitive to the nutritional state and can be increased to a similar rate to that of other proteins.
Cerebrovascular function in pre-symptomatic and symptomatic individuals with hereditary cerebral amyloid angiopathy: a case-control study

Background— Previous work suggests that impairments of cerebrovascular flow or reactivity might be early markers of cerebral amyloid angiopathy (CAA). Hereditary cerebral hemorrhage with amyloidosis–Dutch type (HCHWA-D) is a genetic form of CAA that can diagnosed early by DNA testing, allowing study of CAA before onset of clinical symptoms. The aim of the present study was to investigate whether hemodynamic measures are decreased in HCHWA-D mutation carriers compared to healthy controls. Methods— In this case-control study, we included pre-symptomatic and symptomatic HCHWA-D mutation carriers diagnosed through genetic testing and recruited through the HCHWA-D patient association (Katwijk, Netherlands) and the outpatient clinic of the Department of Neurology of the Leiden University Medical Center (Leiden, Netherlands), and healthy controls. Regional cerebral blood flow (rCBF) was measured using pseudo-continuous arterial spin labeling. Quantitative flow was determined by phase-contrast MR angiography of the cerebropetal vessels. Vascular reactivity was determined by measuring changes in the blood oxygen level-dependent (BOLD) signal after visual stimulation. Data from pre-symptomatic and symptomatic individuals were compared with healthy controls using mixed-model regression analysis. Results— In the study done between 2012 and 2015, we investigated imaging data from 27 HCHWA-D mutation carriers (12 pre-symptomatic and 15 symptomatic) and 33 healthy controls. Compared with controls, symptomatic HCHWA-D carriers had significantly decreased cortical gray matter rCBF in the occipital lobe (mean difference −11.1 ml/ 100g/min, CI −2.8 to −19.3, p=0.010) and decreased flux in the basilar artery (mean difference −0.9ml/s, CI −1.5 to −0.2, p=0.019). However, no changes were observed in the rCBF and flux in pre-symptomatic carriers compared with controls. Vascular reactivity was significantly decreased in the occipital lobe in both pre-symptomatic (BOLD amplitude 1.1±0.5% change, mean difference −0.4% change, CI −0.7 to −0.2, p=0.001; time to baseline 10.1±7.6 s, mean difference 4.6 s, CI 0.4 to 8.8, p=0.032) and symptomatic carriers (BOLD amplitude 0.4±0.1% change, mean difference −0.9% change, CI −1.1 to −0.6, p<0.0001; TTP 14.8±8.6 s, mean difference 12.2 s, CI 8.6 to 15.9,p<0.0001; TTB 20.3±8.4 s, mean difference 13.1s, CI 9.4 to 16.9, p<0.0001) compared with controls.
Use of [F]Fluoro-2-deoxy-D-glucose Positron Emission Tomographic Imaging in the National Lung Screening Trial

METHODS: We analyzed participants in the National Lung Screening Trial (NLST) with positive screening test results and identified individuals with a PET scan performed prior to lung cancer diagnosis (diagnostic PET). Appropriate scan was defined as one performed in a patient with a nodule $ 0.8 cm. Logistic regression was used to assess factors associated with diagnostic PET scan use and appropriateness of PET scan use.
Attitudes Toward Practice Guidelines Among ICU Personnel: A Cross-Sectional Anonymous Survey

Objectives—To assess attitudes of ICU staff members toward practice guidelines in general and toward a specific guideline, CDC's Guideline for Hand Hygiene in Healthcare Settings; to correlate these attitudes with staff and hospital characteristics; and to examine the impact of staff attitudes toward the Hand Hygiene Guideline on self reported implementation of the Guideline. Methods—A cross-sectional survey of staff in 70 ICUs in 39 U.S. hospitals, members of The National Nosocomial Infection Surveillance (NNIS) System. A survey, “Attitudes Regarding Practice Guidelines”, was administered anonymously to all willing staff during a site visit at each hospital; 1,359 ICU personnel: 1,003 nurses (74%), 228 physicians (17%), and 128 others (10%) responded. Results—Significantly more positive attitudes toward practice guidelines were found among staff in pediatric as compared with adult ICUs (p<0.001). Nurses and other staff when compared with physicians had more positive attitudes toward guidelines in general but not toward the specific Hand Hygiene Guideline. Those with more positive attitudes were significantly more likely to report that they had implemented recommendations of the Guideline (p<0.001) and used an alcohol product for hand hygiene (p=0.002). Conclusions—The majority of staff members were familiar with the CDC Hand Hygiene Guideline. Staff attitudes toward practice guidelines varied by type of ICU and by profession, and more positive attitudes were associated with significantly better self-reported guideline implementation. Because differences in staff attitudes might hinder or facilitate their acceptance and adoption of evidence-based practice guidelines, these results may have important implications for the education and/or socialization of ICU staff.
The VIIth Catalogue of Galactic Wolf-Rayet stars

The Vllth catalogue of Galactic Population I Wolf-Rayet stars provides improved coordinates, spectral types and b, v, K photometry of known WR stars, and it adds 62 new WR stars to the previous WR catalogue. The present census of Galactic WR stars stands at 218, including 117 WN stars, 87 we stars, 11 WN/We stars and 3 WO stars.
Explaining the Prospective Association of Positive and Negative Parenting Behaviors and Child ADHD Symptoms: Pathways Through Child Executive Function and Reward Responsivity

Objective: Parenting behavior is a well-established correlate of offspring ADHD. However, little is known about how parenting exerts its effects on offspring ADHD symptomatology. We examined whether prospective associations between positive and negative parenting behaviors and child ADHD symptoms are mediated by deficits in child executive function (EF) and reward responsivity (RR). Method: One hundred and thirty-five children with and without ADHD were assessed across two Waves, when children were mean ages 6 and 8 respectively. Children completed tasks on EF, and parents completed questionnaires about their parenting behaviors and their children’s RR and ADHD symptoms. Results: Negative parenting behavior at Wave 1 was indirectly associated with offspring ADHD symptoms at Wave 2 via offspring EF. Conclusion: Individual differences in EF, but not RR, during early childhood may constitute a potential pathway by which negative parenting behaviors exerts its effects on subsequent offspring ADHD symptomatology. Treatment implications are discussed.
Selection Incentives in the Dutch Basic Health Insurance: To What Extent Does End-of-Life Spending Contribute to Predictable Profits and Losses for Selective Groups?

Existing risk-equalization models in individual health insurance markets with premium-rate restrictions do not completely compensate insurers for predictable profits/losses, confronting insurers with risk selection incentives. To guide further improvement of risk-equalization models, it is important to obtain insight into the drivers of remaining predictable profits/losses. This article studies a specific potential driver: end-of-life spending (defined here as spending in the last 1–5 years of life). Using administrative (N = 16.9 m) and health survey (N = 384 k) data from the Netherlands, we examine the extent to which end-of-life spending contributes to predictable profits/losses for selective groups. We do so by simulating the predictable profits/losses for these groups with and without end-of-life spending while correcting for the overall spending difference between these two situations. Our main finding is that—even under a sophisticated risk-equalization model—end-of-life spending can contribute to predictable losses for specific chronic conditions.
Epidemiologic study of patients after Fontan operation based on Medical Aid Program for Chronic Pediatric Diseases of Specified Categories cohort

Abstract Nationwide registry data of patients with single-ventricle physiology have been rarely reported. The Medical Aid Program for Chronic Pediatric Diseases of Specified Categories (Japan) has contributed to the financial support of medical expense for patients younger than 20 years with chronic paediatric disease, and almost all children in Japan who require disease-specific treatment voluntarily apply to this programme. The epidemiology and medium- to long-term outcome of patients following a Fontan procedure were investigated using the database. The usefulness of this epidemiologic investigation in identifying real-world objectives and clinical applications was also examined. A total of 2862 patients who underwent a Fontan operation were identified from 18,589 patients with chronic heart disease registered to the medical aid programme. The details of symptoms, treatment, and somatic growth were evaluated, from which we were able to clarify the nationwide data regarding the current status of post-Fontan patients younger than 20 years. This study elucidated the current status of post-Fontan patients under 20 years of age in Japan. Data analysis of the Medical Aid Program for Chronic Pediatric Diseases of Specified Categories cohort provided useful information towards understanding the comprehensive status of patients with chronic heart disease and contributed to improved disease management.