tbuckley/cabot-search huggingface dataset:
SM5-1-Conjugated PLA nanoparticles loaded with 5-fluorouracil for targeted hepatocellular carcinoma imaging and therapy
Authors: Xibo Ma, Zhen Cheng, Yushen Jin, Xiaolong Liang, Xin Yang, Zhifei Dai, Jie Tian
Journal: Biomaterials (2014)

SM5-1 is a humanized mouse antibody which has a high binding specificity for a membrane protein of about 230 kDa overexpressed in hepatocellular carcinoma (HCC), melanoma and breast cancer. In this study, SM5-1-conjugated poly D, L (lactide-coglycolide) (PLA) PLA containing Cy7 (PLA-Cy7-SM5-1) was prepared to study the targeting specificity of the bioconjugate to HCC-LM3-fLuc cell. Then, SM5-1-conjugated PLA containing 5-fluorouracil (5-FU) (PLA-5FU-SM5-1) and PLA containing 5-FU (PLA-5FU) were prepared for treatment of subcutaneous HCC-LM3-fLuc tumor mice. The results showed that PLA-5FU-SM5-1, PLA-5FU and 5-FU induced a 45.07%, 23.56% and 19.05% tumor growth inhibition rate, respectively, on day 31 post-treatment as determined by bioluminescent intensity. In addition, in order to evaluate the antitumor efficacy of PLA-5FU-SM5-1, HCC-LM3-fLuc cells were injected into the liver to establish the experimental orthotopic liver tumor models. The experiments showed that PLA-5FU-SM5-1, PLA-5FU and 5-FU induced a 53.24%, 31.00%, and 18.11% tumor growth inhibition rate, respectively, on day 31 post-treatment determined by the bioluminescent intensity of the abdomen in tumor-bearing mice. Furthermore, we have calculated the three-dimensional location of the liver cancer in mice using a multilevel adaptive finite element algorithm based on bioluminescent intensity decay calibration. The reconstruction results demonstrated that PLA-5FU-SM5-1 inhibited the tumor rapid progression, which were consistent with the results of subcutaneous tumor mice experiments and in vitro cell experiment results.
Implantable cardioverter-defibrillator therapy in the absence of significant symptoms. Rhythm diagnosis and management aided by stored electrogram analysis.
Authors: B G Hook, D J Callans, R B Kleiman, B T Flores, F E Marchlinski
Journal: Circulation (1993)

BACKGROUND This report describes the value of stored ventricular electrogram analysis in the diagnosis and management of patients experiencing minimal or no symptoms before implantable cardioverter-defibrillator (ICD) therapy. METHODS AND RESULTS The study population included 48 patients who received the Cadence Tiered Therapy Defibrillator System, an investigational third-generation ICD with ventricular electrogram storage capabilities. Criteria for arrhythmia diagnosis were based on analysis of the electrogram rate, RR interval variability, and morphology. Twenty-nine of the 48 patients (60%) experienced at least one episode of antitachycardia pacing or shock (one shock or more in 25 of 29 patients) that was preceded by minimal or no symptoms during a mean follow-up of 15.1 +/- 7.8 months. There were 194 tachycardia episodes registered by the device, including 101 for which ventricular electrograms were stored and available for analysis. Of the 101 stored electrograms, 74 were classified as ventricular tachycardia (VT), 24 as non-VT rhythms (atrial fibrillation, 13; supraventricular tachycardia, six; rate-sensing lead disruption, four; T wave oversensing, one), and only three as indeterminate rhythms. Based on the electrogram analysis, changes in tachycardia detection criteria and/or antiarrhythmic drug regimens were implemented and were associated with a reduction in the number of device responses for non-VT rhythms from 24 during the initial study period to three during 11.0 +/- 7.2 months of additional follow-up. CONCLUSIONS ICD responses in the absence of symptoms are relatively common in third-generation devices with antitachycardia pacing capabilities. Despite potential limitations such as the effect of bundle branch block on the electrogram morphology during supraventricular tachycardia, the availability of electrogram storage capabilities allowed a presumptive diagnosis of the events precipitating asymptomatic device responses. Device reprogramming based on analysis of stored electrograms was associated with a dramatic reduction in the incidence of ICD responses for non-VT rhythms.
Single-Source Financing Systems
Authors: Richard B. Saltman
Journal: JAMA (1992)

Although tax-based and social insurance-based forms of single-source financing differ in how they raise funds, they share a common set of structural characteristics. In particular, they both enable publicly accountable authorities to control aggregate expenditure levels by creating a countervailing power to pressures for increased expenditures from providers. While major reform initiatives are under way in European single-source financing systems, these initiatives have so far sought to improve the efficiency, effectiveness, and/or responsiveness to patterns of service delivery without reducing their commitment to universal access to necessary care. The article concludes with a review of the advantages and disadvantages that could accompany the introduction of a single-source financing system in the United States.
Effects of coal combustion products and metal compounds on sister chromatid exchange (SCE) in a macrophagelike cell line
Authors: Ole Andersen
Journal: Environmental Health Perspectives (1983)

Investigations of genotoxic effects of particles have almost exclusively been performed by organic extraction, while direct investigations in cells capable of engulfing particles have only been performed in few cases. Thus, in most studies, the eventual effects of particle-associated metal compounds have remained undiscovered. The present study attempted direct measurement of genotoxic effects of particulate coal combustion products by using the P388D1 macrophage cell line. The capability of these cells for phagocytosis was demonstrated with insoluble particles. The sister chromatid exchange (SCE) test was used for measuring genotoxic effects of test compounds.Dimethylnitrosamine and benzo(a)pyrene did not increase SCE, indicating that the P388D1 cell line has lost the capacity for metabolism of latent organic carcinogens, reducing the value of these cells for evaluating genotoxic effects of complex particles. Indirect evidence has been obtained that the cell line may be infected with a virus. Thus, interactions between virus and test compound may lead to erroneous results. This should be kept in mind during evaluation of the results.The effects of metals with reported carcinogenic or mutagenic effects on SCE were compared in P388D1 cells and human lymphocytes: NaAsO2, CdCl2, K2Cr2O7, CoCl2, CH3HgCl and MnSO4 increased SCE in both cell systems. Pb(CH3COO)2, BeSO4 and NiSO4 had a weak effect on SCE in P388D1. Pb(CH3COO)2 and NiSO4, but not BeSO4, increased SCE in human lymphocytes. Cr(CH3COO)3 increased SCE in human lymphocytes at high concentration, but was a strong inducer of increased SCE in P388D1 cells, which take up Cr(III) by phagocytosis. This suggests that the Cr(III) ion is an ultimate carcinogenic form of chromium. Generally P388D1 cells and human lymphocytes respond to in vitro exposure to metals in agreement with reported mutagenic/carcinogenic effects of the metals.Of four precipitated coal fly ash samples tested, only one sample (from an electrostatic precipitator downstream of a cyclone at an electricity generating plant burning pulverized coal) had a clear increasing effect on SCE in P388D1. Extraction of this sample with medium with 10% serum yielded an extract capable of increasing SCE. The extracted particles still increased SCE, but less than unextracted particles.Emission samples taken with impactor sampler after a dilution probe using controlled cooling of the flue gas were obtained from an oil-fired (one sample) and a coal-fired (one sample < 3 μm and one sample < 3 μm) steam boiler. The only sample increasing SCE was the sample < 3 μm from the coal-fired boiler. Extract from this sample also increased SCE.The results demonstrated that the use of phagocytizing cells for assessment of genotoxic effects of particles offers a useful system, since the particles can be investigated directly. Furthermore, particles, extracted particles and extract can be investigated in the same system.
P48 Prevalence And Determinants Of Vitamin D Deficiency In Asthma Patients
Authors: D. Jolliffe, A. Martineau, B. Maclaughlin, K. Kiplin, P. Timms, C. Mein, R. Walton, C. Griffiths
Journal: Thorax (2014)

<h3>Background</h3> Vitamin D deficiency has been reported to associate with susceptibility to acute respiratory infections and exacerbations in asthma patients. Studies investigating the prevalence and determinants of vitamin D deficiency among asthma patients in the UK are lacking. <h3>Methods</h3> We conducted a cross-sectional study in297 asthma patients aged 16–78 years who participated in a clinical trial of vitamin D supplementation. Lifestyle and demographic data were collected by questionnaire and a blood sample was collected for analysis of serum 25-hydroxyvitamin D (25[OH]D) concentration and DNA extraction. Thirty-seven single nucleotide polymorphisms (SNP) in 13 vitamin D-related genes (DBP, DHCR7, CUBN, LRP2, CRTAM, LTA4H, CYP2R1, CYP3A4, CYP27A1, CYP27B1, CYP24A1, VDR, RXRA) were typed using Taqman allelic discrimination assays. Logistic regression was used to identify environmental and genetic factors associated with risk of vitamin D deficiency (25[OH]D concentration &lt; 50 nmol/L). <h3>Results</h3> Mean serum 25(OH)D concentration was 50.6 nmol/L (SD 24.9); 162/297 (54.5%) participants were deficient. The following factors independently associated with increased risk of deficiency: BMI of 25.1–30 kg/m<sup>2 </sup>(OR 2.20, p = 0.004) and &gt;30 kg/m<sup>2 </sup>(OR 1.96, p = 0.03); blood draw during winter season (OR 3.26, p = 0.001); Fitzpatrick skin-type score of 1 (“extremely fair skin; always burn, never tan” – OR 5.15, p = 0.02). The following factors independently associated with decreased risk of deficiency: Caucasian ethnicity (OR 0.23, p = 0.02); &gt;2 h of sun exposure/day (OR 0.48, p = 0.003); 100–400 IU vitamin D supplement, daily (OR 0.22, p &lt; 0.001); and use of a tanning bed in previous year (OR 0.20, p = 0.006). The following genetic factors independently associated with increased risk of deficiency: carriage of the G allele for DBP SNP rs4588 (GT genotype: OR 1.82, p = 0.02; GG genotype: OR 17.4, p = 0.006); GT genotype for CYP2R1 SNP rs10500804 (OR 1.85, p = 0.02); AG genotype for CYP2R1 SNP rs10766197 (OR 1.82, p = 0.03); AA genotype for VDR SNP rs7975232 (OR 2.15, p = 0.02). <h3>Conclusions</h3> Over half of participating asthma patients were vitamin D deficient. Obesity, winter sampling, fair skin, and SNP in DBP, CYP2R1 and VDR genes were risk factors for deficiency. Caucasian ethnicity, sun seeking behaviour, modest daily supplement doses and recent tanning bed use were protective.
Mutations in the Glucocerebrosidase Gene and Parkinson's Disease in Ashkenazi Jews
Authors: Judith Aharon-Peretz, Hanna Rosenbaum, Ruth Gershoni-Baruch
Journal: New England Journal of Medicine (2004)

A clinical association has been reported between type 1 Gaucher's disease, which is caused by a glucocerebrosidase deficiency owing to mutations in the glucocerebrosidase gene (GBA), and parkinsonism. We examined whether mutations in the GBA gene are relevant to idiopathic Parkinson's disease.
Drug Resistant Infections with Methicillin-Resistant Staphylococcus Aureus, Clostridium Difficile, and Vancomycin Resistant Enterococcus Are Associated with a Higher Prevalence of Penicillin Allergy
Authors: Vinitha Reddy, Neil S. Baman, Cynthia Whitener, Faoud T. Ishmael
Journal: Journal of Allergy and Clinical Immunology (2013)
Protein <i>S</i> -Nitrosylation and Cardioprotection
Authors: Junhui Sun, Elizabeth Murphy
Journal: Circulation Research (2010)

Nitric oxide (NO) plays an important role in the regulation of cardiovascular function. In addition to the classic NO activation of the cGMP-dependent pathway, NO can also regulate cell function through protein S-nitrosylation, a redox dependent, thiol-based, reversible posttranslational protein modification that involves attachment of an NO moiety to a nucleophilic protein sulfhydryl group. There are emerging data suggesting that S-nitrosylation of proteins plays an important role in cardioprotection. Protein S-nitrosylation not only leads to changes in protein structure and function but also prevents these thiol(s) from further irreversible oxidative/nitrosative modification. A better understanding of the mechanism regulating protein S-nitrosylation and its role in cardioprotection will provide us new therapeutic opportunities and targets for interventions in cardiovascular diseases.
National Assessment of Physicians' Breast-feeding Knowledge, Attitudes, Training, and Experience
Authors: Gary L. Freed, Sarah J. Clark, James Sorenson, Jacob A. Lohr, Robert Cefalo, Peter Curtis
Journal: JAMA (1995)

<h3>Objective.</h3> —Previous reports have demonstrated that physician counseling can improve rates of breast-feeding initiation and duration but suggest that physicians are ill-prepared for this role. It is unclear whether residency training for pediatricians, obstetrician/gynecologists, and family physicians provides the knowledge and skills necessary for effective breast-feeding promotion. <h3>Design.</h3> —Survey. <h3>Participants.</h3> —A national random sample of 3115 residents and 1920 practicing physicians in pediatrics, obstetrics/gynecology, and family medicine. <h3>Outcomes.</h3> —Assessment of breast-feeding knowledge, attitudes, training, and experience. <h3>Results.</h3> —Overall response rate was 68%. All groups demonstrated significant deficits in knowledge of breast-feeding benefits and clinical management; for example, less than 50% of residents chose appropriate clinical management for a breast-fed jaundiced infant or a breast abscess. Practicing physicians performed slightly better, but still more than 30% chose incorrect advice for mothers with low milk supply. Residents reported that their breast-feeding instruction consisted mainly of didactic lecture, not patient experience. Only 55% of senior residents recalled even one instance of precepting related to breast-feeding, and less than 20% had demonstrated breast-feeding techniques at least five times during residency. Regarding preparation for breast-feeding counseling, more than 50% of all practicing physicians rated their residency training as inadequate. Overall, physician involvement in breast-feeding promotion was endorsed by 90% of respondents, yet only half rated themselves as effective in counseling breast-feeding patients. The greatest predictor of physician self-confidence was previous personal or spousal breast-feeding experience. <h3>Conclusions.</h3> —In this national sample of residents and practicing physicians in three specialties, physicians were ill-prepared to counsel breast-feeding mothers. Deliberate efforts must be made to incorporate clinically based breast-feeding training into residency programs and continuing education workshops to better prepare physicians for their role in breast-feeding promotion. (<i>JAMA</i>. 1995;273:472-476)
Taking a bite: endocytosis in the maintenance of the slit diaphragm
Authors: Rosemary V. Sampogna, Qais Al-Awqati
Journal: Journal of Clinical Investigation (2012)

In the kidney, the slit diaphragm joins adjacent podocytes, forming an epithelial barrier that filters plasma into the urinary space, yet retains blood cells and proteins within the circulation. In this issue of the JCI, Soda et al. have identified clathrin-mediated endocytosis as a central mechanism by which the function and structural integrity of the slit diaphragm are maintained.
Effect of A.C.T.H. and Cortisone Therapy in Blood Disorders
Authors: L. S. P. Davidson, R. H. Girdwood, H. T. Swan
Journal: BMJ (1952)

Council (1952) has given a summary of the responses to A.C.T.H. and cortisone in 88 patients suffering from various blood disorders.The present paper reports in more detail the results of this form of therapy in 24 patients, many of whom were included in the M.R.C. report.The literature on this subject is not yet extensive and is dealt with by Wintrobe et al. (1951).The mechanism of action of these hormones is uncertain, and will not be discussed here.The cases are considered under three headings (a) patients with purpura, (b) those with haemolytic anaemia, and (c) those suffering from miscellaneous blood disorders.Where no clinical or haematological response occurred, the results of treatment are given only in tabular form. PurpuraFourteen cases of purpura have been treated with A.C.T.H. and/or cortisone, and of these 10 had thrombocytopenic purpura.The condition appeared to be idiopathic in all but two.In addition there were four patients suffering from persistent non-thrombocytopenic purpura in whom the exciting factor was unknown.These cases have been grouped together under the heading of " idiopathic non- thrombocytopenic purpura" (possibly allergic).There was some evidence of a response to hormone therapy in the following six patients with thrcmbocytopenic purpura.Case IThis patient, a man aged 55 with no previous history of bleeding, woke up one morning to find his mouth full of blood; this was due to bleeding gums, and continued up to the time of admission three weeks later.He also developed petechiae on the limbs and trunk, and bruised easily; these features, too, were limited to the three weeks before admission.There was no history of the taking of drugs, or of infection, or of exposure to chemicals.Apart from petechiae, bruises, and bleeding gums, the only abnormality found on admission was that the spleen was palpable on deep respiration.The haemoglobin level was 13.3 g.%, platelets 40,000 per c.mm., bleeding-time 29 minutes.The bone marrow contained numerous megakaryo- cytes and was otherwise normal.A diagnosis of idiopathic thrombocytopenic purpura was made.The patient was
Heart Rate and Carbon Monoxide Level After Smoking High-, Low-, and Non-Nicotine Cigarettes
Authors: WlLBERT S. ARONOW
Journal: Annals of Internal Medicine (1971)

Ten cigarette smokers with angina pectoris had blood pressure, heart rate, and expired-air carbon monoxide measurements before and after smoking each of five high-, low-, and non-nicotine cigarettes. There was a significant increase in systolic and diastolic blood pressure after smoking each high- and low-nicotine cigarette, with a significant increase in peak systolic and diastolic blood pressure from cigarette 1 to cigarette 5. There was a significant increase in heart rate after smoking each high- and low-nicotine cigarette but no significant increase in peak heart rate from cigarette 1 to cigarette 5. There was no significant increase in blood pressure or heart rate after smoking a non-nicotine cigarette. There was a significant increase in carbon monoxide level after smoking each high-, low-, and non-nicotine cigarette, with a significant increase in peak carbon monoxide level from cigarette 1 to cigarette 5.
HLA AND CONGENITAL ADRENAL HYPERPLASIA
Authors: S. Zappacosta, M. De Felice, M. Minozzi, G. Lombardi, Rossella Valentino, Giuseppina Vanacore, L.M. Murtaza, I.A. Hughes, J.R. Sibert, I.C. Balfour
Journal: The Lancet (1978)
Perioperative glycemic control and the risk of infectious complications in a cohort of adults with diabetes.
Authors: S H Golden, C Peart-Vigilance, W H Kao, F L Brancati
Journal: Diabetes Care (1999)

OBJECTIVE: Although hyperglycemia is hypothesized to increase the short-term risk of infection, this hypothesis has not been well tested in a clinical setting. This study was designed to assess the relationship of perioperative glycemic control to the subsequent risk of infectious complications. RESEARCH DESIGN AND METHODS: A total of 411 adults with diabetes who underwent coronary artery surgery from 1990 to 1995 in the cardiac surgery service of an urban university hospital were included in a nonconcurrent prospective cohort study based on chart review. Perioperative glycemic control was characterized by the mean of six capillary glucose measurements taken during the 36-h interval following surgery. The major outcomes studied were infections of leg and chest wounds, pneumonia, and urinary tract infections. RESULTS: Mean postoperative glucose levels ranged from 121 to 352 mg/dl and were divided into quartiles: quartile 1 (121-206 mg/dl), quartile 2 (207-229 mg/dl), quartile 3 (230-252 mg/dl), and quartile 4 (253352 mg/dl). After simultaneous adjustment for age, sex, race, underlying comorbidity, acute severity of illness, and the length of the stay in the surgical intensive care unit, patients with higher mean capillary glucose readings were at increased risk of developing infections. Compared with people in the lowest quartile of postoperative glucose, those in quartiles 2 (relative odds of infection [95% CI] = 1.17 [0.57-2.40]), 3 (1.86 [0.94-3.68]), and 4 (1.78 [0.86-3.47]) were at progressively higher risk for infection (P = 0.05 for trend). CONCLUSIONS: In patients with diabetes who undergo coronary artery surgery, postoperative hyperglycemia is an independent predictor of short-term infectious complications. Physicians should consider a glucose concentration target of &amp;lt; or =200 mg/dl to reduce the risk of infection.
Misoprostol for the management of postpartum haemorrhage
Authors: A. Elati, A. Weeks
Journal: BMJ (2011)

No benefit if oxytocin is available, but useful where no other alternatives exist

For decades, oxytocin and ergometrine have been the treatments of choice for postpartum haemorrhage caused by ineffective uterine contraction (uterine atony). Although both drugs are effective, oxytocin is more widely used because it has fewer side effects and can be used safely in women with hypertension and pre-eclampsia. However, in their usual form both drugs can be given only by injection, and both require refrigeration. They are therefore of limited availability and benefit in low resource settings, especially in rural areas. Misoprostol, an orally active and heat stable prostaglandin E1 analogue, has therefore emerged as a popular alternative. Until a year ago, there was limited evidence for its ability to treat postpartum haemorrhage.1 2 However proponents have argued that it should be “parachuted in” to high risk areas despite the lack of evidence.3 This, in part, has been responsible for its inclusion in multiple guidelines on postpartum haemorrhage both in rich and poor settings (despite the call in a systematic review for more studies2).

Since the systematic review of the treatment of postpartum haemorrhage was last updated in 2007,2 three large double blind randomised trials have been published.4 5 6 Few research …
Pravastatin inhibits advanced glycation end products (AGEs)-induced proximal tubular cell apoptosis and injury by reducing receptor for AGEs (RAGE) level
Authors: Yuji Ishibashi, Sho-ichi Yamagishi, Takanori Matsui, Keisuke Ohta, Ryuichiro Tanoue, Masayoshi Takeuchi, Seiji Ueda, Kei-ichiro Nakamura, Seiya Okuda
Journal: Metabolism (2012)
Taking Their Own Lives — The High Rate of Physician Suicide
Authors: Eva Schernhammer
Journal: New England Journal of Medicine (2005)

When I was an oncology fellow in Vienna, a colleague who had attended rounds with me on the ward went home afterward and strangled herself. Only later was it learned that she had suffered from depression. In the course of that same year, three more physicians in my immediate circle — two residents and a department head — took their own lives. This stunning series was my first encounter with physician suicide, and it left many of us doctors with an important message: we must care not only for our patients but also for ourselves. In an effort to prevent . . .
Disclosing Individual Genetic Research Results to Deceased Participants’ Relatives by Means of a Qualified Disclosure Policy
Authors: Annelien L. Bredenoord, Johannes JM van Delden
Journal: The American Journal of Bioethics (2012)

Due to the rapid developments in next-generation sequencing (NGS) technology, the ability to sequence an individual's entire genome is now feasible and affordable and will further accelerate the pa...