tbuckley/cabot-search huggingface dataset:
Wheat Bran, Whole Grain, and Food Synergy
Authors: David R. Jacobs, Lyn M. Steffen
Journal: Diabetes Care (2002)

This issue of Diabetes Care contains an article by Jenkins et al. (1) with a surprising, perhaps counter-intuitive result. The authors studied 23 type 2 diabetic volunteers in a randomized cross-over design with 3 months consumption of wheat bran contributing 19 g fiber per day, compared with 3 months consumption of refined grain with 4 g fiber per day. The wheat bran supplement had no discernible effect on body weight, fasting blood glucose, HbA1c, serum lipids, apolipoproteins, blood pressure, serum uric acid, clotting factors, homocysteine, C-reactive protein, magnesium, calcium, iron, or ferritin. The only statistically significant finding was unanticipated: there was a small increase in LDL oxidation associated with wheat bran. The study was conducted meticulously by investigators well known for their important findings in the effect of foods on human metabolism. We applaud both the execution and the publication of this article.

Despite the applause, all studies have potential flaws, and limitations of this study deserve comment. One remarkable flaw is that 44 of the 67 people who began the study dropped out. There is no way to fully assess whether these dropouts might have biased the findings. In our experience, asking participants to stay with a study for two 3-month periods is very ambitious. According to Dr. Jenkins (personal communication, 14 June 2002), this difficult protocol was carried out without any payment to the participants. Our assumption is that the failure to provide any financial compensation to participants is telling and likely accounts for the high dropout rate. However, it is our opinion that desire to be compensated for research participation is largely unrelated to metabolic outcomes.

Another weakness in the study design is that the participants chose their own diets, except for …
Risk of Invasive<i>Haemophilus influenzae</i>Infection During Pregnancy and Association With Adverse Fetal Outcomes
Authors: Sarah Collins, Mary Ramsay, Mary P. E. Slack, Helen Campbell, Sally Flynn, David Litt, Shamez N. Ladhani
Journal: JAMA (2014)

Unencapsulated Haemophilus influenzae frequently causes noninvasive upper respiratory tract infections in children but can also cause invasive disease, especially in older adults. A number of studies have reported an increased incidence in neonates and suggested that pregnant women may have an increased susceptibility to invasive unencapsulated H. influenzae disease.To describe the epidemiology, clinical characteristics, and outcomes of invasive H. influenzae disease in women of reproductive age during a 4-year period.Public Health England conducts enhanced national surveillance of invasive H. influenzae disease in England and Wales. Clinical questionnaires were sent prospectively to general practitioners caring for all women aged 15 to 44 years with laboratory-confirmed invasive H. influenzae disease during 2009-2012, encompassing 45,215,800 woman-years of follow-up. The final outcome was assessed in June 2013.Invasive H. influenzae disease confirmed by positive culture from a normally sterile site.The primary outcome was H. influenzae infection and the secondary outcomes were pregnancy-related outcomes.In total, 171 women had laboratory-confirmed invasive H. influenzae infection, which included 144 (84.2%; 95% CI, 77.9%-89.3%) with unencapsulated, 11 (6.4%; 95% CI, 3.3%-11.2%) with serotype b, and 16 (9.4%; 95% CI, 5.4%-14.7%) with other encapsulated serotypes. Questionnaire response rate was 100%. Overall, 75 of 171 women (43.9%; 95% CI, 36.3%-51.6%) were pregnant at the time of infection, most of whom were previously healthy and presented with unencapsulated H. influenzae bacteremia. The incidence rate of invasive unencapsulated H. influenzae disease was 17.2 (95% CI, 12.2-24.1; P < .001) times greater among pregnant women (2.98/100,000 woman-years) compared with nonpregnant women (0.17/100,000 woman-years). Unencapsulated H. influenzae infection during the first 24 weeks of pregnancy was associated with fetal loss (44/47; 93.6% [95% CI, 82.5%-98.7%]) and extremely premature birth (3/47; 6.4% [95% CI, 1.3%-17.5%]). Unencapsulated H. influenzae infection during the second half of pregnancy was associated with premature birth in 8 of 28 cases (28.6%; 95% CI, 13.2%-48.7%) and stillbirth in 2 of 28 cases (7.1%; 95% CI, 0.9%-23.5%). The incidence rate ratio for pregnancy loss was 2.91 (95% CI, 2.13-3.88) for all serotypes of H. influenzae and 2.90 (95% CI, 2.11-3.89) for unencapsulated H. influenzae compared with the background rate for pregnant women.Among women in England and Wales, pregnancy was associated with a greater risk of invasive H. influenzae infection. These infections were associated with poor pregnancy outcomes.
Screening for Celiac Disease in Children With Type 1 Diabetes
Authors: Michael Freemark, Lynne L. Levitsky
Journal: Diabetes Care (2003)

Celiac sprue is a chronic intestinal disorder caused by hypersensitivity to prolamins, the glutamine- and proline-rich gluten proteins contained in wheat, rye, and barley. Genetically predisposed subjects who ingest cereal proteins develop an inflammatory enteropathy characterized by proliferation of intraepithelial lymphocytes, crypt hyperplasia, and partial or complete atrophy of small intestinal villi. The inflammatory response is induced by cross-linking and transamidation of gluten peptides by tissue transglutaminase, an enzyme localized to the connective tissue (lamina propria or endomysium) underlying the epithelial cells of the small intestine. Posttranslational modification of gluten enhances its uptake by dendritic cells and its binding to HLA-DQ2 and DQ-8, which induce T-cell activation and cytokine release (1,2). The resulting inflammation is accompanied by development of circulating antibodies to transglutaminase and to the endomysium.

Inflammatory denudation of the villous surface gives rise to malabsorption of foodstuffs, folate, fat-soluble vitamins, and iron. Young children with classical symptomatic celiac disease may present with diarrhea and growth failure, muscle wasting, hypotonia, pallor, edema, anemia, and in some cases, rickets. Older children and adults with classical celiac disease may have episodic diarrhea, steatorrhea, weight loss, and osteoporosis, and the risk of gastrointestinal malignancy is increased (3–7). However, many children and adults with celiac disease have nonclassical forms of the illness. So-called silent celiac disease refers to partial or complete villous atrophy in a seropositive patient who has no gastrointestinal or extra-intestinal complications. Subclinical celiac disease refers to villous atrophy in a seropositive patient who has extra-intestinal complications but few or no gastrointestinal complaints. Extra-intestinal maladies associated with celiac disease may include anovulation, infertility and miscarriage, neurologic disorders and epilepsy, and hepatocellular dysfunction.

Studies in Western Europe, North America, and Australia indicate that the prevalence of celiac disease among children and adults with type 1 diabetes (mean 4.1%, …
A 35 year old smoker with shortness of breath
Authors: G. A. Margaritopoulos, A. G. Nicholson, G. Giannarakis, I. Lambiri, N. M. Siafakas, K. M. Antoniou
Journal: BMJ (2010)

A previously well 35 year old man who currently smoked cigarettes (40 pack years) was referred because of a history of dyspnoea on exertion that had gradually got worse during the two months before presentation and a cough that was initially productive but then dry. He regularly smoked crack cocaine and took cocaine intranasally. At presentation he had hypoxaemia (partial pressure of oxygen 57 mm Hg), with a respiratory rate of 20 breaths/min. Physical examination showed only bilateral fine inspiratory crackles at the middle and lower zones of the chest. Initial blood tests were unremarkable. He had no signs of collagen tissue disorder, his autoantibody profile was negative, and HIV screening was negative. Chest radiography showed a bilateral reticular pattern at the middle and lower zones and bilateral infiltrates in the lower zones of the lung. Pulmonary function testing showed a restrictive pattern (total lung capacity 49%, forced expiratory volume in one second 48%, forced vital capacity 47%, diffusing capacity of the lung for carbon monoxide 36%). A 12 lead resting electrocardiogram showed sinus rhythm and an echocardiogram showed no abnormalities and no indirect evidence of pulmonary hypertension. Baseline saturation was 96% with a heart rate of 100 beats/min. During the six minute walking distance test he desaturated to 83% after three minutes and having completed 110 m. He underwent high resolution computed tomography of the chest (figs 1 and 2⇓ ⇓). Fig 1 High resolution computed tomography of the chest: upper lung zones Fig 2 High resolution computed tomography of the chest: lower lung zones
Comprehensive Geriatric Assessment for Older Patients With Cancer
Authors: Martine Extermann, Arti Hurria
Journal: Journal of Clinical Oncology (2007)

During the last decade, oncologists and geriatricians have begun to work together to integrate the principles of geriatrics into oncology care. The increasing use of a comprehensive geriatric assessment (CGA) is one example of this effort. A CGA includes an evaluation of an older individual's functional status, comorbid medical conditions, cognition, nutritional status, psychological state, and social support; and a review of the patient's medications. This article discusses recent advances on the use of a CGA in older patients with cancer.In this article, we provide an update on the studies that address the domains of a geriatric assessment applied to the oncology patient, review the results of the first studies evaluating the use of a CGA in developing interventions to improve the care of older adults with cancer, and discuss future research directions.The evidence from recent studies demonstrates that a CGA can predict morbidity and mortality in older patients with cancer. Accumulating data show the benefits of incorporating a CGA in the evaluation of older patients with cancer. Prospective trials evaluating the utility of a CGA to guide interventions to improve the quality of cancer care in older adults are justified.Growing evidence demonstrates that the variables examined in a CGA can predict morbidity and mortality in older patients with cancer, and uncover problems relevant to cancer care that would otherwise go unrecognized.
Spindle-Cell Thymoma
Authors: Oz M Shapira, John M Kasznica
Journal: New England Journal of Medicine (2003)

A 77-year-old Chinese woman presented with an abnormality on a chest film obtained as part of her screening for immigration to the United States. A posteroanterior film showed a well-circumscribed mass, 8 cm in diameter, in the lower region of the anterior mediastinum and extending into the right hemithorax (Panel A, arrows). The mass was completely excised through a right thoracotomy. There was no evidence of invasion of adjacent structures. Gross examination of a section of the specimen showed irregular, friable areas of hemorrhage and necrosis (Panel B). Microscopical examination showed mixed spindle and polygonal cells arranged in ill-defined bundles . . .
Abstract 1761: Breast cancers with compromised DNA repair exhibit selective sensitivity to elesclomol-induced oxidative DNA damage
Authors: Elizabeth Alli, James M. Ford
Journal: Cancer Research (2012)

Abstract Hereditary breast cancers due to germline mutations in BRCA1 and sporadic breast cancers of the basal-like subtype are often triple-negative, i.e. lack expression of estrogen and progesterone receptors and lack overexpression/amplification of the HER2/neu oncogene. Given that the triple-negative status of these cancers renders them relatively insensitive to existing “targeted” therapy, improved treatment options are needed. We tested a panel of cell lines that represent the different molecular subtypes of breast cancer for sensitivity to elesclomol, an experimental therapeutic that produces elevated levels of oxidative DNA damage, using the MTT assay. We found that both BRCA1-mutated and basal-like breast cancer cell lines with defective base-excision DNA repair (BER) were markedly more sensitive to elesclomol than cell lines that represent the normal breast or other subtypes of breast cancer with proficient BER. We also assessed sensitivity to elesclomol in breast cancer cell lines that were stably transduced with shRNA to OGG1, a BER glycosylase required for the repair of the most common type of oxidative DNA damage. Two different cell lines with decreased levels of OGG1 (shOGG1A, 50% knock-down; shOGG1B, 20% knock-down) were more sensitive to elesclomol (IC50 = 0.04nM and 0.3nM, respectively) compared to two different isogenic control cell lines (IC50 = 2nM and 3nM, respectively). Taken together, these data suggest that compromised repair of oxidative DNA damage by BER represents a functional target for elesclomol. Overall, BRCA1-mutated and/or basal-like breast cancers may benefit from treatment regimens that include elesclomol. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1761. doi:1538-7445.AM2012-1761
Regulation of membrane chloride currents in rat bile duct epithelial cells.
Authors: J G Fitz, S Basavappa, J McGill, O Melhus, J A Cohn
Journal: Journal of Clinical Investigation (1993)

This study examines the conductive properties of the plasma membrane of cells isolated from the intrahepatic portion of bile ducts. Membrane Cl- conductance was measured in single cells using whole-cell patch clamp recording techniques and in cells in short-term culture using 36Cl and 125I efflux. Separate Ca(2+)- and cAMP-dependent Cl- currents were identified. Ca(2+)-dependent Cl- currents showed outward rectification of the current-voltage relation, time-dependent activation at depolarizing potentials, and reversal near the equilibrium potential for Cl-. Ionomycin (2 microM) increased this current from 357 +/- 72 pA to 1,192 +/- 414 pA (at +80 mV) in 5:7 cells, and stimulated efflux of 125I > 36Cl in 15:15 studies. Ionomycin-stimulated efflux was inhibited by the Cl- channel blocker 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS) (150 microM). A separate cAMP-activated Cl- current showed linear current-voltage relations and no time dependence. Forskolin (10 microM) or cpt-cAMP (500 microM) increased this current from 189 +/- 50 pA to 784 +/- 196 pA (at +80 mV) in 11:16 cells, and stimulated efflux of 36Cl > 125I in 16:16 studies. cAMP-stimulated efflux was unaffected by DIDS. Because the cAMP-stimulated Cl- conductance resembles that associated with cystic fibrosis transmembrane conductance regulator (CFTR), a putative Cl- channel protein, the presence of CFTR in rat liver was examined by immunoblot analyses. CFTR was detected as a 150-165-kD protein in specimens with increased numbers of duct cells. Immunoperoxidase staining confirmed localization of CFTR to bile duct cells but not hepatocytes. These findings suggest that Ca(2+)- and cAMP-regulated Cl- channels may participate in control of fluid and electrolyte secretion by intrahepatic bile duct epithelial cells, and that the cAMP-regulated conductance is associated with endogenous expression of CFTR. Abnormal ductular secretion may contribute to the pathogenesis of cholestatic liver disease in cystic fibrosis.
A Randomized Trial of Inhaled Nitric Oxide to Prevent Ischemia–Reperfusion Injury after Lung Transplantation
Authors: Maureen O. Meade, John T. Granton, Andrea Matte-Martyn, Karen McRae, Bruce Weaver, Paula Cripps, Shaf H. Keshavjee
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Inhalation of nitric oxide (NO) has been advocated as a method to prevent ischemia–reperfusion injury after lung transplantation. We enrolled 84 patients into a concealed, randomized, placebo-controlled trial to evaluate the effect of inhaled NO (20 ppm NO or nitrogen) initiated 10 minutes after reperfusion on outcomes after lung transplantation. The groups (n = 42) were balanced with respect to age, sex, lung disease, procedure, and total ischemic times. PaO2/FIO2 ratios were similar on admission to the intensive care unit (ICU) (NO 361 ± 134; control patients 357 ± 132), and over the duration of the study. There were no differences in hemodynamics between the two groups. Severe reperfusion injury (PaO2/FIO2 < 150) was present at the time of admission to the ICU in 14.6% NO patients versus 9.5% of control patients (p = 0.48). The groups had similar median times to first successful trial of unassisted breathing (25 vs. 27 hours; p = 0.76), successful extubation (32 vs. 34 hours; p = 0.65), ICU discharge (3.0 days for both groups), and hospital discharge (27 vs. 29 days; p = 0.563). Five NO versus six control patients died during their hospital stay. Adjusting for age, sex, lung disease etiology, presence of pulmonary hypertension, and total ischemic time did not alter these results. In conclusion, we did not detect a significant effect of inhaled NO administered 10 minutes after reperfusion on physiologic variables or outcomes in lung transplant patients.
The Resurgence of Measles and Herd Immunity
Authors: Bruce P. Lanphear
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Schlenker et al have documented evidence that immunization levels over 80% provided a significant level of herd immunity.<sup>1</sup>Their study also raises a question that was not addressed by the authors: what is the basis for the resurgence of measles in the preschool-age population? Although it is easy to assume that the resurgence is due to inadequate levels of vaccination, they estimated that the rates of immunization had not changed from 1982 through 1989.<sup>1</sup>Since there has been an increase in the number of births nationally, data were obtained from the Milwaukee (Wis) Public Health Department to determine whether there was any relation between the number of births and the measles epidemic. From 1980 through 1990, there was a 9% increase in the annual number of live births in the city of Milwaukee, from 11772 to 12780 (Gloria Tatum, Milwaukee Public Health Department, oral communication).
The Evils of Camouflage as Illustrated by Thalidomide
Authors: Helen B. Taussig
Journal: New England Journal of Medicine (1963)

THE abrupt decline in the occurrence of phocomelia in West Germany eight months to the day after the public announcement that thalidomide (Contergan) was suspected as the cause offered conclusive evidence that Lenz1 and McBride2 were correct in their belief that the ingestion of this substance in early pregnancy caused phocomelia in the offspring. Indeed, the incidence of phocomelia dropped almost to zero. In September, 1962, I was advised that 1 case had been reported in August; this woman had not heard the warning and had taken thalidomide in early pregnancy. These events show how widespread the publicity was on . . .
TCT-332 Relation Between Fractional Flow Reserve And Coronary Bifurcation Anatomy: A Novel Quantitative Model To Assess The Stenotic Severity Of Bifurcation Lesions
Authors: Shengxian Tu, Mauro Echavarria-Pinto, Clemens von Birgelen, Niels R. Holm, Stylianos A. Pyxaras, Indulis Kumsars, Ming Kai Lam, Ilona Valkenburg, Gabor G. Toth, Yingguang Li, Javier Escaned, William C. Wijns, Johan H. Reiber
Journal: Journal of the American College of Cardiology (2014)
Extensive Ex Vivo Expansion of Functional Human Erythroid Precursors Established From Umbilical Cord Blood Cells by Defined Factors
Authors: Xiaosong Huang, Siddharth Shah, Jing Wang, Zhaohui Ye, Sarah N Dowey, Kit Man Tsang, Laurel G Mendelsohn, Gregory J Kato, Thomas S Kickler, Linzhao Cheng
Journal: Molecular Therapy (2013)

There is a constant shortage of red blood cells (RBCs) from sufficiently matched donors for patients who need chronic transfusion. Ex vivo expansion and maturation of human erythroid precursors (erythroblasts) from the patients or optimally matched donors could represent a potential solution. Proliferating erythroblasts can be expanded from umbilical cord blood mononuclear cells (CB MNCs) ex vivo for 10(6)-10(7)-fold (in ~50 days) before proliferation arrest and reaching sufficient number for broad application. Here, we report that ectopic expression of three genetic factors (Sox2, c-Myc, and an shRNA against TP53 gene) associated with iPSC derivation enables CB-derived erythroblasts to undergo extended expansion (~10(68)-fold in ~12 months) in a serum-free culture condition without change of cell identity or function. These expanding erythroblasts maintain immature erythroblast phenotypes and morphology, a normal diploid karyotype and dependence on a specific combination of growth factors for proliferation throughout expansion period. When being switched to a terminal differentiation condition, these immortalized erythroblasts gradually exit cell cycle, decrease cell size, accumulate hemoglobin, condense nuclei and eventually give rise to enucleated hemoglobin-containing erythrocytes that can bind and release oxygen. Our result may ultimately lead to an alternative approach to generate unlimited numbers of RBCs for personalized transfusion medicine.
Abnormal Pattern of Cortical Activation Associated With Voluntary Movement in Obsessive-Compulsive Disorder: An EEG Study
Authors: Letizia Leocani, Marco Locatelli, Laura Bellodi, Carla Fornara, Marta Hénin, Giuseppe Magnani, Silvia Mennea, Giancarlo Comi
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Converging evidence in patients with obsessive-compulsive disorder (OCD) shows abnormalities of prefrontal areas and basal ganglia, which are also involved in motor control. Event-related desynchronization of mu and beta EEG rhythms is considered a correlate of motor activation during motor preparation and execution, followed by cortical idling or inhibition indicated by event-related synchronization. The authors investigated the circuits involved in motor behavior in OCD by using event-related desynchronization/synchronization. METHOD: Data on alpha and beta event-related desynchronization/synchronization with self-paced movement of the right thumb were obtained by using 29-channel EEG in 10 untreated OCD patients and 10 normal subjects. RESULTS: OCD patients showed delayed onset of mu event-related desynchronization with movement preparation and less postmovement beta synchronization, compared to normal subjects. CONCLUSIONS: Delayed event-related desynchronization in OCD is consistent with involvement of structures related to motor programming, such as basal ganglia. Lower levels of postmovement beta synchronization suggest impairment of the inhibitory system in OCD.