tbuckley/cabot-search huggingface dataset:
A unified model of atrioventricular nodal conduction predicts dynamic changes in Wenckebach periodicity.
Authors: M Talajic, D Papadatos, C Villemaire, L Glass, S Nattel
Journal: Circulation Research (1991)

The atrioventricular (AV) node responds in a complex fashion to changes in activation rate. A variety of approaches have been used to explain these dynamic AV nodal responses, but none has been able to account fully for AV nodal behavior. Three specific rate-dependent properties of the AV node have been described: 1) time-dependent recovery after excitation, 2) an effect of short cycles to advance recovery ("facilitation"), and 3) a gradual slowing of conduction in response to sustained, high-frequency activation ("fatigue"). We hypothesized that a model incorporating quantitative descriptors of all three processes might be able to account for a wide variety of AV nodal behaviors. Quantitative descriptors of AV nodal recovery, facilitation, and fatigue were developed based on AV nodal conduction changes during selective pacing protocols in seven autonomically blocked dogs. These descriptors were incorporated into a set of mathematical equations that define AV nodal conduction of any beat based on activation history. The equations were then applied to predict pacing-induced Wenckebach periodicity in each dog. Experimental data were obtained after nine to 19 step decreases in atrial cycle length into the Wenckebach zone in each animal. Observed behaviors included complex patterns of block, a progressive increase in the level of block over 5 minutes of rapid pacing, and periods of alternating patterns of block. The model accurately predicted the onset of AV block at each cycle length, the relation between conduction ratio and cycle length as a function of time, and the changing patterns of Wenckebach periodicity during sustained atrial pacing. All three terms of the model equation (describing recovery, facilitation, and fatigue) were essential to account fully for the observed behaviors. Elimination of AV nodal fatigue from the model resulted in failure to account for time-dependent changes in Wenckebach patterns, whereas exclusion of facilitation led to consistent overestimation of the degree of AV block at each cycle length. We conclude that a mathematical model incorporating terms to describe recovery, facilitation, and fatigue accurately predicts a wide range of Wenckebach-type behavior and that complex conduction patterns of the AV node can be fully accounted for by simple functional AV nodal properties.
Delirium in Elderly Patients and the Risk of Postdischarge Mortality, Institutionalization, and Dementia
Authors: Joost Witlox, Lisa S. M. Eurelings, Jos F. M. de Jonghe, Kees J. Kalisvaart, Piet Eikelenboom, Willem A. van Gool
Journal: JAMA (2010)

<h3>Context</h3>Delirium is a common and serious complication in elderly patients. Evidence suggests that delirium is associated with long-term poor outcome but delirium often occurs in individuals with more severe underlying disease.<h3>Objective</h3>To assess the association between delirium in elderly patients and long-term poor outcome, defined as mortality, institutionalization, or dementia, while controlling for important confounders.<h3>Data Sources</h3>A systematic search of studies published between January 1981 and April 2010 was conducted using the databases of MEDLINE, EMBASE, PsycINFO, and CINAHL.<h3>Study Selection</h3>Observational studies of elderly patients with delirium as a study variable and data on mortality, institutionalization, or dementia after a minimum follow-up of 3 months, and published in the English or Dutch language. Titles, abstracts, and articles were reviewed independently by 2 of the authors. Of 2939 references in the original search, 51 relevant articles were identified.<h3>Data Extraction</h3>Information on study design, characteristics of the study population, and outcome were extracted. Quality of studies was assessed based on elements of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies.<h3>Data Synthesis</h3>The primary analyses included only high-quality studies with statistical control for age, sex, comorbid illness or illness severity, and baseline dementia. Pooled-effect estimates were calculated with random-effects models. The primary analysis with adjusted hazard ratios (HRs) showed that delirium is associated with an increased risk of death compared with controls after an average follow-up of 22.7 months (7 studies; 271/714 patients [38.0%] with delirium, 616/2243 controls [27.5%]; HR, 1.95 [95% confidence interval {CI}, 1.51-2.52]; I<sup>2</sup>, 44.0%). Moreover, patients who had experienced delirium were also at increased risk of institutionalization (7 studies; average follow-up, 14.6 months; 176/527 patients [33.4%] with delirium and 219/2052 controls [10.7%]; odds ratio [OR], 2.41 [95% CI, 1.77-3.29]; I<sup>2</sup>, 0%) and dementia (2 studies; average follow-up, 4.1 years; 35/56 patients [62.5%] with delirium and 15/185 controls [8.1%]; OR, 12.52 [95% CI, 1.86-84.21]; I<sup>2</sup>, 52.4%). The sensitivity, trim-and-fill, and secondary analyses with unadjusted high-quality risk estimates stratified according to the study characteristics confirmed the robustness of these results.<h3>Conclusion</h3>This meta-analysis provides evidence that delirium in elderly patients is associated with poor outcome independent of important confounders, such as age, sex, comorbid illness or illness severity, and baseline dementia.
Cigarette Smoking and Urinary Estrogens
Authors: Brian MacMahon, Dimitrios Trichopoulos, Philip Cole, James Brown
Journal: New England Journal of Medicine (1982)

IT is known that women who smoke have an earlier menopause than those who do not.1 , 2 Noting recent data suggesting that breast cancer might be somewhat less frequent in smokers than in non-smokers,3 4 5 we thought it would be worthwhile to compare the estrogen profiles of smokers and nonsmokers. A difference might shed light on the mechanisms whereby smoking is associated with early menopause and with a reduction in the risk of breast cancer. Smoking histories were obtained from women for whom urinary estrogen concentrations had been determined previously. As compared with nonsmokers and exsmokers, smokers had substantially and significantly lower . . .
Priorities in Oregon-Reply
Authors: Elliott Fisher
Journal: JAMA (1992)

In Reply.  —As stated in our article, we agree with Dr Caper about the importance of modifying the implementation of constraints on the local bed supply based on detailed knowledge of local conditions. We also recognize that different hospital utilization patterns are observed in areas of greater poverty. We question, however, the degree to which the overall hospitalization rates in poverty areas are determined by morbidity levels.  The study cited by Caper is most consistent, in fact, with the hypothesis that it is the lack of insurance and the lack of adequate access to primary care services, not morbidity, that are the major predictors of higher hospital-use rates among the poor. 1 First, Billings and Hasselblad 1 found similar rates of admission across income levels for conditions in which illness determines the need for hospitalization, such as acute myocardial infarction and hip fracture. Second, the relationship between admission rates and
Abstract B19: Functional genomics approach links anchorage-independence with tumor dormancy in ovarian cancer
Authors: Noriomi Matsumura, Koji Yamanoi, Yasuaki Amano, Junzo Hamanishi, Tsukasa Baba, Susan K. Murphy, Ikuo Konishi
Journal: Clinical Cancer Research (2013)

Abstract Although a number of genes are aberrantly regulated in ovarian cancer, little is known about which genes are functionally important. The aim of this study was to identify new genes relevant to anchorage-independent growth of ovarian cancer cells through a genome-wide functional screening approach. We performed lentiviral transduction of a library of 81,000 shRNAs (Cellecta, Inc.) targeting 15,000 genes into an immortalized human ovarian surface epithelium cell line and 7 ovarian cancer cell lines (OVCA420, OVCA433, OVCA429, CAOV3, SKOV8, Tyk-nu and DOV13) which do not generate anchorage-independent colonies in soft agar. Among these, only OVCA420 generated colonies larger than 100 micrometers after shRNA library transduction. We extracted DNA from these colonies, amplified the shRNA constructs with PCR, and inserted the amplicons back into the original lentiviral vector, thus generating a secondary library of 68 shRNAs. Subsequent analysis, performed to examine the reproducible formation of anchorage-independent colonies using the secondary library, identified 5 shRNAs targeting ABHD2, CYB5R3, MR1, ELAC2 and CCL22. Interestingly, population doubling time was increased following transduction of these shRNAs (44.8, 50.1, 43.9, 28.0 and 33.2 hours, respectively) compared to the original or control shRNA-transducted OVCA420 cells (22.4 and 23.7 hours, respectively). Furthermore, side populations detected by efflux of Hoechst 33342 dye were drastically increased (50.5, 46.6, 55.5, 76.5 and 41.1%, respectively) compared to the original or control shRNA-transducted OVCA420 cells (7.3 and 10.4%, respectively). Although these data are not conclusive, they support that a phenotypic change occurs as ovarian cancer cells leave the primary tumor and are suspended in ascites. We found that repression of any one of these particular genes was sufficient to avoid anoikis. This change was accompanied by suppression of cell proliferation and increased efflux of Hoechst 33342 dye, which indicates activation of pumping function, suggesting a change to chemoresistant dormant cells. In summary, our functional genomics approach suggests a molecular mechanism underlying the process of anchorage independence, tumor dormancy and chemoresistance in ovarian cancer. Citation Format: Noriomi Matsumura, Koji Yamanoi, Yasuaki Amano, Junzo Hamanishi, Tsukasa Baba, Susan K. Murphy, Ikuo Konishi. Functional genomics approach links anchorage-independence with tumor dormancy in ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B19.
Money for Indians' health remains unused
Authors: J Rocha
Journal: BMJ (1994)

A multimillion dollar loan promised by the World Bank to fund health projects among Indian groups in the Amazon basin is still unspent, even though the period of the loan expires in June. The World Bank approved the loan in 1989 as part of an $89m (pounds sterling 59.3m) loan for malaria control in the Amazon basin. It specifically designated $6.6m (pounds sterling 4.4m) for spending on health projects among Indians, both those run by the government and those set up by non-government organisations.

The health problems in many indigenous communities are serious: malaria, cholera, leptospirosis, hepatitis, tuberculosis, and, where gold miners have been at work, possibly mercury contamination. Almost none of the $6.6m has been spent. Instead …
IL-12– and IL-23–modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition
Authors: Mark A. Kroenke, Thaddeus J. Carlson, Anuska V. Andjelkovic, Benjamin M. Segal
Journal: The Journal of Experimental Medicine (2008)

The interleukin (IL)-12p40 family of cytokines plays a critical role in the development of experimental autoimmune encephalomyelitis (EAE). However, the relative contributions of IL-12 and IL-23 to the pathogenic process remain to be elucidated. Here, we show that activation of uncommitted myelin-reactive T cells in the presence of either IL-12p70 or IL-23 confers encephalogenicity. Adoptive transfer of either IL-12p70– or IL-23–polarized T cells into naive syngeneic hosts resulted in an ascending paralysis that was clinically indistinguishable between the two groups. However, histological and reverse transcription–polymerase chain reaction analysis of central nervous system (CNS) tissues revealed distinct histopathological features and immune profiles. IL-12p70–driven disease was characterized by macrophage-rich infiltrates and prominent NOS2 up-regulation, whereas neutrophils and granulocyte–colony-stimulating factor (CSF) were prominent in IL-23–driven lesions. The monocyte-attracting chemokines CXCL9, 10, and 11 were preferentially expressed in the CNS of mice injected with IL-12p70–modulated T cells, whereas the neutrophil-attracting chemokines CXCL1 and CXCL2 were up-regulated in the CNS of mice given IL-23–modulated T cells. Treatment with anti–IL-17 or anti–granulocyte/macrophage-CSF inhibited EAE induced by transfer of IL-23–polarized, but not IL-12p70–polarized, cells. These findings indicate that autoimmunity can be mediated by distinct effector populations that use disparate immunological pathways to achieve a similar clinical outcome.
Medical Therapy for Differentiated Thyroid Carcinoma*
Authors: ANTHONY J. DULGEROFF, JEROME M. HERSHMAN
Journal: Endocrine Reviews (1994)

DIFFERENTIATED thyroid carcinoma (papillary and follicular) is usually an indolent cancer, but it may be aggressive, especially in patients more than 50 yr old. In those with more aggressive rumors, effective therapy may reduce morbidity and mortality. By carefully considering each case, the outcome of treatment can be improved and the costs reduced. Thyroid carcinoma is treated by teams comprised of endocrinologists, surgeons, nuclear medicine specialists, and internists. It is important for physicians treating such patients to become familiar with the current therapy of differentiated thyroid carcinoma. In this review, we discuss nonsurgical therapy of patients with differentiated thyroid carcinoma. Surgical excision is usually the primary treatment for differentiated thyroid carcinoma, but the type and extent of surgery is controversial and the topic of many papers (for review, see Ref. 1). In general, near total or total thyroidectomy is recommended for all malignant lesions larger than 2 cm. In some instances of surgery for the diagnosis of follicular neoplasm based on needle aspiration biopsy, the diagnosis of follicular carcinoma is established after lobectomy.
Three trajectories of activity limitations in early symptomatic knee osteoarthritis: a 5-year follow-up study
Authors: Jasmijn F M Holla, Marike van der Leeden, Martijn W Heymans, Leo D Roorda, Sita M A Bierma-Zeinstra, Maarten Boers, Willem F Lems, Martijn PM Steultjens, Joost Dekker
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Knee osteoarthritis (OA) is a leading cause of activity limitations. The knee OA population is likely to consist of subgroups. The aim of the present study was to identify homogeneous subgroups with distinct trajectories of activity limitations in patients with early symptomatic knee OA and to describe characteristics of these subgroups. <h3>Methods</h3> Follow-up data over a period of 5 years of 697 participants with early symptomatic knee OA from the Cohort Hip and Cohort Knee (CHECK) were used. Activity limitations were measured yearly with the Western Ontario and McMaster Universities Osteoarthritis Index. Latent class growth analyses identified homogeneous subgroups with distinct trajectories of activity limitations. Multivariable regression analyses examined differences in characteristics between the subgroups. <h3>Results</h3> Three subgroups were identified. Participants in Subgroup 1 ('good outcome'; n=330) developed or displayed slight activity limitations over time. Participants in Subgroup 2 ('moderate outcome'; n=257) developed or displayed moderate activity limitations over time. Participants in subgroup 3 ('poor outcome'; n=110) developed or displayed severe activity limitations over time. Compared with the 'good outcome' subgroup, the 'moderate outcome' and 'poor outcome' subgroups were characterised by: younger age, higher body mass index, greater pain, bony tenderness, reduced knee flexion, hip pain, osteophytosis, ≥3 comorbidities, lower vitality or avoidance of activities. <h3>Conclusions</h3> Based on the 5-year course of activity limitations, we identified homogeneous subgroups of knee OA patients with good, moderate or poor outcome. Characteristics of these subgroups were consistent with existing knowledge on prognostic factors regarding activity limitations, which supports the validity of this classification.
Risk Factors for the Emergence of Psychotic Disorders in Adolescents With 22q11.2 Deletion Syndrome
Authors: Doron Gothelf, Carl Feinstein, Tracy Thompson, Eugene Gu, Lauren Penniman, Ellen Van Stone, Hower Kwon, Stephan Eliez, Allan L. Reiss
Journal: American Journal of Psychiatry (2007)

The 22q11.2 deletion syndrome is the most common known genetic risk factor for the development of schizophrenia. The authors conducted a longitudinal evaluation of adolescents with 22q11.2 deletion syndrome to identify early risk factors for the development of psychotic disorders.Sixty children, 31 with 22q11.2 deletion syndrome and 29 comparison subjects with idiopathic developmental disability matched for age and IQ, underwent a baseline evaluation between 1998 and 2000; of these, 51 children (28 and 23 in the two groups, respectively) underwent follow-up evaluation between 2003 and 2005. A standardized comprehensive psychiatric, psychological, and adaptive functioning evaluation was conducted in both waves. Participants with 22q11.2 deletion syndrome were also genotyped for the catechol O-methyltransferase (COMT) Met/Val polymorphism and underwent magnetic resonance imaging scans.The two groups had similar baseline neuropsychiatric profiles. At follow-up, 32.1% of subjects with 22q11.2 deletion syndrome had developed psychotic disorders as compared with 4.3% of comparison subjects. In the 22q11.2 deletion syndrome group, baseline subthreshold psychotic symptoms interacted both with the COMT genotype and with baseline symptoms of anxiety or depression to predict 61% of the variance in severity of psychosis at follow-up evaluation. Lower baseline verbal IQ was also associated with more severe psychotic symptoms at follow-up evaluation.Genetic, cognitive, and psychiatric risk factors for the evolution of psychotic disorders in 22q11.2 deletion syndrome during adolescence were identified. Early intervention in the subgroup of children with subthreshold signs of psychosis and internalizing symptoms (especially anxiety symptoms) may reduce the risk of developing psychotic disorders during adolescence.
Neurologic Symptoms in Licensed Private Pesticide Applicators in the Agricultural Health Study
Authors: Freya Kamel, Lawrence S. Engel, Beth C. Gladen, Jane A. Hoppin, Michael C. R. Alavanja, Dale P. Sandler
Journal: Environmental Health Perspectives (2005)

Exposure to high levels of many pesticides has both acute and long-term neurologic consequences, but little is known about the neurotoxicity of chronic exposure to moderate levels of pesticides. We analyzed cross-sectional data from 18,782 white male licensed private pesticide applicators enrolled in the Agricultural Health Study in 1993-1997. Applicators provided information on lifetime pesticide use and 23 neurologic symptoms typically associated with pesticide intoxication. An indicator of more symptoms (> or = 10 vs. < 10) during the year before enrollment was associated with cumulative lifetime days of insecticide use: odds ratios (95% confidence intervals) were 1.64 (1.36-1.97) for 1-50 days, 1.89 (1.58-2.25) for 51-500 days, and 2.50 (2.00-3.13) for > 500 days, compared with never users. A modest association for fumigants [> 50 days, 1.50 (1.24-1.81)] and weaker relationships for herbicides [> 500 days, 1.32 (0.99-1.75)] and fungicides [> 50 days, 1.23 (1.00-1.50)] were observed. Pesticide use within the year before enrollment was not associated with symptom count. Only associations with insecticides and fumigants persisted when all four pesticide groups were examined simultaneously. Among chemical classes of insecticides, associations were strongest for organophosphates and organochlorines. Associations with cumulative exposure persisted after excluding individuals who had a history of pesticide poisoning or had experienced an event involving high personal pesticide exposure. These results suggest that self-reported neurologic symptoms are associated with cumulative exposure to moderate levels of fumigants and organophosphate and organochlorine insecticides, regardless of recent exposure or history of poisoning.
CD38 gene polymorphism and chronic lymphocytic leukemia: a role in transformation to Richter syndrome?
Authors: Semra Aydin, Davide Rossi, Luciana Bergui, Giovanni D'Arena, Enza Ferrero, Lisa Bonello, Paola Omedé, Domenico Novero, Fortunato Morabito, Antonino Carbone, Gianluca Gaidano, Fabio Malavasi, Silvia Deaglio
Journal: Blood (2008)
Prize Fight: The Race and the Rivalry to Be the First in Science
Authors: Scott C. Molitor
Journal: JAMA (2012)

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London’s last remaining Georgian workhouse infirmary under threat
Authors: Nick Black
Journal: BMJ (2007)

From 1601 until the start of the NHS in 1948, provision of hospital care for the most destitute was a local responsibility. Initially, under the Elizabethan poor law, parishes provided workhouses, which often included some rudimentary infirmary, though little recognisable health care. The oldest one that survives in London was built in 1775-8 in Cleveland Street, Fitzrovia, by the parish of St Paul’s, Covent Garden. The elegant …
Retrograde nontransseptal balloon mitral valvuloplasty: immediate results and intermediate long-term outcome in 441 cases—a multicenter experience
Authors: Christodoulos I Stefanadis, Costas G Stratos, Spyros G Lambrou, Vinay Kumar Bahl, Dennis V Cokkinos, Vassilios A Voudris, Stefanos G Foussas, Costas P Tsioufis, Pavlos K Toutouzas
Journal: Journal of the American College of Cardiology (1998)
Effects of 15-deoxy-Δ12,14-prostaglandin-J2 during hyperdynamic porcine endotoxemia
Authors: Balázs Hauser, Jochen Kick, Zsolt Iványi, Pierre Asfar, Ulrich Ehrmann, Claus-Martin Muth, Maura Albicini, Ulrich Wachter, Josef Vogt, Michael Bauer, Uwe Bernd Brückner, Peter Radermacher, Hendrik Bracht
Journal: Intensive Care Medicine (2006)