tbuckley/cabot-search huggingface dataset:
LR11, an LDL Receptor Gene Family Member, Is a Novel Regulator of Smooth Muscle Cell Migration
Authors: Yanjuan Zhu, Hideaki Bujo, Hiroyuki Yamazaki, Kenji Ohwaki, Meizi Jiang, Satoshi Hirayama, Tatsuro Kanaki, Manabu Shibasaki, Kazuo Takahashi, Wolfgang J. Schneider, Yasushi Saito
Journal: Circulation Research (2004)

LR11, a member of the LDL receptor family, is highly expressed in vascular smooth muscle cells (SMCs) of the hyperplastic intima, and induces enhanced migration of SMCs in vitro via its upregulation of urokinase-type plasminogen activator receptor (uPAR) expression. In this study, we have delineated the mechanism by which LR11 elevates the expression levels of uPAR in SMCs. Secretion of soluble LR11 is induced in SMCs during the rapidly proliferating phase, and the secreted LR11 induces the migration activities of SMCs. Both the cell-anchored and secreted forms of LR11 have the capacity to bind to and form complexes with uPAR. LR11-overexpressing cells show significantly enhanced uPAR binding, but decreased uPAR internalization. LR11 colocalizes with uPAR on the cell surface and inhibits the LDL receptor–related protein (LRP)-mediated binding and internalization of uPAR. Thus, LR11 mediates the uPAR localization to the plasma membrane. LR11 is highly expressed in the atheromatous plaque areas of apoE knockout mice, particularly in the intimal SMCs at the border between intima and media. The neutralization of LR11 function with anti-LR11 antibody reduced cuff-induced intimal thickness in mice. The novel mechanism of regulation of uPAR localization in SMCs accompanied with enhanced migration activity possibly constitutes an important factor in the process of atherosclerosis and arterial remodeling.
Monitoring the Impact of Influenza by Age: Emergency Department Fever and Respiratory Complaint Surveillance in New York City
Authors: Donald R Olson, Richard T Heffernan, Marc Paladini, Kevin Konty, Don Weiss, Farzad Mostashari
Journal: PLoS Medicine (2007)

The importance of understanding age when estimating the impact of influenza on hospitalizations and deaths has been well described, yet existing surveillance systems have not made adequate use of age-specific data. Monitoring influenza-related morbidity using electronic health data may provide timely and detailed insight into the age-specific course, impact and epidemiology of seasonal drift and reassortment epidemic viruses. The purpose of this study was to evaluate the use of emergency department (ED) chief complaint data for measuring influenza-attributable morbidity by age and by predominant circulating virus.We analyzed electronically reported ED fever and respiratory chief complaint and viral surveillance data in New York City (NYC) during the 2001-2002 through 2005-2006 influenza seasons, and inferred dominant circulating viruses from national surveillance reports. We estimated influenza-attributable impact as observed visits in excess of a model-predicted baseline during influenza periods, and epidemic timing by threshold and cross correlation. We found excess fever and respiratory ED visits occurred predominantly among school-aged children (8.5 excess ED visits per 1,000 children aged 5-17 y) with little or no impact on adults during the early-2002 B/Victoria-lineage epidemic; increased fever and respiratory ED visits among children younger than 5 y during respiratory syncytial virus-predominant periods preceding epidemic influenza; and excess ED visits across all ages during the 2003-2004 (9.2 excess visits per 1,000 population) and 2004-2005 (5.2 excess visits per 1,000 population) A/H3N2 Fujian-lineage epidemics, with the relative impact shifted within and between seasons from younger to older ages. During each influenza epidemic period in the study, ED visits were increased among school-aged children, and each epidemic peaked among school-aged children before other impacted age groups.Influenza-related morbidity in NYC was highly age- and strain-specific. The impact of reemerging B/Victoria-lineage influenza was focused primarily on school-aged children born since the virus was last widespread in the US, while epidemic A/Fujian-lineage influenza affected all age groups, consistent with a novel antigenic variant. The correspondence between predominant circulating viruses and excess ED visits, hospitalizations, and deaths shows that excess fever and respiratory ED visits provide a reliable surrogate measure of incident influenza-attributable morbidity. The highly age-specific impact of influenza by subtype and strain suggests that greater age detail be incorporated into ongoing surveillance. Influenza morbidity surveillance using electronic data currently available in many jurisdictions can provide timely and representative information about the age-specific epidemiology of circulating influenza viruses.
Annual High-Dose Oral Vitamin D and Falls and Fractures in Older Women
Authors: Kerrie M. Sanders, Amanda L. Stuart, Elizabeth J. Williamson, Julie A. Simpson, Mark A. Kotowicz, Doris Young, Geoffrey C. Nicholson
Journal: JAMA (2010)

Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor.To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture.A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008.500,000 IU of cholecalciferol or placebo.Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels.Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing.Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.anzctr.org.au Identifier: ACTRN12605000658617; isrctn.org Identifier: ISRCTN83409867.
Cellular versus myocardial basis for the contractile dysfunction of hypertrophied myocardium.
Authors: D L Mann, Y Urabe, R L Kent, S Vinciguerra, G Cooper
Journal: Circulation Research (1991)

Contractile dysfunction has been demonstrated in many previous studies of experimental right ventricular pressure-overload hypertrophy; however, given the complex changes that occur both in the cardiac muscle cell and in the multiple components of the cardiac interstitium, it is not clear whether the contractile dysfunction observed is an intrinsic property of the cardiac muscle cell or whether it is the result of a mechanically normal cardiac muscle cell contracting within an abnormal interstitial environment. The purpose of the present study was to examine the contractile behavior of cardiac muscle cells, or cardiocytes, isolated from seven cat right ventricles that were pressure-overloaded by banding the pulmonary artery; right ventricular cardiocytes from seven sham-operated cats served as controls. Cardiocytes were obtained from these cats via standard cell isolation procedures; contractile function of the cardiocytes in response to graded viscous external loads was defined by laser diffraction. The cells were stimulated to contract at a frequency of 0.25 Hz, using 100-microA direct current pulses of alternating polarity. Hypertrophied right ventricular cardiocytes obtained from banded cats showed marked systolic contractile abnormalities in comparison with right ventricular cardiocytes from sham-operated cats. The peak velocity of sarcomere shortening for the control and hypertrophied cardiocytes in 1-cp superfusate was 3.6 +/- 0.2 and 2.1 +/- 0.1 microns/sec, respectively (p less than 0.001); the maximum extent of sarcomere shortening for the control and hypertrophied cardiocytes was 0.21 +/- 0.01 and 0.14 +/- 0.01 microns, respectively (p less than 0.001). Further, the time to peak shortening in the 1-cp superfusate was significantly longer for the hypertrophied cardiocytes (150.1 +/- 3.3 versus 160.4 +/- 3.7 msec; p less than 0.04). When the relengthening properties of the cells were examined in the 1-cp superfusate, there were significant differences between cardiocyte groups. The peak rate of sarcomere relengthening was 3.5 +/- 0.2 microns/sec in the control cardiocytes and 2.2 +/- 0.17 microns/sec in the hypertrophied cardiocytes (p less than 0.001). Similarly, the time to peak velocity of sarcomere relengthening (48.8 +/- 1.8 versus 57.9 +/- 2.9 msec) and the time to 50% maximal sarcomere relengthening (57.1 +/- 3.1 versus 67.1 +/- 3.1 msec) were both significantly prolonged for the hypertrophied cardiocytes (p less than 0.02). This study shows for the first time that the contractile defect in this model of right ventricular pressure-overload hypertrophy is intrinsic to the cardiac muscle cell itself. This finding provides a basis for further, more focused investigations designed to determine the mechanisms responsible for the contractile dysfunction observed in this form of experimental cardiac hypertrophy.
Increased Levels of COX-2 and Prostaglandin E2 Contribute to Elevated Aromatase Expression in Inflamed Breast Tissue of Obese Women
Authors: Kotha Subbaramaiah, Patrick G. Morris, Xi Kathy Zhou, Monica Morrow, Baoheng Du, Dilip Giri, Levy Kopelovich, Clifford A. Hudis, Andrew J. Dannenberg
Journal: Cancer Discovery (2012)

Abstract Obesity is a risk factor for hormone receptor-positive breast cancer in postmenopausal women. Estrogen synthesis is catalyzed by aromatase, which is encoded by CYP19. We previously showed that aromatase expression and activity are increased in the breast tissue of overweight and obese women in the presence of characteristic inflammatory foci [crown-like structures of the breast (CLS-B)]. In preclinical studies, proinflammatory prostaglandin E2 (PGE2) is a determinant of aromatase expression. We provide evidence that cyclooxygenase (COX)-2–derived PGE2 stimulates the cyclic AMP (cAMP)→PKA signal transduction pathway that activates CYP19 transcription, resulting in increased aromatase expression and elevated progesterone receptor levels in breast tissues from overweight and obese women. We further demonstrate that a measure of in-breast inflammation (CLS-B index) is a better correlate of these biologic end points than body mass index. The obesity→inflammation→aromatase axis is likely to contribute to the increased risk of hormone receptor-positive breast cancer and the worse prognosis of obese patients with breast cancer. Significance: We show that obesity-associated inflammatory foci in the human breast are associated with elevated COX-2 levels and activation of the PGE2→cAMP→PKA signal transduction pathway resulting in increased aromatase expression. These findings help to explain the link among obesity, low-grade chronic inflammation, and breast cancer with important clinical implications. Cancer Discov; 2(4); 356–65. ©2012 AACR. Read the Commentary on this article by Wang and DuBois, p. 308 This article is highlighted in the In This Issue feature, p. 288
Management of severe acute dental infections
Authors: D. P. Robertson, W. Keys, R. Rautemaa-Richardson, R. Burns, A. J. Smith
Journal: BMJ (2015)

#### The bottom line

Acute dental infection typically occurs when bacteria invade the dental pulp (nerve) and spread to tissues surrounding the tooth. Radiological signs of tooth associated infection in the supporting bone are extremely common, affecting 0.5-13.9% (mean 5.4%) of all teeth in a large systematic analysis of cross sectional studies.1 In addition to localised disease, dental infections can spread regionally and haematogenously, causing serious disseminated infections, especially in patients who are medically compromised.2 3 General medical practitioners and those working in emergency departments are frequently asked to treat patients presenting with dental problems but often have little or no training in this area.4 The purpose of this review is to help general practitioners and non-specialists with the initial diagnosis and management of acute dental infections.

#### Sources and selection criteria

We searched Medline 1950-2013 for the keywords “dental abscess”, “odontogenic infection”, “endodontic abscess”, “periapical abscess and microbiology”, and “clinical trials”. Embase was also searched, including the Cochrane database …
Panic Attack as a Risk Factor for Severe Psychopathology
Authors: Renee D. Goodwin, Roselind Lieb, Michael Hoefler, Hildegard Pfister, Antje Bittner, Katja Beesdo, Hans-Ulrich Wittchen
Journal: American Journal of Psychiatry (2004)

The purpose of the study was to examine the relationship between panic attack and the onset of specific mental disorders and severe psychopathology across the diagnostic spectrum among adolescents and young adults.Data were drawn from the Early Developmental Stages of Psychopathology Study (N=3,021), a 5-year prospective longitudinal study of psychopathology among youths ages 14-24 years at baseline in the community. Multiple logistic regression analyses were used to examine the associations between panic attacks at baseline, comorbid mental disorders in adolescence, and the risk of mental disorders across the diagnostic spectrum at follow-up.The large majority of subjects with panic attacks at baseline developed at least one DSM-IV mental disorder at baseline (89.4% versus 52.8% of subjects without panic attacks). Subjects with panic attacks at baseline had significantly higher baseline levels of any anxiety disorder (54.6% versus 25.0%), any mood disorder (42.7% versus 15.5%), and any substance use disorder (60.4% versus 27.5%), compared to subjects without panic attacks at baseline. Preexisting panic attacks significantly increased the risk of onset of any anxiety disorder, social phobia, specific phobia, generalized anxiety disorder, any substance use disorder, and any alcohol use disorder at follow-up in young adulthood, and these associations persisted after adjustment for all comorbid mental disorders assessed at baseline. More than one-third (37.6% versus 9.8%) of the subjects with panic attack at baseline met the criteria for at least three mental disorders at follow-up during young adulthood.Panic attacks are associated with significantly increased odds of mental disorders across the diagnostic spectrum among young persons and appear to be a risk factor for the onset of specific anxiety and substance use disorders. Investigation of key family, environmental, and individual factors associated with the onset of panic attacks, especially in youth, may be an important direction for future research.
Performance of a New Invariants Method on Homogeneous and Nonhomogeneous Quartet Trees
Authors: M Casanellas, J Fernández-Sánchez
Journal: Molecular Biology and Evolution (2006)

An attempt to use phylogenetic invariants for tree reconstruction was made at the end of the 80s and the beginning of the 90s by several researchers (the initial idea due to Lake [1987] and Cavender and Felsenstein [1987]). However, the efficiency of methods based on invariants is still in doubt (Huelsenbeck 1995; Jin and Nei 1990). Probably because these methods only used few generators of the set of phylogenetic invariants. The method studied in this paper was first introduced in Casanellas et al. (2005) and it is the first method based on invariants that uses the “whole” set of generators for DNA data. The simulation studies performed in this paper prove that it is a very competitive and highly efficient phylogenetic reconstruction method, especially for nonhomogeneous models on phylogenetic trees.
Treatment of Chronic Heart Failure With β-Adrenergic Receptor Antagonists
Authors: Michael R. Bristow
Journal: Circulation Research (2011)

Despite the absence of a systematic development plan, β-blockers have reached the top tier of medical therapies for chronic heart failure. The successful outcome was due to the many dedicated investigators who produced, over a 30-year period, increasing evidence that β-blocking agents should or actually did improve the natural history of dilated cardiomyopathies and heart failure. It took 20 years for supportive evidence to become undeniable, at which time in 1993 the formidable drug development resources of large pharmaceutical companies were deployed into Phase 3 trials. Success then came relatively quickly, and within 8 years multiple agents were on the market in the United States and Europe. Importantly, there is ample room to improve antiadrenergic therapy, through novel approaches exploiting the nuances of receptor biology and/or intracellular signaling, as well as through pharmacogenetic targeting.
Sonographic-detected joint effusion compared with physical examination in the assessment of sacroiliac joints in spondyloarthritis
Authors: A Spadaro, A Iagnocco, G Baccano, F Ceccarelli, E Sabatini, G Valesini
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> An observational case–control study was designed to analyse the discriminative value of ultrasound (US)-detected joint effusion compared with physical examination in the assessment of sacroiliac joints (SIJ) in patients with spondyloarthropathy (SpA) with or without inflammatory back pain (IBP). <h3>Methods:</h3> 45 patients with SpA, classified according to European Spondylarthropathy Study Group criteria, and 30 healthy volunteers were studied. All patients had clinical evaluation of the SIJ, Bath ankylosing spondylitis (AS) metrology index, Bath AS disease activity index, Bath AS functional index, health assessment questionnaire, patient's and physician's visual analogue scale on global disease activity. <h3>Results:</h3> Ultrasound showed joint effusion in 38.9% of SIJ of patients with SpA and in 1.7% of SIJ of controls (p&lt;0.001). The presence of IBP was significantly associated with SIJ effusion assessed by US alone or plus at least one SIJ test. SIJ effusion assessed by US alone or plus at least one SIJ test had a positive likelihood ratio (LR) (2.67 and 4.04, respectively) for the presence of IBP higher than LR of single clinical tests. Positive sacral sulcus test, iliac gapping and midline sacral thrust test were associated with SIJ effusion assessed by US, but all clinical tests, singly and in various combinations, had a low LR for the presence of SIJ effusion assessed by US. <h3>Conclusions:</h3> The study suggests that high resolution sonography is useful in the assessment of SIJ involvement in SpA, resulting in images that are fast and inexpensive and may locate, complementing the physical examination, the origin of IBP.
Independent Association Between Obstructive Sleep Apnea Severity and Glycated Hemoglobin in Adults Without Diabetes
Authors: Pascaline Priou, Marc Le Vaillant, Nicole Meslier, Sylvaine Chollet, Philippe Masson, Marie P. Humeau, Thierry Pigeanne, Acya Bizieux-Thaminy, François Goupil, Frédéric Gagnadoux
Journal: Diabetes Care (2012)

We tested the hypothesis of an independent cross-sectional association between obstructive sleep apnea (OSA) severity and glycated hemoglobin (HbA(1c)) in adults without known diabetes.HbA(1c) was measured in whole-blood samples from 2,139 patients undergoing nocturnal recording for suspected OSA. Participants with self-reported diabetes, use of diabetes medication, or HbA(1c) value ≥6.5% were excluded from this study. Our final sample size comprised 1,599 patients.A dose-response relationship was observed between apnea-hypopnea index (AHI) and the percentage of patients with HbA(1c) >6.0%, ranging from 10.8% for AHI <5 to 34.2% for AHI ≥50. After adjustment for age, sex, smoking habits, BMI, waist circumference, cardiovascular morbidity, daytime sleepiness, depression, insomnia, sleep duration, and study site, odds ratios (95% CIs) for HbA(1c) >6.0% were 1 (reference), 1.40 (0.84-2.32), 1.80 (1.19-2.72), 2.02 (1.31-3.14), and 2.96 (1.58-5.54) for AHI values <5, 5 to <15, 15 to <30, 30 to <50, and ≥50, respectively. Increasing hypoxemia during sleep was also independently associated with the odds of HbA(1c) >6.0%.Among adults without known diabetes, increasing OSA severity is independently associated with impaired glucose metabolism, as assessed by higher HbA(1c) values, which may expose them to higher risks of diabetes and cardiovascular disease.
Incidence and prevalence of juvenile chronic arthritis: a population survey.
Authors: B Andersson Gare, A Fasth, J Andersson, G Berglund, H Ekstrom, M Eriksson, L Hammaren, L Holmquist, E Ronge, A Thilen
Journal: Annals of the Rheumatic Diseases (1987)

In a population based epidemiological survey of juvenile chronic arthritis (JCA), performed in Western Sweden in 1983, an incidence of 12/100,000 was found. The estimated prevalence was 56/100,000. Subgroup distribution showed a preponderance of mono- and pauciarticular forms. The peak age of onset was between 0 and 4 years of age. Girls predominated over boys in a ratio of 3:2. Overall, 30% were antinuclear antibody (ANA) positive, 9% rheumatoid factor (RF) positive, and eye involvement occurred in 10% of the children. The results suggest differences in population based studies of JCA compared with previously reported hospital based series.