tbuckley/cabot-search huggingface dataset:
The Behavioral Risk Factors Surveillance System: Past, Present, and Future
Authors: Ali H. Mokdad
Journal: Annual Review of Public Health (2009)

The Behavioral Risk Factor Surveillance System (BRFSS) is a large state-based telephone survey. BRFSS is designed to monitor the leading risk factors for morbidity and mortality in the United States at the local, state, and national levels. The BRFSS has proven to be a powerful tool for building heath-promotion activities. However, the use of telephone-based, random-digit-dial (RDD) methods in public health surveys and surveillance is at a crossroads. Rapid changes in telecommunication, declines in participation rates, increases in the required level of effort and associated costs are becoming key challenges for BRFSS. To maintain the highest data quality and service to the local and state health departments, BRFSS has adopted an ongoing effort to improve coverage and response to the survey. This article provides an overview of the issues faced by BRFSS and the strategies in place to address them.
Long QT Syndrome–Associated Mutations in KCNQ1 and KCNE1 Subunits Disrupt Normal Endosomal Recycling of <i>I</i> <sub>Ks</sub> Channels
Authors: Guiscard Seebohm, Nathalie Strutz-Seebohm, Oana N. Ureche, Ulrike Henrion, Ravshan Baltaev, Andreas F. Mack, Ganna Korniychuk, Katja Steinke, Daniel Tapken, Arne Pfeufer, Stefan Kääb, Cecilia Bucci, Bernard Attali, Jean Merot, Jeremy M. Tavare, Uta C. Hoppe, Michael C. Sanguinetti, Florian Lang
Journal: Circulation Research (2008)

Physical and emotional stress is accompanied by release of stress hormones such as the glucocorticoid cortisol. This hormone upregulates the serum- and glucocorticoid-inducible kinase (SGK)1, which in turn stimulates I(Ks), a slow delayed rectifier potassium current that mediates cardiac action potential repolarization. Mutations in I(Ks) channel alpha (KCNQ1, KvLQT1, Kv7.1) or beta (KCNE1, IsK, minK) subunits cause long QT syndrome (LQTS), an inherited cardiac arrhythmia associated with increased risk of sudden death. Together with the GTPases RAB5 and RAB11, SGK1 facilitates membrane recycling of KCNQ1 channels. Here, we show altered SGK1-dependent regulation of LQTS-associated mutant I(Ks) channels. Whereas some mutant KCNQ1 channels had reduced basal activity but were still activated by SGK1, currents mediated by KCNQ1(Y111C) or KCNQ1(L114P) were paradoxically reduced by SGK1. Heteromeric channels coassembled of wild-type KCNQ1 and the LQTS-associated KCNE1(D76N) mutant were similarly downregulated by SGK1 because of a disrupted RAB11-dependent recycling. Mutagenesis experiments indicate that stimulation of I(Ks) channels by SGK1 depends on residues H73, N75, D76, and P77 in KCNE1. Identification of the I(Ks) recycling pathway and its modulation by stress-stimulated SGK1 provides novel mechanistic insight into potentially fatal cardiac arrhythmias triggered by physical or psychological stress.
Transient forces generated by projectiles on variable quality mouthguards monitored by instrumented impact testing
Authors: L Warnet, A Greasley
Journal: British Journal of Sports Medicine (2001)

(a) To determine the force-time trace that occurs when a spring mounted simulated upper jaw is impacted; (b) to examine if mouthguards of variable quality have significant influence on such force-time traces; (c) to attempt to relate physical events to the profile of the force-time traces recorded.A simulated jaw, consisting of ceramic teeth inserted into a hard rubber arch reinforced with a composite jawbone, was fitted with various mouthguards as part of a previous round robin study. A clinical assessment distinguished good, bad, and poor mouthguards, and these were each fitted to the jaw, which was then submitted to instrumental impact tests under conditions expected to produce tooth fractures. The force-time trace was recorded for such impact events.The spring mounting method caused two distinct peaks in the force-time trace. The initial one was related to inertia effects and showed an increase in magnitude with impactor velocity as expected. The second peak showed features that were related to the differences in the mouthguards selected.The use of a force washer within a conical ended impactor enabled force-time traces to be recorded during the impact of a spring mounted simulated jaw fitted with mouthguards of variable quality. The spring mounting system causes an initial inertial peak followed by a second peak once the spring mount has fully compressed. Good fitting guards, which keep most teeth intact, result in high stiffness targets that in turn generate high reaction forces in the impactor. If the spring mounting is omitted, the two peaks are combined to give even higher reaction forces. The force-time trace offers some potential for assessing both overall mouthguard performance and individual events during the impact sequence. Mouthguards with good retention to the jaw remained attached during the impact event and helped to preserve the structural integrity of the target. This in turn developed high forces in the second part of the force-time trace. Guards that detached during impact and allowed tooth fractures showed lower forces in the second part of the test. The force profile measured offered some quantitative support to, and agreement with, the observed clinical quality of the mouthguards.
Molecular Basis of Klotho: From Gene to Function in Aging
Authors: Yuechi Xu, Zhongjie Sun
Journal: Endocrine Reviews (2015)

The discovery of the Klotho (KL) gene, which was originally identified as a putative aging-suppressor gene, has generated tremendous interest and has advanced understanding of the aging process. In mice, the overexpression of the KL gene extends the life span, whereas mutations to the KL gene shorten the life span. The human KL gene encodes the α-Klotho protein, which is a multifunctional protein that regulates the metabolism of phosphate, calcium, and vitamin D. α-Klotho also may function as a hormone, although the α-Klotho receptor(s) has not been found. Point mutations of the KL gene in humans are associated with hypertension and kidney disease, which suggests that α-Klotho may be essential to the maintenance of normal renal function. Three α-Klotho protein types with potentially different functions have been identified: a full-length transmembrane α-Klotho, a truncated soluble α-Klotho, and a secreted α-Klotho. Recent evidence suggests that α-Klotho suppresses the insulin and Wnt signaling pathways, inhibits oxidative stress, and regulates phosphatase and calcium absorption. In this review, we provide an update on recent advances in the understanding of the molecular, genetic, biochemical, and physiological properties of the KL gene. Specifically, this review focuses on the structure of the KL gene and the factors that regulate KL gene transcription, the key sites in the regulation of α-Klotho enzyme activity, the α-Klotho signaling pathways, and the molecular mechanisms that underlie α-Klotho function. This current understanding of the molecular biology of the α-Klotho protein may offer new insights into its function and role in aging.
Therapeutic potential of sulfamides as enzyme inhibitors
Authors: Jean-Yves Winum, Andrea Scozzafava, Jean-Louis Montero, Claudiu T. Supuran
Journal: Medicinal Research Reviews (2006)

Sulfamide, a quite simple molecule incorporating the sulfonamide functionality, widely used by medicinal chemists for the design of a host of biologically active derivatives with pharmacological applications, may give rise to at least five types of derivatives, by substituting one to four hydrogen atoms present in it, which show specific biological activities. Recently, some of these compounds started to be exploited for the design of many types of therapeutic agents. Among the enzymes for which sulfamide-based inhibitors were designed, are the carbonic anhydrases (CAs), a large number of proteases belonging to the aspartic protease (HIV-1 protease, gamma-secretase), serine protease (elastase, chymase, tryptase, and thrombin among others), and metalloprotease (carboxypeptidase A (CPA) and matrix metalloproteinases (MMP)) families. Some steroid sulfatase (STS) and protein tyrosine phosphatase inhibitors belonging to the sulfamide class of derivatives have also been reported. In all these compounds, many of which show low nanomolar affinity for the target enzymes for which they have been designed, the free or substituted sulfamide moiety plays important roles for the binding of the inhibitor to the active site cavity, either by directly coordinating to a metal ion found in some metalloenzymes (CAs, CPA, STS), usually by means of one of the nitrogen atoms present in the sulfamide motif, or as in the case of the cyclic sulfamides acting as HIV protease inhibitors, interacting with the catalytically critical aspartic acid residues of the active site by means of an oxygen atom belonging to the HN-SO2-NH motif, which substitutes a catalytically essential water molecule. In other cases, the sulfamide moiety is important for inducing desired physico-chemical properties to the drug-like compounds incorporating it, such as enhanced water solubility, better bioavailability, etc., because of the intrinsic properties of this highly polarized moiety when attached to an organic scaffold. This interesting motif is thus of great value for the design of pharmacological agents with a lot of applications.
MRI of enthesitis of the appendicular skeleton in spondyloarthritis
Authors: I. Eshed, M. Bollow, D. G McGonagle, A. L. Tan, C. E Althoff, P. Asbach, K.-G. A Hermann
Journal: Annals of the Rheumatic Diseases (2007)

Entheses are sites where tendons, ligaments, joint capsules or fascia attach to bone. Inflammation of the entheses (enthesitis) is a well-known hallmark of spondyloarthritis (SpA). As entheses are associated with adjacent, functionally related structures, the concepts of an enthesis organ and functional entheses have been proposed. This is important in interpreting imaging findings in entheseal-related diseases. Conventional radiographs and CT are able to depict the chronic changes associated with enthesitis but are of very limited use in early disease. In contrast, MRI is sensitive for detecting early signs of enthesitis and can evaluate both soft-tissue changes and intraosseous abnormalities of active enthesitis. It is therefore useful for the early diagnosis of enthesitis-related arthropathies and monitoring therapy. Current knowledge and typical MRI features of the most commonly involved entheses of the appendicular skeleton in patients with SpA are reviewed. The MRI appearances of inflammatory and degenerative enthesopathy are described. New options for imaging enthesitis, including whole-body MRI and high-resolution microscopy MRI, are briefly discussed.
IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani
Authors: Maira G.R. Pitta, Audrey Romano, Sandrine Cabantous, Sandrine Henri, Awad Hammad, Bouréma Kouriba, Laurent Argiro, Musa el Kheir, Bruno Bucheton, Charles Mary, Sayda Hassan El-Safi, Alain Dessein
Journal: Journal of Clinical Investigation (2009)

IL-17 and IL-22 have been shown to increase protection against certain bacteria and fungal pathogens in experimental models. However, no human studies have demonstrated a crucial role of IL-17 and IL-22 in protection against infections. We show here that Leishmania donovani, which can cause the lethal visceral disease Kala Azar (KA), stimulates the differentiation of Th17 cells, which produce IL-17, IL-22, and IFN-gamma. Analysis of Th1, Th2, and Th17 cytokine responses by cultured PBMCs from individuals in a cohort of subjects who developed KA or were protected against KA during a severe outbreak showed that IL-17 and IL-22 were strongly and independently associated with protection against KA. Our results suggest that, along with Th1 cytokines, IL-17 and IL-22 play complementary roles in human protection against KA, and that a defect in Th17 induction may increase the risk of KA.
Acute generalized exanthematous pustulosis due to diltiazem: confirmation by patch testing
Authors: J.M. Vicente-Calleja, A. Aguirre, N. Landa, V. Crespo, R. González-Pérez, J.L. Diaz-Pérez
Journal: British Journal of Dermatology (1997)

Journal Article Acute generalized exanthematous pustulosis due to diltiazem: confirmation by patch testing Get access J.M. Vicente‐Calleja, J.M. Vicente‐Calleja Department of Dermatology, Hospital de Cruces 4890 3 Baracaldo (Vizcaya), Spain Search for other works by this author on: Oxford Academic Google Scholar A. Aguirre, A. Aguirre Department of Dermatology, Hospital de Cruces 4890 3 Baracaldo (Vizcaya), Spain Search for other works by this author on: Oxford Academic Google Scholar N. Landa, N. Landa Department of Dermatology, Hospital de Cruces 4890 3 Baracaldo (Vizcaya), Spain Search for other works by this author on: Oxford Academic Google Scholar V. Crespo, V. Crespo Department of Allergy, Hospital de Cruces 4890 3 Baracaldo (Vizcaya), Spain Search for other works by this author on: Oxford Academic Google Scholar R. González‐Pérez, R. González‐Pérez Department of Dermatology, Hospital de Cruces 4890 3 Baracaldo (Vizcaya), Spain Search for other works by this author on: Oxford Academic Google Scholar J.L. Diaz‐Pérez J.L. Diaz‐Pérez Department of Dermatology, Hospital de Cruces 4890 3 Baracaldo (Vizcaya), Spain Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 137, Issue 5, 1 November 1997, Pages 837–839, https://doi.org/10.1111/j.1365-2133.1997.tb01139.x Published: 01 November 1997
Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammation
Authors: Hitoshi Takizawa, Roland R. Regoes, Chandra S. Boddupalli, Sebastian Bonhoeffer, Markus G. Manz
Journal: The Journal of Experimental Medicine (2011)

Hematopoietic stem cells (HSCs) maintain blood production. How often mouse HSCs divide and whether each HSC contributes simultaneously, sequentially, or repetitively to hematopoiesis remains to be determined. We track division of 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE)–labeled HSC in vivo. We found that, in steady-state mice, bone marrow cells capable of reconstituting lifelong hematopoiesis are found within both fast-cycling (undergoing five or more divisions in 7 wk) and quiescent (undergoing zero divisions in 12–14 wk) lineage marker–negative c-Kit+ Sca-1+ populations. The contribution of each population to hematopoiesis can fluctuate with time, and cells with extensive proliferative history are prone to return to quiescence. Furthermore, injection of the bacterial component lipopolysaccharide increased the proliferation and self-renewal capacity of HSCs. These findings suggest a model in which all HSCs undergo dynamic and demand-adapted entry into and exit out of the cell cycle over time. This may facilitate a similar degree of turnover of the entire HSC pool at the end of life.
Risk of Hospital Admission for Obstructive Pulmonary Disease in α<sub>1</sub>-Antitrypsin Heterozygotes of Phenotype PiMZ
Authors: NIELS SEERSHOLM, JON TORGNY ROSTRUP WILCKE, AXEL KOK-JENSEN, ASGER DIRKSEN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Whether subjects heterozygous for α1-antitrypsin ( α1-AT) deficiency are at risk for development of obstructive pulmonary disease (OPD) has been discussed for the past three decades. Both cohort and case–control studies have reached different conclusions, with the major problems being small sample sizes. A cohort of heterozygotes with the phenotype PiMZ was retrieved from the Danish Alpha1-Antitrypsin Deficiency Registry. Ten matched controls for each PiMZ subject were identified from the files of the Danish Central Population Registry. Cases and controls were subsequently linked to the files of the Danish Hospital Discharge Registry, and relative risk for OPD was calculated. In the cohort of 1,551 PiMZ subjects (11,678 person-years), we identified 47 subjects with a discharge diagnosis of OPD, as compared with 206 subjects with this diagnosis in the control group (109,748 person-years), yielding a relative risk (RR) of 2.2 (95% confidence interval [CI]: 1.5 to 3.0). This increased risk was present in both men and women and in all age groups; however, it was significant only in the age group from 40 to 79 yr. Of the 1,551 PiMZ subjects, 565 (36%) were first-degree relatives of PiZ index cases, and it appeared that only this group was at increased risk of hospital admission for OPD (RR: 3.4, 95% CI: 2.2 to 5.3). We conclude that α1-AT heterozygotes of phenotype PiMZ are at increased risk of hospital admission for OPD if they are first-degree relatives of PiZ index cases only, and that other, yet unknown genetic or environmental factors contribute to the development of lung disease. Seersholm N, Wilcke JTR, Kok-Jensen A, Dirksen A. Risk of hospital admission for obstructive pulmonary disease in α1-antitrypsin heterozygotes of phenotype PiMZ.
Effects of a Plant-Based High-Carbohydrate/High-Fiber Diet Versus High–Monounsaturated Fat/Low-Carbohydrate Diet on Postprandial Lipids in Type 2 Diabetic Patients
Authors: Claudia De Natale, Giovanni Annuzzi, Lutgarda Bozzetto, Raffaella Mazzarella, Giuseppina Costabile, Ornella Ciano, Gabriele Riccardi, Angela A. Rivellese
Journal: Diabetes Care (2009)

To search for a better dietary approach to treat postprandial lipid abnormalities and improve glucose control in type 2 diabetic patients.According to a randomized crossover design, 18 type 2 diabetic patients (aged 59 +/- 5 years; BMI 27 +/- 3 kg/m(2)) (means +/- SD) in satisfactory blood glucose control on diet or diet plus metformin followed a diet relatively rich in carbohydrates (52% total energy), rich in fiber (28 g/1,000 kcal), and with a low glycemic index (58%) (high-carbohydrate/high-fiber diet) or a diet relatively low in carbohydrate (45%) and rich in monounsaturated fat (23%) (low-carbohydrate/high-monounsaturated fat diet) for 4 weeks. Thereafter, they shifted to the other diet for 4 more weeks. At the end of each period, plasma glucose, insulin, lipids, and lipoprotein fractions (separated by discontinuous density gradient ultracentrifugation) were determined on blood samples taken at fasting and over 6 h after a test meal having a similar composition as the corresponding diet.In addition to a significant decrease in postprandial plasma glucose, insulin responses, and glycemic variability, the high-carbohydrate/high-fiber diet also significantly improved the primary end point, since it reduced the postprandial incremental areas under the curve (IAUCs) of triglyceride-rich lipoproteins, in particular, chylomicrons (cholesterol IAUC: 0.05 +/- 0.01 vs. 0.08 +/- 0.02 mmol/l per 6 h; triglycerides IAUC: 0.71 +/- 0.35 vs. 1.03 +/- 0.58 mmol/l per 6 h, P < 0.05).A diet rich in carbohydrate and fiber, essentially based on legumes, vegetables, fruits, and whole cereals, may be particularly useful for treating diabetic patients because of its multiple effects on different cardiovascular risk factors, including postprandial lipids abnormalities.
Effect of pirfenidone on TGF-β-induced pro-fibrotic effects in primary human lung cells derived from patients with idiopathic pulmonary fibrosis
Authors: Katrin Hostettler, Jun Zhong, Michael Tamm, Didier Lardinois, Michael Roth
Journal: European Respiratory Journal (2014)

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. Pirfenidone is an orally administered pyridine that exhibits anti-fibrotic, anti-oxidant, and anti-inflammatory effects. In patients with mild-to-moderate IPF pirfenidone slowed down the decline in vital capacity and prolonged the progression-free survival. The inhibition of transforming growth factor-beta (TGF-β)-induced effects has been suggested to be part of pirfenidone's anti-fibrotic properties.

Aim: To determine the in vitro effect of pirfenidone on TGF-β1-stimulated primary human lung myofibroblasts and primary human alveolar epithelial type II cells.

Methods: Primary human myofibroblasts and alveolar epithelial type II cells were isolated from lung parenchyma derived from patients with IPF and from non-fibrotic control lungs. After incubation with pirfenidone and stimulation with TGF-β1, myofibroblast proliferation was assessed by automatic cell counting, and the effect on TGF-β1-induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cells was studied.

Results: In IPF myofibroblasts, pirfenidone (1 – 4 mM) dose-dependently prevented the pro-proliferative effect of TGF-β1 (1 ng/ml). TGF-β1 caused EMT in alveolar epithelial cells as demonstrated by morphologic changes, up-regulation of fibronectin and loss of E-cadherin expression, and these effects were partly prevented by pirfenidone (4 mM).

Conclusion: Our data demonstrate that pirfenidone counteracts TGF-β-induced pro-fibrotic effects, and suggest that the inhibition of EMT may account in part for the drug's documented clinically beneficial effect.
Biomarkers of Inflammation and Thrombosis as Predictors of Near-Term Mortality in Patients with Peripheral Arterial Disease: A Cohort Study
Authors: Himabindu Vidula, Lu Tian, Kiang Liu, Michael H. Criqui, Luigi Ferrucci, William H. Pearce, Philip Greenland, David Green, Jin Tan, Daniel B. Garside, Jack Guralnik, Paul M Ridker, Nader Rifai, Mary M. McDermott
Journal: Annals of Internal Medicine (2008)

Background: Traditional atherosclerotic risk factors predict long-term cardiovascular disease events but are poor predictors of near-term events. Objective: To determine whether elevated levels of d-dimer and biomarkers of inflammation were more closely associated with near-term than long-term mortality in patients with lower-extremity peripheral arterial disease (PAD) and whether greater increases in biomarker levels were associated with higher mortality rates during the first year after the increase than during later years. Design: Prospective cohort study with a mean follow-up of 3.4 years. Setting: Academic medical center. Patients: 377 men and women with PAD. Measurements: Mortality within 1 year after biomarker measurement, 1 to 2 years after biomarker measurement, and 2 to 3 years after biomarker measurement. Cox regression analyses were used to evaluate associations of biomarkers levels and changes in biomarkers with cardiovascular and all-cause mortality. Hazard ratios were calculated for each 1-unit increase in log1.5(biomarker level). Analyses were adjusted for age, sex, race, comorbid conditions, ankle–brachial index, and other confounders. Results: Seventy-six patients (20%) died during follow-up. Higher levels of d-dimer, C-reactive protein, and serum amyloid A were associated with higher all-cause mortality among patients who died within 1 year after biomarker measurement (hazard ratio, 1.20 [95% CI, 1.08 to 1.33], 1.13 [CI, 1.05 to 1.21], and 1.12 [CI, 1.04 to 1.20], respectively; P < 0.001, P < 0.001, and P = 0.003) and among patients who died 1 to 2 years after biomarker measurement (hazard ratio, 1.14 [CI, 1.02 to 1.27], 1.15 [CI, 1.06 to 1.24], and 1.13 [CI, 1.04 to 1.24]; P = 0.022, P = 0.001, and P = 0.005]). However, higher levels of each biomarker were not associated with all-cause mortality for deaths occurring 2 to 3 years after biomarker measurement. Similar results were observed for cardiovascular mortality. Greater increases in each biomarker were associated with higher all-cause and cardiovascular mortality during the following year. Limitation: The small number of deaths limited the statistical power of the analyses. Conclusion: Among persons with PAD, circulating levels of d-dimer and inflammatory markers are higher in the 1 to 2 years before death than in periods more remote from death. Increasing levels of d-dimer and inflammatory biomarkers are independently associated with higher mortality in persons with PAD.