The generic unfolding of a codimension-two connection to a two-fold singularity of planar Filippov systems

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Novaes, Douglas D.; Teixeira, Marco A.; Zeli, Iris O.

2018-05-01

Generic bifurcation theory was classically well developed for smooth differential systems, establishing results for k-parameter families of planar vector fields. In the present study we focus on a qualitative analysis of 2-parameter families, , of planar Filippov systems assuming that Z 0,0 presents a codimension-two minimal set. Such object, named elementary simple two-fold cycle, is characterized by a regular trajectory connecting a visible two-fold singularity to itself, for which the second derivative of the first return map is nonvanishing. We analyzed the codimension-two scenario through the exhibition of its bifurcation diagram.

Two-fold Mellin-Barnes transforms of Usyukina-Davydychev functions

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Kniehl, Bernd [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik; Kondrashuk, Igor [Univ. del Bio Bio, Chillan (Chile). Dept. de Ciencias Basicas; Bielefeld Univ. (Germany). Fakultaet fuer Physik; Notte-Cuello, Eduardo A. [Univ. de La Serena (Chile). Dept. de Matematicas; Parra-Ferrada, Ivan [Univ. del Bio Bio, Chillan (Chile). Facultad de Educacion y Humanidades; Rojas-Medar, Marko [Univ. del Bio Bio, Chillan (Chile). Dept. de Ciencias Basicas

2013-04-15

In our previous paper (Nucl.Phys.B 870 (2013) 243) we showed that multi-fold Mellin-Barnes (MB) transforms of the Usyukina-Davydychev (UD) functions may be reduced to two-fold MB transforms. The MB transforms were written there as polynomials of logarithms of ratios of squares of the external momenta with certain coefficients. We also showed that these coefficients have a combinatoric origin. In this paper we present an explicit formula for these coefficients. The procedure of recovering the coefficients is based on taking the double uni-form limit in certain series of smooth functions of two variables which is constructed according to a pre-determined iterative way. The result is obtained by using basic methods of mathematical analysis. We observe that the finiteness of the limit of this iterative chain of smooth functions should reflect itself in other mathematical constructions, too, since it is not related in any way to the explicit form of the MB transforms.

Two-fold Mellin-Barnes transforms of Usyukina-Davydychev functions

International Nuclear Information System (INIS)

Kniehl, Bernd; Kondrashuk, Igor; Bielefeld Univ.; Notte-Cuello, Eduardo A.; Parra-Ferrada, Ivan; Rojas-Medar, Marko

2013-04-01

In our previous paper (Nucl.Phys.B 870 (2013) 243) we showed that multi-fold Mellin-Barnes (MB) transforms of the Usyukina-Davydychev (UD) functions may be reduced to two-fold MB transforms. The MB transforms were written there as polynomials of logarithms of ratios of squares of the external momenta with certain coefficients. We also showed that these coefficients have a combinatoric origin. In this paper we present an explicit formula for these coefficients. The procedure of recovering the coefficients is based on taking the double uni-form limit in certain series of smooth functions of two variables which is constructed according to a pre-determined iterative way. The result is obtained by using basic methods of mathematical analysis. We observe that the finiteness of the limit of this iterative chain of smooth functions should reflect itself in other mathematical constructions, too, since it is not related in any way to the explicit form of the MB transforms.

Scattering of long folded strings and mixed correlators in the two-matrix model

International Nuclear Information System (INIS)

Bourgine, J.-E.; Hosomichi, K.; Kostov, I.; Matsuo, Y.

2008-01-01

We study the interactions of Maldacena's long folded strings in two-dimensional string theory. We find the amplitude for a state containing two long folded strings to come and go back to infinity. We calculate this amplitude both in the worldsheet theory and in the dual matrix model, the matrix quantum mechanics. The matrix model description allows to evaluate the amplitudes involving any number of long strings, which are given by the mixed trace correlators in an effective two-matrix model

Periodic folding of viscous sheets

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Ribe, Neil M.

2003-09-01

The periodic folding of a sheet of viscous fluid falling upon a rigid surface is a common fluid mechanical instability that occurs in contexts ranging from food processing to geophysics. Asymptotic thin-layer equations for the combined stretching-bending deformation of a two-dimensional sheet are solved numerically to determine the folding frequency as a function of the sheet’s initial thickness, the pouring speed, the height of fall, and the fluid properties. As the buoyancy increases, the system bifurcates from “forced” folding driven kinematically by fluid extrusion to “free” folding in which viscous resistance to bending is balanced by buoyancy. The systematics of the numerically predicted folding frequency are in good agreement with laboratory experiments.

Intradomain Confinement of Disulfides in the Folding of Two Consecutive Modules of the LDL Receptor.

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Juan Martínez-Oliván

Full Text Available The LDL receptor internalizes circulating LDL and VLDL particles for degradation. Its extracellular binding domain contains ten (seven LA and three EGF cysteine-rich modules, each bearing three disulfide bonds. Despite the enormous number of disulfide combinations possible, LDLR oxidative folding leads to a single native species with 30 unique intradomain disulfides. Previous folding studies of the LDLR have shown that non native disulfides are initially formed that lead to compact species. Accordingly, the folding of the LDLR has been described as a "coordinated nonvectorial" reaction, and it has been proposed that early compaction funnels the reaction toward the native structure. Here we analyze the oxidative folding of LA4 and LA5, the modules critical for ApoE binding, isolated and in the LA45 tandem. Compared to LA5, LA4 folding is slow and inefficient, resembling that of LA5 disease-linked mutants. Without Ca++, it leads to a mixture of many two-disulfide scrambled species and, with Ca++, to the native form plus two three-disulfide intermediates. The folding of the LA45 tandem seems to recapitulate that of the individual repeats. Importantly, although the folding of the LA45 tandem takes place through formation of scrambled isomers, no interdomain disulfides are detected, i.e. the two adjacent modules fold independently without the assistance of interdomain covalent interactions. Reduction of incredibly large disulfide combinatorial spaces, such as that in the LDLR, by intradomain confinement of disulfide bond formation might be also essential for the efficient folding of other homologous disulfide-rich receptors.

Increased pancreatic cancer risk following radiotherapy for testicular cancer.

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Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S; Stovall, Marilyn; van Leeuwen, Flora E; Rajaraman, Preetha; Smith, Susan A; Weathers, Rita E; Aleman, Berthe M P; Andersson, Michael; Curtis, Rochelle E; Dores, Graça M; Fraumeni, Joseph F; Hall, Per; Holowaty, Eric J; Joensuu, Heikki; Kaijser, Magnus; Kleinerman, Ruth A; Langmark, Frøydis; Lynch, Charles F; Pukkala, Eero; Storm, Hans H; Vaalavirta, Leila; van den Belt-Dusebout, Alexandra W; Morton, Lindsay M; Fossa, Sophie D; Travis, Lois B

2016-09-27

Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear. Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs). Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated with a 2.9-fold (95% confidence interval (CI) 1.0-7.8) increased risk. The OR increased linearly by 0.12 per Gy to the pancreas (P-trendcancer risk, and persists for over 20 years. These excesses, although small, should be considered when radiotherapy with exposure to the pancreas is considered for newly diagnosed patients. Additional data are needed on the role of chemotherapy.

The Risk of Offspring Developing Substance Use Disorders when Exposed to One versus Two Parent(s) with Alcohol Use Disorder

DEFF Research Database (Denmark)

Mellentin, Angelina Isabella; Brink, Maria; Andersen, Lene

2016-01-01

with AUD was linked to a 2.29-fold increased risk (95% CI, 1.64 – 3.20). No significant differences were found in relation to either parental or offspring gender. Conclusions: Exposure to parental AUD is linked to an increased risk of offspring developing SUD. This risk is additive for offspring exposed......Aim: Few population-based, family studies have examined associations between exposure to one vs. two parent(s) with alcohol use disorder (AUD) and the risk of offspring developing substance use disorder (SUD). Moreover, these studies have focused solely on the development of AUD, and not SUD......, in offspring. The purpose of this study was to investigate whether exposure to one vs. two parent(s) with AUD increases the risk of offspring developing SUD. Methods: A population-based, cohort study was conducted in which offspring born in Denmark between 1983 and 1989 were followed through national...

Quantification of acute vocal fold epithelial surface damage with increasing time and magnitude doses of vibration exposure.

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Tsuyoshi Kojima

Full Text Available Because the vocal folds undergo repeated trauma during continuous cycles of vibration, the epithelium is routinely susceptible to damage during phonation. Excessive and prolonged vibration exposure is considered a significant predisposing factor in the development of vocal fold pathology. The purpose of the present study was to quantify the extent of epithelial surface damage following increased time and magnitude doses of vibration exposure using an in vivo rabbit phonation model. Forty-five New Zealand white breeder rabbits were randomized to nine groups and received varying phonation time-doses (30, 60, or 120 minutes and magnitude-doses (control, modal intensity phonation, or raised intensity phonation of vibration exposure. Scanning electron microscopy and transmission electron microscopy was used to quantify the degree of epithelial surface damage. Results revealed a significant reduction in microprojection density, microprojection height, and depth of the epithelial surface with increasing time and phonation magnitudes doses, signifying increased epithelial surface damage risk with excessive and prolonged vibration exposure. Destruction to the epithelial cell surface may provide significant insight into the disruption of cell function following prolonged vibration exposure. One important goal achieved in the present study was the quantification of epithelial surface damage using objective imaging criteria. These data provide an important foundation for future studies of long-term tissue recovery from excessive and prolonged vibration exposure.

Familial risk of inflammatory bowel disease

DEFF Research Database (Denmark)

Trier Møller, Frederik; Andersen, Vibeke; Jess, Tine

2014-01-01

of familial CD cases was 12,15 percent of total CD cases and familial UC accounted for and 8,84 percent of total UC cases from 2007-2011. Patterns of IBD risk in family members to IBD-affected individuals appear from Table 1. The risk of CD was 9-fold increased in 1. degree relatives to at least two...... in the entire population. Individuals receiving at least 2 diagnoses of IBD during the time period (n=45,780) were identified using the Danish National Registry of Patients. Risk of IBD in family members to individuals with IBD was assessed by Poisson regression analysis. Results: The overall proportion...... individuals with IBD, 7.8 -fold increased in 1. degree relatives to one family member with CD, and even 2.8-fold increased if the 1. degree relative had UC. The same pattern was observed for risk of UC. Second-degree relatives to patients with CD or UC were also at significantly increased risk not only...

Prenatal Maternal Smoking and Increased Risk for Tourette Syndrome and Chronic Tic Disorders.

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Browne, Heidi A; Modabbernia, Amirhossein; Buxbaum, Joseph D; Hansen, Stefan N; Schendel, Diana E; Parner, Erik T; Reichenberg, Abraham; Grice, Dorothy E

2016-09-01

We assessed the role of prenatal maternal smoking in risk for Tourette syndrome and chronic tic disorder (TS/CT) and pediatric-onset obsessive-compulsive disorder (OCD). In an analysis of 73,073 singleton pregnancies from the Danish National Birth Cohort, we calculated incidence rates (IR) per 1,000 person-year for TS/CT and OCD. We then determined crude and adjusted hazard ratios and 95% CIs associated with prenatal maternal smoking, considering smoking as a dichotomous (yes/no) variable or a stratified variable (no smoking, light smoking, and heavy smoking [≥10 cigarettes/day]). Additional analyses examined the effect of maternal smoking on risk for TS/CT with other comorbid psychiatric conditions. In final adjusted analyses, heavy smoking was associated with a 66% increased risk for TS/CT (adjusted hazard ratio = 1.66, 95% CI = 1.17-2.35). In addition, heavy smoking was associated with a 2-fold increased risk for TS/CT with comorbid attention-deficit/hyperactivity disorder (ADHD), and both light and heavy smoking were associated with a more than 2-fold increased risk for TS/CT with any non-ADHD psychiatric comorbidity. Our parallel analyses of pediatric-onset OCD were likely underpowered but showed similar relationships. Prenatal maternal smoking was associated with increased risk for TS/CT as well as TS/CT with comorbid psychiatric conditions, even after adjustment for several important variables, including maternal psychiatric history, socioeconomic status, and partner smoking. Our findings point to a pathway linking prenatal tobacco exposure and altered brain development to TS/CT. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Increased Risk of Hemorrhagic and Ischemic Strokes in Patients With Splenic Injury and Splenectomy: A Nationwide Cohort Study.

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Lin, Jiun-Nong; Lin, Cheng-Li; Lin, Ming-Chia; Lai, Chung-Hsu; Lin, Hsi-Hsun; Yang, Chih-Hui; Kao, Chia-Hung

2015-09-01

The spleen is a crucial organ in humans. Little is known about the association between stroke and splenic injury or splenectomy. The aim of this study was to determine the risk of stroke in patients with splenic injury and splenectomy.A nationwide cohort study was conducted by analyzing the National Health Insurance Research Database in Taiwan. For comparison, control patients were selected and matched with splenic injury patients in a ratio of 4:1 according to age, sex, and the year of hospitalization. We analyzed the risks of stroke using a Cox proportional-hazards regression analysis.A total of 11,273 splenic injury patients, including 5294 splenectomized and 5979 nonsplenectomized patients, and 45,092 control patients were included in this study. The incidence rates of stroke were 8.05, 6.53, and 4.25 per 1000 person-years in splenic injury patients with splenectomy, those without splenectomy, and the control cohort, respectively. Compared with the control cohort, splenic injury patients with splenectomy exhibited a 2.05-fold increased risk of stroke (95% confidence interval [CI] 1.8-2.34), whereas those without splenectomy exhibited a 1.74-fold increased risk (95% CI 1.51-2). Splenectomy entailed an additional 1.21-fold increased risk of stroke compared with nonsplenectomy in patients with splenic injury.This study revealed that splenic injury and splenectomy were significantly associated with an increased risk of hemorrhagic and ischemic strokes. The results of this study may alert physicians and patients to the complications of splenic injury and splenectomy.

The consumption of two or more fall risk-increasing drugs rather than polypharmacy is associated with falls.

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Zia, Anam; Kamaruzzaman, Shahrul B; Tan, Maw P

2017-03-01

The presemt study aimed to determine the association between the risk of recurrent and injurious falls with polypharmacy, fall risk-increasing drugs (FRID) and FRID count among community-dwelling older adults. Participants (n = 202) were aged ≥65 years with two or more falls or one injurious fall in the past year, whereas controls (n = 156) included volunteers aged ≥65 years with no falls in the past year. A detailed medication history was obtained alongside demographic data. Polypharmacy was defined as "regular use of five or more prescription drugs." FRID were identified as cardiovascular agents, central nervous system drugs, analgesics and endocrine drugs; multiple FRID were defined as two or more FRID. Multiple logistic regression analyses were used to adjust for confounders. The use of non-steroidal anti-inflammatory drugs was independently associated with an increased risk of falls. Univariate analyses showed both polypharmacy (OR 2.23, 95% CI 1.39-3.56; P = 0.001) and the use of two or more FRID (OR 2.9, 95% CI 1.9-4.5; P = 0.0001) were significantly more likely amongst fallers. After adjustment for age, sex and comorbidities, blood pressure, and physical performance scores, polypharmacy was no longer associated with falls (OR 1.6, 95% CI 0.9-2.9; P = 0.102), whereas the consumption of two or more FRID remained a significant predictor for falls (OR 2.8, 95% CI 1.4-5.3; P = 0.001). Among high risk fallers, the use of two or more FRID was an independent risk factor for falls instead of polypharmacy. Our findings will inform clinical practice in terms of medication reviews among older adults at higher risk of falls. Future intervention studies will seek to confirm whether avoidance or withdrawal of multiple FRID reduces the risk of future falls. Geriatr Gerontol Int 2017; 17: 463-470. © 2016 Japan Geriatrics Society.

Alcohol intake in pregnancy increases the child's risk of atopic dermatitis. the COPSAC prospective birth cohort study of a high risk population

DEFF Research Database (Denmark)

Carson, Charlotte Giwercman; Halkjaer, Liselotte Brydensholt; Jensen, Signe Marie

2012-01-01

Atopic dermatitis has increased four-fold over the recent decades in developed countries, indicating that changes in environmental factors associated with lifestyle may play an important role in this epidemic. It has been proposed that alcohol consumption may be one contributing risk factor...

Increased risk of stroke in contact dermatitis patients

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Chang, Wei-Lun; Hsu, Min-Hsien; Lin, Cheng-Li; Chan, Po-Chi; Chang, Ko-Shih; Lee, Ching-Hsiao; Hsu, Chung-Yi; Tsai, Min-Tein; Yeh, Chung-Hsin; Sung, Fung-Chang

2017-01-01

Abstract Dermatologic diseases are not traditional risk factors of stroke, but recent studies show atopic dermatitis, psoriasis, and bullous skin disease may increase the risk of stroke and other cardiovascular diseases. No previous studies have focused on the association between contact dermatitis and stroke. We established a cohort comprised of 48,169 contact dermatitis patients newly diagnosed in 2000–2003 and 96,338 randomly selected subjects without the disorder, frequency matched by sex, age, and diagnosis year, as the comparison cohort. None of them had a history of stroke. Stroke incidence was assessed by the end of 2011 for both cohorts. The incidence stroke was 1.1-fold higher in the contact dermatitis cohort than in the comparison cohort (5.93 vs 5.37 per 1000 person-years, P contact dermatitis cohort increased with age, from 1.14 (95% CI, 1.03–1.27) for 65 to 74 years; to 1.27 (95% CI, 1.15–1.42) for 75 years and older. The aHR of stroke were 1.16 (95% CI, 1.07–1.27) and 1.09 (95% CI, 1.00–1.18) for men and women, respectively. This study suggests that patients with contact dermatitis were at a modestly increased risk of stroke, significant for ischemic stroke but not for hemorrhagic stroke. Comorbidity, particularly hypertension, increased the hazard of stroke further. PMID:28272195

Ante partum depression and husband’s mental problem increased risk maternity blues

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R. I. Ismail

2006-06-01

Full Text Available Maternity blues disorder (MB is common, and it is usually undiagnosed. This study to identify several risk factors related to MB. Subjects were pregnant women who had antenatal and delivery at the Persahabatan Hospital (RSP Jakarta from 1 November 1999 to 15 August 2001. Consecutive sampling and was followed-up until two-week postpartum. Those who ever had psychiatric disorders (schizophrenia or other psychotic disorders were excluded. MB and ante partum depression (APD detected by using Edinburgh Postnatal Depression Scale (EPDS. Husband’s mental status based on Symptom Check List-90 (SCL-90 respectively. Among 580 subjects, 25% suffering from MB. Compared with those who did not have APD, those who experienced it had more than three-fold increased risk to be MB [adjusted hazard ratio (aHR = 3.57; 95% confidence interval (CI = 2.54;5.03]. Those who had not healthy baby on the first 5 days afterbirth than who had healthy baby had twice increased risk to be MB (aHR = 2.21; 95% CI = 1.34 ; 3.66. Who had husband with problem in mental health had 1.9 increased risk to be MB (aHR = 1.91; 95% CI = 1.36 ; 2.68. Stress during pregnancy had 1.6 increased risk to be MB (aHR = 1.59; 95% CI = 1.14 ; 2.25. To control MB, special attention should be paid to women who had APD history, who had unhealthy baby on 5 first days afterbirth, who had husbands’ mental health problems, and who had stress during pregnancy. (Med J Indones 2006; 15:74-80Keywords: ante partum, maternity blues, depression, mental problem

Vocal Fold Vibratory Changes Following Surgical Intervention.

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Chen, Wenli; Woo, Peak; Murry, Thomas

2016-03-01

High-speed videoendoscopy (HSV) captures direct cycle-to-cycle visualization of vocal fold movement in real time. This ultrafast recording rate is capable of visualizing the vibratory motion of the vocal folds in severely disordered phonation and provides a direct method for examining vibratory changes after vocal fold surgery. The purpose of this study was to examine the vibratory motion before and after surgical intervention. HSV was captured from two subjects with identifiable midvocal fold benign lesions and six subjects with highly aperiodic vocal fold vibration before and after phonosurgery. Digital kymography (DKG) was used to extract high-speed kymographic vocal fold images sampled at the midmembranous, anterior 1/3, and posterior 1/3 region. Spectral analysis was subsequently applied to the DKG to quantify the cycle-to-cycle movements of the left and the right vocal fold, expressed as a spectrum. Before intervention, the vibratory spectrum consisted of decreased and flat-like spectral peaks with robust power asymmetry. After intervention, increases in spectral power and decreases in power symmetry were noted. Spectral power increases were most remarkable in the midmembranous region of the vocal fold. Surgical modification resulted in improved lateral excursion of the vocal folds, vibratory function, and perceptual measures of Voice Handicap Index-10. These changes in vibratory behavior trended toward normal vocal fold vibration. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Previous Fractures at Multiple Sites Increase the Risk for Subsequent Fractures: The Global Longitudinal Study of Osteoporosis in Women

Science.gov (United States)

Gehlbach, Stephen; Saag, Kenneth G.; Adachi, Jonathan D.; Hooven, Fred H.; Flahive, Julie; Boonen, Steven; Chapurlat, Roland D.; Compston, Juliet E.; Cooper, Cyrus; Díez-Perez, Adolfo; Greenspan, Susan L.; LaCroix, Andrea Z.; Netelenbos, J. Coen; Pfeilschifter, Johannes; Rossini, Maurizio; Roux, Christian; Sambrook, Philip N.; Silverman, Stuart; Siris, Ethel S.; Watts, Nelson B.; Lindsay, Robert

2016-01-01

Previous fractures of the hip, spine, or wrist are well-recognized predictors of future fracture, but the role of other fracture sites is less clear. We sought to assess the relationship between prior fracture at 10 skeletal locations and incident fracture. The Global Longitudinal Study of Osteoporosis in Women (GLOW) is an observational cohort study being conducted in 17 physician practices in 10 countries. Women ≥ 55 years answered questionnaires at baseline and at 1 and/or 2 years (fractures in previous year). Of 60,393 women enrolled, follow-up data were available for 51,762. Of these, 17.6%, 4.0%, and 1.6% had suffered 1, 2, or ≥3 fractures since age 45. During the first 2 years of follow-up, 3149 women suffered 3683 incident fractures. Compared with women with no prior fractures, women with 1, 2, or ≥ 3 prior fractures were 1.8-, 3.0-, and 4.8-fold more likely to have any incident fracture; those with ≥3 prior fractures were 9.1-fold more likely to sustain a new vertebral fracture. Nine of 10 prior fracture locations were associated with an incident fracture. The strongest predictors of incident spine and hip fractures were prior spine fracture (hazard ratio 7.3) and hip (hazard ratio 3.5). Prior rib fractures were associated with a 2.3-fold risk of subsequent vertebral fracture, previous upper leg fracture predicted a 2.2-fold increased risk of hip fracture; women with a history of ankle fracture were at 1.8-fold risk of future fracture of a weight-bearing bone. Our findings suggest that a broad range of prior fracture sites are associated with an increased risk of incident fractures, with important implications for clinical assessments and risk model development. PMID:22113888

Cluster analysis to estimate the risk of preeclampsia in the high-risk Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study

Science.gov (United States)

Marttinen, Pekka; Gillberg, Jussi; Lokki, A. Inkeri; Majander, Kerttu; Ordén, Maija-Riitta; Taipale, Pekka; Pesonen, Anukatriina; Räikkönen, Katri; Hämäläinen, Esa; Kajantie, Eero; Laivuori, Hannele

2017-01-01

Objectives Preeclampsia is divided into early-onset (delivery before 34 weeks of gestation) and late-onset (delivery at or after 34 weeks) subtypes, which may rise from different etiopathogenic backgrounds. Early-onset disease is associated with placental dysfunction. Late-onset disease develops predominantly due to metabolic disturbances, obesity, diabetes, lipid dysfunction, and inflammation, which affect endothelial function. Our aim was to use cluster analysis to investigate clinical factors predicting the onset and severity of preeclampsia in a cohort of women with known clinical risk factors. Methods We recruited 903 pregnant women with risk factors for preeclampsia at gestational weeks 12+0–13+6. Each individual outcome diagnosis was independently verified from medical records. We applied a Bayesian clustering algorithm to classify the study participants to clusters based on their particular risk factor combination. For each cluster, we computed the risk ratio of each disease outcome, relative to the risk in the general population. Results The risk of preeclampsia increased exponentially with respect to the number of risk factors. Our analysis revealed 25 number of clusters. Preeclampsia in a previous pregnancy (n = 138) increased the risk of preeclampsia 8.1 fold (95% confidence interval (CI) 5.7–11.2) compared to a general population of pregnant women. Having a small for gestational age infant (n = 57) in a previous pregnancy increased the risk of early-onset preeclampsia 17.5 fold (95%CI 2.1–60.5). Cluster of those two risk factors together (n = 21) increased the risk of severe preeclampsia to 23.8-fold (95%CI 5.1–60.6), intermediate onset (delivery between 34+0–36+6 weeks of gestation) to 25.1-fold (95%CI 3.1–79.9) and preterm preeclampsia (delivery before 37+0 weeks of gestation) to 16.4-fold (95%CI 2.0–52.4). Body mass index over 30 kg/m2 (n = 228) as a sole risk factor increased the risk of preeclampsia to 2.1-fold (95%CI 1.1–3

Risk for obesity in adolescence starts in early childhood.

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Shankaran, S; Bann, C; Das, A; Lester, B; Bada, H; Bauer, C R; La Gasse, L; Higgins, R D

2011-11-01

The objective of this study was to assess the predictive value of body mass index (BMI) at earlier ages on risk of overweight/obesity at age of 11 years. This is a longitudinal study of 907 children from birth to age of 11 years. Predictors include BMI at earlier ages and outcome is overweight/obesity status at age of 11 years. Analyses were adjusted for covariates known to affect BMI. At 11 years, 17% were overweight and 25% were obese. Children whose BMI was measured as ≥85th percentile once at preschool age had a twofold risk for overweight/obesity at 11 years of age. Risk increased by 11-fold if a child's BMI measured was noted more than once during this age. During early elementary years, if a child's BMI was>85th percentile once, risk for overweight/obesity at 11 years was fivefold and increased by 72-fold if noted more than two times. During late elementary years, if a child's BMI was>85th percentile once, risk for overweight/obesity was 26-fold and increased by 351-fold if noted more than two times. Risk of overweight/obesity at 11 years was noted with higher maternal prepregnancy weight, higher birth weight, female gender and increased television viewing. Children in higher BMI categories at young ages have a higher risk of overweight/obesity at 11 years of age. Effect size was greater for measurements taken closer to 11 years of age. Pediatricians need to identify children at-risk for adolescent obesity and initiate counseling and intervention at earlier ages.

Background Paper for the update of meningococcal vaccination recommendations in Germany: use of the serogroup B vaccine in persons at increased risk for meningococcal disease.

Science.gov (United States)

Hellenbrand, Wiebke; Koch, Judith; Harder, Thomas; Bogdan, Christian; Heininger, Ulrich; Tenenbaum, Tobias; Terhardt, Martin; Vogel, Ulrich; Wichmann, Ole; von Kries, Rüdiger

2015-11-01

In December 2013 Bexsero® became available in Germany for vaccination against serogroup B meningococci (MenB). In August 2015 the German Standing Committee on Vaccination (STIKO) endorsed a recommendation for use of this vaccine in persons at increased risk of invasive meningococcal disease (IMD). This background paper summarizes the evidence underlying the recommendation. Bexsero® is based on surface protein antigens expressed by about 80% of circulating serogroup B meningococci in Germany. The paper reviews available data on immunogenicity and safety of Bexsero® in healthy children and adolescents; data in persons with underlying illness and on the effectiveness in preventing clinical outcomes are thus far unavailable.STIKO recommends MenB vaccination for the following persons based on an individual risk assessment: (1) Persons with congenital or acquired immune deficiency or suppression. Among these, persons with terminal complement defects and properdin deficiency, including those under eculizumab therapy, are at highest risk with reported invasive meningococcal disease (IMD) incidences up 10,000-fold higher than in the general population. Persons with asplenia were estimated to have a ~ 20-30-fold increased risk of IMD, while the risk in individuals with other immune defects such as HIV infection or hypogammaglobulinaemia was estimated at no more than 5-10-fold higher than the background risk. (2) Laboratory staff with a risk of exposure to N. meningitidis aerosols, for whom an up to 271-fold increased risk for IMD has been reported. (3) Unvaccinated household (-like) contacts of a MenB IMD index case, who have a roughly 100-200-fold increased IMD risk in the year after the contact despite chemoprophylaxis. Because the risk is highest in the first 3 months and full protective immunity requires more than one dose (particularly in infants and toddlers), MenB vaccine should be administered as soon as possible following identification of the serogroup of the

Perioperative complications increase the risk of venous thromboembolism following bariatric surgery.

Science.gov (United States)

Helm, Melissa C; Simon, Kathleen; Higgins, Rana; Kindel, Tammy L; Gould, Jon C

2017-12-01

Morbidly obese patients are at increased risk of venous thromboembolism (VTE) following surgery. This study explores the impact of a perioperative complication on the risk of VTE after bariatric surgery. Patients who underwent bariatric surgery were identified from the American College of Surgeons National Surgical Quality Improvement Program dataset (2012-2014). The 17 most common perioperative complications were analyzed by multivariate regression analysis to determine the effect of complications on the risk of VTE. The postoperative incidence of VTE was 0.5% (n = 59,424 bariatric surgeries). The average time to diagnosis of VTE was 11.6 days. 80% of VTE events occurred after discharge. A major complication occurred prior to VTE in 22.6% of patients. The more complications experienced by an individual patient, the more likely they were to experience VTE. Unadjusted thirty-day mortality increased 13.89-fold following VTE (p bariatric surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults

Directory of Open Access Journals (Sweden)

Amanda Marie Dibattista

2014-10-01

Full Text Available Alzheimer’s disease (AD risk genes alter brain structure and function decades before disease onset. Apolipoprotein E (APOE is the strongest known genetic risk factor for Alzheimer’s disease, and a related gene, apolipoprotein J (APOJ, also affects disease risk. However, the extent to which these genes affect brain structure in young adults remains unclear. Here, we report that AD risk alleles of these two genes, APOE-ε4 and APOJ-C, cumulatively alter brain volume in young adults. Using voxel-based morphometry in 57 individuals, we examined the entorhinal cortex, one of the earliest brain regions affected in AD pathogenesis. APOE-ε4 carriers exhibited higher right entorhinal cortex volume compared to non-carriers. Interestingly, APOJ-C risk genotype was associated with higher bilateral entorhinal cortex volume in non-APOE-ε4 carriers. To determine the combined disease risk of APOE and APOJ status per subject, we used cumulative odds ratios as regressors for volumetric measurements. Higher disease risk corresponded to greater right entorhinal cortex volume. These results suggest that, years before disease onset, two key AD genetic risk factors may exert influence on the structure of a brain region where AD pathogenesis takes root.

Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults

Science.gov (United States)

DiBattista, Amanda Marie; Stevens, Benson W.; Rebeck, G. William; Green, Adam E.

2014-01-01

Alzheimer’s disease (AD) risk genes alter brain structure and function decades before disease onset. Apolipoprotein E (APOE) is the strongest known genetic risk factor for AD, and a related gene, apolipoprotein J (APOJ), also affects disease risk. However, the extent to which these genes affect brain structure in young adults remains unclear. Here, we report that AD risk alleles of these two genes, APOE-ε4 and APOJ-C, cumulatively alter brain volume in young adults. Using voxel-based morphometry (VBM) in 57 individuals, we examined the entorhinal cortex, one of the earliest brain regions affected in AD pathogenesis. Apolipoprotein E-ε4 carriers exhibited higher right entorhinal cortex volume compared to non-carriers. Interestingly, APOJ-C risk genotype was associated with higher bilateral entorhinal cortex volume in non-APOE-ε4 carriers. To determine the combined disease risk of APOE and APOJ status per subject, we used cumulative odds ratios as regressors for volumetric measurements. Higher disease risk corresponded to greater right entorhinal cortex volume. These results suggest that, years before disease onset, two key AD genetic risk factors may exert influence on the structure of a brain region where AD pathogenesis takes root. PMID:25339884

There and back again: Two views on the protein folding puzzle.

Science.gov (United States)

Finkelstein, Alexei V; Badretdin, Azat J; Galzitskaya, Oxana V; Ivankov, Dmitry N; Bogatyreva, Natalya S; Garbuzynskiy, Sergiy O

2017-07-01

The ability of protein chains to spontaneously form their spatial structures is a long-standing puzzle in molecular biology. Experimentally measured folding times of single-domain globular proteins range from microseconds to hours: the difference (10-11 orders of magnitude) is the same as that between the life span of a mosquito and the age of the universe. This review describes physical theories of rates of overcoming the free-energy barrier separating the natively folded (N) and unfolded (U) states of protein chains in both directions: "U-to-N" and "N-to-U". In the theory of protein folding rates a special role is played by the point of thermodynamic (and kinetic) equilibrium between the native and unfolded state of the chain; here, the theory obtains the simplest form. Paradoxically, a theoretical estimate of the folding time is easier to get from consideration of protein unfolding (the "N-to-U" transition) rather than folding, because it is easier to outline a good unfolding pathway of any structure than a good folding pathway that leads to the stable fold, which is yet unknown to the folding protein chain. And since the rates of direct and reverse reactions are equal at the equilibrium point (as follows from the physical "detailed balance" principle), the estimated folding time can be derived from the estimated unfolding time. Theoretical analysis of the "N-to-U" transition outlines the range of protein folding rates in a good agreement with experiment. Theoretical analysis of folding (the "U-to-N" transition), performed at the level of formation and assembly of protein secondary structures, outlines the upper limit of protein folding times (i.e., of the time of search for the most stable fold). Both theories come to essentially the same results; this is not a surprise, because they describe overcoming one and the same free-energy barrier, although the way to the top of this barrier from the side of the unfolded state is very different from the way from the

Origami-Inspired Folding of Thick, Rigid Panels

Science.gov (United States)

Trease, Brian P.; Thomson, Mark W.; Sigel, Deborah A.; Walkemeyer, Phillip E.; Zirbel, Shannon; Howell, Larry; Lang, Robert

2014-01-01

To achieve power of 250 kW or greater, a large compression ratio of stowed-to-deployed area is needed. Origami folding patterns were used to inspire the folding of a solar array to achieve synchronous deployment; however, origami models are generally created for near-zero-thickness material. Panel thickness is one of the main challenges of origami-inspired design. Three origami-inspired folding techniques (flasher, square twist, and map fold) were created with rigid panels and hinges. Hinge components are added to the model to enable folding of thick, rigid materials. Origami models are created assuming zero (or near zero) thickness. When a material with finite thickness is used, the panels are required to bend around an increasingly thick fold as they move away from the center of the model. The two approaches for dealing with material thickness are to use membrane hinges to connect the panels, or to add panel hinges, or hinges of the same thickness, at an appropriate width to enable folding.

Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

DEFF Research Database (Denmark)

van Eggermond, Anna M; Schaapveld, Michael; Janus, Cécile Pm

2017-01-01

incidence ratios (SIR) was 2.4-fold increased (95% confidence interval (95%CI) 1.8-3.2), leading to 5.7 excess cases per 10 000 patient-years. Risk was still increased 30 years after HL treatment (SIR: 2.8; 95%CI: 1.6-4.6). The highest (SIR: 6.5, 95%CI: 3.3-11.3) was seen for transverse colon cancer (15......BACKGROUND: Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens. METHODS...... a hazard ratio of 6.8 (95%CI: 3.0-15.6) compared with patients receiving neither treatment, which is significantly higher than an additive joint effect (Padditivity=0.004). CONCLUSIONS: Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy...

Double folded Yukawa interaction potential between two heavy ions

International Nuclear Information System (INIS)

Bulgac, A.; Carstoiu, F.; Dumitrescu, O.

1980-02-01

A simple semi-analytical formula for the heavy ion interaction potential within the double-folding model approximation is obtained. The folded interaction is assumed to be expressed in Yukawa terms or the derivatives of them. The densities used can be both experimental or theoretical (of simple ''step-wise'', ''Fermi-Saxon-Woods'' or complicated ''shell model'' structure) densities. A way of inserting the exchange terms is discussed. Numerical calculations for some colliding partners are reported. (author)

Micro-scale truss structures with three-fold and six-fold symmetry formed from self-propagating polymer waveguides

Energy Technology Data Exchange (ETDEWEB)

Jacobsen, Alan J. [HRL Laboratories LLC, Sensors and Materials Laboratory, 3011 Malibu Canyon Road, Malibu, CA 90265-4797 (United States); Department of Aerospace and Mechanical Engineering, University of Southern California, Los Angeles, CA (United States)], E-mail: ajjacobsen@hrl.com; Barvosa-Carter, William [HRL Laboratories LLC, Sensors and Materials Laboratory, 3011 Malibu Canyon Road, Malibu, CA 90265-4797 (United States); Nutt, Steven [Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA (United States)

2008-06-15

A process for interconnecting a three-dimensional pattern of self-propagating polymer waveguides was used to form micro-truss structures with two new unit cell architectures. The structures were formed using a two-dimensional mask with a hexagonal pattern of apertures. Distinct unit cell architectures were possible by exposing the mask to a different number of incident UV exposure beams, which are used to form the waveguides. One unit cell design featured three intersecting waveguides per node, resulting in a structure with three-fold symmetry. The second unit cell design had six-fold symmetry and was characterized by primary nodes with six intersecting waveguides and secondary nodes with two intersecting waveguides. Compression loading experiments were conducted on micro-truss samples with comparable relative density values ({rho}/{rho}{sub s} = 6.5%), but different unit cell architectures. The addition of secondary nodes in the structures based on the second design led to an increase in compressive modulus of up to 70% and an average increase in peak strength of 42%. The increase in compressive strength and modulus was attributed to a reduction in the truss-member slenderness ratio achieved through increased waveguide connectivity.

Micro-scale truss structures with three-fold and six-fold symmetry formed from self-propagating polymer waveguides

International Nuclear Information System (INIS)

Jacobsen, Alan J.; Barvosa-Carter, William; Nutt, Steven

2008-01-01

A process for interconnecting a three-dimensional pattern of self-propagating polymer waveguides was used to form micro-truss structures with two new unit cell architectures. The structures were formed using a two-dimensional mask with a hexagonal pattern of apertures. Distinct unit cell architectures were possible by exposing the mask to a different number of incident UV exposure beams, which are used to form the waveguides. One unit cell design featured three intersecting waveguides per node, resulting in a structure with three-fold symmetry. The second unit cell design had six-fold symmetry and was characterized by primary nodes with six intersecting waveguides and secondary nodes with two intersecting waveguides. Compression loading experiments were conducted on micro-truss samples with comparable relative density values (ρ/ρ s = 6.5%), but different unit cell architectures. The addition of secondary nodes in the structures based on the second design led to an increase in compressive modulus of up to 70% and an average increase in peak strength of 42%. The increase in compressive strength and modulus was attributed to a reduction in the truss-member slenderness ratio achieved through increased waveguide connectivity

Familial Risk of IBD is more pronounced in the younger age groups

DEFF Research Database (Denmark)

Trier Møller, Frederik; Jess, Tine; Andersen, Vibeke

2014-01-01

Background: Inflammatory bowel disease (IBD) – Ulcerative colitis (UC) and Crohns Disease (CD) are caused by complex gene-environment interactions and the risk is increased in family members. We investigated whether the risk of IBD in relatives to IBD patients changes by age of the relatives....... Results The age stratified rates of IBD in 1st degree relatives to an IBD affected case, after controlling for the overall effect of age, appear from Table 1. The rate ratio of CD in individuals with two or more 1st degree relatives with IBD is 1-2 fold increased in relatives aged 60+ years, whereas...... it is 67-fold increased risk in relatives aged 0-10 years and 34-fold increased in relatives aged 10-19 years. The same pattern is seen in 1st degree relatives who have one relative with IBD, where the risk of CD is markedly higher in younger relatives, this risk pattern for CD is seen both if the IBD...

Botulinum toxin in the treatment of vocal fold nodules.

Science.gov (United States)

Allen, Jacqui E; Belafsky, Peter C

2009-12-01

Promising new techniques in the management of vocal fold nodules have been developed in the past 2 years. Simultaneously, the therapeutic use of botulinum toxin has rapidly expanded. This review explores the use of botulinum toxin in treatment of vocal nodules and summarizes current therapeutic concepts. New microsurgical instruments and techniques, refinements in laser technology, radiosurgical excision and steroid intralesional injections are all promising new techniques in the management of vocal nodules. Botulinum toxin-induced 'voice rest' is a new technique we have employed in patients with recalcitrant nodules. Successful resolution of nodules is possible with this technique, without the risk of vocal fold scarring inherent in dissection/excision techniques. Botulinum toxin usage is exponentially increasing, and large-scale, long-term studies demonstrate its safety profile. Targeted vocal fold temporary paralysis induced by botulinum toxin injection is a new, well tolerated and efficacious treatment in patients with persistent vocal fold nodules.

One Peptide Reveals the Two Faces of α-Helix Unfolding-Folding Dynamics.

Science.gov (United States)

Jesus, Catarina S H; Cruz, Pedro F; Arnaut, Luis G; Brito, Rui M M; Serpa, Carlos

2018-04-12

The understanding of fast folding dynamics of single α-helices comes mostly from studies on rationally designed peptides displaying sequences with high helical propensity. The folding/unfolding dynamics and energetics of α-helix conformations in naturally occurring peptides remains largely unexplored. Here we report the study of a protein fragment analogue of the C-peptide from bovine pancreatic ribonuclease-A, RN80, a 13-amino acid residue peptide that adopts a highly populated helical conformation in aqueous solution. 1 H NMR and CD structural studies of RN80 showed that α-helix formation displays a pH-dependent bell-shaped curve, with a maximum near pH 5, and a large decrease in helical content in alkaline pH. The main forces stabilizing this short α-helix were identified as a salt bridge formed between Glu-2 and Arg-10 and the cation-π interaction involving Tyr-8 and His-12. Thus, deprotonation of Glu-2 or protonation of His-12 are essential for the RN80 α-helix stability. In the present study, RN80 folding and unfolding were triggered by laser-induced pH jumps and detected by time-resolved photoacoustic calorimetry (PAC). The photoacid proton release, amino acid residue protonation, and unfolding/folding events occur at different time scales and were clearly distinguished using time-resolved PAC. The partial unfolding of the RN80 α-helix, due to protonation of Glu-2 and consequent breaking of the stabilizing salt bridge between Glu-2 and Arg-10, is characterized by a concentration-independent volume expansion in the sub-microsecond time range (0.8 mL mol -1 , 369 ns). This small volume expansion reports the cost of peptide backbone rehydration upon disruption of a solvent-exposed salt bridge, as well as backbone intrinsic expansion. On the other hand, RN80 α-helix folding triggered by His-12 protonation and subsequent formation of a cation-π interaction leads to a microsecond volume contraction (-6.0 mL mol -1 , ∼1.7 μs). The essential role of two

Asymmetric hindwing foldings in rove beetles.

Science.gov (United States)

Saito, Kazuya; Yamamoto, Shuhei; Maruyama, Munetoshi; Okabe, Yoji

2014-11-18

Foldable wings of insects are the ultimate deployable structures and have attracted the interest of aerospace engineering scientists as well as entomologists. Rove beetles are known to fold their wings in the most sophisticated ways that have right-left asymmetric patterns. However, the specific folding process and the reason for this asymmetry remain unclear. This study reveals how these asymmetric patterns emerge as a result of the folding process of rove beetles. A high-speed camera was used to reveal the details of the wing-folding movement. The results show that these characteristic asymmetrical patterns emerge as a result of simultaneous folding of overlapped wings. The revealed folding mechanisms can achieve not only highly compact wing storage but also immediate deployment. In addition, the right and left crease patterns are interchangeable, and thus each wing internalizes two crease patterns and can be folded in two different ways. This two-way folding gives freedom of choice for the folding direction to a rove beetle. The use of asymmetric patterns and the capability of two-way folding are unique features not found in artificial structures. These features have great potential to extend the design possibilities for all deployable structures, from space structures to articles of daily use.

Tourette syndrome increases risk of bone fractures: a population-based cohort study.

Science.gov (United States)

Lu, Yuan-Yuan; Wang, Ming-Yu; Wei, I-Hua; Lin, Che-Chen; Huang, Chih-Chia

2017-05-01

This study assesses the risk of fractures among children with Tourette syndrome (TS), and identifies the effects of comorbidities and antipsychotics. We randomly sampled the claims data of 1 million enrollees in the National Health Insurance program of Taiwan, and identified 1258 children with TS diagnosed between 2000 and 2010. Additionally, 12,580 children without TS who were frequency matched for sex, age, residential area, parental occupation, and index year were identified for comparison. The children's cases were followed until December 31, 2010, or censored to ascertain incident fractures cases and associations with comorbidities of attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) and treatments with antipsychotics, antidepressants, or clonidine. The TS cohort had a 1.27-fold higher incidence of fractures than did the comparison cohort (190.37 vs. 149.94 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.28 [95% confidence interval (CI) 1.06-1.55] based on multivariable Cox regression analysis. This increased risk of fractures was apparent for fractures of the skull, neck, and spine. Comorbid ADHD and OCD did not result in an additional risk of fractures. The children without both ADHD and OCD were also at a higher risk of fractures, indicating that TS alone increases the risk of fractures. The children taking antipsychotics had a reduced risk of fractures, and the adjusted HR decreased to 1.17 (95% CI 0.90-1.52). Children with TS have an increased risk of fractures. ADHD and OCD do not increase the risk further.

Folding of multidomain proteins: biophysical consequences of tethering even in apparently independent folding.

Science.gov (United States)

Arviv, Oshrit; Levy, Yaakov

2012-12-01

Most eukaryotic and a substantial fraction of prokaryotic proteins are composed of more than one domain. The tethering of these evolutionary, structural, and functional units raises, among others, questions regarding the folding process of conjugated domains. Studying the folding of multidomain proteins in silico enables one to identify and isolate the tethering-induced biophysical determinants that govern crosstalks generated between neighboring domains. For this purpose, we carried out coarse-grained and atomistic molecular dynamics simulations of two two-domain constructs from the immunoglobulin-like β-sandwich fold. Each of these was experimentally shown to behave as the "sum of its parts," that is, the thermodynamic and kinetic folding behavior of the constituent domains of these constructs seems to occur independently, with the folding of each domain uncoupled from the folding of its partner in the two-domain construct. We show that the properties of the individual domains can be significantly affected by conjugation to another domain. The tethering may be accompanied by stabilizing as well as destabilizing factors whose magnitude depends on the size of the interface, the length, and the flexibility of the linker, and the relative stability of the domains. Accordingly, the folding of a multidomain protein should not be viewed as the sum of the folding patterns of each of its parts, but rather, it involves abrogating several effects that lead to this outcome. An imbalance between these effects may result in either stabilization or destabilization owing to the tethering. Copyright © 2012 Wiley Periodicals, Inc.

Three-Fold Symmetry Restrictions on Two-Dimensional Micropolar Materials

DEFF Research Database (Denmark)

Warren, W. E.; Byskov, Esben

that three-fold symmetry requires both the stress and couple stress tensors to be isotropic in the plane. We obtain the constitutive relations for an equilateral triangle structure and for the hexagonal or honeycomb structure, both of which exhibit three-fold symmetry in the plane. These results are compared......Analysis of the mechanical properties of engineering materials with micro-structure generally requires modification of the concept of a simple material. One approach is the theory of micropolar materials which introduces an independent rotation of a material element and the resulting stress...

Longitudinal stability of the folding pattern of the anterior cingulate cortex during development

Directory of Open Access Journals (Sweden)

A. Cachia

2016-06-01

Full Text Available Prenatal processes are likely critical for the differences in cognitive ability and disease risk that unfold in postnatal life. Prenatally established cortical folding patterns are increasingly studied as an adult proxy for earlier development events – under the as yet untested assumption that an individual's folding pattern is developmentally fixed. Here, we provide the first empirical test of this stability assumption using 263 longitudinally-acquired structural MRI brain scans from 75 typically developing individuals spanning ages 7 to 32 years. We focus on the anterior cingulate cortex (ACC – an intensely studied cortical region that presents two qualitatively distinct and reliably classifiable sulcal patterns with links to postnatal behavior. We show – without exception–that individual ACC sulcal patterns are fixed from childhood to adulthood, at the same time that quantitative anatomical ACC metrics are undergoing profound developmental change. Our findings buttress use of folding typology as a postnatally-stable marker for linking variations in early brain development to later neurocognitive outcomes in ex utero life.

Protamine reduces bleeding complications associated with carotid endarterectomy without increasing the risk of stroke.

Science.gov (United States)

Stone, David H; Nolan, Brian W; Schanzer, Andres; Goodney, Philip P; Cambria, Robert A; Likosky, Donald S; Walsh, Daniel B; Cronenwett, Jack L

2010-03-01

Controversy persists regarding the use of protamine during carotid endarterectomy (CEA) based on prior conflicting reports documenting both reduced bleeding as well as increased stroke risk. The purpose of this study was to determine the effect of protamine reversal of heparin anticoagulation on the outcome of CEA in a contemporary multistate registry. We reviewed a prospective regional registry of 4587 CEAs in 4311 patients performed by 66 surgeons from 11 centers in Northern New England from 2003-2008. Protamine use varied by surgeon (38% routine use, 44% rare use, 18% selective use). Endpoints were postoperative bleeding requiring reoperation as well as potential thrombotic complications, including stroke, death, and myocardial infarction (MI). Predictors of endpoints were determined by multivariate logistic regression after associated variables were identified by univariate analysis. Of the 4587 CEAs performed, 46% utilized protamine, while 54% did not. Fourteen patients (0.64%) in the protamine-treated group required reoperation for bleeding compared with 42 patients (1.66%) in the untreated cohort (P = .001). Protamine use did not affect the rate of MI (1.1% vs 0.91%, P = .51), stroke (0.78% vs 1.15%, P = .2), or death (0.23% vs 0.32%, P = .57) between treated and untreated patients, respectively. By multivariate analysis, protamine (odds ratio [OR] 0.32, 95% confidence interval [CI], 0.17-0.63; P = .001) and patch angioplasty (OR 0.46, 95% CI, 0.26-0.81; P = .007) were independently associated with diminished reoperation for bleeding. A single center was associated with a significantly higher rate of reoperation for bleeding (OR 6.47, 95% CI, 3.02-13.9; P < .001). Independent of protamine use, consequences of reoperation for bleeding were significant, with a four-fold increase in MI, a seven-fold increase in stroke, and a 30-fold increase in death. Protamine reduced serious bleeding requiring reoperation during CEA without increasing the risk of MI, stroke

Increased risk of tinnitus in patients with temporomandibular disorder: a retrospective population-based cohort study.

Science.gov (United States)

Lee, Chun-Feng; Lin, Ming-Chia; Lin, Hui-Tzu; Lin, Cheng-Li; Wang, Tang-Chuan; Kao, Chia-Hung

2016-01-01

This study determined whether there is an increased risk of tinnitus in patients with temporomandibular joint (TMJ). We used information from health insurance claims obtained from Taiwan National Health Insurance (TNHI). Patients aged 20 years and older who were newly diagnosed with TMJ disorder served as the study cohort. The demographic factors and comorbidities that may be associated with tinnitus were also identified, including age, sex, and comorbidities of hearing loss, noise effects on the inner ear, and degenerative and vascular ear disorders. A higher proportion of TMJ disorder patients suffered from hearing loss (5.30 vs. 2.11 %), and degenerative and vascular ear disorders (0.20 vs. 0.08 %) compared with the control patients. The crude hazard ratio (HR) of tinnitus in the TMJ disorder cohort was 2.73-fold higher than that in the control patients, with an adjusted HR of 2.62 (95 % CI = 2.29-3.00). The comorbidity-specific TMJ disorder cohort to the control patients' adjusted HR of tinnitus was higher for patients without comorbidity (adjusted HR = 2.75, 95 % CI = 2.39-3.17). We also observed a 3.22-fold significantly higher relative risk of developing tinnitus within the 3-year follow-up period (95 % CI = 2.67-3.89). Patients with TMJ disorder might be at increased risk of tinnitus.

Discriminating trpzip2 and trpzip4 peptides’ folding landscape using the two-dimensional infrared spectroscopy: A simulation study

International Nuclear Information System (INIS)

Wu, Tianmin; Zhang, Ruiting; Li, Huanhuan; Zhuang, Wei; Yang, Lijiang

2014-01-01

We analyzed, based on the theoretical spectroscopic modeling, how the differences in the folding landscapes of two β-hairpin peptides trpzip2 and trpzip4 are reflected in their thermal unfolding infrared measurements. The isotope-edited equilibrium FTIR and two dimensional infrared spectra of the two peptides were calculated, using the nonlinear exciton propagation method, at a series of temperatures. The spectra calculations were based on the configuration distributions generated using the GB OBC implicit solvent MD simulation and the integrated tempering sampling technique. Conformational analysis revealed the different local thermal stabilities for these two peptides, which suggested the different folding landscapes. Our study further suggested that the ellipticities of the isotope peaks in the coherent IR signals are more sensitive to these local stability differences compared with other spectral features such as the peak intensities. Our technique can thus be combined with the relevant experimental measurements to achieve a better understanding of the peptide folding behaviors

Vascular Cognitive Impairment: risk factors and brain MRI correlates

NARCIS (Netherlands)

Reijmer, Y.D.

2012-01-01

Vascular disease plays an important role in the development of dementia, also in patients diagnosed with Alzheimer’s disease. Risk factors such as hypertension, obesity, and type 2 diabetes, are associated with a two-fold increased risk of cognitive dysfunction and dementia. The development of

Functional results after external vocal fold medialization thyroplasty with the titanium vocal fold medialization implant.

Science.gov (United States)

Schneider, Berit; Denk, Doris-Maria; Bigenzahn, Wolfgang

2003-04-01

A persistent insufficiency of glottal closure is mostly a consequence of a unilateral vocal fold movement impairment. It can also be caused by vocal fold atrophy or scarring processes with regular bilateral respiratory vocal fold function. Because of consequential voice, breathing, and swallowing impairments, a functional surgical treatment is required. The goal of the study was to outline the functional results after medialization thyroplasty with the titanium vocal fold medialization implant according to Friedrich. In the period of 1999 to 2001, an external vocal fold medialization using the titanium implant was performed on 28 patients (12 women and 16 men). The patients were in the age range of 19 to 84 years. Twenty-two patients had a paralysis of the left-side vocal fold, and six patients, of the right-side vocal fold. Detailed functional examinations were executed on all patients before and after the surgery: perceptive voice sound analysis according to the "roughness, breathiness, and hoarseness" method, judgment of the s/z ratio and voice dysfunction index, voice range profile measurements, videostroboscopy, and pulmonary function tests. In case of dysphagia/aspiration, videofluoroscopy of swallowing was also performed. The respective data were statistically analyzed (paired t test, Wilcoxon-test). All patients reported on improvement of voice, swallowing, and breathing functions postoperatively. Videostroboscopy revealed an almost complete glottal closure after surgery in all of the patients. All voice-related parameters showed a significant improvement. An increase of the laryngeal resistance by the medialization procedure could be excluded by analysis of the pulmonary function test. The results confirm the external medialization of the vocal folds as an adequate method in the therapy of voice, swallowing, and breathing impairment attributable to an insufficient glottal closure. The titanium implant offers, apart from good tissue tolerability, the

Integration of a Folding Electric two-wheeler vehicle for a future commuting transportation

DEFF Research Database (Denmark)

Gudmundsson, Bjami Freyr; Larsen, Esben

2012-01-01

The paper issues the development, building and testing of a Folding Electric Motorbike, a lightweight, low cost and all-electric two-wheeler vehicle taking full advantage on today's city infrastructure. The technology offers drivers to combine transportation methods, lowering cost, and greenhouse......-electric two-wheeler vehicle taking full advantage on today's city infrastructure is very prospective. The alpha-prototype was successfully constructed and is considered to be ready for further laboratory testing and test driving before continuations on a fully designed beta-prototype....

Risk factors for the appearance of minimal pathologic lesions on vocal folds in vocal professionals

Directory of Open Access Journals (Sweden)

Stojanović Jasmina

2012-01-01

Full Text Available Background/Aim. An excessive use or misuse of voice by vocal professionals may result in symptoms such are husky voice, hoarse voice, total loss of voice, or even organic changes taking place on vocal folds - minimal pathological lesions - MAPLs. The purpose of this study was to identify the type of MAPLs which affects vocal professionals, as well as to identify the risk factors that bring about these changes. Methods. There were 94 vocal professionals who were examined altogether, out of whom 46 were affected by MAPLs, whereas 48 of them were diagnosed with no MAPLs, so that they served as the control group. All these patients were clinically examined (anamnesis, clinical examination, bacteoriological examination of nose and pharynx, radiography of paranasal cavities, allergological processing, phoniatric examination, endo-video-stroboscopic examination, as well as gastroenterologic examination, and finally endocrinological and pulmological analyses. Results. The changes that occurred most often were identified as nodules (50%; n = 23/46 and polyps (24%; n = 11/46. Risk factors causing MAPLs in vocal professionals were as follows: age, which reduced the risk by 23.9% [OR 0.861 (0.786-0.942] whereas the years of career increase the risk [OR 1.114 (1.000-1.241], as well as the presence of a chronic respiratory disease [OR 7.310 (1.712- 31.218], and the presence of gastro-oesophageal reflux disease [OR 4.542 (1.263-16.334]. The following factors did not contribute to development of MAPLs in vocal professionals: sex, a place of residence, irritation, smoking, endocrinologic disease and the presence of poly-sinusitis. Conclusion. It is necessary to introduce comprehensive procedures for prevention of MAPLs, particularly in high-risk groups. Identification of the risk factors for MAPLs and prevention of their influence on vocal professionals (given that their income depends on their vocal ability is of the highest importance.

High intensity interior aircraft noise increases the risk of high diastolic blood pressure in Indonesian Air Force pilots

Directory of Open Access Journals (Sweden)

Minarma Siagian

2009-12-01

Full Text Available Aim: To analyze the effects of aircraft noise, resting pulse rate, and other factors on the risk of high diastolic blood pressure (DBP in Indonesian Air Force pilots.Methods: A nested case-control study was conducted using data extracted from annual medical check-ups indoctrination aerophysiologic training records at the Saryanto Aviation and Aerospace Health Institute (LAKESPRA in Jakarta from January 2003 – September 2008. For analysis of DBP: the case group with DBP ≥ 90 mmHg were compared with contral group with DBP < 79 mmHG. One case matched to 12 controls.Results: Out of 567 pilots, 544 (95.9% had complete medical records. For this analysis there were 40 cases of high DBP and 480 controls for DBP. Pilots exposed to aircraft noise 90-95 dB rather than 70-80 dB had a 2.7-fold increase for high DBP [adjusted odds ratio (ORa = 2.70; 95% confi dence interval (CI = 1.05-6.97]. Pilots with resting pulse rates of ≥ 81/minute rather than ≤ 80/minute had a 2.7-fold increase for high DBP (ORa = 2.66; 95% CI = 1.26-5.61. In terms of total fl ight hours, pilots who had 1401-11125 hours rather than 147-1400 hours had a 3.2-fold increase for high DBP (ORa = 3.18; 95% CI = 1.01-10.03.Conclusion: High interior aircraft noise, high total flight hours,  and high resting pulse rate, increased risk for high DBP. Self assessment of resting pulse rate can be used to control the risk of high DBP. (Med J Indones 2009; 276: 276-82Keywords: diastolic blood pressure, aircraft noise, resting pulse rate, military pilots

Individual and combined effects of maternal anemia and prenatal infection on risk for schizophrenia in offspring.

Science.gov (United States)

Nielsen, Philip R; Meyer, Urs; Mortensen, Preben B

2016-04-01

Maternal iron deficiency and infection during pregnancy have individually been associated with increased risk of schizophrenia in the offspring, but possible interactions between the two remain unidentified thus far. Therefore, we determined the individual and combined effects of maternal infection during pregnancy and prepartum anemia on schizophrenia risk in the offspring. We conducted a population-based study with individual record linkage of the Danish Civil Registration System, the Danish Hospital Register, and the Central Danish Psychiatric Register. In a cohort of Danish singleton births 1,403,183 born between 1977 and 2002, 6729 developed schizophrenia between 1987 and 2012. Cohort members were considered as having a maternal history of anemia if the mother had received a diagnosis of anemia at any time during the pregnancy. Maternal infection was defined based on infections requiring hospital admission during pregnancy. Maternal anemia and infection were both associated with increased risk of schizophrenia in unadjusted analyses (1.45-fold increase for anemia, 95% CI: 1.14-1.82; 1.32-fold increase for infection, 95% CI: 1.17-1.48). The effect of maternal infection remained significant (1.16-fold increase, 95% CI: 1.03-1.31) after adjustment for possible confounding factors. Combined exposure to anemia and an infection increased the effect size to a 2.49-fold increased schizophrenia risk (95% CI: 1.29-4.27). The interaction analysis, however, failed to provide evidence for multiplicative interactions between the two factors. Our findings indicate that maternal anemia and infection have additive but not interactive effects, and therefore, they may represent two independent risk factors of schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

The increased risk of predation enhances cooperation

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Krams, Indrikis; Bērziņš, Arnis; Krama, Tatjana; Wheatcroft, David; Igaune, Kristīne; Rantala, Markus J.

2010-01-01

Theory predicts that animals in adverse conditions can decrease individual risks and increase long-term benefits by cooperating with neighbours. However, some empirical studies suggest that animals often focus on short-term benefits, which can reduce the likelihood that they will cooperate with others. In this experimental study, we tested between these two alternatives by evaluating whether increased predation risk (as a correlate of environmental adversity) enhances or diminishes the occurrence of cooperation in mobbing, a common anti-predator behaviour, among breeding pied flycatchers Ficedula hypoleuca. We tested whether birds would join their mobbing neighbours more often and harass a stuffed predator placed near their neighbours' nests more intensely in areas with a higher perceived risk of predation. Our results show that birds attended mobs initiated by their neighbours more often, approached the stuffed predator significantly more closely, and mobbed it at a higher intensity in areas where the perceived risk of predation was experimentally increased. In such high-risk areas, birds also were more often involved in between-pair cooperation. This study demonstrates the positive impact of predation risk on cooperation in breeding songbirds, which might help in explaining the emergence and evolution of cooperation. PMID:19846454

Excessive application of pig manure increases the risk of P loss in calcic cinnamon soil in China.

Science.gov (United States)

Yang, Yanju; Zhang, Haipeng; Qian, Xiaoqing; Duan, Jiannan; Wang, Gailan

2017-12-31

Soil phosphorus (P) is a critical factor affecting crop yields and water environmental quality. To investigate the degree of loss risk and forms of soil P in calcic cinnamon soil, the P fraction activities in soils were analysed using chemical methods, combined with an in situ field experiment. Seven treatments were set in this study, including control (unfertilized), no P fertilizer (No-P), mineral P fertilizer (Min-P), low (L-Man) and high (H-Man) quantities of pig manure, Min-P+L-Man, and Min-P+H-Man. The results showed that manure fertilizer could not only significantly increase maize yield but could also enhance the accumulation of soil P in organic and inorganic forms. After 23years of repeated fertilization, the soil Olsen-P contents respectively showed 64.7-, 43.7- and 31.9-fold increases in the Min-P+H-Man, Min-P+L-Man and H-Man treatments, while the soil Olsen-P in Min-P treatment only increased 23.7-fold. The soil Olsen-P thresholds ranged from 22.59 to 32.48mgkg -1 in calcic cinnamon soil to maintain a higher maize yield as well as a lower risk of P loss. Therefore, long-term excessive manure application could obviously raise the content of soil Olsen-P and increase the risk of P loss in calcic cinnamon soil. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of snow/sea ice type on the response of albedo and light penetration depth (e-folding depth to increasing black carbon

Directory of Open Access Journals (Sweden)

A. A. Marks

2014-09-01

Full Text Available The optical properties of snow/sea ice vary with age and by the processes they were formed, giving characteristic types of snow and sea ice. The response of albedo and light penetration depth (e-folding depth to increasing mass ratio of black carbon is shown to depend on the snow and sea ice type and the thickness of the snow or sea ice. The response of albedo and e-folding depth of three different types of snow (cold polar snow, wind-packed snow and melting snow and three sea ice (multi-year ice, first-year ice and melting sea ice to increasing mass ratio of black carbon is calculated using a coupled atmosphere–snow/sea ice radiative-transfer model (TUV-snow, over the optical wavelengths of 300–800 nm. The snow and sea ice types are effectively defined by a scattering cross-section, density and asymmetry parameter. The relative change in albedo and e-folding depth of each of the three snow and three sea ice types with increasing mass ratio of black carbon is considered relative to a base case of 1 ng g−1 of black carbon. The relative response of each snow and sea ice type is intercompared to examine how different types of snow and sea ice respond relative to each other. The relative change in albedo of a melting snowpack is a factor of four more responsive to additions of black carbon compared to cold polar snow over a black carbon increase from 1 to 50 ng g−1, while the relative change in albedo of a melting sea ice is a factor of two more responsive to additions of black carbon compared to multi-year ice for the same increase in mass ratio of black carbon. The response of e-folding depth is effectively not dependent on snow/sea ice type. The albedo of sea ice is more responsive to increasing mass ratios of black carbon than snow.

Effects of gravity in folding

Science.gov (United States)

Minkel, Donald Howe

Effects of gravity on buckle folding are studied using a Newtonian fluid finite element model of a single layer embedded between two thicker less viscous layers. The methods allow arbitrary density jumps, surface tension coefficients, resistance to slip at the interfaces, and tracking of fold growth to a large amplitudes. When density increases downward in two equal jumps, a layer buckles less and thickens more than with uniform density. When density increases upward in two equal jumps, it buckles more and thickens less. A low density layer with periodic thickness variations buckles more, sometimes explosively. Thickness variations form, even if not present initially. These effects are greater with; smaller viscosities, larger density jump, larger length scale, and slower shortening rate. They also depend on wavelength and amplitude, and these dependencies are described in detail. The model is applied to the explosive growth of the salt anticlines of the Paradox Basin, Colorado and Utah. There, shale (higher density) overlies salt (lower density). Methods for simulating realistic earth surface erosion and deposition conditions are introduced. Growth rates increase both with ease of slip at the salt-shale interface, and when earth surface relief stays low due to erosion and deposition. Model anticlines grow explosively, attaining growth rates and amplitudes close to those of the field examples. Fastest growing wavelengths are the same as seen in the field. It is concluded that a combination of partial-slip at the salt-shale interface, with reasonable earth surface conditions, promotes sufficiently fast buckling of the salt-shale interface due to density inversion alone. Neither basement faulting, nor tectonic shortening is required to account for the observed structures. Of fundamental importance is the strong tendency of gravity to promote buckling in low density layers with thickness variations. These develop, even if not present initially. folds

Does Bleomycin Lung Toxicity Increase the Risk of Radiation Pneumonitis in Hodgkin Lymphoma?

International Nuclear Information System (INIS)

Abou Yehia, Zeinab; Mikhaeel, George N.; Smith, Grace; Pinnix, Chelsea C.; Milgrom, Sarah A.; Tang, Chad; Jiang, Wen; Fanale, Michelle A.; Oki, Yasuhiro; Shank, JoAnn H.; Horace, Trisha; Reddy, Jay; Akhtari, Mani; Gunther, Jillian R.; Suki, Tina; Allen, Pamela K.; Turner, Shryll; Mawlawi, Osama; Dabaja, Bouthaina S.

2016-01-01

Purpose: Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in patients with Hodgkin lymphoma (HL). We undertook the present study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation therapy (RT) in these patients. Methods and Materials: We identified 123 HL patients treated with ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) followed by RT to the chest from January 2009 to December 2014. The medical records were reviewed for clinical, pathologic, and treatment information and toxicities. Our primary outcome was RP of any grade. Univariate and multivariate analyses were used to assess the association of BPT, baseline patient characteristics, and treatment variables with the incidence of RP. Results: A total of 123 patients were included, of whom 99 (80%) received consolidation intensity modulated RT after ABVD treatment. We identified 31 patients (25.2%) with BPT after frontline ABVD. Seventeen patients (13.8%) developed RP a median of 8 weeks (range 1-39) after RT completion. BPT did not correlate with the risk of developing RP (P=.36). We evaluated the RP outcomes with respect to the bleomycin to RT interval (≤6 weeks vs >6 weeks), and we found that this interval did not predict for RP risk (P=.60). Dosimetric parameters such as the volume covered by 5 Gy and the mean lung dose were analyzed. A volume covered by 5 Gy of >55% and mean lung dose >13.5 Gy increased the risk of RP by 1.14-fold (P=.002) and 4.24-fold (P=.007), respectively. Conclusions: The results of our study suggest that BPT does not increase the risk of developing RP. Furthermore, RT initiation does not need to be delayed after chemotherapy, except to allow for the completion of steroid therapy or clinical recovery from BPT.

Does Bleomycin Lung Toxicity Increase the Risk of Radiation Pneumonitis in Hodgkin Lymphoma?

Energy Technology Data Exchange (ETDEWEB)

Abou Yehia, Zeinab [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mikhaeel, George N. [Department of Clinical Oncology, Guy' s & St Thomas' Hospital, London (United Kingdom); Smith, Grace; Pinnix, Chelsea C.; Milgrom, Sarah A.; Tang, Chad; Jiang, Wen [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fanale, Michelle A.; Oki, Yasuhiro [Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shank, JoAnn H.; Horace, Trisha; Reddy, Jay [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Akhtari, Mani [Department of Radiation Oncology, The University of Texas Medical Branch Hospitals, Galveston, Texas (United States); Gunther, Jillian R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Suki, Tina [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Turner, Shryll [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mawlawi, Osama [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2016-12-01

Purpose: Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in patients with Hodgkin lymphoma (HL). We undertook the present study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation therapy (RT) in these patients. Methods and Materials: We identified 123 HL patients treated with ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) followed by RT to the chest from January 2009 to December 2014. The medical records were reviewed for clinical, pathologic, and treatment information and toxicities. Our primary outcome was RP of any grade. Univariate and multivariate analyses were used to assess the association of BPT, baseline patient characteristics, and treatment variables with the incidence of RP. Results: A total of 123 patients were included, of whom 99 (80%) received consolidation intensity modulated RT after ABVD treatment. We identified 31 patients (25.2%) with BPT after frontline ABVD. Seventeen patients (13.8%) developed RP a median of 8 weeks (range 1-39) after RT completion. BPT did not correlate with the risk of developing RP (P=.36). We evaluated the RP outcomes with respect to the bleomycin to RT interval (≤6 weeks vs >6 weeks), and we found that this interval did not predict for RP risk (P=.60). Dosimetric parameters such as the volume covered by 5 Gy and the mean lung dose were analyzed. A volume covered by 5 Gy of >55% and mean lung dose >13.5 Gy increased the risk of RP by 1.14-fold (P=.002) and 4.24-fold (P=.007), respectively. Conclusions: The results of our study suggest that BPT does not increase the risk of developing RP. Furthermore, RT initiation does not need to be delayed after chemotherapy, except to allow for the completion of steroid therapy or clinical recovery from BPT.

Vocal fold hemorrhage associated with coumadin therapy in an opera singer.

Science.gov (United States)

Neely, J L; Rosen, C

2000-06-01

Vocal fold hemorrhage can represent a disastrous and potentially career ending injury to a singer or professional voice user. The risk factors of vocal fold hemorrhage, including laryngeal trauma, phonotrauma, aspirin and nonsteroidal antiinflammatories, and hormonal imbalances are well known. We present a case of an opera singer who developed recurrent vocal fold hemorrhage associated with coumadin anticoagulation therapy. This case highlights the importance of the risk of vocal fold hemorrhage to professional singers and professional voice users and offers an alternative to long-term coumadin therapy in this select population.

RNAiFold: a web server for RNA inverse folding and molecular design.

Science.gov (United States)

Garcia-Martin, Juan Antonio; Clote, Peter; Dotu, Ivan

2013-07-01

Synthetic biology and nanotechnology are poised to make revolutionary contributions to the 21st century. In this article, we describe a new web server to support in silico RNA molecular design. Given an input target RNA secondary structure, together with optional constraints, such as requiring GC-content to lie within a certain range, requiring the number of strong (GC), weak (AU) and wobble (GU) base pairs to lie in a certain range, the RNAiFold web server determines one or more RNA sequences, whose minimum free-energy secondary structure is the target structure. RNAiFold provides access to two servers: RNA-CPdesign, which applies constraint programming, and RNA-LNSdesign, which applies the large neighborhood search heuristic; hence, it is suitable for larger input structures. Both servers can also solve the RNA inverse hybridization problem, i.e. given a representation of the desired hybridization structure, RNAiFold returns two sequences, whose minimum free-energy hybridization is the input target structure. The web server is publicly accessible at http://bioinformatics.bc.edu/clotelab/RNAiFold, which provides access to two specialized servers: RNA-CPdesign and RNA-LNSdesign. Source code for the underlying algorithms, implemented in COMET and supported on linux, can be downloaded at the server website.

Inadequate exercise as a risk factor for sepsis mortality.

Science.gov (United States)

Williams, Paul T

2013-01-01

Test whether inadequate exercise is related to sepsis mortality. Mortality surveillance of an epidemiological cohort of 155,484 National Walkers' and Runners' Health Study participants residing in the United States. Deaths were monitored for an average of 11.6-years using the National Death index through December 31, 2008. Cox proportional hazard analyses were used to compare sepsis mortality (ICD-10 A40-41) to inadequate exercise (<1.07 METh/d run or walked) as measured on their baseline questionnaires. Deaths occurring within one year of the baseline survey were excluded. Sepsis was the underlying cause in 54 deaths (sepsis(underlying)) and a contributing cause in 184 deaths (sepsis(contributing)), or 238 total sepsis-related deaths (sepsis(total)). Inadequate exercise was associated with 2.24-fold increased risk for sepsis(underlying) (95%CI: 1.21 to 4.07-fold, P = 0.01), 2.11-fold increased risk for sepsis(contributing) (95%CI: 1.51- to 2.92-fold, P<10(-4)), and 2.13-fold increased risk for sepsis(total) (95%CI: 1.59- to 2.84-fold, P<10(-6)) when adjusted for age, sex, race, and cohort. The risk increase did not differ significantly between runners and walkers, by sex, or by age. Sepsis(total) risk was greater in diabetics (P = 10(-5)), cancer survivors (P = 0.0001), and heart attack survivors (P = 0.003) and increased with waist circumference (P = 0.0004). The sepsis(total) risk associated with inadequate exercise persisted when further adjusted for diabetes, prior cancer, prior heart attack and waist circumference, and when excluding deaths with cancer, or cardiovascular, respiratory, or genitourinary disease as the underlying cause. Inadequate exercise also increased sepsis(total) risk in 2163 baseline diabetics (4.78-fold, 95%CI: 2.1- to 13.8-fold, P = 0.0001) when adjusted, which was significantly greater (P = 0.03) than the adjusted risk increase in non-diabetics (1.80-fold, 95%CI: 1.30- to 2.46-fold, P = 0

Family history of esophageal cancer increases the risk of esophageal squamous cell carcinoma

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Chen, Tiantian; Cheng, Hongwei; Chen, Xingdong; Yuan, Ziyu; Yang, Xiaorong; Zhuang, Maoqiang; Lu, Ming; Jin, Li; Ye, Weimin

2015-01-01

A population-based case-control was performed to explore familial aggregation of esophageal squamous cell carcinoma (ESCC). Family history of cancer was assessed by a structured questionnaire, and from which 2 cohorts of relatives of cases and controls were reconstructed. Unconditional logistic regression and Cox proportional hazards regression were applied for case-control design and reconstructed cohort design, respectively. We observed a close to doubled risk of ESCC associated with a positive family history of esophageal cancer among first degree relatives (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.42–2.41), after adjusting age, sex, family size and other confounders. The excess risks of ESCC increased with the increasing of first-degree relatives affected by esophageal cancer (p < 0.001). In particular, those individuals whose both parents with esophageal cancer had an 8-fold excess risk of ESCC (95% CI: 1.74–36.32). The reconstructed cohort analysis showed that the cumulative risk of esophageal cancer to age 75 was 12.2% in the first-degree relatives of cases and 7.0% in those of controls (hazard ratio = 1.91, 95% CI: 1.54–2.37). Our results suggest family history of esophageal cancer significantly increases the risk for ESCC. Future studies are needed to understand how the shared genetic susceptibility and/or environmental exposures contribute to the observed excess risk. PMID:26526791

The Arterial Folding Point During Flexion of the Hip Joint

International Nuclear Information System (INIS)

Park, Sung Il; Won, Je Hwan; Kim, Byung Moon; Kim, Jae Keun; Lee, Do Yun

2005-01-01

Purpose: Endovascular stents placed in periarticular vessels may be at a greater risk of neointimal hyperplasia and eventual occlusion than those placed in non-periarticular vessels. The purpose of this study was to investigate the location of maximal conformational change along the iliac and femoral artery, the folding point, during flexion of the hip joint and its location relative to the hip joint and the inguinal ligament. Methods: Seventy patients undergoing femoral artery catheterization were evaluated. The patients were 47 men and 23 women and ranged in age from 26 to 75 years (mean 54 years). The arteries (right:left = 34:36) were measured using a marked catheter for sizing vessels. Fluoroscopic images were obtained in anteroposterior and lateral projections in neutral position, and in the lateral projection in flexed position of the hip joint. The folding point was determined by comparing the lateral projection images in the neutral and flexed positions. The distance from the acetabular roof to the folding point and the distance from the inguinal ligament to the folding point was evaluated. Results: : The folding point was located 42.8 ± 28.6 mm cranial to the acetabular roof and 35.1 ± 30.1 mm cranial to the inguinal ligament. As the patient’s age increased, the folding point was located more cranially (p < 0.001). Conclusions: The folding point during flexion of the hip joint was located 42.8 ± 28.6 mm cranial to the acetabular roof and 35.1 ± 30.1 mm cranial to the inguinal ligament. As the patient's age increased, the folding point was located more cranially. When a stent is inserted over this region, more attention may be needed during follow-up to monitor possible occlusion and stent failure.

Dysphonia and vocal fold telangiectasia in hereditary hemorrhagic telangiectasia.

Science.gov (United States)

Chang, Joseph; Yung, Katherine C

2014-11-01

This case report is the first documentation of dysphonia and vocal fold telangiectasia as a complication of hereditary hemorrhagic telangiectasia (HHT). Case report of a 40-year-old man with HHT presenting with 2 years of worsening hoarseness. Hoarseness corresponded with a period of anticoagulation. Endoscopy revealed vocal fold scarring, vocal fold telangiectasias, and plica ventricular is suggestive of previous submucosal vocal fold hemorrhage and subsequent counterproductive compensation with ventricular phonation. Hereditary hemorrhagic telangiectasia may present as dysphonia with vocal fold telangiectasias and place patients at risk of vocal fold hemorrhage. © The Author(s) 2014.

Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins syndrome

DEFF Research Database (Denmark)

Dixon, J; Brakebusch, C; Fässler, R

2000-01-01

mice die perinatally as a result of severe craniofacial anomalies that include agenesis of the nasal passages, abnormal development of the maxilla, exencephaly and anophthalmia. These defects arise due to a massive increase in the levels of apoptosis in the prefusion neural folds, which are the site...

Comparison of posterior capsule folds following intracapsular implantation of three types of intraocular lenses with different haptic design

Directory of Open Access Journals (Sweden)

Ling-Lin Zhang

2018-04-01

Full Text Available AIM: To compare the incidence of posterior capsule folds among different types of intraocular lens(IOLto determine risk factors of posterior capsule folds. METHODS:It was a retrospective study. We collected the cases in which the patients underwent phacoemulsification(PHACOand IOL implantation and at least one of the three types of IOL was implanted, including 2-haptic 3-piece IOLs(HOYA PY60AD, 4-haptic 1-piece IOLs(Bausch & Lomb AO, 2-haptic 1-piece IOLs(AMO Tecnis ZCB00. The posterior capsule folds were measured using slit lamp microscope 2d after the surgery. Information of patient's age, gender, length of ocular axis, intraocular pressure, types of IOL were recorded. Posterior capsule fold risk indicators were identified by using logistic regression analysis. RESULTS: One hundred eighty-seven patients(242 eyeshad been collected, including 80 eyes implanted with HOYA PY60AD IOLs, 81 eyes implanted with Bausch & Lomb AO IOLs, 81 eyes implanted with AMO Tecnis ZCB00 IOLs. The incidence of posterior capsule folds of patients implanted with HOYA PY60AD IOLs was significantly higher than those of patients implanted with AMO Tecnis ZCB00 IOLs(56.3% vs 38.3%, P=0.027. While the incidence of patients implanted with Bausch & Lomb AO IOLs was significantly lower than those of patients implanted with AMO Tecnis ZCB00 IOLs(14.8% vs 38.3%, P=0.001. Multi-factor logistics regression analysis demonstrated that independent risk factors were type of IOLs and length of ocular axis. Compared with AMO Tecnis ZCB00 IOLs, using HOYA PY60AD IOLs increased the risk of posterior capsule folds \\〖P=0.020, OR(95%CI=2.145(1.129,4.073\\〗, while using Bausch & Lomb AO IOLs reduced the risk \\〖P=0.001, OR(95%CI=0.274(0.127, 0.591\\〗. Shorter ocular axis might increase the risk of posterior capsule folds \\〖P=0.012, OR(95%CI=0.669(0.489, 0.915\\〗. CONCLUSION: Haptic design should be an important consideration in IOL design. Compared with AMO Tecnis ZCB00 IOLs

PREFACE Protein folding: lessons learned and new frontiers Protein folding: lessons learned and new frontiers

Science.gov (United States)

Pappu, Rohit V.; Nussinov, Ruth

2009-03-01

In appropriate physiological milieux proteins spontaneously fold into their functional three-dimensional structures. The amino acid sequences of functional proteins contain all the information necessary to specify the folds. This remarkable observation has spawned research aimed at answering two major questions. (1) Of all the conceivable structures that a protein can adopt, why is the ensemble of native-like structures the most favorable? (2) What are the paths by which proteins manage to robustly and reproducibly fold into their native structures? Anfinsen's thermodynamic hypothesis has guided the pursuit of answers to the first question whereas Levinthal's paradox has influenced the development of models for protein folding dynamics. Decades of work have led to significant advances in the folding problem. Mean-field models have been developed to capture our current, coarse grain understanding of the driving forces for protein folding. These models are being used to predict three-dimensional protein structures from sequence and stability profiles as a function of thermodynamic and chemical perturbations. Impressive strides have also been made in the field of protein design, also known as the inverse folding problem, thereby testing our understanding of the determinants of the fold specificities of different sequences. Early work on protein folding pathways focused on the specific sequence of events that could lead to a simplification of the search process. However, unifying principles proved to be elusive. Proteins that show reversible two-state folding-unfolding transitions turned out to be a gift of natural selection. Focusing on these simple systems helped researchers to uncover general principles regarding the origins of cooperativity in protein folding thermodynamics and kinetics. On the theoretical front, concepts borrowed from polymer physics and the physics of spin glasses led to the development of a framework based on energy landscape theories. These

OGG1 Mutations and Risk of Female Breast Cancer: Meta-Analysis and Experimental Data

Directory of Open Access Journals (Sweden)

Kashif Ali

2015-01-01

Full Text Available In first part of this study association between OGG1 polymorphisms and breast cancer susceptibility was explored by meta-analysis. Second part of the study involved 925 subjects, used for mutational analysis of OGG1 gene using PCR-SSCP and sequencing. Fifteen mutations were observed, which included five intronic mutations, four splice site mutations, two 3′UTR mutations, three missense mutations, and a nonsense mutation. Significantly (pG and 3′UTR variant g.9798848G>A. Among intronic mutations, highest (~15 fold increase in breast cancer risk was associated with g.9793680G>A (p<0.009. Similarly ~14-fold increased risk was associated with Val159Gly (p<0.01, ~17-fold with Gly221Arg (p<0.005, and ~18-fold with Ser326Cys (p<0.004 in breast cancer patients compared with controls, whereas analysis of nonsense mutation showed that ~13-fold (p<0.01 increased breast cancer risk was associated with Trp375STOP in patients compared to controls. In conclusion, a significant association was observed between OGG1 germ line mutations and breast cancer risk. These findings provide evidence that OGG1 may prove to be a good candidate of better diagnosis, treatment, and prevention of breast cancer.

Spherical images and inextensible curved folding

Science.gov (United States)

Seffen, Keith A.

2018-02-01

In their study, Duncan and Duncan [Proc. R. Soc. London A 383, 191 (1982), 10.1098/rspa.1982.0126] calculate the shape of an inextensible surface folded in two about a general curve. They find the analytical relationships between pairs of generators linked across the fold curve, the shape of the original path, and the fold angle variation along it. They present two special cases of generator layouts for which the fold angle is uniform or the folded curve remains planar, for simplifying practical folding in sheet-metal processes. We verify their special cases by a graphical treatment according to a method of Gauss. We replace the fold curve by a piecewise linear path, which connects vertices of intersecting pairs of hinge lines. Inspired by the d-cone analysis by Farmer and Calladine [Int. J. Mech. Sci. 47, 509 (2005), 10.1016/j.ijmecsci.2005.02.013], we construct the spherical images for developable folding of successive vertices: the operating conditions of the special cases in Duncan and Duncan are then revealed straightforwardly by the geometric relationships between the images. Our approach may be used to synthesize folding patterns for novel deployable and shape-changing surfaces without need of complex calculation.

Communicating Zika Risk: Using Metaphor to Increase Perceived Risk Susceptibility.

Science.gov (United States)

Lu, Hang; Schuldt, Jonathon P

2018-02-27

Effectively communicating the risks associated with emerging zoonotic diseases remains an important challenge. Drawing on research into the psychological effects of metaphoric framing, we explore the conditions under which exposure to the "nation as a body" metaphor influences perceived risk susceptibility, behavioral intentions, and policy support in the context of Zika virus. In a between-subjects experiment, 354 U.S. adults were randomly assigned to one of four experimental conditions as part of a 2 (severity message: high vs. low) × 2 (U.S. framing: metaphoric vs. literal) design. Results revealed an interaction effect such that metaphoric (vs. literal) framing increased perceived risk susceptibility in the high-severity condition only. Further analyses revealed that perceived risk susceptibility and negative affect mediated the path between the two-way interaction and policy support and behavioral intentions regarding Zika prevention. Overall, these findings complement prior work on the influence of metaphoric framing on risk perceptions, while offering practical insights for risk communicators seeking to communicate about Zika and other zoonotic diseases. © 2018 Society for Risk Analysis.

Sport specialization's association with an increased risk of developing anterior knee pain in adolescent female athletes.

Science.gov (United States)

Hall, Randon; Barber Foss, Kim; Hewett, Timothy E; Myer, Gregory D

2015-02-01

To determine if sport specialization increases the risk of anterior knee pain in adolescent female athletes. Retrospective cohort epidemiology study. Female basketball, soccer, and volleyball players (N = 546) were recruited from a single county public school district in Kentucky consisting of 5 middle schools and 4 high schools. A total of 357 multisport and 189 single-sport (66 basketball, 57 soccer, and 66 volleyball) athlete subjects were included due to their diagnosis of patellofemoral pain (PFP) on physical exam. Testing consisted of a standardized history and physician-administered physical examination to determine the presence of PFP. This study compared self-reported multisport athletes with sport-specialized athletes participating in only 1 sport. The sports-participation data were normalized by sport season, with each sport accounting for 1 season of exposure. Incidence rate ratios and 95% confidence intervals (CI) were calculated and used to determine significant differences between athletes who specialized in sport in early youth and multisport athletes. Specialization in a single sport increased the relative risk of PFP incidence 1.5-fold (95% CI 1.0-2.2, P = .038) for cumulative PFP diagnoses. Specific diagnoses such as Sinding Larsen Johansson/ patellar tendinopathy (95% CI 1.5-10.1, P = .005) and Osgood Schlatter disease (95% CI 1.5-10.1, P = .005) demonstrated a 4-fold greater relative risk in single-sport compared with multisport athletes. Incidence of other specific PFP diagnoses such as fat pad, plica, trauma, pes anserine bursitis, and iliotibial-band tendonitis was not different between single-sport and multisport participants (P > .05). Early sport specialization in female adolescents is associated with increased risk of anterior knee-pain disorders including PFP, Osgood Schlatter, Sinding Larsen-Johansson compared with multisport athletes.

Evaluating the diet of children at increased risk for type 1 diabetes: first results from the TEENDIAB study.

Science.gov (United States)

Weber, Katharina Susanne; Raab, Jennifer; Haupt, Florian; Aschemeier, Bärbel; Wosch, Anja; Ried, Christiane; Kordonouri, Olga; Ziegler, Anette-Gabriele; Winkler, Christiane

2015-01-01

The development of type 1 diabetes (T1D) is potentially influenced by nutrition. The aim of our study was to assess food and nutrient intakes of children at increased risk of T1D. Dietary intake of the last 4 weeks was assessed using a diet history interview. The daily nutrient and food intakes were compared with the German Dietary Reference Intakes, the Optimized Mixed Diet recommendations and those of a representative sample of children from the EsKiMo study. Children included in the analysis participated in the prospective TEENDIAB study. First-degree relatives of people with T1D (n 268), aged 8-12 years. The TEENDIAB children consumed 52·0 % of their total energy from carbohydrates, 32·6 % from fat and 14·3 % from protein. Compared with the reference values, their intake was lowest for folate at 61·3 % of the reference, for iodine at 58·1 % and for vitamin D at 8·9 %, and exceeded the reference for vitamin K about 5-fold, for Na about 3·5-fold and for protein about 1·5-fold. Their nutrient intakes were similar to those of a control cohort without increased T1D risk. The consumption of non-desirable food groups (meat products, sweets/snacks) was above the recommendations and the consumption of desirable food groups (fruits, vegetables, carbohydrate-rich foods) was below the recommendations. The TEENDIAB children had intakes considerably below the recommendations for vitamin D, iodine, folate and plant-based foods, and intakes above for vitamin K, Na, protein, meat products and sweets/snacks. They showed similar dietary patterns to non-risk children.

Childhood trauma increases the risk of post-traumatic stress disorder in response to first-episode psychosis.

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Bendall, Sarah; Alvarez-Jimenez, Mario; Hulbert, Carol A; McGorry, Patrick D; Jackson, Henry J

2012-01-01

To investigate the relationship between childhood trauma, post-traumatic stress symptoms due to the experience of childhood trauma, and post-traumatic stress symptoms due to the experience of psychosis. The current study assessed childhood trauma and post-traumatic stress disorder (PTSD) symptoms as a result of both childhood trauma and psychosis using the Impact of Events Scale - Revised, in a group of 36 people with first-episode psychosis. Reported rates of clinical level post-psychotic PTSD symptoms, childhood trauma and childhood trauma-related clinical level PTSD symptoms were 47% (95% CI 31-64%), 64% (95% CI 48-80%) and 39% (95% CI 23-55%), respectively. Reporting childhood trauma increased the risk of developing post-psychosis PTSD 27-fold (95% CI 2.96-253.80, p = 0.01). Having childhood trauma-related PTSD increased the risk of developing post-psychosis PTSD 20-fold (95% CI 3.38-123.25, p = 0.01). These risks were not explained by illness factors such as duration of untreated psychosis, age of onset or severity of psychotic symptoms. Those without post-psychotic PTSD symptoms at clinical levels were unlikely to report childhood trauma (6%; 95% CI 3-8%). These results suggest the cognitive, social and biological consequences of childhood trauma can prevent effective recovery from the trauma of acute first-episode psychosis resulting in post-psychotic PTSD. Treatment strategies for post-psychotic PTSD must address childhood trauma and related PTSD.

Increased Risk of HIV-1 Transmission in Pregnancy: A Prospective Study among African HIV-1 Serodiscordant Couples

Science.gov (United States)

MUGO, Nelly R.; HEFFRON, Renee; DONNELL, Deborah; WALD, Anna; WERE, Edwin O.; REES, Helen; CELUM, Connie; KIARIE, James N.; COHEN, Craig R.; KAYINTEKORE, Kayitesi; BAETEN, Jared M.

2011-01-01

Background Physiologic and behavioral changes during pregnancy may alter HIV-1 susceptibility and infectiousness. Prospective studies exploring pregnancy and HIV-1 acquisition risk in women have found inconsistent results. No study has explored the effect of pregnancy on HIV-1 transmission risk from HIV-1 infected women to male partners. Methods In a prospective study of African HIV-1 serodiscordant couples, we evaluated the relationship between pregnancy and the risk of 1) HIV-1 acquisition among women and 2) HIV-1 transmission from women to men. Results 3321 HIV-1 serodiscordant couples were enrolled, 1085 (32.7%) with HIV-1 susceptible female partners and 2236 (67.3%) with susceptible male partners. HIV-1 incidence in women was 7.35 versus 3.01 per 100 person-years during pregnant and non-pregnant periods (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.33–4.09). This effect was attenuated and not statistically significant after adjusting for sexual behavior and other confounding factors (adjusted HR 1.71, 95% CI 0.93–3.12). HIV-1 incidence in male partners of infected women was 3.46 versus 1.58 per 100 person-years when their partners were pregnant versus not pregnant (HR 2.31, 95% CI 1.22–4.39). This effect was not attenuated in adjusted analysis (adjusted HR 2.47, 95% CI 1.26–4.85). Conclusions HIV-1 risk increased two-fold during pregnancy. Elevated risk of HIV-1 acquisition in pregnant women appeared in part to be explained by behavioral and other factors. This is the first study to show pregnancy increased the risk of female-to-male HIV-1 transmission, which may reflect biological changes of pregnancy that could increase HIV-1 infectiousness. PMID:21785321

The Complexity of Folding Self-Folding Origami

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Stern, Menachem; Pinson, Matthew B.; Murugan, Arvind

2017-10-01

Why is it difficult to refold a previously folded sheet of paper? We show that even crease patterns with only one designed folding motion inevitably contain an exponential number of "distractor" folding branches accessible from a bifurcation at the flat state. Consequently, refolding a sheet requires finding the ground state in a glassy energy landscape with an exponential number of other attractors of higher energy, much like in models of protein folding (Levinthal's paradox) and other NP-hard satisfiability (SAT) problems. As in these problems, we find that refolding a sheet requires actuation at multiple carefully chosen creases. We show that seeding successful folding in this way can be understood in terms of subpatterns that fold when cut out ("folding islands"). Besides providing guidelines for the placement of active hinges in origami applications, our results point to fundamental limits on the programmability of energy landscapes in sheets.

Multidimensional effects of voice therapy in patients affected by unilateral vocal fold paralysis due to cancer.

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Barcelos, Camila Barbosa; Silveira, Paula Angélica Lorenzon; Guedes, Renata Lígia Vieira; Gonçalves, Aline Nogueira; Slobodticov, Luciana Dall'Agnol Siqueira; Angelis, Elisabete Carrara-de

2017-08-24

Patients with unilateral vocal fold paralysis may demonstrate different degrees of voice perturbation depending on the position of the paralyzed vocal fold. Understanding the effectiveness of voice therapy in this population may be an important coefficient to define the therapeutic approach. To evaluate the voice therapy effectiveness in the short, medium and long-term in patients with unilateral vocal fold paralysis and determine the risk factors for voice rehabilitation failure. Prospective study with 61 patients affected by unilateral vocal fold paralysis enrolled. Each subject had voice therapy with an experienced speech pathologist twice a week. A multidimensional assessment protocol was used pre-treatment and in three different times after voice treatment initiation: short-term (1-3 months), medium-term (4-6 months) and long-term (12 months); it included videoendoscopy, maximum phonation time, GRBASI scale, acoustic voice analysis and the portuguese version of the voice handicap index. Multiple comparisons for GRBASI scale and VHI revealed statistically significant differences, except between medium and long term (pvocal improvement over time with stabilization results after 6 months (medium term). From the 28 patients with permanent unilateral vocal fold paralysis, 18 (69.2%) reached complete glottal closure following vocal therapy (p=0.001). The logistic regression method indicated that the Jitter entered the final model as a risk factor for partial improvement. For every unit of increased jitter, there was an increase of 0.1% (1.001) of the chance for partial improvement, which means an increase on no full improvement chance during rehabilitation. Vocal rehabilitation improves perceptual and acoustic voice parameters and voice handicap index, besides favor glottal closure in patients with unilateral vocal fold paralysis. The results were also permanent during the period of 1 year. The Jitter value, when elevated, is a risk factor for the voice therapy

Single injection of basic fibroblast growth factor to treat severe vocal fold lesions and vocal fold paralysis.

Science.gov (United States)

Kanazawa, Takeharu; Komazawa, Daigo; Indo, Kanako; Akagi, Yusuke; Lee, Yogaku; Nakamura, Kazuhiro; Matsushima, Koji; Kunieda, Chikako; Misawa, Kiyoshi; Nishino, Hiroshi; Watanabe, Yusuke

2015-10-01

Severe vocal fold lesions such as vocal fold sulcus, scars, and atrophy induce a communication disorder due to severe hoarseness, but a treatment has not been established. Basic fibroblast growth factor (bFGF) therapies by either four-time repeated local injections or regenerative surgery for vocal fold scar and sulcus have previously been reported, and favorable outcomes have been observed. In this study, we modified bFGF therapy using a single of bFGF injection, which may potentially be used in office procedures. Retrospective chart review. Five cases of vocal fold sulcus, six cases of scars, seven cases of paralysis, and 17 cases of atrophy were treated by a local injection of bFGF. The injection regimen involved injecting 50 µg of bFGF dissolved in 0.5 mL saline only once into the superficial lamina propria using a 23-gauge injection needle. Two months to 3 months after the injection, phonological outcomes were evaluated. The maximum phonation time (MPT), mean airflow rate, pitch range, speech fundamental frequency, jitter, and voice handicap index improved significantly after the bFGF injection. Furthermore, improvement in the MPT was significantly greater in patients with (in increasing order) vocal fold atrophy, scar, and paralysis. The improvement in the MPT among all patients was significantly correlated with age; the MPT improved more greatly in younger patients. Regenerative treatments by bFGF injection—even a single injection—effectively improve vocal function in vocal fold lesions. 4 © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

The Complexity of Folding Self-Folding Origami

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Menachem Stern

2017-12-01

Full Text Available Why is it difficult to refold a previously folded sheet of paper? We show that even crease patterns with only one designed folding motion inevitably contain an exponential number of “distractor” folding branches accessible from a bifurcation at the flat state. Consequently, refolding a sheet requires finding the ground state in a glassy energy landscape with an exponential number of other attractors of higher energy, much like in models of protein folding (Levinthal’s paradox and other NP-hard satisfiability (SAT problems. As in these problems, we find that refolding a sheet requires actuation at multiple carefully chosen creases. We show that seeding successful folding in this way can be understood in terms of subpatterns that fold when cut out (“folding islands”. Besides providing guidelines for the placement of active hinges in origami applications, our results point to fundamental limits on the programmability of energy landscapes in sheets.

Teaching computers to fold proteins

DEFF Research Database (Denmark)

Winther, Ole; Krogh, Anders Stærmose

2004-01-01

A new general algorithm for optimization of potential functions for protein folding is introduced. It is based upon gradient optimization of the thermodynamic stability of native folds of a training set of proteins with known structure. The iterative update rule contains two thermodynamic averages...

High-speed Imaging of Vocal Fold Vibration Onset Delay: Normal Versus Abnormal.

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Woo, Peak

2017-05-01

Vocal fold vibration onset delay (VFVOD) is heard frequently in spasmodic dysphonia and in muscle tension dysphonia. VFVOD changes due to other vocal pathologies have not been investigated. VFVOD during sustained vowel production was estimated with high-speed video in 10 normal and 40 pathologic subjects (scars, vocal fold paralysis, vocal fold nodules, and polyps). Analysis of high-speed video was done using digital kymography. VFVOD can be divided into two portions. Pre-phonation delay (PPD) is the duration when the vocal folds are nearly approximated to the time of first observed oscillation. Steady state delay (SSD) is the time when vocal folds are observed to come into oscillation until steady state of oscillation is observed. Normal subjects have almost zero PPD with vocal fold oscillation observed before full vocal fold adduction. Pathologic cases showed prolonged PPD because of (1) false cord adduction, (2) prolonged true vocal fold adduction, and (3) delay to onset of vocal fold vibration. Normal subjects have SSD of three to five cycles before steady state. Pathologic states result in increased SSD. Causes for increased SSD include (1) slow ramping up to steady state, (2) partial vibration of vocal folds, and (3) diplophonia with alternating beats before achieving steady state. There are significant differences between normal and pathology groups in both PPD and SSD. VFVOD is elevated in pathologic states. This can be due to increase in PPD or SSD. VFVOD is an under-recognized phenomenon that may contribute to complaints of vocal fatigue and dysphonia. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Evidence of non-coincidence of normalized sigmoidal curves of two different structural properties for two-state protein folding/unfolding

International Nuclear Information System (INIS)

Rahaman, Hamidur; Khan, Md. Khurshid Alam; Hassan, Md. Imtaiyaz; Islam, Asimul; Moosavi-Movahedi, Ali Akbar; Ahmad, Faizan

2013-01-01

Highlights: ► Non-coincidence of normalized sigmoidal curves of two different structural properties is consistence with the two-state protein folding/unfolding. ► DSC measurements of denaturation show a two-state behavior of g-cyt-c at pH 6.0. ► Urea-induced denaturation of g-cyt-c is a variable two- state process at pH 6.0. ► GdmCl-induced denaturation of g-cyt-c is a fixed two- state process at pH 6.0. -- Abstract: In practice, the observation of non-coincidence of normalized sigmoidal transition curves measured by two different structural properties constitutes a proof of existence of thermodynamically stable intermediate(s) on the folding ↔ unfolding pathway of a protein. Here we give first experimental evidence that this non-coincidence is also observed for a two-state protein denaturation. Proof of this evidence comes from our studies of denaturation of goat cytochrome-c (g-cyt-c) at pH 6.0. These studies involve differential scanning calorimetry (DSC) measurements in the absence of urea and measurements of urea-induced denaturation curves monitored by observing changes in absorbance at 405, 530, and 695 nm and circular dichroism (CD) at 222, 405, and 416 nm. DSC measurements showed that denaturation of the protein is a two-state process, for calorimetric and van’t Hoff enthalpy changes are, within experimental errors, identical. Normalization of urea-induced denaturation curves monitored by optical properties leads to noncoincident sigmoidal curves. Heat-induced transition of g-cyt-c in the presence of different urea concentrations was monitored by CD at 222 nm and absorption at 405 nm. It was observed that these two different structural probes gave not only identical values of T m (transition temperature), ΔH m (change in enthalpy at T m ) and ΔC p (constant-pressure heat capacity change), but these thermodynamic parameters in the absence of urea are also in agreement with those obtained from DSC measurements

Cathepsin D SNP associated with increased risk of variant Creutzfeldt-Jakob disease

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Sanchez-Juan Pascual

2008-04-01

Full Text Available Abstract Background Variant Creutzfeldt-Jakob disease (vCJD originally resulted from the consumption of foodstuffs contaminated by bovine spongiform encephalopathy (BSE material, with 163 confirmed cases in the UK to date. Many thousands are likely to have been exposed to dietary infection and so it is important (for surveillance, epidemic modelling, public health and understanding pathogenesis to identify genetic factors that may affect individual susceptibility to infection. This study looked at a polymorphism in the cathepsin D gene (refSNP ID: rs17571 previously examined in Alzheimer's disease (AD. Methods Blood samples taken from 110 vCJD patients were tested for the C-T base change, and genotype data were compared with published frequencies for a control population using multiple logistic regression. Results There was a significant excess of the cathepsin D polymorphism TT genotype in the vCJD cohort compared to controls. The TT genotype was found to have a 9.75 fold increase in risk of vCJD compared to the CT genotype and a 10.92 fold increase compared to the CC genotype. Conclusion This mutation event has been observed to alter the protease activity of the cathepsin D protein and has been linked to an increase in amyloid beta plaque formation in AD. vCJD neuropathology is characterised by the presence of amyloid plaques, formed from the prion protein, and therefore alterations in the amyloid processing activity of cathepsin D may affect the neuropathogenesis of this disease.

Folding of the natural hammerhead ribozyme is enhanced by interaction of auxiliary elements

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PENEDO, J. CARLOS; WILSON, TIMOTHY J.; JAYASENA, SUMEDHA D.; KHVOROVA, ANASTASIA; LILLEY, DAVID M.J.

2004-01-01

It has been shown that the activity of the hammerhead ribozyme at μM magnesium ion concentrations is markedly increased by the inclusion of loops in helices I and II. We have studied the effect of such loops on the magnesium ion-induced folding of the ribozyme, using fluorescence resonance energy transfer. We find that with the loops in place, folding into the active conformation occurs in a single step, in the μM range of magnesium ion concentration. Disruption of the loop–loop interaction leads to a reversion to two-step folding, with the second stage requiring mM concentrations of magnesium ion. Sodium ions also promote the folding of the natural form of the ribozyme at high concentrations, but the folding occurs as a two-stage process. The loops clearly act as important auxiliary elements in the function of the ribozyme, permitting folding to occur efficiently under physiological conditions. PMID:15100442

Dynamics of Folds in the Plane

Science.gov (United States)

Krylov, Nikolai A.; Rogers, Edwin L.

2011-01-01

Take a strip of paper and fold a crease intersecting the long edges, creating two angles. Choose one edge and consider the angle with the crease. Fold the opposite edge along the crease, creating a new crease that bisects the angle. Fold again, this time using the newly created crease and the initial edge, creating a new angle along the chosen…

Agrochemicals increase risk of human schistosomiasis by supporting higher densities of intermediate hosts.

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Halstead, Neal T; Hoover, Christopher M; Arakala, Arathi; Civitello, David J; De Leo, Giulio A; Gambhir, Manoj; Johnson, Steve A; Jouanard, Nicolas; Loerns, Kristin A; McMahon, Taegan A; Ndione, Raphael A; Nguyen, Karena; Raffel, Thomas R; Remais, Justin V; Riveau, Gilles; Sokolow, Susanne H; Rohr, Jason R

2018-02-26

Schistosomiasis is a snail-borne parasitic disease that ranks among the most important water-based diseases of humans in developing countries. Increased prevalence and spread of human schistosomiasis to non-endemic areas has been consistently linked with water resource management related to agricultural expansion. However, the role of agrochemical pollution in human schistosome transmission remains unexplored, despite strong evidence of agrochemicals increasing snail-borne diseases of wildlife and a projected 2- to 5-fold increase in global agrochemical use by 2050. Using a field mesocosm experiment, we show that environmentally relevant concentrations of fertilizer, a herbicide, and an insecticide, individually and as mixtures, increase densities of schistosome-infected snails by increasing the algae snails eat and decreasing densities of snail predators. Epidemiological models indicate that these agrochemical effects can increase transmission of schistosomes. Identifying agricultural practices or agrochemicals that minimize disease risk will be critical to meeting growing food demands while improving human wellbeing.

A four-way junction accelerates hairpin ribozyme folding via a discrete intermediate

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Tan, Elliot; Wilson, Timothy J.; Nahas, Michelle K.; Clegg, Robert M.; Lilley, David M. J.; Ha, Taekjip

2003-01-01

The natural form of the hairpin ribozyme comprises two major structural elements: a four-way RNA junction and two internal loops carried by adjacent arms of the junction. The ribozyme folds into its active conformation by an intimate association between the loops, and the efficiency of this process is greatly enhanced by the presence of the junction. We have used single-molecule spectroscopy to show that the natural form fluctuates among three distinct states: the folded state and two additional, rapidly interconverting states (proximal and distal) that are inherited from the junction. The proximal state juxtaposes the two loop elements, thereby increasing the probability of their interaction and thus accelerating folding by nearly three orders of magnitude and allowing the ribozyme to fold rapidly in physiological conditions. Therefore, the hairpin ribozyme exploits the dynamics of the junction to facilitate the formation of the active site from its other elements. Dynamic interplay between structural elements, as we demonstrate for the hairpin ribozyme, may be a general theme for other functional RNA molecules. PMID:12883002

Collagen Content Limits Optical Coherence Tomography Image Depth in Porcine Vocal Fold Tissue.

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Garcia, Jordan A; Benboujja, Fouzi; Beaudette, Kathy; Rogers, Derek; Maurer, Rie; Boudoux, Caroline; Hartnick, Christopher J

2016-11-01

Vocal fold scarring, a condition defined by increased collagen content, is challenging to treat without a method of noninvasively assessing vocal fold structure in vivo. The goal of this study was to observe the effects of vocal fold collagen content on optical coherence tomography imaging to develop a quantifiable marker of disease. Excised specimen study. Massachusetts Eye and Ear Infirmary. Porcine vocal folds were injected with collagenase to remove collagen from the lamina propria. Optical coherence tomography imaging was performed preinjection and at 0, 45, 90, and 180 minutes postinjection. Mean pixel intensity (or image brightness) was extracted from images of collagenase- and control-treated hemilarynges. Texture analysis of the lamina propria at each injection site was performed to extract image contrast. Two-factor repeated measure analysis of variance and t tests were used to determine statistical significance. Picrosirius red staining was performed to confirm collagenase activity. Mean pixel intensity was higher at injection sites of collagenase-treated vocal folds than control vocal folds (P Fold change in image contrast was significantly increased in collagenase-treated vocal folds than control vocal folds (P = .002). Picrosirius red staining in control specimens revealed collagen fibrils most prominent in the subepithelium and above the thyroarytenoid muscle. Specimens treated with collagenase exhibited a loss of these structures. Collagen removal from vocal fold tissue increases image brightness of underlying structures. This inverse relationship may be useful in treating vocal fold scarring in patients. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

ETIOLOGICAL FACTORS FOR VOCAL FOLD POLYP FORMATION

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DAŠA GLUVAJIĆ

2016-05-01

Full Text Available Background: Vocal fold polyp is one of the most common causes for hoarseness. Many different etiological factors contribute to vocal fold polyp formation. The aim of the study was to find out whether the etiological factors for polyp formation have changed in the last 30 years.Methods: Eighty-one patients with unilateral vocal fold polyp were included in the study. A control group was composed of 50 volunteers without voice problems who matched the patients by age and gender. The data about etiological factors and the findings of phoniatric examination were obtained from the patients' medical documentation and from the questionnaires for the control group. The incidence of etiological factors was compared between the two groups. The program SPSS, Version 18 was used for statistical analysis.Results: The most frequent etiological factors were occupational voice load, GER, allergy and smoking. In 79% of patients 2 – 6 contemporary acting risk factors were found. Occupational voice load (p=0,018 and GER (p=0,004 were significantly more frequent in the patients than in the controls. The other factors did not significantly influence the polyp formation.Conclusions: There are several factors involved simultaneously in the formation of vocal fold polyps both nowadays and 30 years ago. Some of the most common factors remain the same (voice load, smoking, others are new (GER, allergy, which is probably due to the different lifestyle and working conditions than 30 years ago. Occupational voice load and GER were significantly more frequently present in the patients with polyp than in the control group. Regarding the given results it is important to instruct workers with professional vocal load about etiological factors for vocal fold polyp formation.

NoFold: RNA structure clustering without folding or alignment.

Science.gov (United States)

Middleton, Sarah A; Kim, Junhyong

2014-11-01

Structures that recur across multiple different transcripts, called structure motifs, often perform a similar function-for example, recruiting a specific RNA-binding protein that then regulates translation, splicing, or subcellular localization. Identifying common motifs between coregulated transcripts may therefore yield significant insight into their binding partners and mechanism of regulation. However, as most methods for clustering structures are based on folding individual sequences or doing many pairwise alignments, this results in a tradeoff between speed and accuracy that can be problematic for large-scale data sets. Here we describe a novel method for comparing and characterizing RNA secondary structures that does not require folding or pairwise alignment of the input sequences. Our method uses the idea of constructing a distance function between two objects by their respective distances to a collection of empirical examples or models, which in our case consists of 1973 Rfam family covariance models. Using this as a basis for measuring structural similarity, we developed a clustering pipeline called NoFold to automatically identify and annotate structure motifs within large sequence data sets. We demonstrate that NoFold can simultaneously identify multiple structure motifs with an average sensitivity of 0.80 and precision of 0.98 and generally exceeds the performance of existing methods. We also perform a cross-validation analysis of the entire set of Rfam families, achieving an average sensitivity of 0.57. We apply NoFold to identify motifs enriched in dendritically localized transcripts and report 213 enriched motifs, including both known and novel structures. © 2014 Middleton and Kim; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Cation-induced folding of alginate-bearing bilayer gels: an unusual example of spontaneous folding along the long axis.

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Athas, Jasmin C; Nguyen, Catherine P; Kummar, Shailaa; Raghavan, Srinivasa R

2018-04-04

The spontaneous folding of flat gel films into tubes is an interesting example of self-assembly. Typically, a rectangular film folds along its short axis when forming a tube; folding along the long axis has been seen only in rare instances when the film is constrained. Here, we report a case where the same free-swelling gel film folds along either its long or short axis depending on the concentration of a solute. Our gels are sandwiches (bilayers) of two layers: a passive layer of cross-linked N,N'-dimethylyacrylamide (DMAA) and an active layer of cross-linked DMAA that also contains chains of the biopolymer alginate. Multivalent cations like Ca2+ and Cu2+ induce these bilayer gels to fold into tubes. The folding occurs instantly when a flat film of the gel is introduced into a solution of these cations. The likely cause for folding is that the active layer stiffens and shrinks (because the alginate chains in it get cross-linked by the cations) whereas the passive layer is unaffected. The resulting mismatch in swelling degree between the two layers creates internal stresses that drive folding. Cations that are incapable of cross-linking alginate, such as Na+ and Mg2+, do not induce gel folding. Moreover, the striking aspect is the direction of folding. When the Ca2+ concentration is high (100 mM or higher), the gels fold along their long axis, whereas when the Ca2+ concentration is low (40 to 80 mM), the gels fold along their short axis. We hypothesize that the folding axis is dictated by the inhomogeneous nature of alginate-cation cross-linking, i.e., that the edges get cross-linked before the faces of the gel. At high Ca2+ concentration, the stiffer edges constrain the folding; in turn, the gel folds such that the longer edges are deformed less, which explains the folding along the long axis. At low Ca2+ concentration, the edges and the faces of the gel are more similar in their degree of cross-linking; therefore, the gel folds along its short axis. An analogy

Glass ionomer application for vocal fold augmentation: Histopathological analysis on rabbit vocal fold.

Science.gov (United States)

Demirci, Sule; Tuzuner, Arzu; Callıoglu, Elif Ersoy; Yumusak, Nihat; Arslan, Necmi; Baltacı, Bülent

2016-04-01

The aim of this study was to investigate the use of glass ionomer cement (GIC) as an injection material for vocal fold augmentation and to evaluate the biocompatibility of the material. Ten adult New Zealand rabbits were used. Under general anesthesia, 0.1-cc GIC was injected to one vocal fold and the augmentation of vocal fold was observed. No injection was applied to the opposite side, which was accepted as the control group. The animals were sacrificed after 3 months and the laryngeal specimens were histopathologically evaluated. The injected and the noninjected control vocal folds were analyzed. The GIC particles were observed in histological sections on the injected side, and no foreign body giant cells, granulomatous inflammation, necrosis, or marked chronic inflammation were detected around the glass ionomer particles. Mild inflammatory reactions were noticed in only two specimens. The noninjected sides of vocal folds were completely normal. The findings of this study suggest that GIC is biocompatible and may be further investigated as an alternative injection material for augmentation of the vocal fold. Further studies are required to examine the viscoelastic properties of GIC and the long-term effects in experimental studies. NA. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Recurrence of vocal fold leukoplakia after carbon dioxide laser therapy.

Science.gov (United States)

Chen, Min; Chen, Jian; Cheng, Lei; Wu, Haitao

2017-09-01

This work aims to analyze the recurrence of vocal fold leukoplakia after carbon dioxide (CO 2 ) laser resection. In this retrospective study, all patients undergoing CO 2 laser resection of vocal fold leukoplakia were followed up for at least 2 years. Recurrence was diagnosed as any presence of leukoplakia in the vocal cord subsequent to previous successful complete resection. A total of 326 patients with complete resection of vocal fold leukoplakia and follow-up subsequent surveillance laryngoscopy were studied. The recurrence rate, the recurrence time, and risk factors were evaluated. Of these, 52 (16.0%) patients experienced recurrence with a mean follow-up time of 50.5 ± 15.4 months. The mean time to recurrence was 16.2 ± 14.1 months. Univariate analysis showed that the size of lesion (P vocal fold leukoplakia, long-term follow-up is required after CO 2 laser resection. In conclusion, the size of lesion combined with the pathological grade are important risk factors that predict vocal fold leukoplakia recurrence.

Tobacco (kretek) smoking, betel quid chewing and risk of oral cancer in a selected Jakarta population.

Science.gov (United States)

Amtha, Rahmi; Razak, Ishak Abduk; Basuki, Bastaman; Roeslan, Boedi Oetomo; Gautama, Walta; Puwanto, Denny Joko; Ghani, Wan Maria Nabillah; Zain, Rosnah Binti

2014-01-01

This study aimed to determine the association between tobacco consumption (kretek) and betel quid chewing with oral cancer risk. A total of 81 cases of oral cancers were matched with 162 controls in this hospital-based study. Information on sociodemographic characteristics and details of risk habits (duration, frequency and type of tobacco consumption and betel quid chewing) were collected. Association between smoking and betel quid chewing with oral cancer were analysed using conditional logistic regression. Slightly more than half of the cases (55.6%) were smokers where 88.9% of them smoked kretek. After adjusting for confounders, smokers have two fold increased risk, while the risk for kretek consumers and those smoking for more than 10 years was increased to almost three-fold. Prevalence of betel quid chewing among cases and controls was low (7.4% and 1.9% respectively). Chewing of at least one quid per day, and quid combination of betel leaf, areca nut, lime and tobacco conferred a 5-6 fold increased risk. Smoking is positively associated with oral cancer risk. A similar direct association was also seen among betel quid chewers.

Effect of superconductivity on the cubic to tetragonal structural transition due to a two-fold degenerate electronic band

International Nuclear Information System (INIS)

Ghatak, S.K.; Khanra, B.C.; Ray, D.K.

1978-01-01

The effect of the BCS superconductivity on the cubic to tetragonal structural transition arising from a two-fold degenerate electronic band is investigated within the mean field approximation. The phase diagram of the two transitions is given for a half filled esub(g)-band. Modification of the two transitions when they are close together is also discussed. (author)

Factors increasing the risk of inactivity among administrative, technical, and manual workers in Warszawa public institutions.

Science.gov (United States)

Biernat, Elżbieta

2015-01-01

The research aims to assess the level of physical activity among administrative, technical, and manual workers employed in Warszawa public institutions and to analyze the factors that increase the risk of failing to meet World Health Organization (WHO) recommendations. The study comprised 373 employees of randomly selected institutions. A short version of International Physical Activity Questionnaire (IPAQ) was applied. The correlation between the mean values of duration, days, MET-min/week of efforts, gender, and type of work was analyzed using the Tukey's honest significant difference (HSD) test, while the correlation between the level of physical activity and the socio-demographic characteristics was assessed with the Chi2 test. The strength of the relationship between socio-demographic characteristics and fulfilment of WHO standards was expressed by the odds ratio (OR) and 95% confidence interval (95% CI). The significance level was p = 0.05. High levels of physical activity were declared by 41.8% of the manual workers, 14.7% of the administration staff, and 7.3% of the technicians; 19%, 31.5% and 54.5%, respectively, reported low levels of physical activity. Factors determining the fulfilment of the WHO recommendations include: the nature of work (p = 0.003), education (p = 0.004), and income (p = 0.003). The risk of being inactive nearly doubles in the case of administration staff (31.5%) and increases more than 4 times in the case of technicians (54.5%). Respondents with secondary school education (31.6%) are exposed to a 3-fold higher risk of inactivity, while in respondents with higher education (37.2%), the level of the risk is 4-fold higher. Compared to those in the highest income group (23.4%), people who earn less (34.1%) are inactive almost twice as often. Urgent intervention is necessary in all studied groups: increased energy expenditure for recreation and locomotion, educational offers of employers to promote healthy lifestyle, management of

Debunking vaccination myths: strong risk negations can increase perceived vaccination risks.

Science.gov (United States)

Betsch, Cornelia; Sachse, Katharina

2013-02-01

Information about risks is often contradictory, especially in the health domain. A vast amount of bizarre information on vaccine-adverse events (VAE) can be found on the Internet; most are posted by antivaccination activists. Several actors in the health sector struggle against these statements by negating claimed risks with scientific explanations. The goal of the present work is to find optimal ways of negating risk to decrease risk perceptions. In two online experiments, we varied the extremity of risk negations and their source. Perception of the probability of VAE, their expected severity (both variables serve as indicators of perceived risk), and vaccination intentions. Paradoxically, messages strongly indicating that there is "no risk" led to a higher perceived vaccination risk than weak negations. This finding extends previous work on the negativity bias, which has shown that information stating the presence of risk decreases risk perceptions, while information negating the existence of risk increases such perceptions. Several moderators were also tested; however, the effect occurred independently of the number of negations, recipient involvement, and attitude. Solely the credibility of the information source interacted with the extremity of risk negation: For credible sources (governmental institutions), strong and weak risk negations lead to similar perceived risk, while for less credible sources (pharmaceutical industries) weak negations lead to less perceived risk than strong negations. Optimal risk negation may profit from moderate rather than extreme formulations as a source's trustworthiness can vary.

A low threshold nanocavity in a two-dimensional 12-fold photonic quasicrystal

Science.gov (United States)

Ren, Jie; Sun, XiaoHong; Wang, Shuai

2018-05-01

In this article, a low threshold nanocavity is built and investigated in a two-dimensional 12-fold holographic photonic quasicrystal (PQC). The cavity is formed by using the method of multi-beam common-path interference. By finely adjusting the structure parameters of the cavity, the Q factor and the mode volume are optimized, which are two keys to low-threshold on the basis of Purcell effect. Finally, an optimal cavity is obtained with Q value of 6023 and mode volume of 1.24 ×10-12cm3 . On the other hand, by Fourier Transformation of the electric field components in the cavity, the in-plane wave vectors are calculated and fitted to evaluate the cavity performance. The performance analysis of the cavity further proves the effectiveness of the optimization process. This has a guiding significance for the research of low threshold nano-laser.

Improving protein fold recognition by extracting fold-specific features from predicted residue-residue contacts.

Science.gov (United States)

Zhu, Jianwei; Zhang, Haicang; Li, Shuai Cheng; Wang, Chao; Kong, Lupeng; Sun, Shiwei; Zheng, Wei-Mou; Bu, Dongbo

2017-12-01

Accurate recognition of protein fold types is a key step for template-based prediction of protein structures. The existing approaches to fold recognition mainly exploit the features derived from alignments of query protein against templates. These approaches have been shown to be successful for fold recognition at family level, but usually failed at superfamily/fold levels. To overcome this limitation, one of the key points is to explore more structurally informative features of proteins. Although residue-residue contacts carry abundant structural information, how to thoroughly exploit these information for fold recognition still remains a challenge. In this study, we present an approach (called DeepFR) to improve fold recognition at superfamily/fold levels. The basic idea of our approach is to extract fold-specific features from predicted residue-residue contacts of proteins using deep convolutional neural network (DCNN) technique. Based on these fold-specific features, we calculated similarity between query protein and templates, and then assigned query protein with fold type of the most similar template. DCNN has showed excellent performance in image feature extraction and image recognition; the rational underlying the application of DCNN for fold recognition is that contact likelihood maps are essentially analogy to images, as they both display compositional hierarchy. Experimental results on the LINDAHL dataset suggest that even using the extracted fold-specific features alone, our approach achieved success rate comparable to the state-of-the-art approaches. When further combining these features with traditional alignment-related features, the success rate of our approach increased to 92.3%, 82.5% and 78.8% at family, superfamily and fold levels, respectively, which is about 18% higher than the state-of-the-art approach at fold level, 6% higher at superfamily level and 1% higher at family level. An independent assessment on SCOP_TEST dataset showed consistent

Cigarette graphic warning labels increase both risk perceptions and smoking myth endorsement.

Science.gov (United States)

Evans, Abigail T; Peters, Ellen; Shoben, Abigail B; Meilleur, Louise R; Klein, Elizabeth G; Tompkins, Mary Kate; Tusler, Martin

2018-02-01

Cigarette graphic warning labels elicit negative emotion, which increases risk perceptions through multiple processes. We examined whether this emotion simultaneously affects motivated cognitions like smoking myth endorsement (e.g. 'exercise can undo the negative effects of smoking') and perceptions of cigarette danger versus other products. 736 adult and 469 teen smokers/vulnerable smokers viewed one of three warning label types (text-only, low emotion graphic or high emotion graphic) four times over two weeks. Emotional reactions to the warnings were reported during the first and fourth exposures. Participants reported how often they considered the warnings, smoking myth endorsement, risk perceptions and perceptions of cigarette danger relative to smokeless tobacco and electronic cigarettes. In structural equation models, emotional reactions influenced risk perceptions and smoking myth endorsement through two processes. Emotion acted as information about risk, directly increasing smoking risk perceptions and decreasing smoking myth endorsement. Emotion also acted as a spotlight, motivating consideration of the warning information. Warning consideration increased risk perceptions, but also increased smoking myth endorsement. Emotional reactions to warnings decreased perceptions of cigarette danger relative to other products. Emotional reactions to cigarette warnings increase smoking risk perceptions, but also smoking myth endorsement and misperceptions that cigarettes are less dangerous than potentially harm-reducing tobacco products.

Multiple molecule effects on the cooperativity of protein folding transitions in simulations

Science.gov (United States)

Lewis, Jacob I.; Moss, Devin J.; Knotts, Thomas A.

2012-06-01

Though molecular simulation of proteins has made notable contributions to the study of protein folding and kinetics, disagreement between simulation and experiment still exists. One of the criticisms levied against simulation is its failure to reproduce cooperative protein folding transitions. This weakness has been attributed to many factors such as a lack of polarizability and adequate capturing of solvent effects. This work, however, investigates how increasing the number of proteins simulated simultaneously can affect the cooperativity of folding transitions — a topic that has received little attention previously. Two proteins are studied in this work: phage T4 lysozyme (Protein Data Bank (PDB) ID: 7LZM) and phage 434 repressor (PDB ID: 1R69). The results show that increasing the number of proteins molecules simulated simultaneously leads to an increase in the macroscopic cooperativity for transitions that are inherently cooperative on the molecular level but has little effect on the cooperativity of other transitions. Taken as a whole, the results identify one area of consideration to improving simulations of protein folding.

Magnetocrystalline two-fold symmetry in CaFe2O4 single crystal

International Nuclear Information System (INIS)

Gandhi, Ashish Chhaganlal; Das, Rajasree; Chou, Fang-Cheng; Lin, Jauyn Grace

2017-01-01

Understanding of magnetocrystalline anisotropy in CaFe 2 O 4 is a matter of importance for its future applications. A high quality single crystal CaFe 2 O 4 sample is studied by using synchrotron x-ray diffraction, a magnetometer and the electron spin resonance (ESR) technique. A broad feature of the susceptibility curve around room temperature is observed, indicating the development of 1D spin interactions above the on-set of antiferromagnetic transition. The angular dependency of ESR reveals an in-plane two-fold symmetry, suggesting a strong correlation between the room temperature spin structure and magnetocrystalline anisotropy. This finding opens an opportunity for the device utilizing the anisotropy field of CaFe 2 O 4 . (paper)

Magnetocrystalline two-fold symmetry in CaFe2O4 single crystal

Science.gov (United States)

Chhaganlal Gandhi, Ashish; Das, Rajasree; Chou, Fang-Cheng; Lin, Jauyn Grace

2017-05-01

Understanding of magnetocrystalline anisotropy in CaFe2O4 is a matter of importance for its future applications. A high quality single crystal CaFe2O4 sample is studied by using synchrotron x-ray diffraction, a magnetometer and the electron spin resonance (ESR) technique. A broad feature of the susceptibility curve around room temperature is observed, indicating the development of 1D spin interactions above the on-set of antiferromagnetic transition. The angular dependency of ESR reveals an in-plane two-fold symmetry, suggesting a strong correlation between the room temperature spin structure and magnetocrystalline anisotropy. This finding opens an opportunity for the device utilizing the anisotropy field of CaFe2O4.

Vocal fold ion transport and mucin expression following acrolein exposure.

Science.gov (United States)

Levendoski, Elizabeth Erickson; Sivasankar, M Preeti

2014-05-01

The vocal fold epithelium is exposed to inhaled particulates including pollutants during breathing in everyday environments. Yet, our understanding of the effects of pollutants on vocal fold epithelial function is extremely limited. The objective of this study was to investigate the effect of the pollutant acrolein on two vocal fold epithelial mechanisms: ion transport and mucin (MUC) synthesis. These mechanisms were chosen as each plays a critical role in vocal defense and in maintaining surface hydration which is necessary for optimal voice production. Healthy, native porcine vocal folds (N = 85) were excised and exposed to an acrolein or sham challenge. A 60-min acrolein, but not sham challenge significantly reduced ion transport and inhibited cyclic adenosine monophosphate-dependent, increases in ion transport. Decreases in ion transport were associated with reduced sodium absorption. Within the same timeline, no significant acrolein-induced changes in MUC gene or protein expression were observed. These results improve our understanding of the effects of acrolein on key vocal fold epithelial functions and inform the development of future investigations that seek to elucidate the impact of a wide range of pollutant exposures on vocal fold health.

Protein Folding Free Energy Landscape along the Committor - the Optimal Folding Coordinate.

Science.gov (United States)

Krivov, Sergei V

2018-06-06

Recent advances in simulation and experiment have led to dramatic increases in the quantity and complexity of produced data, which makes the development of automated analysis tools very important. A powerful approach to analyze dynamics contained in such data sets is to describe/approximate it by diffusion on a free energy landscape - free energy as a function of reaction coordinates (RC). For the description to be quantitatively accurate, RCs should be chosen in an optimal way. Recent theoretical results show that such an optimal RC exists; however, determining it for practical systems is a very difficult unsolved problem. Here we describe a solution to this problem. We describe an adaptive nonparametric approach to accurately determine the optimal RC (the committor) for an equilibrium trajectory of a realistic system. In contrast to alternative approaches, which require a functional form with many parameters to approximate an RC and thus extensive expertise with the system, the suggested approach is nonparametric and can approximate any RC with high accuracy without system specific information. To avoid overfitting for a realistically sampled system, the approach performs RC optimization in an adaptive manner by focusing optimization on less optimized spatiotemporal regions of the RC. The power of the approach is illustrated on a long equilibrium atomistic folding simulation of HP35 protein. We have determined the optimal folding RC - the committor, which was confirmed by passing a stringent committor validation test. It allowed us to determine a first quantitatively accurate protein folding free energy landscape. We have confirmed the recent theoretical results that diffusion on such a free energy profile can be used to compute exactly the equilibrium flux, the mean first passage times, and the mean transition path times between any two points on the profile. We have shown that the mean squared displacement along the optimal RC grows linear with time as for

Flips for 3-folds and 4-folds

CERN Document Server

Corti, Alessio

2007-01-01

This edited collection of chapters, authored by leading experts, provides a complete and essentially self-contained construction of 3-fold and 4-fold klt flips. A large part of the text is a digest of Shokurov's work in the field and a concise, complete and pedagogical proof of the existence of 3-fold flips is presented. The text includes a ten page glossary and is accessible to students and researchers in algebraic geometry.

The formation of a native-like structure containing eight conserved hydrophobic residues is rate limiting in two-state protein folding of ACBP

DEFF Research Database (Denmark)

Kragelund, Birthe Brandt; Osmark, Peter; Neergaard, Thomas B.

1999-01-01

The acyl-coenzyme A-binding proteins (ACBPs) contain 26 highly conserved sequence positions. The majority of these have been mutated in the bovine protein, and their influence on the rate of two-state folding and unfolding has been measured. The results identify eight sequence positions, out of 24...... probed, that are critical for fast productive folding. The residues are all hydrophobic and located in the interface between the N- and C-terminal helices. The results suggest that one specific site dominated by conserved hydrophobic residues forms the structure of the productive rate-determining folding...... step and that a sequential framework model can describe the protein folding reaction....

The influence of thyroarytenoid and cricothyroid muscle activation on vocal fold stiffness and eigenfrequencies

Science.gov (United States)

Yin, Jun; Zhang, Zhaoyan

2013-01-01

The influence of the thyroarytenoid (TA) and cricothyroid (CT) muscle activation on vocal fold stiffness and eigenfrequencies was investigated in a muscularly controlled continuum model of the vocal folds. Unlike the general understanding that vocal fold fundamental frequency was determined by vocal fold tension, this study showed that vocal fold eigenfrequencies were primarily determined by vocal fold stiffness. This study further showed that, with reference to the resting state of zero strain, vocal fold stiffness in both body and cover layers increased with either vocal fold elongation or shortening. As a result, whether vocal fold eigenfrequencies increased or decreased with CT/TA activation depended on how the CT/TA interaction influenced vocal fold deformation. For conditions of strong CT activation and thus an elongated vocal fold, increasing TA contraction reduced the degree of vocal fold elongation and thus reduced vocal fold eigenfrequencies. For conditions of no CT activation and thus a resting or slightly shortened vocal fold, increasing TA contraction increased the degree of vocal fold shortening and thus increased vocal fold eigenfrequencies. In the transition region of a slightly elongated vocal fold, increasing TA contraction first decreased and then increased vocal fold eigenfrequencies. PMID:23654401

Cesarean section and offspring's risk of multiple sclerosis

DEFF Research Database (Denmark)

Nielsen, Nete M; Bager, Peter; Stenager, Egon

2013-01-01

Apart from a recent study reporting a 2- to 3-fold increased risk of multiple sclerosis (MS) among women and men who were delivered by Cesarean section (C-section), little attention has been given to the possible association between mode of delivery and the risk of MS.......Apart from a recent study reporting a 2- to 3-fold increased risk of multiple sclerosis (MS) among women and men who were delivered by Cesarean section (C-section), little attention has been given to the possible association between mode of delivery and the risk of MS....

Self-folding origami at any energy scale

Science.gov (United States)

Pinson, Matthew B.; Stern, Menachem; Carruthers Ferrero, Alexandra; Witten, Thomas A.; Chen, Elizabeth; Murugan, Arvind

2017-05-01

Programmable stiff sheets with a single low-energy folding motion have been sought in fields ranging from the ancient art of origami to modern meta-materials research. Despite such attention, only two extreme classes of crease patterns are usually studied; special Miura-Ori-based zero-energy patterns, in which crease folding requires no sheet bending, and random patterns with high-energy folding, in which the sheet bends as much as creases fold. We present a physical approach that allows systematic exploration of the entire space of crease patterns as a function of the folding energy. Consequently, we uncover statistical results in origami, finding the entropy of crease patterns of given folding energy. Notably, we identify three classes of Mountain-Valley choices that have widely varying `typical' folding energies. Our work opens up a wealth of experimentally relevant self-folding origami designs not reliant on Miura-Ori, the Kawasaki condition or any special symmetry in space.

Vfold: a web server for RNA structure and folding thermodynamics prediction.

Science.gov (United States)

Xu, Xiaojun; Zhao, Peinan; Chen, Shi-Jie

2014-01-01

The ever increasing discovery of non-coding RNAs leads to unprecedented demand for the accurate modeling of RNA folding, including the predictions of two-dimensional (base pair) and three-dimensional all-atom structures and folding stabilities. Accurate modeling of RNA structure and stability has far-reaching impact on our understanding of RNA functions in human health and our ability to design RNA-based therapeutic strategies. The Vfold server offers a web interface to predict (a) RNA two-dimensional structure from the nucleotide sequence, (b) three-dimensional structure from the two-dimensional structure and the sequence, and (c) folding thermodynamics (heat capacity melting curve) from the sequence. To predict the two-dimensional structure (base pairs), the server generates an ensemble of structures, including loop structures with the different intra-loop mismatches, and evaluates the free energies using the experimental parameters for the base stacks and the loop entropy parameters given by a coarse-grained RNA folding model (the Vfold model) for the loops. To predict the three-dimensional structure, the server assembles the motif scaffolds using structure templates extracted from the known PDB structures and refines the structure using all-atom energy minimization. The Vfold-based web server provides a user friendly tool for the prediction of RNA structure and stability. The web server and the source codes are freely accessible for public use at "http://rna.physics.missouri.edu".

Utility of Eating Assessment Tool-10 in Predicting Aspiration in Patients with Unilateral Vocal Fold Paralysis.

Science.gov (United States)

Zuniga, Steven A; Ebersole, Barbara; Jamal, Nausheen

2018-03-01

Objective Examine the incidence of penetration/aspiration in patients with unilateral vocal fold immobility and investigate the relationship with self-reported perception of dysphagia. Study Design Case series with chart review. Setting Academic cancer center. Subjects and Methods Adult patients with unilateral vocal fold immobility diagnosed between 2014 and 2016 were reviewed. Patients were stratified into an aspiration group and a nonaspiration group using objective findings on flexible endoscopic evaluation of swallowing, as scored using Rosenbek's Penetration Aspiration Scale. Objective findings were compared to patient perception of dysphagia. Bivariate linear correlation analysis was performed to evaluate correlation between Eating Assessment Tool-10 scores and presence of aspiration. Tests of diagnostic accuracy were calculated to investigate the predictive value of Eating Assessment Tool-10 scores >9 on aspiration risk. Results Of the 35 patients with new-onset unilateral vocal fold immobility were evaluated, 25.7% (9/35) demonstrated tracheal aspiration. Mean ± SD Eating Assessment Tool-10 scores were 19.2 ± 13.7 for aspirators and 7.0 ± 7.8 for nonaspirators ( P = .016). A statistically significant correlation was demonstrated between increasing Eating Assessment Tool-10 scores and Penetration Aspiration Scale scores ( r = 0.511, P = .002). Diagnostic accuracy analysis for aspiration risk in patients with an Eating Assessment Tool-10 score >9 revealed a sensitivity of 77.8% and a specificity of 73.1%. Conclusion Patient perception of swallowing difficulty may have utility in predicting aspiration risk. An EAT-10 of >9 in patients with unilateral vocal fold immobility may portend up to a 5 times greater risk of aspiration. Routine swallow testing to assess for penetration/aspiration may be indicated in patients with unilateral vocal fold immobility.

RNA folding: structure prediction, folding kinetics and ion electrostatics.

Science.gov (United States)

Tan, Zhijie; Zhang, Wenbing; Shi, Yazhou; Wang, Fenghua

2015-01-01

Beyond the "traditional" functions such as gene storage, transport and protein synthesis, recent discoveries reveal that RNAs have important "new" biological functions including the RNA silence and gene regulation of riboswitch. Such functions of noncoding RNAs are strongly coupled to the RNA structures and proper structure change, which naturally leads to the RNA folding problem including structure prediction and folding kinetics. Due to the polyanionic nature of RNAs, RNA folding structure, stability and kinetics are strongly coupled to the ion condition of solution. The main focus of this chapter is to review the recent progress in the three major aspects in RNA folding problem: structure prediction, folding kinetics and ion electrostatics. This chapter will introduce both the recent experimental and theoretical progress, while emphasize the theoretical modelling on the three aspects in RNA folding.

Structural Variations in β-(BDA-TTP)2FeCl4 at Low Temperature and under Pressure: Charge-Ordered State with a Two-Fold Crystal Structure

Science.gov (United States)

Sasamori, Kota; Takahashi, Kazuyuki; Kodama, Takeshi; Fujita, Wataru; Kikuchi, Koichi; Yamada, Jun-ichi

2013-05-01

The pressure-induced organic superconductor β-(BDA-TTP)2FeCl4 [BDA-TTP = 2,5-bis(1,3-dithian-2-ylidene)-1,3,4,6-tetrathiapentalene], which shows a metal--insulator (MI) transition at TMI = 113 K under ambient pressure, has been found by X-ray study to have a two-fold crystal structure along the c-axis in the insulating state at 10 K. In the donor layer, there are four independent BDA-TTP molecules, which are divided into two charge-poor ones and two charge-rich ones on the basis of the folding dihedral angles around the intramolecular sulfur-to-sulfur axes of two outer dithiane rings in BDA-TTP. The charge separation leads to the formation of two types of dimers: a dimer consisting of two charge-poor donors and a dimer consisting of two charge-rich ones. The tight-binding band calculation revealed a band gap of 5.3 meV in the energy dispersion. The MI transition can be therefore accounted for by the charge separation. In addition, we investigated the crystal and electronic structures of β-(BDA-TTP)2FeCl4 at different pressures up to 21 kbar, and found that the application of pressures causes variations in both the conformation of donor molecule and the donor arrangement, which are responsible for almost uniform interaction in the donor stacking and for an increase in bandwidth (W). As a result, the suppression of MI transition and subsequent occurrence of superconductivity in β-(BDA-TTP)2FeCl4 would be observed with increasing pressure.

Schooling increases risk exposure for fish navigating past artificial barriers.

Directory of Open Access Journals (Sweden)

Bertrand H Lemasson

Full Text Available Artificial barriers have become ubiquitous features in freshwater ecosystems and they can significantly impact a region's biodiversity. Assessing the risk faced by fish forced to navigate their way around artificial barriers is largely based on assays of individual swimming behavior. However, social interactions can significantly influence fish movement patterns and alter their risk exposure. Using an experimental flume, we assessed the effects of social interactions on the amount of time required for juvenile palmetto bass (Morone chrysops × M. saxatilis to navigate downstream past an artificial barrier. Fish were released either individually or in groups into the flume using flow conditions that approached the limit of their expected swimming stamina. We compared fish swimming behaviors under solitary and schooling conditions and measured risk as the time individuals spent exposed to the barrier. Solitary fish generally turned with the current and moved quickly downstream past the barrier, while fish in groups swam against the current and displayed a 23-fold increase in exposure time. Solitary individuals also showed greater signs of skittish behavior than those released in groups, which was reflected by larger changes in their accelerations and turning profiles. While groups displayed fission-fusion dynamics, inter-individual positions were highly structured and remained steady over time. These spatial patterns align with theoretical positions necessary to reduce swimming exertion through either wake capturing or velocity sheltering, but diverge from any potential gains from channeling effects between adjacent neighbors. We conclude that isolated performance trials and projections based on individual behaviors can lead to erroneous predictions of risk exposure along engineered structures. Our results also suggest that risk perception and behavior may be more important than a fish's swimming stamina in artificially modified systems.

Schooling increases risk exposure for fish navigating past artificial barriers.

Science.gov (United States)

Lemasson, Bertrand H; Haefner, James W; Bowen, Mark D

2014-01-01

Artificial barriers have become ubiquitous features in freshwater ecosystems and they can significantly impact a region's biodiversity. Assessing the risk faced by fish forced to navigate their way around artificial barriers is largely based on assays of individual swimming behavior. However, social interactions can significantly influence fish movement patterns and alter their risk exposure. Using an experimental flume, we assessed the effects of social interactions on the amount of time required for juvenile palmetto bass (Morone chrysops × M. saxatilis) to navigate downstream past an artificial barrier. Fish were released either individually or in groups into the flume using flow conditions that approached the limit of their expected swimming stamina. We compared fish swimming behaviors under solitary and schooling conditions and measured risk as the time individuals spent exposed to the barrier. Solitary fish generally turned with the current and moved quickly downstream past the barrier, while fish in groups swam against the current and displayed a 23-fold increase in exposure time. Solitary individuals also showed greater signs of skittish behavior than those released in groups, which was reflected by larger changes in their accelerations and turning profiles. While groups displayed fission-fusion dynamics, inter-individual positions were highly structured and remained steady over time. These spatial patterns align with theoretical positions necessary to reduce swimming exertion through either wake capturing or velocity sheltering, but diverge from any potential gains from channeling effects between adjacent neighbors. We conclude that isolated performance trials and projections based on individual behaviors can lead to erroneous predictions of risk exposure along engineered structures. Our results also suggest that risk perception and behavior may be more important than a fish's swimming stamina in artificially modified systems.

5-fold increase of hydrogen uptake in MOF74 through linker decorations

Science.gov (United States)

Thonhauser, T.; Zuluaga, S.; Harrison, D.; Welchman, E.; Arter, C.

We present ab initio results for linker decorations in Mg-MOF74-i.e. attaching various metals  = Li, Na, K, Sc, Cr, Mn, Fe, Ni, Cu, Zn, Rb, Pd, Ag, and Pt near the ring of the linker-creating new strong adsorption sites and thus maximizing small molecule uptake. We find that in most cases these decorations influence the overall form and structure of Mg-MOF74 only marginally. After the initial screening we chose metals that bind favorably to the linker and further investigate adsorption of H2, CO2, and H2O for  = Li, Na, K, and Sc. For the case of H2 we show that up to 24 additional guest molecules can be adsorbed in the MOF unit cell, with binding energies comparable to the original open-metal sites at the six corners of the channel. This leads to a 5-fold increase of the molecule uptake in Mg-MOF74, with tremendous impact on many applications in general and hydrogen storage in particular-where the gravimetric hydrogen density increases from 1 . 63 mass% to 7 . 28 mass% and the volumetric density from 15.10 g H2 L-1 to 75.50 g H2 L-1. This work was supported by NSF Grant No. DMR-1145968.

Probabilistic risk assessment as an aid to risk management

International Nuclear Information System (INIS)

Garrick, B.J.

1982-01-01

Probabilistic risk assessments are providing important insights into nuclear power plant safety. Their value is two-fold: first as a means of quantifying nuclear plant risk including contributors to risk, and second as an aid to risk management. A risk assessment provides an analytical plant model that can be the basis for performing meaningful decision analyses for controlling safety. It is the aspect of quantitative risk management that makes probabilistic risk assessment an important technical discipline of the future

Women referred for occupational risk assessment in pregnancy have no increased risk of adverse obstetric outcomes

DEFF Research Database (Denmark)

Bidstrup, Signe Brøker; Kaerlev, Linda; Thulstrup, Ane Marie

2015-01-01

.72-1.17). CONCLUSION: The women who are referred for occupational risk assessment at two large occupational university departments are not at an increased risk of preterm birth or of delivering low birth weight children. This may reflect that reproductive hazards in Danish workplaces are limited and......INTRODUCTION: Our aim was to study the association between pregnant women's referral status for occupational risk assessment, and their risk of preterm delivery (... pregnant women referred to two Danish clinics of occupational medicine (Copenhagen and Aarhus) from 1984 to 2010 were compared with the referred women's 1,077 non-referred pregnancy outcomes and with the pregnancy outcomes of 345,467 gainfully employed women from the same geographical areas and time period...

Radiation Fibrosis of the Vocal Fold: From Man to Mouse

Science.gov (United States)

Johns, Michael M.; Kolachala, Vasantha; Berg, Eric; Muller, Susan; Creighton, Frances X.; Branski, Ryan C.

2013-01-01

Objectives To characterize fundamental late tissue effects in the human vocal fold following radiation therapy. To develop a murine model of radiation fibrosis to ultimately develop both treatment and prevention paradigms. Design Translational study using archived human and fresh murine irradiated vocal fold tissue. Methods 1) Irradiated vocal fold tissue from patients undergoing laryngectomy for loss of function from radiation fibrosis were identified from pathology archives. Histomorphometry, immunohistochemistry, and whole-genome microarray as well as real-time transcriptional analyses was performed. 2) Focused radiation to the head and neck was delivered to mice in a survival fashion. One month following radiation, vocal fold tissue was analyzed with histomorphometry, immunohistochemistry, and real-time PCR transcriptional analysis for selected markers of fibrosis. Results Human irradiated vocal folds demonstrated increased collagen transcription with increased deposition and disorganization of collagen in both the thyroarytenoid muscle and the superficial lamina propria. Fibronectin were increased in the superficial lamina propria. Laminin decreased in the thyroarytenoid muscle. Whole genome microarray analysis demonstrated increased transcription of markers for fibrosis, oxidative stress, inflammation, glycosaminoglycan production and apoptosis. Irradiated murine vocal folds demonstrated increases in collagen and fibronectin transcription and deposition in the lamina propria. Transforming growth factor (TGF)-β increased in the lamina propria. Conclusion Human irradiated vocal folds demonstrate molecular changes leading to fibrosis that underlie loss of vocal fold pliability that occurs in patients following laryngeal irradiation. Irradiated murine tissue demonstrates similar findings, and this mouse model may have utility in creating prevention and treatment strategies for vocal fold radiation fibrosis. PMID:23242839

Has risk associated with smoking increased?

DEFF Research Database (Denmark)

Prescott, E; Osler, M; Andersen, P K

1997-01-01

BACKGROUND: Two recent much cited publications have raised the concern that risk associated with cigarette smoking has so far been underestimated. In this study we wish to determine whether excess all-cause mortality associated with smoking has increased during the last 20-30 years in a study...... population representative of the general Danish population and whether any such changes relate to changes in smoking behaviour. METHODS: Pooled data from three prospective population studies conducted in Copenhagen with detailed information on smoking habits. A total of 31,194 subjects, 17,669 males and 13......,525 females, initially examined between 1964 and 1992 with examinations repeated at intervals from 1-10 years, were followed until 1995 for all-cause mortality. Relative mortality risk in smokers versus never-smokers was calculated within periods of five calendar years and compared throughout the study period...

Trends in Utilization of Vocal Fold Injection Procedures.

Science.gov (United States)

Rosow, David E

2015-11-01

Office-based vocal fold injections have become increasingly popular over the past 15 years. Examination of trends in procedure coding for vocal fold injections in the United States from 2000 to 2012 was undertaken to see if they reflect this shift. The US Part B Medicare claims database was queried from 2000 through 2012 for multiple Current Procedural Terminology codes. Over the period studied, the number of nonoperative laryngoscopic injections (31513, 31570) and operative medialization laryngoplasties (31588) remained constant. Operative vocal fold injection (31571) demonstrated marked linear growth over the 12-year study period, from 744 procedures in 2000 to 4788 in 2012-an increase >640%. The dramatic increased incidence in the use of code 31571 reflects an increasing share of vocal fold injections being performed in the operating room and not in an office setting, running counter to the prevailing trend toward awake, office-based injection procedures. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Vocal fold varices and risk of hemorrhage.

Science.gov (United States)

Tang, Christopher Guan-Zhong; Askin, Gülce; Christos, Paul J; Sulica, Lucian

2016-05-01

To establish risk of hemorrhage in patients with varices compared to those without, determine additional risk factors, and make evidence-based treatment recommendations. Retrospective cohort study. Patients who were vocal performers presenting for care during a 24-month period were analyzed to determine incidence of hemorrhage. Patients with varices were compared to those without. Demographic information and examination findings (presence, location, character, and size of varices; presence of mucosal lesions or paresis) were analyzed to determine predictors of hemorrhage. A total of 513 patients (60.4% female, mean age 36.6 years ± 13.95 years) were evaluated; 14 patients presenting with hemorrhage were excluded. One hundred and twelve (22.4%) patients had varices; 387 (77.6%) did not. The rate of hemorrhage in patients with varices was 2.68% at 12 months compared to 0.8% in patients without. Cox proportional hazard regression analysis revealed a hazard ratio of 10.1 for patients with varix developing hemorrhage compared to nonvarix patients (P hemorrhage was 3.3 cases per 1,000 person-months for varix patients compared to 0.5 cases per 1,000 person-months in the nonvarix group. There was no significant difference in the incidence of paresis, mucosal lesions, location of varix (left or right side; medial or lateral), or varix morphology (pinpoint, linear, lake) between patients who hemorrhaged and those that did not. The presence of varices increases the risk of hemorrhage. Varix patients had 10 times the rate of hemorrhage compared to nonvarix patients, although the overall incidence is low. This data may be used to inform treatment of patients with varices. 4. Laryngoscope, 126:1163-1168, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Histological Effect of Basic Fibroblast Growth Factor on Chronic Vocal Fold Scarring in a Rat Model.

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Tateya, Ichiro; Tateya, Tomoko; Sohn, Jin-Ho; Bless, Diane M

2016-03-01

Vocal fold scarring is one of the most challenging laryngeal disorders to treat and there are currently no consistently effective treatments available. Our previous studies have shown the therapeutic potential of basic fibroblast growth factor (bFGF) for vocal fold scarring. However, the histological effects of bFGF on scarred vocal fold have not been elucidated. The aim of this study was to examine the histological effects of bFGF on chronic vocal fold scarring. Sprague-Dawley rats were divided into phosphate buffered saline (sham) and bFGF groups. Unilateral vocal fold stripping was performed and the drug was injected into the scarred vocal fold for each group 2 months postoperatively. Injections were performed weekly for 4 weeks. Two months after the last injection, larynges were harvested and histologically analyzed. A significant increase of hyaluronic acid was observed in the vocal fold of the bFGF group compared with that of the sham group. However, there was no remarkable change in collagen expression nor in vocal fold contraction. Significant increase of hyaluronic acid by local bFGF injection was thought to contribute to the therapeutic effects on chronic vocal fold scarring.

LRRK2 G2385R and R1628P Mutations Are Associated with an Increased Risk of Parkinson's Disease in the Malaysian Population

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Chua, Jing Yi; Lim, Thien Thien; Mohamed Ibrahim, Norlinah; Tan, Ai Huey; Eow, Gaik Bee; Abdul Aziz, Zariah; Puvanarajah, Santhi Datuk; Viswanathan, Shanthi; Lim, Soo Kun; Tan, Li Ping; Chong, Yip Boon; Tan, Chong Tin; Zhao, Yi; Tan, E. K.

2014-01-01

The LRRK2 gene has been associated with both familial and sporadic forms of Parkinson's disease (PD). The G2019S variant is commonly found in North African Arab and Caucasian PD patients, but this locus is monomorphic in Asians. The G2385R and R1628P variants are associated with a higher risk of developing PD in certain Asian populations but have not been studied in the Malaysian population. Therefore, we screened the G2385R and R1628P variants in 1,202 Malaysian subjects consisting of 695 cases and 507 controls. The G2385R and R1628P variants were associated with a 2.2-fold (P = 0.019) and 1.2-fold (P = 0.054) increased risk of PD, respectively. Our data concur with other reported findings in Chinese, Taiwanese, Singaporean, and Korean studies. PMID:25243190

Increased risks of tic disorders in children with epilepsy: A nation-wide population-based case-control study in Taiwan.

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Weng, Wen-Chin; Huang, Hui-Ling; Wong, Lee Chin; Jong, Yuh-Jyh; Yin, Yun-Ju; Chen, Hong-An; Lee, Wang-Tso; Ho, Shinn-Ying

2016-01-01

Both epilepsy and tic disorders may share common mechanisms with the involvement of abnormal cortical-basal ganglion circuit connection and dopaminergic dysfunction. However, the association between epilepsy and tic disorders has never been studied. This study investigated the risks of developing tic disorders among children with epilepsy using databases of a universal health insurance system in Taiwan. The data analyzed in this study were retrieved from the National Health Insurance Research Database in Taiwan. The study cohort included children with epilepsy between 2001 and 2007 (n=2629) and a three-fold age- and gender-matched controls (n=7887). All subjects were followed up for 3 years from the date of cohort entry to identify their admissions due to tic disorders (ICD-9-CM codes 307.2, 307.20-307.23). Cox hazard regression analysis was performed to estimate the effect of epilepsy on the occurrence of tics. The epilepsy cohort had a higher prevalence of tics (1.7% vs. 0.2%), and a 8.70-fold increased risk of developing a tic disorder compared with the controls (adjusted hazard ratio (AHR) 8.70, 95% confidence interval (CI) 4.26-16.37, ptic disorder (AHR 1.90, 95% CI=1.04-3.46, ptic disorders. This nationwide population-based cohort study, for the first time, demonstrated that there is a significantly increased risk for tic disorders among children with epilepsy. We also found males, attention deficit disorder and the use of multiple AEDs to be independent risk factors of tic disorders. Closely evaluating possible tic disorders would be crucial for improving the outcome and life quality in children with epilepsy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tat proteins as novel thylakoid membrane anchors organize a biosynthetic pathway in chloroplasts and increase product yield 5-fold

DEFF Research Database (Denmark)

Henriques de Jesus, Maria Perestrello Ramos; Nielsen, Agnieszka Janina Zygadlo; Mellor, Silas Busck

2017-01-01

to their complex structures. Some of the crucial enzymes catalyzing their biosynthesis are the cytochromes P450 (P450s) situated in the endoplasmic reticulum (ER), powered by electron transfers from NADPH. Dhurrin is a cyanogenic glucoside and its biosynthesis involves a dynamic metabolon formed by two P450s....... Nevertheless, translocation of the pathway from the ER to the chloroplast creates other difficulties, such as the loss of metabolon formation and intermediate diversion into other metabolic pathways. We show here that co-localization of these enzymes in the thylakoid membrane leads to a significant increase...... in product formation, with a concomitant decrease in off-pathway intermediates. This was achieved by exchanging the membrane anchors of the dhurrin pathway enzymes to components of the Twin-arginine translocation pathway, TatB and TatC, which have self-assembly properties. Consequently, we show 5-fold...

A comparison of RNA folding measures

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Gardner Paul P

2005-10-01

Full Text Available Abstract Background In the last few decades there has been a great deal of discussion concerning whether or not noncoding RNA sequences (ncRNAs fold in a more well-defined manner than random sequences. In this paper, we investigate several existing measures for how well an RNA sequence folds, and compare the behaviour of these measures over a large range of Rfam ncRNA families. Such measures can be useful in, for example, identifying novel ncRNAs, and indicating the presence of alternate RNA foldings. Results Our analysis shows that ncRNAs, but not mRNAs, in general have lower minimal free energy (MFE than random sequences with the same dinucleotide frequency. Moreover, even when the MFE is significant, many ncRNAs appear to not have a unique fold, but rather several alternative folds, at least when folded in silico. Furthermore, we find that the six investigated measures are correlated to varying degrees. Conclusion Due to the correlations between the different measures we find that it is sufficient to use only two of them in RNA folding studies, one to test if the sequence in question has lower energy than a random sequence with the same dinucleotide frequency (the Z-score and the other to see if the sequence has a unique fold (the average base-pair distance, D.

A new polymorphism biomarker rs629367 associated with increased risk and poor survival of gastric cancer in chinese by up-regulated miRNA-let-7a expression.

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Qian Xu

Full Text Available BACKGROUND: Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP associated with the risk and prognosis of gastric cancer (GC as predicting biomarkers, and furthermore, its possible mechanisms. METHODS: A two-stage case-control study was designed to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588 in 107 GC patients, 107 atrophic gastritis (AG, and matched 124 controls using PCR-RFLP. Two promising SNPs were validated in another independent 1949 samples (including 579 gastric cancer patients, 649 atrophic gastritis and 721 controls using Sequenom MassARRAY platform and sequencing. RESULTS: We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of gastric cancer and atrophic gastritis by 1.83-fold and 1.86-fold, respectively. For gastric cancer prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P = 0.004. We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the atrophic gastritis group (P = 0.043. Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (P<0.001. CONCLUSIONS: pri-let-7a-2 rs629367 CC genotype could increase the risks of gastric cancer as well as atrophic gastritis and was also associated with poor survival of gastric cancer, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of gastric cancer.

Vocal-fold vibration of patients with Reinke's edema observed using high-speed digital imaging.

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Watanabe, Takeshi; Kaneko, Kenichi; Sakaguchi, Koichi; Takahashi, Haruo

2016-12-01

We aimed to assess the vocal-fold vibration of patients with moderate-to-severe Reinke's edema using high-speed digital imaging (HSDI) and videostroboscopy and to confirm HSDI usefulness in examining the vocal folds with Reinke's edema. We examined the vocal folds of seven patients (six severe and one moderate; six females and one male; aged 55-74 years; mean 64.7 years) with Reinke's edema using HSDI and videostroboscopy. The following characteristics were analyzed: glottic closure, mucosal-wave propagation, left-right asymmetry, phase shift, frequency difference, periodicity, and contact of the true vocal fold with the false vocal fold. HSDI revealed complete glottic closure, anterior-posterior phase shift, and obvious contact of at least one side of the edematous true vocal fold with the ipsilateral false vocal fold in all patients. Mucosal-wave propagation increased in six patients and decreased in one. Left-right asymmetry was observed in six patients. Left-right phase shifts and left-right frequency differences were observed in four and two patients, respectively. The vibration was periodic in four patients, quasi-periodic in three, and aperiodic in none. Anterior-posterior frequency differences were not observed for any patient. The vocal-fold vibration always synchronized with strobolights in two patients, while the vibration occasionally and never synchronized in two and three patients, respectively. In one patient whose vibration occasionally synchronized, videostroboscopy could not reveal the slight left-right frequency difference of the vibration. It was often difficult to observe vocal-fold vibration correctly in patients with severe Reinke's edema using videostroboscopy. However, HSDI was useful for examining these patients. Our results suggest that HSDI can be very useful for examining the vocal folds of patients with severe Reinke's edema. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Frustration in Condensed Matter and Protein Folding

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Li, Z.; Tanner, S.; Conroy, B.; Owens, F.; Tran, M. M.; Boekema, C.

2014-03-01

By means of computer modeling, we are studying frustration in condensed matter and protein folding, including the influence of temperature and Thomson-figure formation. Frustration is due to competing interactions in a disordered state. The key issue is how the particles interact to reach the lowest frustration. The relaxation for frustration is mostly a power function (randomly assigned pattern) or an exponential function (regular patterns like Thomson figures). For the atomic Thomson model, frustration is predicted to decrease with the formation of Thomson figures at zero kelvin. We attempt to apply our frustration modeling to protein folding and dynamics. We investigate the homogeneous protein frustration that would cause the speed of the protein folding to increase. Increase of protein frustration (where frustration and hydrophobicity interplay with protein folding) may lead to a protein mutation. Research is supported by WiSE@SJSU and AFC San Jose.

Economic inequality increases risk taking.

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Payne, B Keith; Brown-Iannuzzi, Jazmin L; Hannay, Jason W

2017-05-02

Rising income inequality is a global trend. Increased income inequality has been associated with higher rates of crime, greater consumer debt, and poorer health outcomes. The mechanisms linking inequality to poor outcomes among individuals are poorly understood. This research tested a behavioral account linking inequality to individual decision making. In three experiments ( n = 811), we found that higher inequality in the outcomes of an economic game led participants to take greater risks to try to achieve higher outcomes. This effect of unequal distributions on risk taking was driven by upward social comparisons. Next, we estimated economic risk taking in daily life using large-scale data from internet searches. Risk taking was higher in states with greater income inequality, an effect driven by inequality at the upper end of the income distribution. Results suggest that inequality may promote poor outcomes, in part, by increasing risky behavior.

Metabolic Syndrome Increases the Risk of Sudden Sensorineural Hearing Loss in Taiwan: A Case-Control Study.

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Chien, Chen-Yu; Tai, Shu-Yu; Wang, Ling-Feng; Hsi, Edward; Chang, Ning-Chia; Wu, Ming-Tsang; Ho, Kuen-Yao

2015-07-01

Sudden sensorineural hearing loss has been reported to be associated with diabetes mellitus, hypertension, and hyperlipidemia in previous studies. The aim of this study was to examine whether metabolic syndrome increases the risk of sudden sensorineural hearing loss in Taiwan. A case-control study. Tertiary university hospital. We retrospectively investigated 181 cases of sudden sensorineural hearing loss and 181 controls from the Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, in southern Taiwan from 2010 to 2012, comparing their clinical variables. We analyzed the relationship between metabolic syndrome and sudden sensorineural hearing loss. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III with Asian modifications. The demographic and clinical characteristics, audiometry results, and outcome were reviewed. Subjects with metabolic syndrome had a 3.54-fold increased risk (95% confidence interval [CI] = 2.00-6.43, P diabetes mellitus, hypertension, and hyperlipidemia. With increases in the number of metabolic syndrome components, the risk of sudden sensorineural hearing loss increased (P for trend Vertigo was associated with a poor outcome (P = .02; 95% CI = 1.13~5.13, adjusted odds ratio = 2.39). The hearing loss pattern may influence the outcome of sudden sensorineural hearing loss (P Vertigo and total hearing loss were indicators of a poor outcome in sudden sensorineural hearing loss. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Future risk of diabetes in mother and child after gestational diabetes mellitus

DEFF Research Database (Denmark)

Damm, Peter; Damm, Peter

2009-01-01

diabetes, later in life. Moreover, the risk of the metabolic syndrome is increased 3-fold in these women. Their offspring have an 8-fold risk of diabetes/prediabetes at 19-27 years of age. Thus, GDM is part of a vicious circle which increases the development of diabetes in the coming generations....

Covering folded shapes

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Oswin Aichholzer

2014-05-01

Full Text Available Can folding a piece of paper flat make it larger? We explore whether a shape S must be scaled to cover a flat-folded copy of itself. We consider both single folds and arbitrary folds (continuous piecewise isometries \\(S\\to\\mathbb{R}^2\\. The underlying problem is motivated by computational origami, and is related to other covering and fixturing problems, such as Lebesgue's universal cover problem and force closure grasps. In addition to considering special shapes (squares, equilateral triangles, polygons and disks, we give upper and lower bounds on scale factors for single folds of convex objects and arbitrary folds of simply connected objects.

Anatomy and Histology of an Epicanthal Fold.

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Park, Jae Woo; Hwang, Kun

2016-06-01

The aim of this study is to elucidate the precise anatomical and histological detail of the epicanthal fold.Thirty-two hemifaces of 16 Korean adult cadavers were used in this study (30 hemifaces with an epicanthal fold, 2 without an epicanthal fold). In 2 patients who had an epicanthoplasty, the epicanthal folds were sampled.In a dissection, the periorbital skin and subcutaneous tissues were removed and the epicanthal fold was observed in relation to each part of the orbicularis oculi muscle. Specimens including the epicanthal fold were embeddedin in paraffin, sectioned at 10 um, and stained with Hematoxylin-Eosin. The horizontal section in the level of the paplebral fissure was made and the prepared slides were observed under a light microscope.In the specimens without an epicanthal fold, no connection between the upper preseptal muscle and the lower preseptal muscle was found. In the specimens with an epicanthal fold, a connection of the upper preseptal muscle to the lower preseptal muscle was observed. It was present in all 15 hemifaces (100%). There was no connection between the pretarsal muscles. In a horizontal section, the epicanthal fold was composed of 3 compartments: an outer skin lining, a core structure, and an innerskin lining. The core structure was mainly composed of muscular fibers and fibrotic tissue and they were intermingled.Surgeons should be aware of the anatomical details of an epicanthal fold. In removing or reconstructing an epicanthal fold, the fibromuscular core band should also be removed or reconstructed.

Circuit topology of self-interacting chains: implications for folding and unfolding dynamics.

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Mugler, Andrew; Tans, Sander J; Mashaghi, Alireza

2014-11-07

Understanding the relationship between molecular structure and folding is a central problem in disciplines ranging from biology to polymer physics and DNA origami. Topology can be a powerful tool to address this question. For a folded linear chain, the arrangement of intra-chain contacts is a topological property because rearranging the contacts requires discontinuous deformations. Conversely, the topology is preserved when continuously stretching the chain while maintaining the contact arrangement. Here we investigate how the folding and unfolding of linear chains with binary contacts is guided by the topology of contact arrangements. We formalize the topology by describing the relations between any two contacts in the structure, which for a linear chain can either be in parallel, in series, or crossing each other. We show that even when other determinants of folding rate such as contact order and size are kept constant, this 'circuit' topology determines folding kinetics. In particular, we find that the folding rate increases with the fractions of parallel and crossed relations. Moreover, we show how circuit topology constrains the conformational phase space explored during folding and unfolding: the number of forbidden unfolding transitions is found to increase with the fraction of parallel relations and to decrease with the fraction of series relations. Finally, we find that circuit topology influences whether distinct intermediate states are present, with crossed contacts being the key factor. The approach presented here can be more generally applied to questions on molecular dynamics, evolutionary biology, molecular engineering, and single-molecule biophysics.

Increased circulating D-lactate levels predict risk of mortality after hemorrhage and surgical trauma in baboons.

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Sobhian, Babak; Kröpfl, Albert; Hölzenbein, Thomas; Khadem, Anna; Redl, Heinz; Bahrami, Soheyl

2012-05-01

Patients with hemorrhagic shock and/or trauma are at risk of developing colonic ischemia associated with bacterial translocation that may lead to multiple organ failure and death. Intestinal ischemia is difficult to diagnose noninvasively. The present retrospective study was designed to determine whether circulating plasma D-lactate is associated with mortality in a clinically relevant two-hit model in baboons. Hemorrhagic shock was induced in anesthetized baboons (n = 24) by controlled bleeding (mean arterial pressure, 40 mmHg), base excess (maximum -5 mmol/L), and time (maximum 3 h). To mimic clinical setting more closely, all animals underwent a surgical trauma after resuscitation including midshaft osteotomy stabilized with reamed femoral interlocking nailing and were followed for 7 days. Hemorrhagic shock/surgical trauma resulted in 66% mortality by day 7. In nonsurvivor (n = 16) hemorrhagic shock/surgical trauma baboons, circulating D-lactate levels were significantly increased (2-fold) at 24 h compared with survivors (n = 8), whereas the early increase during hemorrhage and resuscitation declined during the early postresuscitation phase with no difference between survivors and nonsurvivors. Moreover, D-lactate levels remained elevated in the nonsurvival group until death, whereas it decreased to baseline in survivors. Prediction of death (receiver operating characteristic test) by D-lactate was accurate with an area under the curve (days 1-3 after trauma) of 0.85 (95% confidence interval, 0.72-0.93). The optimal D-lactate cutoff value of 25.34 μg/mL produced sensitivity of 73% to 99% and specificity of 50% to 83%. Our data suggest that elevation of plasma D-lactate after 24 h predicts an increased risk of mortality after hemorrhage and trauma.

100-fold but not 50-fold dystrophin overexpression aggravates electrocardiographic defects in the mdx model of Duchenne muscular dystrophy

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Yongping Yue

2016-01-01

Full Text Available Dystrophin gene replacement holds the promise of treating Duchenne muscular dystrophy. Supraphysiological expression is a concern for all gene therapy studies. In the case of Duchenne muscular dystrophy, Chamberlain and colleagues found that 50-fold overexpression did not cause deleterious side effect in skeletal muscle. To determine whether excessive dystrophin expression in the heart is safe, we studied two lines of transgenic mdx mice that selectively expressed a therapeutic minidystrophin gene in the heart at 50-fold and 100-fold of the normal levels. In the line with 50-fold overexpression, minidystrophin showed sarcolemmal localization and electrocardiogram abnormalities were corrected. However, in the line with 100-fold overexpression, we not only detected sarcolemmal minidystrophin expression but also observed accumulation of minidystrophin vesicles in the sarcoplasm. Excessive minidystrophin expression did not correct tachycardia, a characteristic feature of Duchenne muscular dystrophy. Importantly, several electrocardiogram parameters (QT interval, QRS duration and the cardiomyopathy index became worse than that of mdx mice. Our data suggests that the mouse heart can tolerate 50-fold minidystrophin overexpression, but 100-fold overexpression leads to cardiac toxicity.

Increased risk of epilepsy in children with Tourette syndrome: A population-based case-control study.

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Wong, Lee Chin; Huang, Hui-Ling; Weng, Wen-Chin; Jong, Yuh-Jyh; Yin, Yun-Ju; Chen, Hong-An; Lee, Wang-Tso; Ho, Shinn-Ying

2016-01-01

The association between epilepsy and Tourette syndrome has rarely been investigated. In this retrospective cohort study, we analyzed a dataset of 1,000,000 randomly sampled individuals from the Taiwan National Health Insurance Research Database to determine the risk of epilepsy in children with Tourette syndrome. The study cohort consisted of 1062 patients with Tourette syndrome aged ≤ 18 years, and the control group consisted of three times the number of age- and sex-matched patients without Tourette syndrome, who were insurants, from the same database during the same period. The Tourette syndrome group had an 18.38-fold increased risk of epilepsy than the control group [hazard ratio=18.38, 95% confidence interval (CI)=8.26-40.92; PTourette syndrome group with comorbidities remained high (hazard ratio=16.27, 95% CI=6.26-18.46; PTourette syndrome is associated with a higher risk of epilepsy. A close follow-up of children with Tourette syndrome for the development of epilepsy is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thermodynamic properties of an extremely rapid protein folding reaction.

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Schindler, T; Schmid, F X

1996-12-24

The cold-shock protein CspB from Bacillus subtilis is a very small beta-barrel protein, which folds with a time constant of 1 ms (at 25 degrees C) in a U reversible N two-state reaction. To elucidate the energetics of this extremely fast reaction we investigated the folding kinetics of CspB as a function of both temperature and denaturant concentration between 2 and 45 degrees C and between 1 and 8 M urea. Under all these conditions unfolding and refolding were reversible monoexponential reactions. By using transition state theory, data from 327 kinetic curves were jointly analyzed to determine the thermodynamic activation parameters delta H H2O++, delta S H2O++, delta G H2O++, and delta C p H2O++ for unfolding and refolding and their dependences on the urea concentration. 90% of the total change in heat capacity and 96% of the change in the m value (m = d delta G/d[urea]) occur between the unfolded state and the activated state. This suggests that for CspB the activated state of folding is unusually well structured and almost equivalent to the native protein in its interactions with the solvent. As a consequence of this native-like activated state a strong temperature-dependent enthalpy/entropy compensation is observed for the refolding kinetics, and the barrier to refolding shifts from being largely enthalpic at low temperature to largely entropic at high temperature. This shift originates not from the changes in the folding protein chains itself, but from the changes in the protein-solvent interactions. We speculate that the absence of intermediates and the native-like activated state in the folding of CspB are correlated with the small size and the structural type of this protein. The stabilization of a small beta-sheet as in CspB requires extensive non-local interactions, and therefore incomplete sheets are unstable. As a consequence, the critical activated state is reached only very late in folding. The instability of partially folded structure is a means to

Alcohol intake in pregnancy increases the child's risk of atopic dermatitis. the COPSAC prospective birth cohort study of a high risk population.

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Charlotte Giwercman Carson

Full Text Available BACKGROUND: Atopic dermatitis has increased four-fold over the recent decades in developed countries, indicating that changes in environmental factors associated with lifestyle may play an important role in this epidemic. It has been proposed that alcohol consumption may be one contributing risk factor in this development. OBJECTIVE: To analyze the impact of alcohol intake during pregnancy on the development of atopic dermatitis during the first 7 years of life. METHOD: The COPSAC cohort is a prospective, longitudinal, birth cohort study of 411 children born to mothers with a history of asthma, followed up for 7 years with scheduled visits every 6 months as well as visits for acute exacerbations of atopic dermatitis. Risk of atopic dermatitis from any alcohol consumption during pregnancy was analyzed as time-to-diagnosis and adjusted for known risk factors. RESULTS: 177 of 411 children developed atopic dermatitis before age 7 years. We found a significant effect of alcohol intake during pregnancy on atopic dermatitis development (HR 1.44, 95% CI 1.05-1.99 p=0.024. This conclusion was unaffected after adjustment for smoking, mother's education and mother's atopic dermatitis. LIMITATIONS: The selection of a high-risk cohort, with all mothers suffering from asthma, and all children having a gestational age above 35 weeks with no congenital abnormality, systemic illness, or history of mechanical ventilation or lower airway infection. CONCLUSION: Alcohol intake by pregnant women with a history of asthma, is significantly associated with an increased risk for the child for developing atopic dermatitis during the first 7 years of life.

Radiometric Dating of Folds: A new approach to determine the timing of deformation at shallow-crustal conditions, with examples from the Mexican Fold-Thrust Belt

Science.gov (United States)

Fitz Diaz, E.; van der Pluijm, B. A.

2012-12-01

We are developing a robust method to obtain absolute ages of folds that were formed at shallow crustal conditions. The method takes advantage of illite neocrystallization in folded, clay-bearing layers and the ability to obtain accurate retention and total gas ages from small size fractions using encapsulated Ar analysis, analogous to prior work on fault gouge dating. We illustrate our approach in folded Cretaceous shale-bentonitic layers that are interbedded with carbonates of the Zimapán and the Tampico-Misantla cretaceous basins in central-eastern Mexico. Basinal carbonates were buried by syntectonic turbidites and inverted during the formation of the Mexican Fold-Thrust in the Late Cretaceous. Results were obtained from four chevron folds that are representative of different stages of deformation, burial/temperature conditions and location within this thin-skinned orogenic wedge: two from the Zimapán Basin (Folds 1 and 2) in the west and two from the Tampico-Misantla Basin (Folds 3 and 4) in the east. Mineralogic compositions and variations in illite-polytypes, crystallite-size (CS) and Ar/Ar ages were obtained from size fractions in limbs and hinges of folded layers. Ar retention ages produce a folding age of ~81 Ma for Fold 1 and ~69 Ma for Fold 2, which are fully consistent with stratigraphic limits from syn-orogenic turbidities and observed overprinting events in the Mexican Fold-Thrust Belt. The total gas age of Fold 3, on the easternmost margin of the Tampico-Misantla Basin is similar to that of Fold 2, indicating that the second event is regional in scale. In addition to presenting a new, reliable method to constrain the timing of local deformation, we interpret folding and associated clay neo-mineralization in terms of the regional burial history, and localization and propagation of deformation within a heterogeneous orogenic wedge involving progressive deformation of two basins separated by a platform block.

Enhancement of the output power of terahertz folded waveguide oscillator by two parallel electron beams

International Nuclear Information System (INIS)

Li, Ke; Cao, Miaomiao; Liu, Wenxin; Wang, Yong; Liao, Suying

2015-01-01

A novel two-beam folded waveguide (FW) oscillator is presented for the purpose of gaining higher power with a small-size circuit compared with the normal FW oscillator. The high-frequency characteristics of the two-beam FW, including dispersion and interaction impedance, were investigated by the numerical simulation and compared with the one-beam FW. The radio-frequency loss of the two-beam FW was also analyzed. A 3-D particle-in-cell code CHIPIC was applied to analyze and optimize the performance of a G-band two-beam FW oscillator. The influences of the distance between the two beam tunnels, beam voltage, the number of periods, magnetic field, radius of beam tunnel, and the packing ratio on the circuit performance are investigated in detail. Compared with a one-beam circuit, a larger output power of the two-beam circuit with the same beam power was observed by the simulation. Moreover, the start-oscillation current of two-beam circuit is much lower than the one-beam circuit with better performance. It will favor the miniaturized design of the high-power terahertz oscillator

Enhancement of the output power of terahertz folded waveguide oscillator by two parallel electron beams

Energy Technology Data Exchange (ETDEWEB)

Li, Ke, E-mail: like.3714@163.com; Cao, Miaomiao, E-mail: mona486@yeah.net [Key Laboratory of High Power Microwave Sources and Technologies, Institute of Electronics, Chinese Academy of Sciences, Beijing 100190 (China); University of Chinese Academy of Sciences, Beijing 100190 (China); Liu, Wenxin, E-mail: lwenxin@mail.ie.ac.cn; Wang, Yong, E-mail: wangyong3845@sina.com [Key Laboratory of High Power Microwave Sources and Technologies, Institute of Electronics, Chinese Academy of Sciences, Beijing 100190 (China); Liao, Suying, E-mail: suying-liao@163.com [Air Force Airborne Academy, Guilin, Guangxi 541003 (China)

2015-11-15

A novel two-beam folded waveguide (FW) oscillator is presented for the purpose of gaining higher power with a small-size circuit compared with the normal FW oscillator. The high-frequency characteristics of the two-beam FW, including dispersion and interaction impedance, were investigated by the numerical simulation and compared with the one-beam FW. The radio-frequency loss of the two-beam FW was also analyzed. A 3-D particle-in-cell code CHIPIC was applied to analyze and optimize the performance of a G-band two-beam FW oscillator. The influences of the distance between the two beam tunnels, beam voltage, the number of periods, magnetic field, radius of beam tunnel, and the packing ratio on the circuit performance are investigated in detail. Compared with a one-beam circuit, a larger output power of the two-beam circuit with the same beam power was observed by the simulation. Moreover, the start-oscillation current of two-beam circuit is much lower than the one-beam circuit with better performance. It will favor the miniaturized design of the high-power terahertz oscillator.

Benign Proliferative Breast Lesions and Risk of Cancer

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Serap Erel

2010-06-01

Full Text Available Benign breast lesions (BBL includes a wide variety of histologic entities, which have been broadly classified into non-proliferative lesions, proliferative lesions without atypia, and hyperplasia with atypia. With the increased use of mammography, more benign lesions are being detected, and in order to estimate the risk of breast cancer for specific histologic categories is of great importance to guide clinical management. Women with proliferative lesions without atypia are at slightly increased risk of subsequent breast cancer, whereas women with proliferative lesions with atypia have a higher risk. The risk is 1.5- 2-fold in women with proliferative lesions without atypia, 4-5-fold in women with proliferative lesions with atypia, and 8-10 fold in women with ductal carcinoma in situ. Age at diagnosis of BBL, menopausal status, family history of breast cancer in a first-degree relative, and time since BBL diagnosis on risk of breast cancer are important for risk evaluation. [Archives Medical Review Journal 2010; 19(3.000: 155-167

Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk?

Science.gov (United States)

Lopez, David S; Advani, Shailesh; Tsilidis, Konstantinos K; Wang, Run; Canfield, Steven

2017-06-01

For more than 70 years, the contention that high levels of testosterone or that the use of testosterone therapy (TTh) increases the development and progression of prostate cancer (PCa) has been widely accepted and practiced. Yet, the increasing and emerging evidence on testosterone research seems to challenge that contention. To review literature on the associations of endogenous and exogenous testosterone with decreased-, increased-, or null-risk of PCa, and to further evaluate only those studies that reported magnitude of associations from multivariable modeling as it minimizes confounding effects. We conducted a literature search to identify studies that investigated the association of endogenous total testosterone [continuous (per 1 unit increment and 5 nmol/L increment) and categorical (high vs. low)] and use of TTh with PCa events [1990-2016]. Emphasis was given to studies/analyses that reported magnitude of associations [odds ratio (OR), relative risk (RR) and hazard ratios (HRs)] from multivariable analyses to determine risk of PCa and their statistical significance. Most identified studies/analyses included observational and randomized placebo-controlled trials. This review was organized in three parts: (I) association of endogenous total testosterone (per 1 unit increment and 5 nmol/L increment) with PCa; (II) relationship of endogenous total testosterone (categorical high vs. low) with PCa; and (III) association of use of TTh with PCa in meta-analyses of randomized placebo-controlled trials. The first part included 31 observational studies [20 prospective (per 5 nmol/L increment) and 11 prospective and retrospective cohort studies (per 1 unit increment)]. None of the 20 prospective studies found a significant association between total testosterone (5 nmol/L increment) and increased- or decreased-risk of PCa. Two out of the 11 studies/analyses showed a significant decreased-risk of PCa for total testosterone per 1 unit increment, but also two other

Vocal Fold Paralysis

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... here Home » Health Info » Voice, Speech, and Language Vocal Fold Paralysis On this page: What is vocal fold ... Where can I get additional information? What is vocal fold paralysis? Structures involved in speech and voice production ...

LRRK2 G2385R and R1628P Mutations Are Associated with an Increased Risk of Parkinson’s Disease in the Malaysian Population

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Aroma Agape Gopalai

2014-01-01

Full Text Available The LRRK2 gene has been associated with both familial and sporadic forms of Parkinson’s disease (PD. The G2019S variant is commonly found in North African Arab and Caucasian PD patients, but this locus is monomorphic in Asians. The G2385R and R1628P variants are associated with a higher risk of developing PD in certain Asian populations but have not been studied in the Malaysian population. Therefore, we screened the G2385R and R1628P variants in 1,202 Malaysian subjects consisting of 695 cases and 507 controls. The G2385R and R1628P variants were associated with a 2.2-fold (P=0.019 and 1.2-fold (P=0.054 increased risk of PD, respectively. Our data concur with other reported findings in Chinese, Taiwanese, Singaporean, and Korean studies.

Women referred for occupational risk assessment in pregnancy have no increased risk of adverse obstetric outcomes

DEFF Research Database (Denmark)

Bidstrup, Signe Brøker; Kaerlev, Linda; Thulstrup, Ane Marie

2015-01-01

.72-1.17). CONCLUSION: The women who are referred for occupational risk assessment at two large occupational university departments are not at an increased risk of preterm birth or of delivering low birth weight children. This may reflect that reproductive hazards in Danish workplaces are limited and....../or that the occupational risk assessment and counselling of pregnant women are preventing these selected adverse pregnancy outcomes. FUNDING: The Research Unit at Department of Occupational and Environmental Medicine at Bispebjerg Hospital supported the study financially. TRIAL REGISTRATION: not relevant. The study......INTRODUCTION: Our aim was to study the association between pregnant women's referral status for occupational risk assessment, and their risk of preterm delivery (

Protein folding: Over half a century lasting quest. Comment on "There and back again: Two views on the protein folding puzzle" by Alexei V. Finkelstein et al.

Science.gov (United States)

Krokhotin, Andrey; Dokholyan, Nikolay V.

2017-07-01

Most proteins fold into unique three-dimensional (3D) structures that determine their biological functions, such as catalytic activity or macromolecular binding. Misfolded proteins can pose a threat through aberrant interactions with other proteins leading to a number of diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis [1,2]. What does determine 3D structure of proteins? The first clue to this question came more than fifty years ago when Anfinsen demonstrated that unfolded proteins can spontaneously fold to their native 3D structures [3,4]. Anfinsen's experiments lead to the conclusion that proteins fold to unique native structure corresponding to the stable and kinetically accessible free energy minimum, and protein native structure is solely determined by its amino acid sequence. The question of how exactly proteins find their free energy minimum proved to be a difficult problem. One of the puzzles, initially pointed out by Levinthal, was an inconsistency between observed protein folding times and theoretical estimates. A self-avoiding polymer model of a globular protein of 100-residues length on a cubic lattice can sample at least 1047 states. Based on the assumption that conformational sampling occurs at the highest vibrational mode of proteins (∼picoseconds), predicted folding time by searching among all the possible conformations leads to ∼1027 years (much larger than the age of the universe) [5]. In contrast, observed protein folding time range from microseconds to minutes. Due to tremendous theoretical progress in protein folding field that has been achieved in past decades, the source of this inconsistency is currently understood that is thoroughly described in the review by Finkelstein et al. [6].

Unilateral Vocal Fold Paralysis and Risk of Pneumonia: A Nationwide Population-Based Cohort Study.

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Tsai, Ming-Shao; Yang, Yao-Hsu; Liu, Chia-Yen; Lin, Meng-Hung; Chang, Geng-He; Tsai, Yao-Te; Li, Hsueh-Yu; Tsai, Ying-Huang; Hsu, Cheng-Ming

2018-05-01

Objective To investigate pneumonia risk among patients with unilateral vocal fold paralysis (UVFP). Study Design Retrospective population-based cohort study. Setting This study used data from the National Health Insurance Research Database of Taiwan, a nationwide population-based database. Subjects and Methods A total of 419 patients newly diagnosed with UVFP between January 1, 1997, and December 31, 2013, were identified from the Longitudinal Health Insurance Database 2000, a nationally representative database of 1 million randomly selected patients. Moreover, 1676 patients without UVFP were matched to patients with UVFP at a 1:4 ratio based on age, sex, socioeconomic status, urbanization level, and site-specific cancers. Patients were followed up until death or the end of the study period (December 31, 2013). The primary outcome was the occurrence of pneumonia. Results The cumulative incidence of pneumonia was significantly higher for patients with UVFP than those without UFVP ( P < .001). The adjusted Cox proportional hazard model showed that UVFP was significantly associated with a higher incidence of pneumonia (hazard ratio, 1.97; 95% CI, 1.35-2.86; P < .001). Subgroup analyses demonstrated that UVFP was an independent risk factor of pneumonia for 4 subgroups: young (18-50 years), older (≥51 years), male, and cancer. Conclusion This is the first nationwide population-based cohort study to investigate the association between UVFP and pneumonia. The findings indicate that UVFP is an independent risk factor of pneumonia. Given the study results, physicians should be aware of the potential for pneumonia occurrence following UVFP.

Incidence of vocal fold immobility in patients with dysphagia.

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Leder, Steven B; Ross, Douglas A

2005-01-01

This study prospectively investigated the incidence of vocal fold immobility, unilateral and bilateral, and its influence on aspiration status in a referred population of 1452 patients for a dysphagia evaluation from a large, urban, tertiary-care, teaching hospital. Main outcome measures included overall incidence of vocal fold immobility and aspiration status, with specific emphasis on age, etiology, and side of vocal fold immobility, i.e., right, left, or bilateral. Overall incidence of vocal fold immobility was 5.6% (81 of 1452 patients), including 47 males (mean age 55.7 yr) and 34 females (mean age 59.7 yr). In the subgroup of patients with vocal fold immobility, 31% (25 of 81) exhibited unilateral right, 60% (49 of 81) unilateral left, and 9% (7 of 81) bilateral impairment. Overall incidence of aspiration was found to be 29% (426 of 1452) of all patients referred for a swallow evaluation. Aspiration was observed in 44% (36 of 81) of patients presenting with vocal fold immobility, i.e., 44% (11 of 25) unilateral right, 43% (21 of 49) unilateral left, and 57% (4 of 7) bilateral vocal fold immobility. Left vocal fold immobility occurred most frequently due to surgical trauma. A liquid bolus was aspirated more often than a puree bolus. Side of vocal fold immobility and age were not factors that increased incidence of aspiration. In conclusion, vocal fold immobility, with an incidence of 5.6%, is not an uncommon finding in patients referred for a dysphagia evaluation in the acute-care setting, and vocal fold immobility, when present, was associated with a 15% increased incidence of aspiration when compared with a population already being evaluated for dysphagia.

Using Trial Vocal Fold Injection to Select Vocal Fold Scar Patients Who May Benefit From More Durable Augmentation.

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Carroll, Thomas L; Dezube, Aaron; Bauman, Laura A; Mallur, Pavan S

2018-02-01

Clinical indications for vocal fold injection augmentation (VFI) are expanding. Prior studies demonstrate the benefit of trial VFI for select causes of glottic insufficiency. No studies have examined trial VFI for glottic insufficiency resulting from true vocal fold (TVF) scar. Retrospective chart review of patients who underwent trial VFI for a dominant pathology of TVF scar causing dysphonia. Patients who subsequently underwent durable augmentation were identified. The primary study outcome was the difference in Voice Handicap Index-10 (VHI-10) score from pretrial VFI to post-durable augmentation. Twenty-eight patients underwent trial VFI for TVF scar, 22 of whom reported a positive response. Fifteen of 22 subjects who underwent durable augmentation had viable data for analysis. Mean VHI-10 improved from 26.9 to 18.6 ( P 5). A trial VFI is a potentially useful, low-risk procedure that appears to help the patient and clinician identify when global augmentation might improve the voice when vocal fold scar is present. Patients who reported successful trial VFI often demonstrated significant improvement in their VHI-10 after subsequent durable augmentation.

A comparison of RNA folding measures

DEFF Research Database (Denmark)

Freyhult, E.; Gardner, P. P.; Moulton, V.

2005-01-01

the behaviour of these measures over a large range of Rfam ncRNA families. Such measures can be useful in, for example, identifying novel ncRNAs, and indicating the presence of alternate RNA foldings. Results Our analysis shows that ncRNAs, but not mRNAs, in general have lower minimal free energy (MFE) than....... Conclusion Due to the correlations between the different measures we find that it is sufficient to use only two of them in RNA folding studies, one to test if the sequence in question has lower energy than a random sequence with the same dinucleotide frequency (the Z-score) and the other to see......Background In the last few decades there has been a great deal of discussion concerning whether or not noncoding RNA sequences (ncRNAs) fold in a more well-defined manner than random sequences. In this paper, we investigate several existing measures for how well an RNA sequence folds, and compare...

Prolonged phonation impairs the integrity and barrier function of porcine vocal fold epithelium: a preliminary study.

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Zhang, Chi; Paddock, Kieran; Chou, Adriana; Scholp, Austin; Gong, Ting; Jiang, Jack J

2018-04-18

Voice abuse is known to be a common risk factor of voice disorders and prolonged; high-intensity phonation has been shown to damage the vocal fold epithelium. We aim to evaluate the effects of phonation on the integrity and barrier function of vocal fold epithelium using a porcine laryngeal model. Ex vivo porcine larynges were phonated at low intensity or high intensity for 15, 30, or 60 min within 4 h after harvest. Vocal fold epithelium was visualized using transmission electron microscopy (TEM). The barrier function of vocal fold epithelium was evaluated by measuring the permeability to model molecules, fluorescein (376 Da), and fluorescein isothiocyanate (FITC)-dextrans of 4000 and 10,000 Da (FD4, FD10), in a Franz diffusing cell. Cell death and dilated intercellular space after phonation were observed using TEM. Thickness of vocal fold epithelium was significantly reduced after low-intensity phonation for 30 and 60 min and high-intensity phonation for 15, 30, and 60 min. Epithelial permeability to fluorescein was significantly increased after low-intensity phonation for 30 and 60 min, and high-intensity phonation. Permeability to FD4 was significantly increased after high-intensity phonation for 30 and 60 min. Phonation did not alter the permeability to FD10 significantly. Long-duration phonation destroys the integrity and barrier function of vocal fold epithelium. These effects likely make vocal folds more vulnerable to other environmental irritants, such as tobacco smoke, reflux components, allergens, and inhaled pollutants. Destroyed barrier function may be an important factor in the pathogenesis of voice lesions related to voice abuse.

Value of routine blood tests for prediction of mortality risk in hip fracture patients

DEFF Research Database (Denmark)

Mosfeldt, Mathias; Pedersen, Ole Birger Vesterager; Riis, Troels

2012-01-01

There is a 5- to 8-fold increased risk of mortality during the first 3 months after a hip fracture. Several risk factors are known. We studied the predictive value (for mortality) of routine blood tests taken on admission.......There is a 5- to 8-fold increased risk of mortality during the first 3 months after a hip fracture. Several risk factors are known. We studied the predictive value (for mortality) of routine blood tests taken on admission....

A bidirectional shape memory alloy folding actuator

International Nuclear Information System (INIS)

Paik, Jamie K; Wood, Robert J

2012-01-01

This paper presents a low-profile bidirectional folding actuator based on annealed shape memory alloy sheets applicable for meso- and microscale systems. Despite the advantages of shape memory alloys—high strain, silent operation, and mechanical simplicity—their application is often limited to unidirectional operation. We present a bidirectional folding actuator that produces two opposing 180° motions. A laser-patterned nickel alloy (Inconel 600) heater localizes actuation to the folding sections. The actuator has a thin ( < 1 mm) profile, making it appropriate for use in robotic origami. Various design parameters and fabrication variants are described and experimentally explored in the actuator prototype. (paper)

Nested folded-beam suspensions with low longitudinal stiffness for comb-drive actuators

International Nuclear Information System (INIS)

Hou, Max T; Huang, Ming-Xian; Chang, Chao-Min

2014-01-01

Nested folded-beam suspensions with a low longitudinal spring constant and a high lateral spring constant have been used in comb-drive actuators. In the new design, every two flexible beams and two stiff members form a parallelogram flexure, which is considered as an ‘element’ of the nested folded-beam suspension. A set of these flexures of increasing size were placed one outside another to compose a nested structure. In this way, a serial mechanical connection between adjacent parallelogram flexures was formed; thus, a longer output stroke was obtained by combining the stroke displacements of all flexures in an additive fashion. The designed suspensions were theoretically analyzed and numerically simulated. Furthermore, comb-drive actuators with conventional and new suspensions were fabricated and tested to verify the predicted function. In the testing cases, the longitudinal spring constants of suspensions with two (conventional), three and four parallelogram flexures on each side were measured as 2.77, 1.75 and 1.36 N m −1 . The ratio among these three values was approximately 6:4:3, which is consistent with the theoretical predictions and simulation results. Microfabricated folded beams in series were achieved. (paper)

THE INFLUENCE OF FOLD AND FRACTURE DEVELOPMENT ON RESERVOIR BEHAVIOR OF THE LISBURNE GROUP OF NORTHERN ALASKA

Energy Technology Data Exchange (ETDEWEB)

Wesley K. Wallace; Catherine L. Hanks; Michael T. Whalen; Jerry Jensen; Paul K. Atkinson; Joseph S. Brinton

2000-05-01

-and-thrust belt. The steep forelimbs of angular asymmetrical folds typically have been cut and displaced by thrust faults, resulting in superposition of a fault-bend fold geometry on the truncated folds. Remnant uncut folds within trains of thrust-truncated folds and the predominance of detachment folds to the north suggest that these folds originated as detachment folds. Fold asymmetry and a more uniformly competent Lisburne Limestone may have favored accommodation of a significant proportion of shortening by thrust faulting, in contrast with the dominance of fold shortening to the north. Two dominant sets of fractures are present in the least deformed Lisburne Limestone: Early extension fractures normal to the regional fold trend and late extension and shear fractures parallel to the regional fold trend. These two major fracture sets remain as deformation increases, but they are more variable in orientation, character, and relative age. Compared to fold limbs, the fold hinges display greater density and extent of fractures, more conjugate and shear fractures, and more evidence of penetrative strain. This suggests that hinges remained fixed during fold growth. Late extension fractures normal to the fold axis are common even where penetrative strain is greatest. Fracture density is greater in fine-grained carbonates than in coarse-grained carbonates over the entire spectrum of deformation.

Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk?

Science.gov (United States)

Advani, Shailesh; Tsilidis, Konstantinos K.; Wang, Run; Canfield, Steven

2017-01-01

For more than 70 years, the contention that high levels of testosterone or that the use of testosterone therapy (TTh) increases the development and progression of prostate cancer (PCa) has been widely accepted and practiced. Yet, the increasing and emerging evidence on testosterone research seems to challenge that contention. To review literature on the associations of endogenous and exogenous testosterone with decreased-, increased-, or null-risk of PCa, and to further evaluate only those studies that reported magnitude of associations from multivariable modeling as it minimizes confounding effects. We conducted a literature search to identify studies that investigated the association of endogenous total testosterone [continuous (per 1 unit increment and 5 nmol/L increment) and categorical (high vs. low)] and use of TTh with PCa events [1990–2016]. Emphasis was given to studies/analyses that reported magnitude of associations [odds ratio (OR), relative risk (RR) and hazard ratios (HRs)] from multivariable analyses to determine risk of PCa and their statistical significance. Most identified studies/analyses included observational and randomized placebo-controlled trials. This review was organized in three parts: (I) association of endogenous total testosterone (per 1 unit increment and 5 nmol/L increment) with PCa; (II) relationship of endogenous total testosterone (categorical high vs. low) with PCa; and (III) association of use of TTh with PCa in meta-analyses of randomized placebo-controlled trials. The first part included 31 observational studies [20 prospective (per 5 nmol/L increment) and 11 prospective and retrospective cohort studies (per 1 unit increment)]. None of the 20 prospective studies found a significant association between total testosterone (5 nmol/L increment) and increased- or decreased-risk of PCa. Two out of the 11 studies/analyses showed a significant decreased-risk of PCa for total testosterone per 1 unit increment, but also two other

Women referred for occupational risk assessment in pregnancy have no increased risk of adverse obstetric outcomes

DEFF Research Database (Denmark)

Bidstrup, Signe Brøker; Kaerlev, Linda; Thulstrup, Ane Marie

2015-01-01

INTRODUCTION: Our aim was to study the association between pregnant women's referral status for occupational risk assessment, and their risk of preterm delivery (METHODS: In a cohort study, 1,202 deliveries among....../or that the occupational risk assessment and counselling of pregnant women are preventing these selected adverse pregnancy outcomes. FUNDING: The Research Unit at Department of Occupational and Environmental Medicine at Bispebjerg Hospital supported the study financially. TRIAL REGISTRATION: not relevant. The study.......72-1.17). CONCLUSION: The women who are referred for occupational risk assessment at two large occupational university departments are not at an increased risk of preterm birth or of delivering low birth weight children. This may reflect that reproductive hazards in Danish workplaces are limited and...

Higher energy efficient homes are associated with increased risk of doctor diagnosed asthma in a UK subpopulation.

Science.gov (United States)

Sharpe, Richard A; Thornton, Christopher R; Nikolaou, Vasilis; Osborne, Nicholas J

2015-02-01

The United Kingdom (UK) has one of the highest prevalence of asthma in the world, which represents a significant economic and societal burden. Reduced ventilation resulting from increased energy efficiency measures acts as a modifier for mould contamination and risk of allergic diseases. To our knowledge no previous study has combined detailed asset management property and health data together to assess the impact of household energy efficiency (using the UK Government's Standard Assessment Procedure) on asthma outcomes in an adult population residing in social housing. Postal questionnaires were sent to 3867 social housing properties to collect demographic, health and environmental information on all occupants. Detailed property data, residency periods, indices of multiple deprivation (IMD) and household energy efficiency ratings were also investigated. Logistic regression was used to calculate odds ratios and confidence intervals while allowing for clustering of individuals coming from the same location. Eighteen percent of our target social housing population were recruited into our study. Adults had a mean age of 59 (SD±17.3) years and there was a higher percentage of female (59%) and single occupancy (58%) respondents. Housing demographic characteristics were representative of the target homes. A unit increase in household Standard Assessment Procedure (SAP) rating was associated with a 2% increased risk of current asthma, with the greatest risk in homes with SAP >71. We assessed exposure to mould and found that the presence of a mouldy/musty odour was associated with a two-fold increased risk of asthma (OR 2.2 95%; CI 1.3-3.8). A unit increase in SAP led to a 4-5% reduction in the risk of visible mould growth and a mouldy/musty odour. In contrast to previous research, we report that residing in energy efficient homes may increase the risk of adult asthma. We report that mould contamination increased the risk of asthma, which is in agreement with existing

Two-dimensional NMR and photo-CIDNP studies of the insulin monomer: Assignment of aromatic resonances with application to protein folding, structure, and dynamics

International Nuclear Information System (INIS)

Weiss, M.A.; Shoelson, S.E.; Nguyen, D.T.; O'Shea, E.; Karplus, M.; Khait, I.; Neuringer, L.J.; Inouye, K.; Frank, B.H.; Beckage, M.

1989-01-01

The aromatic 1 H NMR resonances of the insulin monomer are assigned at 500 MHz by comparative studies of chemically modified and genetically altered variants, including a mutant insulin (PheB25 → Leu) associated with diabetes mellitus. The two histidines, three phenylalanines, and four tyrosines are observed to be in distinct local environments; their assignment provides sensitive markers for studies of tertiary structure, protein dynamics, and protein folding. The environments of the tyrosine residues have also been investigated by photochemically induced dynamic nuclear polarization (photo-CIDNP) and analyzed in relation to packing constrains in the crystal structures of insulin. Dimerization involving specific B-chain interactions is observed with increasing protein concentration and is shown to depend on temperature, pH, and solvent composition. The differences between proinsulin and mini-proinsulin suggest a structural mechanism for the observation that the fully reduced B29-A1 analogue folds more efficiently than proinsulin to form the correct pattern of disulfide bonds. These results are discussed in relation to molecular mechanics calculations of insulin based on the available crystal structures

Controllable group velocity of the probe light in a Λ-type system with two fold levels

International Nuclear Information System (INIS)

Jin Lihui; Gong Shangqing; Niu Yueping; Li Ruxin; Jin Shiqi

2006-01-01

The group velocities of the probe laser field are studied in a Λ-type system where one lower state has two fold levels coupled by a control field. It is found that the interaction of double dark states leads to controllable group velocity of the probe field in this system. It can be easily realized, due to the interacting double dark resonances, that one of the group velocities at transparency positions is much slower than the other by tuning the control field to be off resonance. In particular, when the control field is on resonance, we can obtain two equal slow group velocities with a broader EIT width, which provides potential applications in quantum storage and retrieval of light

Ligand-promoted protein folding by biased kinetic partitioning.

Science.gov (United States)

Hingorani, Karan S; Metcalf, Matthew C; Deming, Derrick T; Garman, Scott C; Powers, Evan T; Gierasch, Lila M

2017-04-01

Protein folding in cells occurs in the presence of high concentrations of endogenous binding partners, and exogenous binding partners have been exploited as pharmacological chaperones. A combined mathematical modeling and experimental approach shows that a ligand improves the folding of a destabilized protein by biasing the kinetic partitioning between folding and alternative fates (aggregation or degradation). Computationally predicted inhibition of test protein aggregation and degradation as a function of ligand concentration are validated by experiments in two disparate cellular systems.

Strange temperature dependence of the folding rate of a 16-residue β-hairpin

International Nuclear Information System (INIS)

Xu Yao; Wang Ting; Gai Feng

2006-01-01

The folding/unfolding kinetics of a 16-residue β-hairpin that undergoes cold denaturation at ambient temperatures were investigated by time-resolved infrared spectroscopy coupled with the laser-induced temperature jump (T-jump) initiation method. We found that the relaxation kinetics of this β-hairpin following a T-jump, obtained by probing the amide I' band of the peptide backbone, show strange temperature dependence. At temperatures below approximately 35 deg. C where this β-hairpin mainly exhibits cold denaturation, the T-jump induced relaxation rate is ∼5 μs -1 , whereas at temperatures where heat denaturation takes place, the relaxation rate increases to ∼1 μs -1 . These results cannot be readily explained by a two-state folding model that has been used to describe the folding thermodynamics of this β-hairpin. In addition, these results suggest that the folding free energy barrier separating the cold-denatured state from the folded state is different from that separating the heat-denatured state from the folded state, coinciding with the idea that the mechanism leading to cold denaturation is different from that leading to heat denaturation

Confirmation of the reported association of clonal chromosomal mosaicism with an increased risk of incident hematologic cancer.

Directory of Open Access Journals (Sweden)

Ursula M Schick

Full Text Available Chromosomal abnormalities provide clinical utility in the diagnosis and treatment of hematologic malignancies, and may be predictive of malignant transformation in individuals without apparent clinical presentation of a hematologic cancer. In an effort to confirm previous reports of an association between clonal mosaicism and incident hematologic cancer, we applied the anomDetectBAF algorithm to call chromosomal anomalies in genotype data from previously conducted Genome Wide Association Studies (GWAS. The genotypes were initially collected from DNA derived from peripheral blood of 12,176 participants in the Group Health electronic Medical Records and Genomics study (eMERGE and the Women's Health Initiative (WHI. We detected clonal mosaicism in 169 individuals (1.4% and large clonal mosaic events (>2 mb in 117 (1.0% individuals. Though only 9.5% of clonal mosaic carriers had an incident diagnosis of hematologic cancer (multiple myeloma, myelodysplastic syndrome, lymphoma, or leukemia, the carriers had a 5.5-fold increased risk (95% CI: 3.3-9.3; p-value = 7.5×10(-11 of developing these cancers subsequently. Carriers of large mosaic anomalies showed particularly pronounced risk of subsequent leukemia (HR = 19.2, 95% CI: 8.9-41.6; p-value = 7.3×10(-14. Thus we independently confirm the association between detectable clonal mosaicism and hematologic cancer found previously in two recent publications.

Smoking increases the risk of early meniscus repair failure.

Science.gov (United States)

Blackwell, Ryan; Schmitt, Laura C; Flanigan, David C; Magnussen, Robert A

2016-05-01

The goal of this study is to determine whether patients who smoke cigarettes at the time of surgery are at significantly increased risk of early meniscus repair failure relative to non-smokers. Retrospective chart review identified 64 current smokers within a series of 444 consecutive patients who underwent meniscus repair during a 7 years period. Fifty-two of these 64 smokers were available for follow-up and were matched by age, sex, and ACL status with non-smokers from the same cohort. Records of these 104 patients with a total of 120 meniscus repairs were reviewed to identify meniscus repair failure (defined as repeat surgery on the index meniscus) during the median 13-month (range: 3-79 months) follow-up period. The smoking and non-smoking groups were similar in age, sex, ACL status, BMI, meniscus repair technique, and meniscus involved. Meniscus repair failure occurred in 19 of the 112 menisci in 104 patients, for an overall failure risk of 17 %. Of the 19 failures, 14 occurred in 79 repaired medial menisci (18 % failure risk) and 5 occurred in 33 repaired lateral menisci (15 % failure risk). Meniscus repair failure occurred in significantly more smokers (15 failures in 56 menisci in 52 patients -27 % failure risk) than non-smokers (4 failures in 56 menisci in 52 patients -7 % failure risk) (p = 0.0076). Smoking is associated with significantly increased risk of early meniscus repair failure as defined by the incidence of repeat surgery on the index meniscus. III.

COX-1 (PTGS1) and COX-2 (PTGS2) polymorphisms, NSAID interactions, and risk of colon and rectal cancer in two independent populations

Science.gov (United States)

Makar, Karen W; Poole, Elizabeth M; Resler, Alexa J; Seufert, Brenna; Curtin, Karen; Kleinstein, Sarah E; Duggan, David; Kulmacz, Richard J; Hsu, Li; Whitton, John; Carlson, Christopher S; Rimorin, Christine F; Caan, Bette J; Baron, John A; Potter, John D; Slattery, Martha L; Ulrich, Cornelia M

2014-01-01

Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) target the prostaglandin H synthase enzymes, cyclooxygenase (COX)-1 and -2, and reduce colorectal cancer risk. Genetic variation in the genes encoding these enzymes may be associated with changes in colon and rectal cancer risk and in NSAID efficacy. Methods We genotyped candidate polymorphisms and tagSNPs in PTGS1 (COX-1) and PTGS2 (COX-2) in a population-based case-control study (Diet, Activity and Lifestyle Study, DALS) of colon cancer (n=1470 cases/1837 controls) and rectal cancer (n=583/775), and independently among cases and controls from the Colon Cancer Family Registry (CCFR; colon n= 959/1535, rectal n= 505/839). Results In PTGS2, a functional polymorphism (−765G>C; rs20417) was associated with a 2-fold increased rectal cancer risk (p=0.05) in the DALS study. This association replicated with a significant nearly 5-fold increased risk of rectal cancer in the CCFR study (ORCC vs GG=4.88; 95%CI=1.54–15.45; ORGC vs GG=1.36; 95%CI: 0.95–1.94). Genotype-NSAID interactions were observed in the DALS study for PTGS1 and rectal cancer risk, and for PTGS2 and colon cancer risk, but were no longer significant after correcting for multiple comparisons and did not replicate in the CCFR. No significant associations between PTGS1 polymorphisms and colon or rectal cancer risk were observed. Conclusions These findings suggest that polymorphisms in PTGS2 may be associated with rectal cancer risk and impact the protective effects of NSAIDs. PMID:24022467

MiR-27a rs895819 is involved in increased atrophic gastritis risk, improved gastric cancer prognosis and negative interaction with Helicobacter pylori

Science.gov (United States)

Xu, Qian; Chen, Tie-jun; He, Cai-yun; Sun, Li-ping; Liu, Jing-wei; Yuan, Yuan

2017-01-01

MiR-27a rs895819 is a loop-stem structure single nucleotide polymorphism affecting mature miR-27a function. In this study, we performed a comprehensive analysis about the association of rs895819 with gastric cancer risk and prognosis, atrophic gastritis risk, as well as the interactions with environmental factors. A total of 939 gastric cancer patients, 1,067 atrophic gastritis patients and 1,166 healthy controls were screened by direct sequencing and MALDI-TOF-MS. The association of rs895819 with clinical pathological parameters and prognostic survival in 357 gastric cancer patients was also been analyzed. The rs895819 variant genotype increased the risk for atrophic gastritis (1.58-fold) and gastric cancer (1.24-fold). While in stratified analysis, the risk effect was demonstrated more significantly in the female, age >60y, Helicobacter pylori (H. pylori) negative and non-drinker subgroups. Rs895819 and H. pylori showed an interaction effect for atrophic gastritis risk. In the survival analysis, the rs895819 AG heterozygosis was associated with better survival than the AA wild-type in the TNM stage I–II subgroup. In vitro study by overexpressing miR-27a, cells carrying polymorphic-type G allele expressed lower miR-27a than wild-type A allele. In conclusion, miR-27a rs895819 is implicated as a biomarker for gastric cancer and atrophic gastritis risk, and interacts with H. pylori in gastric carcinogenesis. PMID:28150722

Risk factors for visceral Leishmaniasis among residents and migrants in Kafta-Humera, Ethiopia.

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Daniel Argaw

2013-11-01

Full Text Available BACKGROUND: Visceral leishmaniasis is a lethal parasitic disease transmitted by phlebotomine sand flies. The largest focus of VL in Ethiopia is located in the lowland region bordering Sudan, where the epidemiology is complicated by the presence of thousands of seasonal agricultural workers who live under precarious conditions. METHODOLOGY/PRINCIPAL FINDINGS: We conducted two parallel case-control studies to identify factors associated with VL risk in residents and migrants. The studies were conducted from 2009 to 2011 and included 151 resident cases and 157 migrant cases, with 2 matched controls per case. In multivariable conditional regression models, sleeping under an acacia tree at night (odds ratios (OR 5.2 [95% confidence interval 1.7-16.4] for residents and 4.7 [1.9-12.0] for migrants, indicators of poverty and lower educational status were associated with increased risk in both populations. Strong protective effects were observed for bed net use (OR 0.24 [0.12-0.48] for net use in the rainy season among residents, OR 0.20 [0.10-0.42] for any net use among migrants. For residents, living in a house with thatch walls conferred 5-fold and sleeping on the ground 3-fold increased risk. Among migrants, the risk associated with HIV status was borderline significant and sleeping near dogs was associated with 7-fold increased risk. CONCLUSIONS/SIGNIFICANCE: Preventive strategies should focus on ways to ensure net usage, especially among migrant workers without fixed shelters. More research is needed to understand migration patterns of seasonal labourers and vector bionomics.

Low physical activity work-related and other risk factors increased the risk of poor physical fitness in cement workers

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Ditha Diana

2009-09-01

Full Text Available Aim Low physical activity causes poor physical fitness, which leads to low productivity. The objective of this study was to determine the effects of low work-related physical activity and other risk factors on physical fitness.Methods This study was done in February 2008. Subjects were workers from 15 departments in PT Semen Padang, West Sumatera (Indonesia. Data on physical activities were collected using the questionnaire from the Student Field Work I Guidebook and Hypertension – Geriatric Integrated Program of the Faculty of Medicine, Universitas Indonesia2003. Physical fitness was measured using the Harvard Step Test.Results A number of 937 male workers aged 18 – 56 years participated in this study. Poor physical fitness was found in 15.9% of the subjects. Low work-related physical activity, smoking, lack of exercise, hypertension, diabetes mellitus, and asthma were dominant risk factors related to poor physical fi tness. Subjects with low compared to high work-related activity had a ten-fold risk of poor physical fitness [adjusted odds ratio (ORa = 10.71; 95% confidence interval (CI = 4.71–24.33]. In term of physical exercise, subjects who had no compared to those who had physical exercise had a six-fold risk of poor physical fitness (ORa = 6.30; 95%CI = 3.69-10.75.Conclusion Low work-related physical activities, smoking, lack of exercise, hypertension, diabetes mellitus, and sthma were correlated to poor physical fi tness. It is, among others, therefore necessary to implement exercises for workers with poor physical fitness. (Med J Indones. 2009;18:201-5Key words: exercise test, occupational healths, physical fitness

The MMP-9 -1562 C/T polymorphism in the presence of metabolic syndrome increases the risk of clinical events in patients with coronary artery disease.

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Trine B Opstad

Full Text Available Elevated levels of matrix metalloproteinase (MMP-9 have been associated with the metabolic syndrome (MetS and cardiovascular events. The MMP-9 -1562 C/T polymorphism has furthermore been shown as a risk factor for coronary artery disease (CAD. The non-favourable cardiometabolic state in MetS may increase the risk. We aimed to investigate the influence of MMP-9 -1562 C/T polymorphism in subjects with CAD and MetS.Patients (n = 1000 with verified CAD stratified in Mets +/- (n = 244/756, were analyzed for the MMP-9 -1562 C/T polymorphism and related to clinical events after 2 years follow-up. Serum levels of total MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP-1 were analyzed in all, whereas MMP-9 activity, extracellular matrix metalloproteinase inducer (EMMPRIN, and expression of the two genes were analyzed in a subset of 240 randomly selected patients.Totally, 106 clinical endpoints were recorded. In MetS; the T-allele associated with 5.5 fold increase in event rate (p<0.0001, increased with number of MetS components, a 117% increase in total MMP-9 levels (TT homozygous, p = 0.05, significantly higher total- and endogenous active MMP-9 and TIMP-1 levels (p<0.01 all, and EMMPRIN was inversely correlated with pro- and endogenous active MMP-9 (p<0.05, both. In non-MetS; the T-allele was not associated with new events, nor higher MMP-9 levels. EMMPRIN was significantly correlated with total MMP-9 and TIMP-1 (p<0.01, both and the two genes were inter-correlated (p<0.001.In CAD patients with MetS, the MMP-9 T-allele increased the risk of clinical events, probably mediated through elevated MMP-9 levels and altered MMP-9 regulation.

Force generation by titin folding.

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Mártonfalvi, Zsolt; Bianco, Pasquale; Naftz, Katalin; Ferenczy, György G; Kellermayer, Miklós

2017-07-01

Titin is a giant protein that provides elasticity to muscle. As the sarcomere is stretched, titin extends hierarchically according to the mechanics of its segments. Whether titin's globular domains unfold during this process and how such unfolded domains might contribute to muscle contractility are strongly debated. To explore the force-dependent folding mechanisms, here we manipulated skeletal-muscle titin molecules with high-resolution optical tweezers. In force-clamp mode, after quenching the force (force trace contained rapid fluctuations and a gradual increase of average force, indicating that titin can develop force via dynamic transitions between its structural states en route to the native conformation. In 4 M urea, which destabilizes H-bonds hence the consolidated native domain structure, the net force increase disappeared but the fluctuations persisted. Thus, whereas net force generation is caused by the ensemble folding of the elastically-coupled domains, force fluctuations arise due to a dynamic equilibrium between unfolded and molten-globule states. Monte-Carlo simulations incorporating a compact molten-globule intermediate in the folding landscape recovered all features of our nanomechanics results. The ensemble molten-globule dynamics delivers significant added contractility that may assist sarcomere mechanics, and it may reduce the dissipative energy loss associated with titin unfolding/refolding during muscle contraction/relaxation cycles. © 2017 The Protein Society.

Laryngeal ultrasound and pediatric vocal fold nodules.

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Ongkasuwan, Julina; Devore, Danielle; Hollas, Sarah; Jones, Jeremy; Tran, Brandon

2017-03-01

The term vocal fold nodules refers to bilateral thickening of the membranous folds with minimal impairment of the vibratory properties of the mucosa. Nodules are thought to be related to repetitive mechanical stress, associated with voice use patterns. Diagnosis is typically made in the office via either rigid or flexible laryngeal stroboscopy. Depending on the individual child, obtaining an optimal view of the larynx can be difficult if not impossible. Recent advances in high-frequency ultrasonography allows for transcervical examination of laryngeal structures. The goal of this project was to determine if laryngeal ultrasound (LUS) can be used to identify vocal fold nodules in dysphonic children. Prospective case-control study in which the patient acted as his or her own control. Forty-six pediatric patients were recruited for participation in this study; the mean age was 4.8 years. Twenty-three did not have any vocal fold lesions and 23 had a diagnosis of vocal fold nodules on laryngeal stroboscopy. Recorded LUSs were reviewed by two pediatric radiologists who were blinded to the nodule status. There was substantial inter-rater agreement (κ = 0.70, 95% confidence interval [CI]: 0.50-0.89) between the two radiologists regarding the presence of nodules. There was also substantial agreement (κ = 0.87, 95% CI: 0.72-1) between LUS and laryngeal stroboscopy. Sensitivity of LUS was 100% (95% CI: 85%-100%) and specificity was 87% (95% CI: 66%-97%). LUS can be used to identify vocal fold nodules in children with substantial agreement with laryngeal stroboscopy. 3b Laryngoscope, 127:676-678, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Ectasias and varices of the vocal fold: clearing the striking zone.

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Hochman, I; Sataloff, R T; Hillman, R E; Zeitels, S M

1999-01-01

Vascular malformations such as ectasias and varices (Es and Vs) are frequently encountered in patients who present with recurrent vocal fold hemorrhage and/or other traumatic vocal fold lesions. This study examined Es and Vs with regard to their anatomic presentation, phonomicrosurgical management, and treatment outcome. Forty-two patients (39 of them singers) were treated for a total of 87 Es and Vs: 67 of 87 (77%) were on the superior surface of the vocal fold and 20 of 87 (23%) were on the medial surface of the vocal fold. Eighty-three percent were located in the middle musculomembranous region (the striking zone), where the greatest aerodynamically induced shearing stresses occur during phonation. Treatment was performed with carbon dioxide laser cauterization (13 patients), or a new technique utilizing cold instrument excision by means of epithelial cordotomies (23 patients), while a combined approach was employed in 6 patients. Comparisons of preoperative and postoperative stroboscopy revealed improvement or no significant change in all patients in whom the cold instrument technique was used, and increased epithelial stiffness was noted in 4 of 19 patients in whom the carbon dioxide laser was used. Clearing the striking zone appears to have halted further hemorrhages by removing the the fragile Es and Vs from this injury-prone region of the vocal fold. Interpretations of stroboscopic examinations were directed at providing new insights into the biomechanical forces of vocal fold vibration that probably contribute to the genesis of Es and Vs in the vocal folds.

Women referred for occupational risk assessment in pregnancy have no increased risk of adverse obstetric outcomes

DEFF Research Database (Denmark)

Bidstrup, Signe Brøker; Kaerlev, Linda; Thulstrup, Ane Marie

2015-01-01

pregnant women referred to two Danish clinics of occupational medicine (Copenhagen and Aarhus) from 1984 to 2010 were compared with the referred women's 1,077 non-referred pregnancy outcomes and with the pregnancy outcomes of 345,467 gainfully employed women from the same geographical areas and time period.......72-1.17). CONCLUSION: The women who are referred for occupational risk assessment at two large occupational university departments are not at an increased risk of preterm birth or of delivering low birth weight children. This may reflect that reproductive hazards in Danish workplaces are limited and....../or that the occupational risk assessment and counselling of pregnant women are preventing these selected adverse pregnancy outcomes. FUNDING: The Research Unit at Department of Occupational and Environmental Medicine at Bispebjerg Hospital supported the study financially. TRIAL REGISTRATION: not relevant. The study...

Possible association between Helicobacter pylori infection and vocal fold leukoplakia.

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Chen, Min; Chen, Jian; Yang, Yue; Cheng, Lei; Wu, Hai-Tao

2018-03-06

Several studies have indicated the larynx as possible Helicobacter pylori (H. pylori) reservoirs. This study explored the association between H. pylori and vocal fold leukoplakia. The case-control study involved 51 patients with vocal fold leukoplakia and 35 control patients with vocal polyps. Helicobacter pylori was detected in tissues by the rapid urease test, nested polymerase chain reaction (PCR), and single-step PCR. The H. pylori-specific immunoglobulin antibodies were detected in plasma by enzyme-linked immunosorbent assay (ELISA). Helicobacter pylori-positive rate of vocal fold leukoplakia and vocal polyps was 23.5% versus 11.4% (P = .157), 37.2% versus 14.3% (P = .020), 27.5% versus 8.6% (P = .031), and 70.6% versus 68.6% (P = .841) detected by rapid urease test, nested PCR, single-step PCR, and ELISA, respectively. Regression analysis indicated that H. pylori infection (P = .044) was the independent risk factor for vocal fold leukoplakia. Helicobacter pylori infection exists in the larynx and may be associated with vocal fold leukoplakia. © 2018 Wiley Periodicals, Inc.

Increased Risk of Clinically Significant Gallstones following an Appendectomy: A Five-Year Follow-Up Study.

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Shiu-Dong Chung

Full Text Available Although the vermiform appendix is commonly considered a vestigial organ, adverse health consequences after an appendectomy have garnered increasing attention. In this study, we investigated the risks of gallstone occurrence during a 5-year follow-up period after an appendectomy, using a population-based dataset. We used data from the Taiwan Longitudinal Health Insurance Database 2005. The exposed cohort included 4916 patients who underwent an appendectomy. The unexposed cohort was retrieved by randomly selecting 4916 patients matched with the exposed cohort in terms of sex, age, and year. We individually tracked each patient for a 5-year period to identify those who received a diagnosis of gallstones during the follow-up period. Cox proportional hazard regressions were performed for the analysis. During the 5-year follow-up period, the incidence rate per 1000 person-years was 4.71 for patients who had undergone an appendectomy, compared to a rate of 2.59 for patients in the unexposed cohort (p<0.001. Patients who had undergone an appendectomy were independently associated with a 1.79 (95% CI = 1.29~2.48-fold increased risk of being diagnosed with gallstones during the 5-year follow-up period. We found that among female patients, the adjusted hazard ratio of gallstones was 2.25 (95% CI = 1.41~3.59 for patients who underwent an appendectomy compared to unexposed patients. However, for male patients, we failed to observe an increased hazard for gallstones among patients who underwent an appendectomy compared to unexposed patients. We found an increased risk of a subsequent gallstone diagnosis within 5 years after an appendectomy.

A New Polymorphism Biomarker rs629367 Associated with Increased Risk and Poor Survival of Gastric Cancer in Chinese by Up-Regulated miRNA-let-7a Expression

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Xu, Qian; Dong, Qiguan; He, Caiyun; Liu, Wenjing; Sun, Liping; Liu, Jingwei; Xing, Chengzhong; Li, Xiaohang; Wang, Bengang; Yuan, Yuan

2014-01-01

Background Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP) associated with the risk and prognosis of gastric cancer (GC) as predicting biomarkers, and furthermore, its possible mechanisms. Methods A two-stage case-control study was designed to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588) in 107 GC patients, 107 atrophic gastritis (AG), and matched 124 controls using PCR-RFLP. Two promising SNPs were validated in another independent 1949 samples (including 579 gastric cancer patients, 649 atrophic gastritis and 721 controls) using Sequenom MassARRAY platform and sequencing. Results We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of gastric cancer and atrophic gastritis by 1.83-fold and 1.86-fold, respectively. For gastric cancer prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P = 0.004). We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the atrophic gastritis group (P = 0.043). Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (Pcancer as well as atrophic gastritis and was also associated with poor survival of gastric cancer, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of gastric cancer. PMID:24760009

Intermediates and the folding of proteins L and G

Energy Technology Data Exchange (ETDEWEB)

Brown, Scott; Head-Gordon, Teresa

2003-07-01

We use a minimalist protein model, in combination with a sequence design strategy, to determine differences in primary structure for proteins L and G that are responsible for the two proteins folding through distinctly different folding mechanisms. We find that the folding of proteins L and G are consistent with a nucleation-condensation mechanism, each of which is described as helix-assisted {beta}-1 and {beta}-2 hairpin formation, respectively. We determine that the model for protein G exhibits an early intermediate that precedes the rate-limiting barrier of folding and which draws together misaligned secondary structure elements that are stabilized by hydrophobic core contacts involving the third {beta}-strand, and presages the later transition state in which the correct strand alignment of these same secondary structure elements is restored. Finally the validity of the targeted intermediate ensemble for protein G was analyzed by fitting the kinetic data to a two-step first order reversible reaction, proving that protein G folding involves an on-pathway early intermediate, and should be populated and therefore observable by experiment.

Group theoretical classification of broken symmetry states of the two-fold degenerate Hubbard model on a triangular lattice

International Nuclear Information System (INIS)

Masago, Akira; Suzuki, Naoshi

2001-01-01

By a group theoretical procedure we derive the possible spontaneously broken-symmetry states for the two-fold degenerate Hubbard model on a two-dimensional triangular lattice. For ordering wave vectors corresponding to the points Γ and K in the first BZ we find 22 states which include 16 collinear and six non-collinear states. The collinear states include the usual SDW and CDW states which appear also in the single-band Hubbard model. The non-collinear states include exotic ordering states of orbitals and spins as well as the triangular arrangement of spins

Transiently disordered tails accelerate folding of globular proteins.

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Mallik, Saurav; Ray, Tanaya; Kundu, Sudip

2017-07-01

Numerous biological proteins exhibit intrinsic disorder at their termini, which are associated with multifarious functional roles. Here, we show the surprising result that an increased percentage of terminal short transiently disordered regions with enhanced flexibility (TstDREF) is associated with accelerated folding rates of globular proteins. Evolutionary conservation of predicted disorder at TstDREFs and drastic alteration of folding rates upon point-mutations suggest critical regulatory role(s) of TstDREFs in shaping the folding kinetics. TstDREFs are associated with long-range intramolecular interactions and the percentage of native secondary structural elements physically contacted by TstDREFs exhibit another surprising positive correlation with folding kinetics. These results allow us to infer probable molecular mechanisms behind the TstDREF-mediated regulation of folding kinetics that challenge protein biochemists to assess by direct experimental testing. © 2017 Federation of European Biochemical Societies.

Design and numerical analysis of an SMA mesh-based self-folding sheet

International Nuclear Information System (INIS)

Peraza-Hernandez, Edwin A; Hartl, Darren J; Malak Jr, Richard J

2013-01-01

Origami engineering, which is the practice of creating useful three-dimensional structures through folding and fold-like operations applied to initially two-dimensional entities, has the potential to impact several areas of design and manufacturing. In some instances, however, it may be impractical to apply external manipulations to produce the desired folds (e.g., as in remote applications such as space systems). In such cases, self-folding capabilities are valuable. A self-folding material or material system is one that can perform folding operations without manipulations from external forces. This work considers a concept for a self-folding material system. The system extends the ‘programmable matter’ concept and consists of an active, self-morphing sheet composed of two meshes of thermally actuated shape memory alloy (SMA) wire separated by a compliant passive layer. The geometric and power input parameters of the self-folding sheet are optimized to achieve the tightest local fold possible subject to stress and temperature constraints. The sheet folding performance considering folds at different angles relative to the orientation of the wire mesh is also analyzed. The optimization results show that a relatively low elastomer thickness is preferable to generate the tightest fold possible. The results also show that the self-folding sheet does not require large power inputs to achieve an optimal folding performance. It was shown that the self-folding sheet is capable of creating similar quality folds at different orientations. (paper)

MARATHON DESPITE UNILATERAL VOCAL FOLD PARALYSIS

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Matthias Echternach

2008-06-01

Full Text Available The principal symptoms of unilateral vocal fold paralysis are hoarseness and difficulty in swallowing. Dyspnea is comparatively rare (Laccourreye et al., 2003. The extent to which unilateral vocal fold paralysis may lead to respiratory problems at all - in contrast to bilateral vocal fold paralysis- has not yet well been determined. On the one hand, inspiration is impaired with unilateral vocal fold paralysis; on the other hand, neither the position of the vocal fold paralysis nor the degree of breathiness correlates with respiratory parameters (Cantarella et al., 2003; 2005. The question of what respiratory stress a patient with a vocal fold paresis can endure has not yet been dealt with.A 43 year-old female patient was suffering from recurrent unspecific respiratory complaints for four months after physical activity. During training for a marathon, she experienced no difficulty in breathing. These unspecific respiratory complaints occurred only after athletic activity and persisted for hours. The patient observed neither an increased coughing nor a stridor. Her voice remained unaltered during the attacks, nor were there any signs of a symptomatic gastroesophageal reflux or infectious disease. A cardio-pulmonary and a radiological examination by means of an X-ray of the thorax also revealed no pathological phenomena. As antiallergic and antiobstructive therapy remained unsuccessful, a laryngological examination was performed in order to exclude a vocal cord dysfunction.Surprisingly enough, the laryngostroboscopy showed, as an initial description, a vocal fold paralysis of the left vocal fold in median position (Figure 1. The anamnestic background for the cause was unclear. The only clue was a thoracotomy on the left side due to a pleuritis in childhood. A subsequent laryngoscopic examination had never been performed. Good mucosa waves and amplitudes were shown bilateral with complete glottal closure. Neither in the acoustic analysis, nor in the

Caesarean section greatly increases risk of scar endometriosis.

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Nominato, Nilo Sérgio; Prates, Luis Felipe Victor Spyer; Lauar, Isabela; Morais, Jaqueline; Maia, Laura; Geber, Selmo

2010-09-01

To estimate the incidence of scar endometriosis after different surgical procedures. A retrospective study of 72 patients diagnosed with scar endometriosis between 1978 and 2003 was performed. Patient age, site of endometriosis, previous operations, time-gap between last surgery and onset of symptoms, nodule characteristics, and recurrence were evaluated. Age ranged from 16 to 48 years. Location varied according to the previous surgery: 46 caesarean section, one hysterectomy, one in abdominal surgery, 19 episiotomy, one was a relapse and two pelvic floor procedures, two women with no previous surgery. The incidence of scar endometriosis after caesarean section was significantly higher than after episiotomy (0.2 and 0.06%, respectively: p<0.00001) with a relative risk of 3.3. Pain was the most frequent symptom. The mean time between surgery and onset of symptoms was 3.7 years. Our findings confirm that scar endometriosis is a rare condition and indicate, probably for the first time, that caesarean section greatly increases the risk of developing scar endometriosis. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Increased risk of flooding on the coast of Alicante (Region of Valencia, Spain

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J. Olcina Cantos

2010-11-01

Full Text Available In the past two decades, episodes of flooding on the coast of Alicante (Spain have led to substantial losses in human life in economic terms. With increased exposure to these phenomena comes also increased vulnerability. Given the various effects of flooding in areas of similar exposure, differences in vulnerability across regions at risk need to be analysed also in terms of the socioeconomic factors of the groups of society that may be affected, and of their perception of risk. This paper studies the increased risk of flooding in three locations on the Alicante coast as a result of urban occupation of areas subject to this hazard. The consequences of the most recent episodes in this area are analysed and a risk assessment, using survey-based research in the affected areas, is performed.

Clinical Significance of Contralateral Reactive Lesion in Vocal Fold Polyp and Cyst.

Science.gov (United States)

Cho, Jung-Hae; Choi, Yong-Sug; Joo, Young-Hoon; Park, Young-Hak; Sun, Dong-Il

2018-01-01

We investigated the clinical significance of contralateral reactive lesions in patients undergoing laryngeal microsurgery for benign vocal fold lesions such as vocal polyps and cysts. This was a retrospective, single institution cohort study. Patient medical records were reviewed for demographic characteristics; acoustic, aerodynamic, and perceptual analyses; and Voice Handicap Index score before and after laryngeal microsurgery. Definitive diagnoses were made via intraoperative microlaryngoscopic evaluations. Clinical parameters were assessed to identify risk factors for contralateral reactive lesions. We evaluated surgical outcome using voice analysis. We enrolled 268 patients (109 men and 159 women) with benign vocal fold lesions. A total of 195 (72.8%) had a contralateral reactive vocal fold lesion. A multivariable analysis revealed that being a never smoker and having a hoarseness duration ≥6 months, vocal polyps, and small primary lesions were independent risk factors for contralateral reactive lesions (P vocal fold lesions are frequently detected in patients with vocal polyp and cyst. The reactive lesions had an adverse effect on voice quality. Simultaneous excision of primary and contralateral reactive lesions may be an alternative treatment for better voice outcome. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Measurement of microparticle tissue factor activity in clinical samples: A summary of two tissue factor-dependent FXa generation assays.

Science.gov (United States)

Hisada, Yohei; Alexander, Wyeth; Kasthuri, Raj; Voorhees, Peter; Mobarrez, Fariborz; Taylor, Angela; McNamara, Coleen; Wallen, Hakan; Witkowski, Marco; Key, Nigel S; Rauch, Ursula; Mackman, Nigel

2016-03-01

Thrombosis is a leading cause of morbidity and mortality. Detection of a prothrombotic state using biomarkers would be of great benefit to identify patients at risk of thrombosis that would benefit from thromboprophylaxis. Tissue factor (TF) is a highly procoagulant protein that under normal conditions is not present in the blood. However, increased levels of TF in the blood in the form of microparticles (MPs) (also called extracellular vesicles) are observed under various pathological conditions. In this review, we will discuss studies that have measured MP-TF activity in a variety of diseases using two similar FXa generation assay. One of the most robust signals for MP-TF activity (16-26 fold higher than healthy controls) is observed in pancreatic cancer patients with venous thromboembolism. In this case, the TF+ MPs appear to be derived from the cancer cells. Surprisingly, cirrhosis and acute liver injury are associated with 17-fold and 38-fold increases in MP-TF activity, respectively. Based on mouse models, we speculate that the TF+ MPs are derived from hepatocytes. More modest increases are observed in patients with urinary tract infections (6-fold) and in a human endotoxemia model (9-fold) where monocytes are the likely source of the TF+ MPs. Finally, there is no increase in MP-TF activity in the majority of cardiovascular disease patients. These studies indicate that MP-TF activity may be a useful biomarker to identify patients with particular diseases that have an increased risk of thrombosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interrater Reliability in Analysis of Laryngoscopic Features for Unilateral Vocal Fold Paresis.

Science.gov (United States)

Isseroff, Tova F; Parasher, Arjun K; Richards, Amanda; Sivak, Mark; Woo, Peak

2016-11-01

The diagnosis of paresis in patients with vocal fold motion impairment remains a challenge. In particular, laryngoscopy examination may result in significant disagreement in diagnosis among providers. We hypothesize that systematically evaluating for a standard set of clinical parameters will increase the diagnostic concordance among providers. Prospective case series conducted at a Tertiary referral Laryngology office. Two laryngologists (rater 1) and two trainees (rater 2) rated laryngoscopy findings in 19 patients suspected of paresis. The diagnosis was confirmed with laryngeal electromyogram. A standard set of 27 ratings was used for each examination that included movement, laryngeal configuration, and stroboscopy signs. A kappa coefficient was calculated for agreement in laryngoscopy findings and effectiveness in predicting the laterality of paresis. A substantial agreement (kappa coefficient > 0.61) existed between the raters for vocal fold length, vocal fold thickness, bowing, and reduction in movement. A moderate agreement (kappa coefficient > 0.41) existed between raters for piriform opening and reduced kinesis. The senior author was accurately able to diagnose the side of paresis in 89.5% of cases for a kappa coefficient of 0.78, whereas the trainees correctly predicted the side of paresis in 63.1% for a kappa coefficient of 0.35. The raters agreed on the diagnosis in 73.7% of cases for a kappa coefficient of 0.50. Using a standard set of laryngoscopy findings may improve the provider's ability to identify the laterality of vocal fold paresis and increase interrater reliability compared with other series. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

An expanded view of the protein folding landscape of PDZ domains

DEFF Research Database (Denmark)

Hultqvist, Greta; Pedersen, Søren W; Chi, Celestine N.

2012-01-01

state. In light of these results, we have re-analyzed previous folding data on PDZ domains and present a unified folding mechanism with three distinct transition states separated by two high-energy intermediates. Our data show that sequence composition tunes the relative stabilities of folding...

Three-dimensional biomechanical properties of human vocal folds: Parameter optimization of a numerical model to match in vitro dynamics

Science.gov (United States)

Yang, Anxiong; Berry, David A.; Kaltenbacher, Manfred; Döllinger, Michael

2012-01-01

The human voice signal originates from the vibrations of the two vocal folds within the larynx. The interactions of several intrinsic laryngeal muscles adduct and shape the vocal folds to facilitate vibration in response to airflow. Three-dimensional vocal fold dynamics are extracted from in vitro hemilarynx experiments and fitted by a numerical three-dimensional-multi-mass-model (3DM) using an optimization procedure. In this work, the 3DM dynamics are optimized over 24 experimental data sets to estimate biomechanical vocal fold properties during phonation. Accuracy of the optimization is verified by low normalized error (0.13 ± 0.02), high correlation (83% ± 2%), and reproducible subglottal pressure values. The optimized, 3DM parameters yielded biomechanical variations in tissue properties along the vocal fold surface, including variations in both the local mass and stiffness of vocal folds. That is, both mass and stiffness increased along the superior-to-inferior direction. These variations were statistically analyzed under different experimental conditions (e.g., an increase in tension as a function of vocal fold elongation and an increase in stiffness and a decrease in mass as a function of glottal airflow). The study showed that physiologically relevant vocal fold tissue properties, which cannot be directly measured during in vivo human phonation, can be captured using this 3D-modeling technique. PMID:22352511

A new feature constituting approach to detection of vocal fold pathology

Science.gov (United States)

Hariharan, M.; Polat, Kemal; Yaacob, Sazali

2014-08-01

In the last two decades, non-invasive methods through acoustic analysis of voice signal have been proved to be excellent and reliable tool to diagnose vocal fold pathologies. This paper proposes a new feature vector based on the wavelet packet transform and singular value decomposition for the detection of vocal fold pathology. k-means clustering based feature weighting is proposed to increase the distinguishing performance of the proposed features. In this work, two databases Massachusetts Eye and Ear Infirmary (MEEI) voice disorders database and MAPACI speech pathology database are used. Four different supervised classifiers such as k-nearest neighbour (k-NN), least-square support vector machine, probabilistic neural network and general regression neural network are employed for testing the proposed features. The experimental results uncover that the proposed features give very promising classification accuracy of 100% for both MEEI database and MAPACI speech pathology database.

Powered two-wheeler drivers' risk of hitting a pedestrian in towns.

Science.gov (United States)

Clabaux, Nicolas; Fournier, Jean-Yves; Michel, Jean-Emmanuel

2014-12-01

The risk of collision between pedestrians and powered two-wheelers is poorly understood today. The objective of this research is to determine the risk for powered two-wheeler drivers of hitting and injuring a pedestrian per kilometer driven in towns and to compare this risk with that run by four-wheeled vehicle drivers. Using the bodily injury accidents recorded by the police on nine roads in the city of Marseille in 2011 and a campaign of observations of powered two-wheeler traffic, we estimated the risk per kilometer driven by powered two-wheeler drivers of hitting a pedestrian and compared it with the risk run by four-wheeled vehicle drivers. The results show that the risk for powered two-wheeler drivers of hitting and injuring a pedestrian is significantly higher than the risk run by four-wheeled vehicle drivers. On the nine roads studied, it is on average 3.33 times higher (95% CI: 1.63; 6.78). Taking four more years into account made it possible to consolidate these results and to tighten the confidence interval. There does indeed seem to be problems in the interactions between pedestrians and powered two-wheeler users in urban traffic. These interaction problems lead to a higher risk of hitting and injuring a pedestrian for powered two-wheeler drivers than for four-wheeled vehicle drivers. The analysis of the police reports suggests that part of this increased risk comes from filtering maneuvers by powered two-wheelers. Possible countermeasures deal with the urban street layout. Measures consisting in reducing the width and the number of traffic lanes to a strict minimum and installing medians or pedestrian islands could be an effective way for the prevention of urban accidents between pedestrians and powered two-wheelers. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

Increase of Meningitis Risk in Stroke Patients in Taiwan

Directory of Open Access Journals (Sweden)

Chie-Hong Wang

2018-03-01

Full Text Available Background and purposeThe blood–brain barrier (BBB not only provides a physical obstruction but also recruits and activates neutrophils in cases of infection. Hemorrhagic or ischemic stroke reportedly induces the disruption of the BBB. However, few studies have reported a correlation between the incidence of meningitis in patients with a history of stroke. This study tested the hypothesis that patients with a history of stroke may be more vulnerable to meningitis.MethodsStroke and age-matched comparison (n = 29,436 and 87,951, respectively cohorts were recruited from the Taiwan National Health Insurance database (2000–2011. Correlations between the two cohorts were evaluated by Cox proportional hazard regression model, Kaplan–Meier curve, and log-rank tests.ResultsThe incidence of meningitis was higher in the stroke cohort compared to that in the comparison cohort [hazard ratio (HR, 2.89; 95% confidence interval (CI, 2.23–3.74, p < 0.001]. After adjusting for age, sex, and comorbidities, the estimated HR in the stroke cohort was 2.55-fold higher than that in the comparison cohort (CI, 1.94–3.37; p < 0.001. Notably, patients who had experienced hemorrhagic stroke had a higher incidence rate of meningitis than those with a history of ischemic stroke, except for patients older than 75 years (incidence rates in hemorrhagic/ischemic stroke patients, 3.14/1.48 in patients younger than 45 years, 1.52/0.41 in 45- to 64-year group, 1.15/0.90 in 65- to 74-year group, 0.74/0.93 in patients older than 75 years. Moreover, stroke patients who had undergone head surgery had the highest meningitis risk (adjusted HR, 8.66; 95% CI, 5.55–13.5; p < 0.001 followed by stroke patients who had not undergone head surgery (adjusted HR, 2.11; 95% CI, 1.57–2.82; p < 0.001.ConclusionOur results indicated that stroke patients have higher risks of meningitis. Compromised BBB integrity in stroke patients may lead to increased

High birth weight is associated with obesity and increased carotid wall thickness in young adults: the cardiovascular risk in young Finns study.

Science.gov (United States)

Skilton, Michael R; Siitonen, Niina; Würtz, Peter; Viikari, Jorma S A; Juonala, Markus; Seppälä, Ilkka; Laitinen, Tomi; Lehtimäki, Terho; Taittonen, Leena; Kähönen, Mika; Celermajer, David S; Raitakari, Olli T

2014-05-01

There is some evidence that people born with high birth weight may be at increased risk of cardiovascular disease in adulthood. Details of the underlying mechanisms remain unknown. We sought to determine whether people born large for gestational age have poor arterial health, increased adiposity, and a poor cardiovascular risk factor profile. Carotid intima-media thickness, brachial flow-mediated dilatation, and cardiovascular risk factors were compared between young adults (24-45 years) born at term who were large for gestational age (birth weight >90th percentile; n=171), and a control group with normal birth weight (50-75th percentile; n=525), in the Cardiovascular Risk in Young Finns Study. Those born large for gestational age had higher body mass index throughout childhood, adolescence, and as young adults (26.4 kg/m(2) [SD 4.9], versus normal birth weight 25.1 kg/m(2) [SD 4.6]; P=0.002), and 2-fold greater risk of obesity. Other cardiovascular risk factors and arterial function did not differ; however, carotid intima-media thickness was increased in people born large for gestational age (0.60 mm [SD 0.09], versus normal birth weight 0.57 mm [SD 0.09]; P=0.003), independent of cardiovascular risk factors (P=0.001 after adjustment). Both obesity and high birth weight were independently associated with carotid intima-media thickness in a graded and additive fashion. Young adults born large for gestational age are more likely to be obese, yet have an otherwise healthy cardiovascular risk profile. Nonetheless, they have increased carotid intima-media thickness, a marker of subclinical atherosclerosis, consistent with an increased risk of cardiovascular disease.

Nucleation phenomena in protein folding: the modulating role of protein sequence

International Nuclear Information System (INIS)

Travasso, Rui D M; FaIsca, Patricia F N; Gama, Margarida M Telo da

2007-01-01

For the vast majority of naturally occurring, small, single-domain proteins, folding is often described as a two-state process that lacks detectable intermediates. This observation has often been rationalized on the basis of a nucleation mechanism for protein folding whose basic premise is the idea that, after completion of a specific set of contacts forming the so-called folding nucleus, the native state is achieved promptly. Here we propose a methodology to identify folding nuclei in small lattice polymers and apply it to the study of protein molecules with a chain length of N = 48. To investigate the extent to which protein topology is a robust determinant of the nucleation mechanism, we compare the nucleation scenario of a native-centric model with that of a sequence-specific model sharing the same native fold. To evaluate the impact of the sequence's finer details in the nucleation mechanism, we consider the folding of two non-homologous sequences. We conclude that, in a sequence-specific model, the folding nucleus is, to some extent, formed by the most stable contacts in the protein and that the less stable linkages in the folding nucleus are solely determined by the fold's topology. We have also found that, independently of the protein sequence, the folding nucleus performs the same 'topological' function. This unifying feature of the nucleation mechanism results from the residues forming the folding nucleus being distributed along the protein chain in a similar and well-defined manner that is determined by the fold's topological features

At-Risk Variant in TCF7L2 for Type II Diabetes Increases Risk of Schizophrenia

DEFF Research Database (Denmark)

Hansen, Thomas; Ingason, Andrés; Djurovic, Srdjan

2011-01-01

BACKGROUND: Schizophrenia is associated with increased risk of type II diabetes and metabolic disorders. However, it is unclear whether this comorbidity reflects shared genetic risk factors, at-risk lifestyle, or side effects of antipsychotic medication. METHODS: Eleven known risk variants of type...... (SGENE+) using Mantel-Haenszel test. RESULTS: One type II diabetes at-risk allele located in TCF7L2, rs7903146 [T], was associated with schizophrenia in the discovery sample (p = .0052) and in the replication with an odds ratio of 1.07 (95% confidence interval 1.01-1.14, p = .033). CONCLUSION...... II diabetes were genotyped in patients with schizophrenia in a sample of 410 Danish patients, each matched with two healthy control subjects on sex, birth year, and month. Replication was carried out in a large multinational European sample of 4089 patients with schizophrenia and 17,597 controls...

Symptoms of Knee Instability are Risk Factors for Recurrent Falls

Science.gov (United States)

Nevitt, Michael C; Tolstykh, Irina; Shakoor, Najia; Nguyen, Uyen-Sa D.T.; Segal, Neil A; Lewis, Cora; Felson, David T

2016-01-01

Objectives Whether knee instability contributes to the increased risk of falls and fractures observed in persons with knee osteoarthritis (OA) has not been studied. We examined the association of knee buckling with the risk of falling and fall-related consequences in older adults with, or at high risk for, knee OA. Methods At the 60 month visit of the Multicenter Osteoarthritis Study, men and women ages 55 to 84 were asked about knee buckling in the past 3 months and whether they fell when a knee buckled. Falls and fall-related injuries in the past 12 months and balance confidence were assessed at 60 and 84 months. Multivariate logistic regression was used to assess the association of knee buckling with falls and their consequences. Results 1,842 subjects (59% women, mean [SD] age= 66.9 [7.8] and BMI= 30.3 [5.7]) were included. At 60 months 16.8% reported buckling and at 84 months 14.1% had recurrent (≥2) falls. Bucklers at 60 months had a 1.6 to 2.5-fold greater odds of recurrent falls, fear of falling and poor balance confidence at 84 months. Those who fell when a knee buckled at baseline had a 4.5-fold, 2-fold and 3-fold increased odds two years later of recurrent falls, significant fall injuries and fall injuries that limited activity, respectively, and were 4 times more likely to have poor balance confidence. Conclusion Interventions that reduce knee buckling may help prevent falls, fall-related injuries and adverse psychological consequences of falls in persons with knee OA. PMID:26853236

SDEM modelling of fault-propagation folding

DEFF Research Database (Denmark)

Clausen, O.R.; Egholm, D.L.; Poulsen, Jane Bang

2009-01-01

and variations in Mohr-Coulomb parameters including internal friction. Using SDEM modelling, we have mapped the propagation of the tip-line of the fault, as well as the evolution of the fold geometry across sedimentary layers of contrasting rheological parameters, as a function of the increased offset......Understanding the dynamics and kinematics of fault-propagation-folding is important for evaluating the associated hydrocarbon play, for accomplishing reliable section balancing (structural reconstruction), and for assessing seismic hazards. Accordingly, the deformation style of fault-propagation...... a precise indication of when faults develop and hence also the sequential evolution of secondary faults. Here we focus on the generation of a fault -propagated fold with a reverse sense of motion at the master fault, and varying only the dip of the master fault and the mechanical behaviour of the deformed...

Splenectomy correlates with increased risk of pulmonary tuberculosis: a case-control study in Taiwan.

Science.gov (United States)

Lai, S-W; Wang, I-K; Lin, C-L; Chen, H-J; Liao, K-F

2014-08-01

This study investigated whether there was an association between splenectomy and pulmonary tuberculosis. This was a case-control study using the database of the Taiwan National Health Insurance Programme. We identified 18 960 patients (aged 20 years or older) with newly diagnosed pulmonary tuberculosis as the case group and 73 988 participants without pulmonary tuberculosis as the control group from 1998 to 2011. Both groups were matched for sex, age (per 5 years) and index year of pulmonary tuberculosis diagnosis. The risk of pulmonary tuberculosis associated with splenectomy and other co-morbidities was estimated. After controlling for confounders, multivariable logistic regression analysis showed that the odds of pulmonary tuberculosis were 1.91 in patients with splenectomy (95% CI 1.06-3.44), compared with the participants without splenectomy. Chronic obstructive pulmonary diseases (OR 3.07, 95% CI 2.94-3.21), pneumoconiosis (OR 2.20, 95% CI 1.90-2.56), chronic kidney diseases (OR 1.49, 95% CI 1.33-1.67), diabetes mellitus (OR 1.57, 95% CI 1.50-1.64) and chronic liver diseases (OR 1.31, 95% CI 1.25-1.37) were associated with an increased risk of pulmonary tuberculosis. The sub-analysis demonstrated that the odds of pulmonary tuberculosis were 4.81 (95% CI 2.31-10.0) for patients co-morbid with splenectomy and any of the above diseases. Splenectomy is associated with a 1.9-fold increased risk of pulmonary tuberculosis in Taiwan. There is a synergistic effect between splenectomy and other co-morbidities on the risk of pulmonary tuberculosis. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Does red noise increase or decrease extinction risk? Single extreme events versus series of unfavorable conditions.

Science.gov (United States)

Schwager, Monika; Johst, Karin; Jeltsch, Florian

2006-06-01

Recent theoretical studies have shown contrasting effects of temporal correlation of environmental fluctuations (red noise) on the risk of population extinction. It is still debated whether and under which conditions red noise increases or decreases extinction risk compared with uncorrelated (white) noise. Here, we explain the opposing effects by introducing two features of red noise time series. On the one hand, positive autocorrelation increases the probability of series of poor environmental conditions, implying increasing extinction risk. On the other hand, for a given time period, the probability of at least one extremely bad year ("catastrophe") is reduced compared with white noise, implying decreasing extinction risk. Which of these two features determines extinction risk depends on the strength of environmental fluctuations and the sensitivity of population dynamics to these fluctuations. If extreme (catastrophic) events can occur (strong noise) or sensitivity is high (overcompensatory density dependence), then temporal correlation decreases extinction risk; otherwise, it increases it. Thus, our results provide a simple explanation for the contrasting previous findings and are a crucial step toward a general understanding of the effect of noise color on extinction risk.

Rare disaster information can increase risk-taking

Science.gov (United States)

Newell, Ben R.; Rakow, Tim; Yechiam, Eldad; Sambur, Michael

2016-02-01

The recent increase in the frequency and impact of natural disasters highlights the need to provide the public with accurate information concerning disaster prevalence. Most approaches to this problem assume that providing summaries of the nature and scale of disasters will lead people to reduce their exposure to risk. Here we present experimental evidence that such ex post `news reports’ of disaster occurrences can increase the tolerance for risk-taking (which implies that rare events are underweighted). This result is robust across several hundred rounds of choices in a simulated microworld, persists even when the long-run expected value of risky choices is substantially lower than safe choices, and is contingent on providing risk information about disasters that have been (personally) experienced and those that have been avoided (`forgone’ outcomes). The results suggest that augmenting personal experience with information summaries of the number of adverse events (for example, storms, floods) in different regions may, paradoxically, increase the appeal of a disaster-prone region. This finding implies a need to communicate long-term trends in severe climatic events, thereby reinforcing the accumulation of events, and the increase in their associated risks, across time.

Multiple Sclerosis Increases Fracture Risk: A Meta-Analysis

Directory of Open Access Journals (Sweden)

Guixian Dong

2015-01-01

Full Text Available Purpose. The association between multiple sclerosis (MS and fracture risk has been reported, but results of previous studies remain controversial and ambiguous. To assess the association between MS and fracture risk, a meta-analysis was performed. Method. Based on comprehensive searches of the PubMed, Embase, and Web of Science, we identified outcome data from all articles estimating the association between MS and fracture risk. The pooled risk ratios (RRs with 95% confidence intervals (CIs were calculated. Results. A significant association between MS and fracture risk was found. This result remained statistically significant when the adjusted RRs were combined. Subgroup analysis stratified by the site of fracture suggested significant associations between MS and tibia fracture risk, femur fracture risk, hip fracture risk, pelvis fracture risk, vertebrae fracture risk, and humerus fracture risk. In the subgroup analysis by gender, female MS patients had increased fracture risk. When stratified by history of drug use, use of antidepressants, hypnotics/anxiolytics, anticonvulsants, and glucocorticoids increased the risk of fracture risk in MS patients. Conclusions. This meta-analysis demonstrated that MS was significantly associated with fracture risk.

High Pressure ZZ-Exchange NMR Reveals Key Features of Protein Folding Transition States.

Science.gov (United States)

Zhang, Yi; Kitazawa, Soichiro; Peran, Ivan; Stenzoski, Natalie; McCallum, Scott A; Raleigh, Daniel P; Royer, Catherine A

2016-11-23

Understanding protein folding mechanisms and their sequence dependence requires the determination of residue-specific apparent kinetic rate constants for the folding and unfolding reactions. Conventional two-dimensional NMR, such as HSQC experiments, can provide residue-specific information for proteins. However, folding is generally too fast for such experiments. ZZ-exchange NMR spectroscopy allows determination of folding and unfolding rates on much faster time scales, yet even this regime is not fast enough for many protein folding reactions. The application of high hydrostatic pressure slows folding by orders of magnitude due to positive activation volumes for the folding reaction. We combined high pressure perturbation with ZZ-exchange spectroscopy on two autonomously folding protein domains derived from the ribosomal protein, L9. We obtained residue-specific apparent rates at 2500 bar for the N-terminal domain of L9 (NTL9), and rates at atmospheric pressure for a mutant of the C-terminal domain (CTL9) from pressure dependent ZZ-exchange measurements. Our results revealed that NTL9 folding is almost perfectly two-state, while small deviations from two-state behavior were observed for CTL9. Both domains exhibited large positive activation volumes for folding. The volumetric properties of these domains reveal that their transition states contain most of the internal solvent excluded voids that are found in the hydrophobic cores of the respective native states. These results demonstrate that by coupling it with high pressure, ZZ-exchange can be extended to investigate a large number of protein conformational transitions.

Tranfusion risk: is "two-step" vaginal delivery a risk for postpartum hemorrhage?

Science.gov (United States)

Straface, Gianluca; Bassi, Emma; De Santis, Marco; Scambia, Giovanni; Zanardo, Vincenzo

2015-01-01

In the active management strategy of third stage of labor, the optimal timing for clamping the umbilical cord after birth has been a subject of controversy. We want to evaluate if "two-step" delivery is a risk factor for postpartum hemorrhage (PPH), defined as need of transfusion, comparing to operative delivery, elective caesarean delivery and emergency caesarean delivery. This is a retrospective cohort study conducted in division of Perinatal Medicine, Policlinico Abano Terme. We evaluated the need of transfusion in all cases of PPH verified in all single deliveries between January 2011 and December 2012. The main outcome measure was blood loss and red blood cell transfusion. We found 17 cases of PPH (0.88%). The distribution of PPH in relation to mode of delivery was 0.71%, 2.46% and 1.98% respectively for two-step vaginal delivery (RR = 0.81 (0.56-1.22)), emergency cesarean section (RR = 2.88 (1.27-7.77)) and operative vaginal delivery (RR = 2.88 (0.59-5.66)). In labor induction there is a stronger relative risk association between PPH and as emergency cesarean delivery (p < 0.05) as operative vaginal delivery (p < 0.05). "Two-step" delivery approach did not increase the risk of PPH with respect to operative delivery, elective caesarean section and emergency caesarean section.

Analysis of high-fold gamma data

International Nuclear Information System (INIS)

Radford, D. C.; Cromaz, M.; Beyer, C. J.

1999-01-01

Historically, γ-γ and γ-γ-γ coincidence spectra were utilized to build nuclear level schemes. With the development of large detector arrays, it has became possible to analyze higher fold coincidence data sets. This paper briefly reports on software to analyze 4-fold coincidence data sets that allows creation of 4-fold histograms (hypercubes) of at least 1024 channels per side (corresponding to a 43 gigachannel data space) that will fit onto a few gigabytes of disk space, and extraction of triple-gated spectra in a few seconds. Future detector arrays may have even much higher efficiencies, and detect as many as 15 or 20 γ rays simultaneously; such data will require very different algorithms for storage and analysis. Difficulties inherent in the analysis of such data are discussed, and two possible new solutions are presented, namely adaptive list-mode systems and 'list-list-mode' storage

Use of Inhaled and Oral Corticosteroids in Pregnancy and the Risk of Malformations or Miscarriage

DEFF Research Database (Denmark)

Bjørn, Anne-Mette Bay; Ehrenstein, Vera; Nøhr, Ellen Aagaard

2015-01-01

databases, this MiniReview provides an overview of inhaled and oral corticosteroid use in pregnancy with specific emphasis on the association between use of corticosteroids during pregnancy and risk of miscarriage and congenital malformations in offspring. Use of corticosteroids among pregnant women ranged...... from 0.2% to 10% and increased nearly two-fold in recent years. Taken together, the evidence suggests that use of corticosteroids in early pregnancy is not associated with an increased risk of congenital malformations overall or oral clefts in offspring; at the same time, published estimates...

Non-cylindrical fold growth in the Zagros fold and thrust belt (Kurdistan, NE-Iraq)

Science.gov (United States)

Bartl, Nikolaus; Bretis, Bernhard; Grasemann, Bernhard; Lockhart, Duncan

2010-05-01

The Zagros mountains extends over 1800 km from Kurdistan in N-Iraq to the Strait of Hormuz in Iran and is one of the world most promising regions for the future hydrocarbon exploration. The Zagros Mountains started to form as a result of the collision between the Eurasian and Arabian Plates, whose convergence began in the Late Cretaceous as part of the Alpine-Himalayan orogenic system. Geodetic and seismological data document that both plates are still converging and that the fold and thrust belt of the Zagros is actively growing. Extensive hydrocarbon exploration mainly focuses on the antiforms of this fold and thrust belt and therefore the growth history of the folds is of great importance. This work investigates by means of structural field work and quantitative geomorphological techniques the progressive fold growth of the Permam, Bana Bawi- and Safeen- Anticlines located in the NE of the city of Erbil in the Kurdistan region of Northern Iraq. This part of the Zagros fold and thrust belt belongs to the so-called Simply Folded Belt, which is dominated by gentle to open folding. Faults or fault related folds have only minor importance. The mechanical anisotropy of the formations consisting of a succession of relatively competent (massive dolomite and limestone) and incompetent (claystone and siltstone) sediments essentially controls the deformation pattern with open to gentle parallel folding of the competent layers and flexural flow folding of the incompetent layers. The characteristic wavelength of the fold trains is around 10 km. Due to faster erosion of the softer rock layers in the folded sequence, the more competent lithologies form sharp ridges with steeply sloping sides along the eroded flanks of the anticlines. Using an ASTER digital elevation model in combination with geological field data we quantified 250 drainage basins along the different limbs of the subcylindrical Permam, Bana Bawi- and Safeen- Anticlines. Geomorphological indices of the drainage

Thalidomide increases human keratinocyte migration and proliferation.

Science.gov (United States)

Nasca, M R; O'Toole, E A; Palicharla, P; West, D P; Woodley, D T

1999-11-01

Thalidomide is reported to have therapeutic utility in the treatment of pyoderma gangrenosum, Behçet's disease, aphthous ulcers, and skin wounds. We investigated the effect of thalidomide on human keratinocyte proliferation and migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 microM did not affect keratinocyte viability. Using a thymidine incorporation assay, we found that thalidomide, at therapeutic concentrations, induced more than a 2. 5-fold increase in the proliferative potential of the cells. Keratinocyte migration was assessed by two independent motility assays: a colloidal gold assay and an in vitro scratch assay. At optimal concentrations, thalidomide increased keratinocyte migration on a collagen matrix more than 2-fold in the colloidal gold assay and more than 3-fold in the scratch assay over control. Although pro-migratory, thalidomide did not alter the level of metalloproteinase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4-fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellular autocrine factor. Human keratinocyte migration and proliferation are essential for re-epithelialization of skin wounds. Interleukin-8 increases human keratinocyte migration and proliferation and is chemotactic for keratinocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.

Multi-objective room acoustic optimization of timber folded plate structure

DEFF Research Database (Denmark)

Skov, Rasmus; Parigi, Dario; Damkilde, Lars

2017-01-01

This paper investigates the application of multi-objective optimization in the design of timber folded plate structures in the scope of the architectural design process. Considering contrasting objectives of structural displacement, early decay time (EDT), clarity (C50) and sound strength (G......), the methodology applied in two benchmarks tests, encompasses both structural and acoustic performance when determining folding characteristics and directionality of surfaces in a timber folded plate structure....

Detection of micro calcifications in breast specimen by 4-fold DIMA direct magnification radiography compared to 1.5-fold conventional magnification radiography

International Nuclear Information System (INIS)

Grunert, J.H.; Borchert, B.; Farber, A.; Gmelin, E.

1999-01-01

Aims of the study: The purpose of this study was to investigate the efficacy of 4-fold magnification breast specimen radiography (direct magnification, DIMA) compared to conventional 1.5-fold magnification radiography in evaluating the presence of absence of carcinoma at the surgical margins by detection of microcalcification. Results: In 50 specimen 2821 (1305 within 3 mm distance to the margins) microcalcifications were detected with the DIMA mammography technique compared to 1608 (446) microcalcifications with the conventional technique. This increased detection rate by DIMA-magnetification radiography was accompanied by a decreased specificity in comparison to the conventional magnification radiography (33,3% DIMA versus 83,3% conventional) regarding the evaluation of presence or absence of carcinoma at the surgical margins. Differentiating the microcalcifications into calcifications belonging to the suspicious cluster and those that are located outside the cluster led to an increase in specificity (83,3% DIMA versus 100% conventional). Conclusions: The efficacy of breast specimens radiography in evaluating the presence or absence of carcinoma at the surgical margins by detection of microcalcification is not improved by 4-fold magnification radiography (direct magnification, DIMA) compared to conventional 1.5-fold magnification radiography due to an increase in false-positive results. Analysis of the attachement of the microcalcifications to the cluster can improve the specificity. (orig.) [de

The distribution of deformation in parallel fault-related folds with migrating axial surfaces: comparison between fault-propagation and fault-bend folding

Science.gov (United States)

Salvini, Francesco; Storti, Fabrizio

2001-01-01

In fault-related folds that form by axial surface migration, rocks undergo deformation as they pass through axial surfaces. The distribution and intensity of deformation in these structures has been impacted by the history of axial surface migration. Upon fold initiation, unique dip panels develop, each with a characteristic deformation intensity, depending on their history. During fold growth, rocks that pass through axial surfaces are transported between dip panels and accumulate additional deformation. By tracking the pattern of axial surface migration in model folds, we predict the distribution of relative deformation intensity in simple-step, parallel fault-bend and fault-propagation anticlines. In both cases the deformation is partitioned into unique domains we call deformation panels. For a given rheology of the folded multilayer, deformation intensity will be homogeneously distributed in each deformation panel. Fold limbs are always deformed. The flat crests of fault-propagation anticlines are always undeformed. Two asymmetric deformation panels develop in fault-propagation folds above ramp angles exceeding 29°. For lower ramp angles, an additional, more intensely-deformed panel develops at the transition between the crest and the forelimb. Deformation in the flat crests of fault-bend anticlines occurs when fault displacement exceeds the length of the footwall ramp, but is never found immediately hinterland of the crest to forelimb transition. In environments dominated by brittle deformation, our models may serve as a first-order approximation of the distribution of fractures in fault-related folds.

Recurrent Shoulder Dystocia: Risk Factors and Counseling.

Science.gov (United States)

Gurewitsch Allen, Edith D

2016-12-01

A prior history of delivery complicated by shoulder dystocia confers a 6-fold to nearly 30-fold increased risk of shoulder dystocia recurrence in a subsequent vaginal delivery, with most reported rates between 12% and 17%. Whereas prevention of shoulder dystocia in the general population is neither feasible nor cost-effective, directing intervention efforts at the particular subgroup of women with a prior history of shoulder dystocia has merit. Potentially modifiable risk factors and individualized management strategies that may reduce shoulder dystocia recurrence and its associated significant morbidities are reviewed.

Folding System for the Clothes by a Robot and Tools

OpenAIRE

大澤, 文明; 関, 啓明; 神谷, 好承

2004-01-01

The works of a home robot has the laundering. The purpose of this study is to find a means of folding of the clothes and store the clothes in a drawer by a home robot. Because the shape of cloth tends to change in various ways depending on the situation, it is difficult for robot hands to fold the clothes. In this paper, we propose a realistic folding system for the clothes by a robot and tools. The function of a tool is folding the clothes in half by inserting the clothes using two plates. T...

Fluorescence of Alexa fluor dye tracks protein folding.

Directory of Open Access Journals (Sweden)

Simon Lindhoud

Full Text Available Fluorescence spectroscopy is an important tool for the characterization of protein folding. Often, a protein is labeled with appropriate fluorescent donor and acceptor probes and folding-induced changes in Förster Resonance Energy Transfer (FRET are monitored. However, conformational changes of the protein potentially affect fluorescence properties of both probes, thereby profoundly complicating interpretation of FRET data. In this study, we assess the effects protein folding has on fluorescence properties of Alexa Fluor 488 (A488, which is commonly used as FRET donor. Here, A488 is covalently attached to Cys69 of apoflavodoxin from Azotobacter vinelandii. Although coupling of A488 slightly destabilizes apoflavodoxin, the three-state folding of this protein, which involves a molten globule intermediate, is unaffected. Upon folding of apoflavodoxin, fluorescence emission intensity of A488 changes significantly. To illuminate the molecular sources of this alteration, we applied steady state and time-resolved fluorescence techniques. The results obtained show that tryptophans cause folding-induced changes in quenching of Alexa dye. Compared to unfolded protein, static quenching of A488 is increased in the molten globule. Upon populating the native state both static and dynamic quenching of A488 decrease considerably. We show that fluorescence quenching of Alexa Fluor dyes is a sensitive reporter of conformational changes during protein folding.

Water dynamics clue to key residues in protein folding

International Nuclear Information System (INIS)

Gao, Meng; Zhu, Huaiqiu; Yao, Xin-Qiu; She, Zhen-Su

2010-01-01

A computational method independent of experimental protein structure information is proposed to recognize key residues in protein folding, from the study of hydration water dynamics. Based on all-atom molecular dynamics simulation, two key residues are recognized with distinct water dynamical behavior in a folding process of the Trp-cage protein. The identified key residues are shown to play an essential role in both 3D structure and hydrophobic-induced collapse. With observations on hydration water dynamics around key residues, a dynamical pathway of folding can be interpreted.

Safety from physical viewpoint: ''two-risk model in multiple risk problem''

International Nuclear Information System (INIS)

Kuz'Min, I.I.; Akimov, V.A.

1998-01-01

Full text of publication follows: the problem of safety provision for people and environment within the framework of a certain socio-economic system (SES) as a problem of managing a great number of interacting risks characterizing numerous hazards (natural, manmade, social, economic once, etc.) inherent in the certain SES has been discussed. From the physical point of view, it can be considered a problem of interaction of many bodies which has no accurate mathematical solution even if the laws of interaction of this bodies are known. In physics, to solve this problem, an approach based on the reduction of the above-mentioned problem of the problem of two-body interaction which can be solved accurately in mathematics has been used. The report presents a similar approach to the problem of risk management in the SES. This approach includes the subdivision of numerous hazards inherent within the framework of the SES into two classes of hazards, so that each of the classes could be considered an integrated whole one, each of them being characterized by the appropriate risk. Consequently, problem of 'multiple-risk' management (i.e. the problem of many bodies, as represented in physics) can be reduced to the 'two-risk' management problem (that is, to the problem two-bodies). Within the framework of the two-risk model the optimization of costs to reduce the two kinds of risk, that is, the risk inherent in the SES as a whole, as well as the risk potentially provoked by lots of activities to be introduced in the SES economy has been described. The model has made it possible to formulate and prove the theorem of equilibrium in risk management. Using the theorem, a relatively simple and practically applicable procedure of optimizing the threshold costs to reduce diverse kinds of risk has been elaborated. The procedure provides to assess the minimum value of the cost that can be achieved regarding the socio-economic factors typical of the SES under discussion. The aimed

Comparing apples and oranges: fold-change detection of multiple simultaneous inputs.

Directory of Open Access Journals (Sweden)

Yuval Hart

Full Text Available Sensory systems often detect multiple types of inputs. For example, a receptor in a cell-signaling system often binds multiple kinds of ligands, and sensory neurons can respond to different types of stimuli. How do sensory systems compare these different kinds of signals? Here, we consider this question in a class of sensory systems - including bacterial chemotaxis- which have a property known as fold-change detection: their output dynamics, including amplitude and response time, depends only on the relative changes in signal, rather than absolute changes, over a range of several decades of signal. We analyze how fold-change detection systems respond to multiple signals, using mathematical models. Suppose that a step of fold F1 is made in input 1, together with a step of F2 in input 2. What total response does the system provide? We show that when both input signals impact the same receptor with equal number of binding sites, the integrated response is multiplicative: the response dynamics depend only on the product of the two fold changes, F1F2. When the inputs bind the same receptor with different number of sites n1 and n2, the dynamics depend on a product of power laws, [Formula: see text]. Thus, two input signals which vary over time in an inverse way can lead to no response. When the two inputs affect two different receptors, other types of integration may be found and generally the system is not constrained to respond according to the product of the fold-change of each signal. These predictions can be readily tested experimentally, by providing cells with two simultaneously varying input signals. The present study suggests how cells can compare apples and oranges, namely by comparing each to its own background level, and then multiplying these two fold-changes.

T4 fibrations over Calabi–Yau two-folds and non-Kähler manifolds in string theory

Directory of Open Access Journals (Sweden)

Hai Lin

2016-08-01

Full Text Available We construct a geometric model of eight-dimensional manifolds and realize them in the context of type II string theory. These eight-manifolds are constructed by non-trivial T4 fibrations over Calabi–Yau two-folds. These give rise to eight-dimensional non-Kähler Hermitian manifolds with SU(4 structure. The eight-manifold is also a circle fibration over a seven-dimensional G2 manifold with skew torsion. The eight-manifolds of this type appear as internal manifolds with SU(4 structure in type IIB string theory with F3 and F7 fluxes. These manifolds have generalized calibrated cycles in the presence of fluxes.

Increased subsequent risk of erectile dysfunction among middle and old age males with chronic osteomyelitis: a nationwide population-based cohort study.

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Wang, H-Y; Chao, C-H; Lin, C-L; Tseng, C-H; Kao, C-H

2016-07-01

Chronic inflammation may cause endothelial dysfunction and atherosclerosis, resulting in subsequent erectile dysfunction (ED). We examined the relationship between chronic osteomyelitis, which is a chronic inflammatory disease, and ED. A retrospective cohort study was conducted using data from the National Health Insurance Research Database. After excluding patients <40 years of age, 677 male patients newly diagnosed with chronic osteomyelitis (COM) from 1 January 2000 to 31 December 2011 were identified for the study. The non-osteomyelitis comparison cohort consisted of 2706 male participants. The incidence of ED was 2.66-fold higher in the COM cohort than in the non-osteomyelitis cohort (4.01 vs 1.51 per 10 000 person-years). After adjusting for age and comorbidities of coronary heart disease, hypertension, hyperlipidemia, depression, stroke, diabetes, peripheral vascular disease, chronic kidney disease, chronic obstructive pulmonary disease and asthma, the patients with COM had a 2.82-fold risk of ED (95% confidence interval=1.44-5.56). The incidence of ED increased with that of comorbidities in both cohorts. The highest hazard ratio was in patients between 40 and 59 years of age who had COM. Our data showed, for the first time, that COM is a possible risk factor for the development of ED.

Is use of fall risk-increasing drugs in an elderly population associated with an increased risk of hip fracture, after adjustment for multimorbidity level

DEFF Research Database (Denmark)

Thorell, Kristine; Ranstad, Karin; Midlöv, Patrik

2014-01-01

BACKGROUND: Risk factors for hip fracture are well studied because of the negative impact on patients and the community, with mortality in the first year being almost 30% in the elderly. Age, gender and fall risk-increasing drugs, identified by the National Board of Health and Welfare in Sweden......, are well known risk factors for hip fracture, but how multimorbidity level affects the risk of hip fracture during use of fall risk-increasing drugs is to our knowledge not as well studied. This study explored the relationship between use of fall risk-increasing drugs in combination with multimorbidity...... level and risk of hip fracture in an elderly population. METHODS: Data were from Östergötland County, Sweden, and comprised the total population in the county aged 75 years and older during 2006. The odds ratio (OR) for hip fracture during use of fall risk-increasing drugs was calculated by multivariate...

Effects of thermo-mechanical behavior and hinge geometry on folding response of shape memory polymer sheets

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Mailen, Russell W.; Dickey, Michael D.; Genzer, Jan; Zikry, Mohammed

2017-11-01

Shape memory polymer (SMP) sheets patterned with black ink hinges change shape in response to external stimuli, such as absorbed thermal energy from an infrared (IR) light. The geometry of these hinges, including size, orientation, and location, and the applied thermal loads significantly influence the final folded shape of the sheet, but these variables have not been fully investigated. We perform a systematic study on SMP sheets to fundamentally understand the effects of single and double hinge geometries, hinge orientation and spacing, initial temperature, heat flux intensity, and pattern width on the folding behavior. We have developed thermo-viscoelastic finite element models to characterize and quantify the stresses, strains, and temperatures as they relate to SMP shape changes. Our predictions indicate that hinge orientation can be used to reduce the total bending angle, which is the angle traversed by the folding face of the sheet. Two parallel hinges increase the total bending angle, and heat conduction between the hinges affects the transient folding response. IR intensity and initial temperatures can also influence the transient folding behavior. These results can provide guidelines to optimize the transient folding response and the three-dimensional folded structure obtained from self-folding polymer origami sheets that can be applied for myriad applications.

Increased risk for CRC in diabetic patients with the nonrisk allele of SNPs at 8q24.

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Ishimaru, Shinya; Mimori, Koshi; Yamamoto, Ken; Inoue, Hiroshi; Imoto, Seiya; Kawano, Shuichi; Yamaguchi, Rui; Sato, Tetsuya; Toh, Hiroyuki; Iinuma, Hisae; Maeda, Toyoki; Ishii, Hideshi; Suzuki, Sadao; Tokudome, Shinkan; Watanabe, Masahiko; Tanaka, Jun-ichi; Kudo, Shin-ei; Sugihara, Ken-ichi; Hase, Kazuo; Mochizuki, Hidetaka; Kusunoki, Masato; Yamada, Kazutaka; Shimada, Yasuhiro; Moriya, Yoshihiro; Barnard, Graham F; Miyano, Satoru; Mori, Masaki

2012-09-01

Colorectal cancer (CRC) oncogenesis was considered to be determined by interactions between genetic and environmental factors. Specific interacting factors that influence CRC morbidity have yet to be fully investigated. A multi-institutional collaborative study with 1511 CRC patients and 2098 control subjects was used to compare the odds ratios for the occurrence of polymorphisms at 11 known single nucleotide polymorphisms (SNPs). TaqMan PCR and questionnaires were used to evaluate the effects of environmental exposures. Variants of rs6983267 on 8q24 were the most significant markers of risk for CRC (odds ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.0015). Non-insulin-dependent diabetes mellitus (DM), a higher body mass index at age 20, and meat consumption were environmental risk factors, whereas a tuna-rich diet and vitamin intake were protective factors. The cohort of rs6983267 SNP major (T) allele at 8q24 and DM had a 1.66-fold higher risk ratio than the cohort of major allele patients without DM. We confirmed that interactions between the genetic background and environmental factors are associated with increased risk for CRC. There is a robust risk of the minor G allele at the 8q24 rs6983267 SNP; however, a major T allele SNP could more clearly reveal a correlation with CRC specifically when DM is present.

Glycoprotein folding and quality-control mechanisms in protein-folding diseases

Directory of Open Access Journals (Sweden)

Sean P. Ferris

2014-03-01

Full Text Available Biosynthesis of proteins – from translation to folding to export – encompasses a complex set of events that are exquisitely regulated and scrutinized to ensure the functional quality of the end products. Cells have evolved to capitalize on multiple post-translational modifications in addition to primary structure to indicate the folding status of nascent polypeptides to the chaperones and other proteins that assist in their folding and export. These modifications can also, in the case of irreversibly misfolded candidates, signal the need for dislocation and degradation. The current Review focuses on the glycoprotein quality-control (GQC system that utilizes protein N-glycosylation and N-glycan trimming to direct nascent glycopolypeptides through the folding, export and dislocation pathways in the endoplasmic reticulum (ER. A diverse set of pathological conditions rooted in defective as well as over-vigilant ER quality-control systems have been identified, underlining its importance in human health and disease. We describe the GQC pathways and highlight disease and animal models that have been instrumental in clarifying our current understanding of these processes.

Relationship Between Maternal Obesity And Increased Risk Of ...

African Journals Online (AJOL)

Introduction: The incidence of obesity has risen over the past several decades and in spite of advancement in modern medicine, it remains a risk factor for maternal morbidity and mortality. Objective: To determine the association between obesity (increased body mass index) and increased risk of preeclampsia. The possible ...

Nanoscale Dewetting Transition in Protein Complex Folding

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Hua, Lan; Huang, Xuhui; Liu, Pu; Zhou, Ruhong; Berne, Bruce J.

2011-01-01

In a previous study, a surprising drying transition was observed to take place inside the nanoscale hydrophobic channel in the tetramer of the protein melittin. The goal of this paper is to determine if there are other protein complexes capable of displaying a dewetting transition during their final stage of folding. We searched the entire protein data bank (PDB) for all possible candidates, including protein tetramers, dimers, and two-domain proteins, and then performed the molecular dynamics (MD) simulations on the top candidates identified by a simple hydrophobic scoring function based on aligned hydrophobic surface areas. Our large scale MD simulations found several more proteins, including three tetramers, six dimers, and two two-domain proteins, which display a nanoscale dewetting transition in their final stage of folding. Even though the scoring function alone is not sufficient (i.e., a high score is necessary but not sufficient) in identifying the dewetting candidates, it does provide useful insights into the features of complex interfaces needed for dewetting. All top candidates have two features in common: (1) large aligned (matched) hydrophobic areas between two corresponding surfaces, and (2) large connected hydrophobic areas on the same surface. We have also studied the effect on dewetting of different water models and different treatments of the long-range electrostatic interactions (cutoff vs PME), and found the dewetting phenomena is fairly robust. This work presents a few proteins other than melittin tetramer for further experimental studies of the role of dewetting in the end stages of protein folding. PMID:17608515

Acute Acrolein Exposure Induces Impairment of Vocal Fold Epithelial Barrier Function.

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Liu, Xinxin; Zheng, Wei; Sivasankar, M Preeti

2016-01-01

Acrolein is a ubiquitous pollutant abundant in cigarette smoke, mobile exhaust, and industrial waste. There is limited literature on the effects of acrolein on vocal fold tissue, although there are clinical reports of voice changes after pollutant exposures. Vocal folds are responsible for voice production. The overall objective of this study was to investigate the effects of acrolein exposure on viable, excised vocal fold epithelial tissue and to characterize the mechanism underlying acrolein toxicity. Vocal fold epithelia were studied because they form the outermost layer of the vocal folds and are a primary recipient of inhaled pollutants. Porcine vocal fold epithelia were exposed to 0, 50, 100, 500, 900 or 1300 μM of acrolein for 3 hours; the metabolic activity, epithelial resistance, epithelial permeability, tight junction protein (occludin and claudin 3) expression, cell membrane integrity and lipid peroxidation were investigated. The data demonstrated that acrolein exposure at 500 μM significantly reduced vocal fold epithelial metabolic activity by 27.2% (p≤0.001). Incubation with 100 μM acrolein caused a marked increase in epithelial permeability by 130.5% (pacrolein-treated samples, the cell membrane integrity was significantly damaged with a 45.6% increase of lipid peroxidation as compared to controls (pacrolein exposure impairs vocal fold epithelial barrier integrity. Lipid peroxidation-induced cell membrane damage may play an important role in reducing the barrier function of the epithelium.

Endometriosis and the subsequent risk of epithelial ovarian cancer

Directory of Open Access Journals (Sweden)

Wen-Hsun Chang

2014-12-01

Conclusion: Taiwanese women with endometriosis really had a risk of newly developed EOC, especially those who had a surgical diagnosis, and this three-fold increase of risk was neither influenced by exposure time nor biased by surveillance.

Pet ownership increases human risk of encountering ticks.

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Jones, E H; Hinckley, A F; Hook, S A; Meek, J I; Backenson, B; Kugeler, K J; Feldman, K A

2018-02-01

We examined whether pet ownership increased the risk for tick encounters and tickborne disease among residents of three Lyme disease-endemic states as a nested cohort within a randomized controlled trial. Information about pet ownership, use of tick control for pets, property characteristics, tick encounters and human tickborne disease were captured through surveys, and associations were assessed using univariate and multivariable analyses. Pet-owning households had 1.83 times the risk (95% CI = 1.53, 2.20) of finding ticks crawling on and 1.49 times the risk (95% CI = 1.20, 1.84) of finding ticks attached to household members compared to households without pets. This large evaluation of pet ownership, human tick encounters and tickborne diseases shows that pet owners, whether of cats or dogs, are at increased risk of encountering ticks and suggests that pet owners are at an increased risk of developing tickborne disease. Pet owners should be made aware of this risk and be reminded to conduct daily tick checks of all household members, including the pets, and to consult their veterinarian regarding effective tick control products. © 2017 Blackwell Verlag GmbH.

Cold working room temperature increased moderate/severe qualitative work stressor risk in Air Traffic Controllers

Directory of Open Access Journals (Sweden)

Dewi Astuti

2012-07-01

work load stressor among the ATCs.Methods:  This  cross-sectional  study  was  conducted  in November  2008  at  Soekarno-Hatta  International Airport. Subjects consisted of active ATCs with a minimum of six months total working tenure. The study used standard diagnostic as well as home stressor questionnaire surveys. All questionnaires were filled in by the participants.Results: Subjects were aged 27–55 years, consisted of 112 ATCs who had moderate and 13 (9.6% ATCs who had slight QLWS. Those who felt than did not feel the working room temperature was not too cold had 11-fold moderate/severe QLWS [adjusted odds ratio (ORa = 10.63: 95% confidence interval (CI = 1.79-65.59]. Those who had than did not have moderate/severe role ambiguity stressor had 8.2-fold risk of moderate/severe QLWS (ORa = 8.23: 95% CI = 1.13-59.90. Those who had than did not have moderate/severe personal responsibility stressor had 6,6-fold risk for moderate/severe QLWS (ORa = 6.64: 95% CI = 1.13-38.85. In terms of the career development stressor, those who had it than did not have it had a 3.7-fold risk for moderate/severe QLWS (ORa = 3,67: 95% CI = 0.88-15.35; P = 0.075.Conclusion:  Those who felt the room temperature was too cold, moderate/severe role ambiguity, personal responsibility, as well as career development stressor were at increased risk for moderate/severe QLWS. (Health Science Indones 2011;2:58-65. 

Responding to bioterror concerns by increasing milk pasteurization temperature would increase estimated annual deaths from listeriosis.

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Stasiewicz, Matthew J; Martin, Nicole; Laue, Shelley; Gröhn, Yrjo T; Boor, Kathryn J; Wiedmann, Martin

2014-05-01

In a 2005 analysis of a potential bioterror attack on the food supply involving a botulinum toxin release into the milk supply, the authors recommended adopting a toxin inactivation step during milk processing. In response, some dairy processors increased the times and temperatures of pasteurization well above the legal minimum for high temperature, short time pasteurization (72 °C for 15 s), with unknown implications for public health. The present study was conducted to determine whether an increase in high temperature, short time pasteurization temperature would affect the growth of Listeria monocytogenes, a potentially lethal foodborne pathogen normally eliminated with proper pasteurization but of concern when milk is contaminated postpasteurization. L. monocytogenes growth during refrigerated storage was higher in milk pasteurized at 82 °C than in milk pasteurized at 72 °C. Specifically, the time lag before exponential growth was decreased and the maximum population density was increased. The public health impact of this change in pasteurization was evaluated using a quantitative microbial risk assessment of deaths from listeriosis attributable to consumption of pasteurized fluid milk that was contaminated postprocessing. Conservative estimates of the effect of pasteurizing all fluid milk at 82 °C rather than 72 °C are that annual listeriosis deaths from consumption of this milk would increase from 18 to 670, a 38-fold increase (8.7- to 96-fold increase, 5th and 95th percentiles). These results exemplify a situation in which response to a rare bioterror threat may have the unintended consequence of putting the public at increased risk of a known, yet severe harm and illustrate the need for a paradigm shift toward multioutcome risk benefit analyses when proposing changes to established food safety practices.

BMI and risk of dementia in two million people over two decades: a retrospective cohort study.

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Qizilbash, Nawab; Gregson, John; Johnson, Michelle E; Pearce, Neil; Douglas, Ian; Wing, Kevin; Evans, Stephen J W; Pocock, Stuart J

2015-06-01

Dementia and obesity are increasingly important public health issues. Obesity in middle age has been proposed to lead to dementia in old age. We investigated the association between BMI and risk of dementia. For this retrospective cohort study, we used a cohort of 1,958,191 individuals derived from the United Kingdom Clinical Practice Research Datalink (CPRD) which included people aged 40 years or older in whom BMI was recorded between 1992 and 2007. Follow-up was until the practice's final data collection date, patient death or transfer out of practice, or first record of dementia (whichever occurred first). People with a previous record of dementia were excluded. We used Poisson regression to calculate incidence rates of dementia for each BMI category. Our cohort of 1,958,191 people from UK general practices had a median age at baseline of 55 years (IQR 45-66) and a median follow-up of 9·1 years (IQR 6·3-12·6). Dementia occurred in 45,507 people, at a rate of 2·4 cases per 1000 person-years. Compared with people of a healthy weight, underweight people (BMI risk of dementia. Furthermore, the incidence of dementia continued to fall for every increasing BMI category, with very obese people (BMI >40 kg/m(2)) having a 29% lower (95% CI 22-36) dementia risk than people of a healthy weight. These patterns persisted throughout two decades of follow-up, after adjustment for potential confounders and allowance for the J-shape association of BMI with mortality. Being underweight in middle age and old age carries an increased risk of dementia over two decades. Our results contradict the hypothesis that obesity in middle age could increase the risk of dementia in old age. The reasons for and public health consequences of these findings need further investigation. None. Copyright © 2015 Elsevier Ltd. All rights reserved.

Metal cofactor modulated folding and target recognition of HIV-1 NCp7.

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Ren, Weitong; Ji, Dongqing; Xu, Xiulian

2018-01-01

The HIV-1 nucleocapsid 7 (NCp7) plays crucial roles in multiple stages of HIV-1 life cycle, and its biological functions rely on the binding of zinc ions. Understanding the molecular mechanism of how the zinc ions modulate the conformational dynamics and functions of the NCp7 is essential for the drug development and HIV-1 treatment. In this work, using a structure-based coarse-grained model, we studied the effects of zinc cofactors on the folding and target RNA(SL3) recognition of the NCp7 by molecular dynamics simulations. After reproducing some key properties of the zinc binding and folding of the NCp7 observed in previous experiments, our simulations revealed several interesting features in the metal ion modulated folding and target recognition. Firstly, we showed that the zinc binding makes the folding transition states of the two zinc fingers less structured, which is in line with the Hammond effect observed typically in mutation, temperature or denaturant induced perturbations to protein structure and stability. Secondly, We showed that there exists mutual interplay between the zinc ion binding and NCp7-target recognition. Binding of zinc ions enhances the affinity between the NCp7 and the target RNA, whereas the formation of the NCp7-RNA complex reshapes the intrinsic energy landscape of the NCp7 and increases the stability and zinc affinity of the two zinc fingers. Thirdly, by characterizing the effects of salt concentrations on the target RNA recognition, we showed that the NCp7 achieves optimal balance between the affinity and binding kinetics near the physiologically relevant salt concentrations. In addition, the effects of zinc binding on the inter-domain conformational flexibility and folding cooperativity of the NCp7 were also discussed.

Metal cofactor modulated folding and target recognition of HIV-1 NCp7.

Directory of Open Access Journals (Sweden)

Weitong Ren

Full Text Available The HIV-1 nucleocapsid 7 (NCp7 plays crucial roles in multiple stages of HIV-1 life cycle, and its biological functions rely on the binding of zinc ions. Understanding the molecular mechanism of how the zinc ions modulate the conformational dynamics and functions of the NCp7 is essential for the drug development and HIV-1 treatment. In this work, using a structure-based coarse-grained model, we studied the effects of zinc cofactors on the folding and target RNA(SL3 recognition of the NCp7 by molecular dynamics simulations. After reproducing some key properties of the zinc binding and folding of the NCp7 observed in previous experiments, our simulations revealed several interesting features in the metal ion modulated folding and target recognition. Firstly, we showed that the zinc binding makes the folding transition states of the two zinc fingers less structured, which is in line with the Hammond effect observed typically in mutation, temperature or denaturant induced perturbations to protein structure and stability. Secondly, We showed that there exists mutual interplay between the zinc ion binding and NCp7-target recognition. Binding of zinc ions enhances the affinity between the NCp7 and the target RNA, whereas the formation of the NCp7-RNA complex reshapes the intrinsic energy landscape of the NCp7 and increases the stability and zinc affinity of the two zinc fingers. Thirdly, by characterizing the effects of salt concentrations on the target RNA recognition, we showed that the NCp7 achieves optimal balance between the affinity and binding kinetics near the physiologically relevant salt concentrations. In addition, the effects of zinc binding on the inter-domain conformational flexibility and folding cooperativity of the NCp7 were also discussed.

DAP1 high expression increases risk of lymph node metastases in squamous cell carcinoma of the oral cavity.

Science.gov (United States)

Santos, M; Maia, L L; Silva, C V M; Peterle, G T; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

2015-09-08

Death-associated protein 1 (DAP1) is a member of the DAP family. Its expression is associated with cell growth and normal death of the neoplastic cells, regulated by the mammalian target of the rapamycin protein. Activated DAP1 negatively regulates autophagy, which has been associated with the development and progression of several diseases, such as cancer, and with prognosis and survival of diverse tumor types. Therefore, in this study we analyzed DAP1 expression in 54 oral squamous cell carcinoma tumor samples and in 20 non-tumoral margins by immunohistochemistry. The results showed that DAP1 is more frequently expressed in tumor tissues compared with marginal non-tumoral cells. Additionally, high DAP1 expression is associated with a 4-fold increase in the risk of lymph node metastases. Our results suggest that the DAP1 protein can be used as a potential marker of lymph node metastases predisposition, helping define the best therapy for each patient to minimize risk of developing metastases.

Bidi smokers at increased risk of oral cancer.

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Warnakulasuriya, Saman

2005-01-01

Source articles were searched for using Medline, the Cochrane Library and within the references lists of identified articles. Articles were selected that included data enabling construction of 2 x 2 tables to estimate odds ratios (OR) and 95% confidence intervals (CI). For each study, two-way contingency tables were constructed, based on exposure frequency distributions, for cases and controls. Unadjusted OR and 95% CI were recalculated based on the reported data using standard procedures. Separate contingency tables were made for bidi smoking, cigarette smoking and both types of smoking if the data were available in the same article. The overall OR combined across all studies, and its 95% CI, was calculated using a random-effects model for bidi and cigarette smoking. Tests for publication bias and heterogeneity were conducted. Confounding factors, for example, betel quid chewing or alcohol use, were not included in the meta-regression model. An increased risk of oral cancer was found for bidi smokers compared with people who had never smoked (OR, 3.1; 95% CI, 2.0-5.0) whereas no significant pattern of risk was found for cigarette smokers (OR, 1.1; 95% CI, 0.7-1.8). There was substantial heterogeneity in the pooled OR estimate. The results clearly indicate that bidi smokers are at increased risk of oral cancer. It is important that this information be incorporated into smoking prevention and cessation efforts, particularly in the urban poor and rural mass in south Asian countries where bidi smoking is widespread.

Folding models for elastic and inelastic scattering

International Nuclear Information System (INIS)

Satchler, G.R.

1982-01-01

The most widely used models are the optical model potential (OMP) for elastic scattering, and its generalization to non-spherical shapes, the deformed optical model potential (DOMP) for inelastic scattering. These models are simple and phenomenological; their parameters are adjusted so as to reproduce empirical data. Nonetheless, there are certain, not always well-defined, constraints to be imposed. The potential shapes and their parameter values must be reasonable and should vary in a smooth and systematic way with the masses of the colliding nuclei and their energy. One way of satisfying these constraints, without going back to a much more fundamental theory, is through the use of folding models. The basic justification for using potentials of the Woods-Saxon shape for nucleon-nucleus scattering, for example, is our knowledge that a nuclear density distribution is more-or-less constant in the nuclear interior with a diffuse surface. When this is folded with a short-range nucleon-nucleon interaction, the result is a similar shape with a more diffuse surface. Folding procedures allow us to incorporate many aspects of nuclear structure (although the nuclear size is one of the most important), as well as theoretical ideas about the effective interaction of two nucleons within nuclear matter. It also provides us with a means of linking information obtained from nuclear (hadronic) interactions with that from other sources, as well as correlating that from the use of different hadronic probes. Folding model potentials, single-folded potentials, and the double-folding model including applications to heavy-ion scattering are discussed

Is there any relationship between food habits in the last two decades and gastric cancer in North-Western Iran?

Science.gov (United States)

Somi, Mohammad Hossein; Mousavi, Seyed Mohsen; Naghashi, Shahnaz; Faramarzi, Elnaz; Jafarabadi, Mohammad Asghari; Ghojazade, Morteza; Majdi, Alireza; Naseri Alavi, Seyed Ahmad

2015-01-01

The aims of this case-control study were to assess the correlation between some food habits in the last two decades and gastric cancer in East Azerbaijan of Iran. In this hospital based case control study, 616 patients (212 gastric cancer patients, 404 cancer free patients) were recruited. Food habits of patients over the past two decades were assessed with a structured questionnaire. We used conditional logistic regression analysis for estimating crude and adjusted odds ratios (OR) and their respective 95% confidence intervals (95%CI). In this study, over-eating, consumption of high fat milk and yogurt and especial types of cheese increased the risk of gastric cancer (Allespecial cheeses such as Koze and Khiki increased the risk of gastric cancer by 12.6 fold (95% CI:1.99-79.36) and 7.36 fold (95% CI:1.33- 40.54), respectively. In addition, high fat food, moldy food, and pickled vegetables consumption as well as reuse of cooking oil for frying were significantly associated with gastric cancer risk. Furthermore, intake of Ghorme (deep fried meat) was positively correlated with gastric cancer risk (OR:1.31;95%CI: 0.91-1.87). It can be confirmed that particular food habits which have been very common in East-Azerbaijan in the last two past decades increase risk of gastric cancer. According to our results and taking into account the long latency period of gastric cancer it can be concluded that nutrition education for a healthy diet should be performed from early childhood. However, further well designed cohort studies are needed to achieve more clear results.

[Influence of low birth weight on the increased risk of post-partum hypertension].

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Wang, Lijiao; Tian, Qi; Wu, Aiping; Kan, Shuting; Tao, Jie; Dong, Yan; Han, Hongfeng; Gao, Xinying; Zheng, Yao; Chen, Shuohua; Wu, Shouling

2014-07-01

To compare the prevalence of hypertension between low birth weight infant (LBWI) women and non-LBWI women. A retrospective cohort study was applied and 3 172 pregnant women giving births during October 1976 to December 2008 in our hospital and underwent physical check-up between 2010 and 2011 at the Kailuan medical group were included and divided into LBWI group and non-LBWI group by the history of LBWI. Prevalence of hypertension was obtained during the follow-up program. Multiple logistic regression analysis was used to assess the relative risk of hypertension. A total number of 3 172 women, with an average age of 42.3 years old were divided into LBWI group (n = 147) and non-LBWI group (n = 3 025), with the average birth weights of their infants were 2.31 kg and 3.39 kg, respectively. The prevalence of hypertension from the follow-up program was significantly higher in LBWI group than that in the non-LBWI group (23.8% vs. 16.9%, P hypertension in LBWI group was 1.60 (95%CI:1.02-2.53) folds higher than that in the non-LBWI group. Prevalence of hypertension in women with LBWI was higher than that in those women without LBWI. History of LBWI seemed to have had an increased risk to develop hypertension.

Folding propensity of intrinsically disordered proteins by osmotic stress

International Nuclear Information System (INIS)

Mansouri, Amanda L.; Grese, Laura N.; Rowe, Erica L.

2016-01-01

Proteins imparted with intrinsic disorder conduct a range of essential cellular functions. To better understand the folding and hydration properties of intrinsically disordered proteins (IDPs), we used osmotic stress to induce conformational changes in nuclear co-activator binding domain (NCBD) and activator for thyroid hormone and retinoid receptor (ACTR). Osmotic stress was applied by the addition of small and polymeric osmolytes, where we discovered that water contributions to NCBD folding always exceeded those for ACTR. Both NCBD and ACTR were found to gain a-helical structure with increasing osmotic stress, consistent with their folding upon NCBD/ACTR complex formation. Using small-angle neutron scattering (SANS), we further characterized NCBD structural changes with the osmolyte ethylene glycol. Here a large reduction in overall size initially occurred before substantial secondary structural change. In conclusion, by focusing on folding propensity, and linked hydration changes, we uncover new insights that may be important for how IDP folding contributes to binding.

The association between caudal anesthesia and increased risk of postoperative surgical complications in boys undergoing hypospadias repair.

Science.gov (United States)

Taicher, Brad M; Routh, Jonathan C; Eck, John B; Ross, Sherry S; Wiener, John S; Ross, Allison K

2017-07-01

Recent reports have suggested that caudal anesthesia may be associated with an increased risk of postoperative surgical complications. We examined our experience with caudal anesthesia in hypospadias repair to evaluate for increased risk of urethrocutaneous fistula or glanular dehiscence. All hypospadias repairs performed by a single surgeon in 2001-2014 were reviewed. Staged or revision surgeries were excluded. Patient age, weight, hypospadias severity, surgery duration, month and year of surgery, caudal anesthesia use, and postoperative complications were recorded. Bivariate and multivariate statistical analyses were performed. We identified 395 single-stage primary hypospadias repairs. Mean age was 15.6 months; 326 patients had distal (83%) and 69 had proximal (17%) hypospadias. Caudal anesthetics were used in 230 (58%) cases; 165 patients (42%) underwent local penile block at the discretion of the surgeon and/or anesthesiologist. Complications of urethrocutaneous fistula or glanular deshiscence occurred in 22 patients (5.6%) and were associated with caudal anesthetic use (OR 16.5, 95% CI 2.2-123.8, P = 0.007), proximal hypospadias (OR 8.2, 95% CI 3.3-20.0, P anesthesia was associated with an over 13-fold increase in the odds of developing postoperative surgical complications in boys undergoing hypospadias repair even after adjusting for urethral meatus location. Until further investigation occurs, clinicians should carefully consider the use of caudal anesthesia for children undergoing hypospadias repair. © 2017 John Wiley & Sons Ltd.

Ultrasonography of the larynx for diagnosis of the vocal folds mobility impairment

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Petr S. Vetshev

2017-03-01

Full Text Available Purpose. To study a possibility of performance and diagnostic accuracy of ultrasonography (US of a larynx in identification of motility disorders of VF (vocal folds in comparison with the laryngoscope which is traditionally applied for this purpose. Materials and methods. According to the objectives of the study, two patient groups were formed. In first group of patients (n = 466 we studied acceptability of ultrasonografy to discriminate various laryngeal structures. In second group of patient (n = 432 we evaluated the diagnostic accuracy of ultrasonography in point of detection of vocal muscles paresis. Results. Laryngeal structures were available to examination by ultrasound (without taking in account age and sex in 92.7% of patients. Two patterns have been identified in the course of this part of the study: deterioration of visibility of the vocal folds with increasing patient age and better visibility of the vocal folds in women than in men. According to the comparative analysis, ultrasonography accuracy rate (in those patients who had had clearly visible vocal folds during ultrasonography did not differ from that during videolaryngoscopy. Conclusion. During the conducted research it was found that the US of the larynx is an effective and perspective method for detection of a paresis of VF with sensitivity and specificity 93,55% and 100% respectively. Among those patients who' VF are available to ultrasound evaluation the accuracy of method is comparable with a videolaryngoscopy and can be used with success in daily work of units of endocrine surgery.

Eating disorder behaviors are increasing: findings from two sequential community surveys in South Australia.

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Phillipa J Hay

Full Text Available BACKGROUND: Evidence for an increase in the prevalence of eating disorders is inconsistent. Our aim was to determine change in the population point prevalence of eating disorder behaviors over a 10-year period. METHODOLOGY/PRINCIPAL FINDINGS: Eating disorder behaviors were assessed in consecutive general population surveys of men and women conducted in 1995 (n = 3001, 72% respondents and 2005 (n = 3047, 63.1% respondents. Participants were randomly sampled from households in rural and metropolitan South Australia. There was a significant (all p<0.01 and over two-fold increase in the prevalence of binge eating, purging (self-induced vomiting and/or laxative or diuretic misuse and strict dieting or fasting for weight or shape control among both genders. The most common diagnosis in 2005 was either binge eating disorder or other "eating disorders not otherwise specified" (EDNOS; n = 119, 4.2%. CONCLUSIONS/SIGNIFICANCE: In this population sample the point prevalence of eating disorder behaviors increased over the past decade. Cases of anorexia nervosa and bulimia nervosa, as currently defined, remain uncommon.

Increased colon cancer risk after severe Salmonella infection.

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Lapo Mughini-Gras

Full Text Available Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans.We performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999-2015 for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264 were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1-2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA and Statistics Netherlands (CBS allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD, and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09-2.10 among patients with Salmonella infection diagnosed <60 years of age. Such increased risk concerned specifically the ascending/transverse colon (SIR 2.12; 95%CI 1.38-3.09 after S. Enteritidis infection (SIR 2.97; 95%CI 1.73-4.76. Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade

Self-folding micropatterned polymeric containers.

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Azam, Anum; Laflin, Kate E; Jamal, Mustapha; Fernandes, Rohan; Gracias, David H

2011-02-01

We demonstrate self-folding of precisely patterned, optically transparent, all-polymeric containers and describe their utility in mammalian cell and microorganism encapsulation and culture. The polyhedral containers, with SU-8 faces and biodegradable polycaprolactone (PCL) hinges, spontaneously assembled on heating. Self-folding was driven by a minimization of surface area of the liquefying PCL hinges within lithographically patterned two-dimensional (2D) templates. The strategy allowed for the fabrication of containers with variable polyhedral shapes, sizes and precisely defined porosities in all three dimensions. We provide proof-of-concept for the use of these polymeric containers as encapsulants for beads, chemicals, mammalian cells and bacteria. We also compare accelerated hinge degradation rates in alkaline solutions of varying pH. These optically transparent containers resemble three-dimensional (3D) micro-Petri dishes and can be utilized to sustain, monitor and deliver living biological components.

Modeling Vocal Fold Intravascular Flow using Synthetic Replicas

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Terry, Aaron D.; Ricks, Matthew T.; Thomson, Scott L.

2017-11-01

Vocal fold vibration that is induced by air flowing from the lungs is believed to decrease blood flow through the vocal folds. This is important due to the critical role of blood flow in maintaining tissue health. However, the precise mechanical relationships between vocal fold vibration and blood perfusion remain understudied. A platform for studying liquid perfusion in a synthetic, life-size, self-oscillating vocal fold replica has recently been developed. The replicas are fabricated using molded silicone with material properties comparable to those of human vocal fold tissues and that include embedded microchannels through which liquid is perfused. The replicas are mounted on an air flow supply tube to initiate flow-induced vibration. A liquid reservoir is attached to the microchannel to cause liquid to perfuse through replica in the anterior-posterior direction. As replica vibration is initiated and amplitude increases, perfusion flow rate decreases. In this presentation, the replica design will be presented, along with data quantifying the relationships between parameters such as replica vibration amplitude, stiffness, microchannel diameter, and perfusion flow rate. This work was supported by Grant NIDCD R01DC005788 from the National Institutes of Health.

Stratigraphy and Folding in the Cenozoic Cover of a Fold-Thrust Belt in the Nallıhan Region (Ankara, Central Turkey)

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Karaaǧaç, Serdal; Koral, Hayrettin

2017-04-01

This study investigates stratigraphy and structural features in the Cenozoic sedimentary sequence of the fold-thrust belt of the Nallıhan-Ankara region, located to the north of the İzmir-Ankara-Erzincan Suture Zone. Permian-Triassic age marble intercalated with schist-phyllites, the upper Jurassic-lower Cretaceous age limestone and the upper Cretaceous age sandstone-shale alternation compose the basement in the study area. These rocks are unconformably overlain by the Cenozoic age terrestrial sedimentary and volcanic units. The Cenozoic stratigraphy begins with the Paleocene-Eocene age coal-bearing, at times, volcanic intercalated conglomerate-sandstone-mudstone alternation of alluvial-fluvial origins (Aksaklar Formation) and the tuff intercalated with lacustrine limestone, bituminous limestone (Kabalar Formation). These units are conformably overlain by the Eocene age basalt-andesite and pyroclastic rocks (Meyildere volcanics). The Paleocene-Eocene aged units are unconformably overlain by the conglomerate-sandstone-mudstone-marl of a lower-middle Miocene lacustrine environment (Hançili Formation). The terrestrial conglomerate-sandstone alternation (Örencik Formation) is the youngest unit in the Cenozoic stratigraphy, and is assumed to be of Pliocene age based its stratigraphic position on older units. Field study shows existence of both folds and faults in the sedimentary cover. Stereographic projections of bedding measured in the field shows N25W/45NW and N60W/4SE-oriented fold axes in the Paleocene-Eocene age units. There are also N76W/12SE and N88E/8NE-oriented folds. The difference in fold-axis orientations suggests that some folds may have been rotated in blocks bound by faults during the post-Paleocene/Eocene period. Whereas, the lower-middle Miocene units manifest N88W/13SE-oriented fold axes. It is thus proposed that the observed difference in the azimuth of fold axes represent two different folding phases, one with NE-SW and the other with N

Analysis of hyaluronic acid concentration in rat vocal folds during estral and gravidic puerperal cycles.

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Pedroso, José Eduardo de Sá; Brasil, Osíris Camponês do; Martins, João Roberto Maciel; Nader, Helena Bociane; Simões, Manuel de Jesus

2009-01-01

Hormone plays an important role in the larynx. Among other substances, vocal folds contain hyaluronic acid, which tissue concentration may vary according to hormone action. the objective of this study is to analyze hyaluronic acid concentration in the vocal folds during estral and gravidic-puerperal cycles. Experimental study. 40 adult rats were divided into two groups. In the first group we used 20 rats to establish the concentration of hyaluronic acid during the estral cycle and in the second group, 20 animals were submitted to the same procedure but during the gravidic-puerperal cycle. Variations in hyaluronic acid concentration was not observed during the estral cycle. In the gravidic puerperal cycle group, an increase in hyaluronic acid concentration was observed in the puerperal subgroup. Comparing the two groups of estral and gravidic-puerperal cycles, no difference was observed. In comparing all subgroups of estral and gravidic-puerperal cycles, an increase in hyaluronic acid concentration was noticed only in the puerperal phase.

Impact of hydrodynamic interactions on protein folding rates depends on temperature

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Zegarra, Fabio C.; Homouz, Dirar; Eliaz, Yossi; Gasic, Andrei G.; Cheung, Margaret S.

2018-03-01

We investigated the impact of hydrodynamic interactions (HI) on protein folding using a coarse-grained model. The extent of the impact of hydrodynamic interactions, whether it accelerates, retards, or has no effect on protein folding, has been controversial. Together with a theoretical framework of the energy landscape theory (ELT) for protein folding that describes the dynamics of the collective motion with a single reaction coordinate across a folding barrier, we compared the kinetic effects of HI on the folding rates of two protein models that use a chain of single beads with distinctive topologies: a 64-residue α /β chymotrypsin inhibitor 2 (CI2) protein, and a 57-residue β -barrel α -spectrin Src-homology 3 domain (SH3) protein. When comparing the protein folding kinetics simulated with Brownian dynamics in the presence of HI to that in the absence of HI, we find that the effect of HI on protein folding appears to have a "crossover" behavior about the folding temperature. This means that at a temperature greater than the folding temperature, the enhanced friction from the hydrodynamic solvents between the beads in an unfolded configuration results in lowered folding rate; conversely, at a temperature lower than the folding temperature, HI accelerates folding by the backflow of solvent toward the folded configuration of a protein. Additionally, the extent of acceleration depends on the topology of a protein: for a protein like CI2, where its folding nucleus is rather diffuse in a transition state, HI channels the formation of contacts by favoring a major folding pathway in a complex free energy landscape, thus accelerating folding. For a protein like SH3, where its folding nucleus is already specific and less diffuse, HI matters less at a temperature lower than the folding temperature. Our findings provide further theoretical insight to protein folding kinetic experiments and simulations.

Computational Modeling of Proteins based on Cellular Automata: A Method of HP Folding Approximation.

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Madain, Alia; Abu Dalhoum, Abdel Latif; Sleit, Azzam

2018-06-01

The design of a protein folding approximation algorithm is not straightforward even when a simplified model is used. The folding problem is a combinatorial problem, where approximation and heuristic algorithms are usually used to find near optimal folds of proteins primary structures. Approximation algorithms provide guarantees on the distance to the optimal solution. The folding approximation approach proposed here depends on two-dimensional cellular automata to fold proteins presented in a well-studied simplified model called the hydrophobic-hydrophilic model. Cellular automata are discrete computational models that rely on local rules to produce some overall global behavior. One-third and one-fourth approximation algorithms choose a subset of the hydrophobic amino acids to form H-H contacts. Those algorithms start with finding a point to fold the protein sequence into two sides where one side ignores H's at even positions and the other side ignores H's at odd positions. In addition, blocks or groups of amino acids fold the same way according to a predefined normal form. We intend to improve approximation algorithms by considering all hydrophobic amino acids and folding based on the local neighborhood instead of using normal forms. The CA does not assume a fixed folding point. The proposed approach guarantees one half approximation minus the H-H endpoints. This lower bound guaranteed applies to short sequences only. This is proved as the core and the folds of the protein will have two identical sides for all short sequences.

Synergistic cooperation of PDI family members in peroxiredoxin 4-driven oxidative protein folding.

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Sato, Yoshimi; Kojima, Rieko; Okumura, Masaki; Hagiwara, Masatoshi; Masui, Shoji; Maegawa, Ken-ichi; Saiki, Masatoshi; Horibe, Tomohisa; Suzuki, Mamoru; Inaba, Kenji

2013-01-01

The mammalian endoplasmic reticulum (ER) harbors disulfide bond-generating enzymes, including Ero1α and peroxiredoxin 4 (Prx4), and nearly 20 members of the protein disulfide isomerase family (PDIs), which together constitute a suitable environment for oxidative protein folding. Here, we clarified the Prx4 preferential recognition of two PDI family proteins, P5 and ERp46, and the mode of interaction between Prx4 and P5 thioredoxin domain. Detailed analyses of oxidative folding catalyzed by the reconstituted Prx4-PDIs pathways demonstrated that, while P5 and ERp46 are dedicated to rapid, but promiscuous, disulfide introduction, PDI is an efficient proofreader of non-native disulfides. Remarkably, the Prx4-dependent formation of native disulfide bonds was accelerated when PDI was combined with ERp46 or P5, suggesting that PDIs work synergistically to increase the rate and fidelity of oxidative protein folding. Thus, the mammalian ER seems to contain highly systematized oxidative networks for the efficient production of large quantities of secretory proteins.

The risk of developing cervical cancer in Mexican women is associated to CYP1A1 MspI polymorphism.

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Juárez-Cedillo, Teresa; Vallejo, Maite; Fragoso, José Manuel; Hernández-Hernández, Dulce Maria; Rodríguez-Pérez, José Manuel; Sánchez-García, Sergio; del Carmen García-Peña, María; García-Carrancá, Alejandro; Mohar-Betancourt, Alejandro; Granados, Julio; Vargas-Alarcón, Gilberto

2007-07-01

The aim of the study was to evaluate the association of two CYP1A1 polymorphisms (Msp1 and exon 7) with cervical cancer in Mexican women considering their smoking habit. The polymorphisms were determined in 310 individuals (155 with cervical cancer and 155 healthy controls). Women with MspI T/C or C/C showed increased risk of developing cervical cancer (3.7- and 8.3-fold increase, respectively) compared to women with T/T genotype. When smoking habit was considered, the risk for non-smokers with T/C and C/C genotypes was similar (5.2 and 4.1, respectively), whereas smoking women with C/C genotype showed a 19.4-fold increase of cervical cancer. Number of child births, number of sexual partners and marital status were strong risk factors for developing cervical cancer in women with T/T genotype; however, in women with T/C genotype, only the number of child births and sexual partners had a significant influence. These results suggest an important role of the CYP1A1 MspI polymorphism in the risk of developing cervical cancer.

Increased cancer risk in patients with periodontitis.

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Dizdar, Omer; Hayran, Mutlu; Guven, Deniz Can; Yılmaz, Tolga Birtan; Taheri, Sahand; Akman, Abdullah C; Bilgin, Emre; Hüseyin, Beril; Berker, Ezel

2017-12-01

Previous studies have noted a possible association between periodontal diseases and the risk of various cancers. We assessed cancer risk in a cohort of patients with moderate to severe periodontitis. Patients diagnosed with moderate to severe periodontitis by a periodontist between 2001 and 2010 were identified from the hospital registry. Patients younger than 35 years of age or with a prior cancer diagnosis were excluded. The age- and gender-standardized incidence rates (SIR) were calculated by dividing the number of observed cases by the number of expected cases from Turkish National Cancer Registry 2013 data. A total of 280 patients were included (median age 49.6, 54% female). Median follow-up was 12 years. Twenty-five new cancer cases were observed. Patients with periodontitis had 77% increased risk of cancer (SIR 1.77, 95% CI 1.17-2.58, p = .004). Women with periodontitis had significantly higher risk of breast cancer (SIR 2.40, 95% CI 0.88-5.33) and men with periodontitis had significantly higher risk of prostate cancer (SIR 3.75, 95% CI 0.95-10.21) and hematological cancers (SIR 6.97, 95% CI 1.77-18.98). Although showing a causal association necessitates further investigation, our results support the idea that periodontitis might be associated with increased cancer risk, particularly with hematological, breast and prostate cancers.

A case of successfully cured carcinoma of the true vocal folds in the larynx

International Nuclear Information System (INIS)

Shivarov, G.; Tomov, D.

2017-01-01

Objective and subject of the study: Laryngeal carcinoma is a socially significant malignancy in our country as well. Between 1981 and 2010, standardized morbidity (global standard) of 100,000 in Bulgaria increased in men from 6.4 to 9.1, and in women - from 0.3 to 0.7. Recently, a number of reports were published, showing that timely individualized treatment leads to definitive curing of patients with this disease. Methods used: A 37 years old man was hospitalized with a complaint of dysphonia persisting despite conservative treatment for two months. Results: Objectively thickened vocal folds were observed. In this case, the left one was uneven, bruised and with unrestricted mobility. The histological examination of the biopsy material shows moderately differentiated spinocellular carcinoma in the left and squamous papilloma T1 No Mx - in the right fold. A planned hemylarringectomy was performed. Intraoperatively, a susceptible stretch in the right vocal fold was detected, proved in two weeks to be squamous cell carcinoma. A lower tracheotomy was performed, followed by telangatherapy alone. The four-year follow-up indicates a favorable course of the disease and a lack of relapse. Conclusion: The combination of surgical intervention with telegamma therapy in cases of isolated carcinoma of the true vocal folds in the larynx can be applied to strictly selected patients in order to achieve optimal therapeutic outcomes. [bg

Protein solubility and folding enhancement by interaction with RNA.

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Seong Il Choi

Full Text Available While basic mechanisms of several major molecular chaperones are well understood, this machinery has been known to be involved in folding of only limited number of proteins inside the cells. Here, we report a chaperone type of protein folding facilitated by interaction with RNA. When an RNA-binding module is placed at the N-terminus of aggregation-prone target proteins, this module, upon binding with RNA, further promotes the solubility of passenger proteins, potentially leading to enhancement of proper protein folding. Studies on in vitro refolding in the presence of RNA, coexpression of RNA molecules in vivo and the mutants with impaired RNA binding ability suggests that RNA can exert chaperoning effect on their bound proteins. The results suggest that RNA binding could affect the overall kinetic network of protein folding pathway in favor of productive folding over off-pathway aggregation. In addition, the RNA binding-mediated solubility enhancement is extremely robust for increasing soluble yield of passenger proteins and could be usefully implemented for high-throughput protein expression for functional and structural genomic research initiatives. The RNA-mediated chaperone type presented here would give new insights into de novo folding in vivo.

[Gastro-Esophageal Reflux Disease and Malignant Progression - Equal Risk for Men and Women?

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Pech, O

2016-12-01

Gastroesophageal reflux disease (GERD) is highly prevalent in the Western world. Patients with GERD have a 10-fold increased risk to develop a Barrett's esophagus. Patients with Barrett's esophagus have a higher risk for an esophageal adenocarcinoma. Men have more severe reflux with a higher grade of inflammation and acid reflux. This seems to be the reason why men develop a Barrett's esophagus more frequently - the risk is approximately 2-3-fold and the risk for an esophageal adenocarcinoma is even 3-6 times higher. © Georg Thieme Verlag KG Stuttgart · New York.

Chloroplast Chaperonin: An Intricate Protein Folding Machine for Photosynthesis

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Qian Zhao

2018-01-01

Full Text Available Group I chaperonins are large cylindrical-shaped nano-machines that function as a central hub in the protein quality control system in the bacterial cytosol, mitochondria and chloroplasts. In chloroplasts, proteins newly synthesized by chloroplast ribosomes, unfolded by diverse stresses, or translocated from the cytosol run the risk of aberrant folding and aggregation. The chloroplast chaperonin system assists these proteins in folding into their native states. A widely known protein folded by chloroplast chaperonin is the large subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco, an enzyme responsible for the fixation of inorganic CO2 into organic carbohydrates during photosynthesis. Chloroplast chaperonin was initially identified as a Rubisco-binding protein. All photosynthetic eucaryotes genomes encode multiple chaperonin genes which can be divided into α and β subtypes. Unlike the homo-oligomeric chaperonins from bacteria and mitochondria, chloroplast chaperonins are more complex and exists as intricate hetero-oligomers containing both subtypes. The Group I chaperonin requires proper interaction with a detachable lid-like co-chaperonin in the presence of ATP and Mg2+ for substrate encapsulation and conformational transition. Besides the typical Cpn10-like co-chaperonin, a unique co-chaperonin consisting of two tandem Cpn10-like domains joined head-to-tail exists in chloroplasts. Since chloroplasts were proposed as sensors to various environmental stresses, this diversified chloroplast chaperonin system has the potential to adapt to complex conditions by accommodating specific substrates or through regulation at both the transcriptional and post-translational levels. In this review, we discuss recent progress on the unique structure and function of the chloroplast chaperonin system based on model organisms Chlamydomonas reinhardtii and Arabidopsis thaliana. Knowledge of the chloroplast chaperonin system may ultimately lead

Analysis of laryngoscopic features in patients with unilateral vocal fold paresis.

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Woo, Peak; Parasher, Arjun K; Isseroff, Tova; Richards, Amanda; Sivak, Mark

2016-08-01

The diagnosis of paresis in patients with vocal fold motion impairment remains a challenge. More than 27 clinical parameters have been cited that may signify paresis. We hypothesize that some features are more significant than others. Prospective case series. Two laryngologists rated laryngoscopy findings in 19 patients suspected of paresis. The diagnosis was confirmed with laryngeal electromyography. A standard set of 27 ratings was used for each examination that included movement, laryngeal configuration, and stroboscopy signs. A Fisher exact test was completed for each measure. A kappa coefficient was calculated for effectiveness in predicting the laterality of paresis. Left-sided vocal fold paresis (n = 13) was significantly associated with ipsilateral axis deviation, thinner vocal fold, bowing, reduced movement, reduced kinesis, and phase lag (P vocal fold paresis (n = 6) was significantly associated with ipsilateral shorter vocal fold, axis deviation, reduced movement, and reduced kinesis (P vocal fold, vocal fold bowing, reduced movement, reduced kinesis, and phase lag were more likely to be associated with vocal fold paresis. 4 Laryngoscope, 126:1831-1836, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Behavioural adjustment in response to increased predation risk: a study in three duck species.

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Cédric Zimmer

Full Text Available Predation directly triggers behavioural decisions designed to increase immediate survival. However, these behavioural modifications can have long term costs. There is therefore a trade-off between antipredator behaviours and other activities. This trade-off is generally considered between vigilance and only one other behaviour, thus neglecting potential compensations. In this study, we considered the effect of an increase in predation risk on the diurnal time-budget of three captive duck species during the wintering period. We artificially increased predation risk by disturbing two groups of 14 mallard and teals at different frequencies, and one group of 14 tufted ducks with a radio-controlled stressor. We recorded foraging, vigilance, preening and sleeping durations the week before, during and after disturbance sessions. Disturbed groups were compared to an undisturbed control group. We showed that in all three species, the increase in predation risk resulted in a decrease in foraging and preening and led to an increase in sleeping. It is worth noting that contrary to common observations, vigilance did not increase. However, ducks are known to be vigilant while sleeping. This complex behavioural adjustment therefore seems to be optimal as it may allow ducks to reduce their predation risk. Our results highlight the fact that it is necessary to encompass the whole individual time-budget when studying behavioural modifications under predation risk. Finally, we propose that studies of behavioural time-budget changes under predation risk should be included in the more general framework of the starvation-predation risk trade-off.

Adjustable thermal resistor by reversibly folding a graphene sheet.

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Song, Qichen; An, Meng; Chen, Xiandong; Peng, Zhan; Zang, Jianfeng; Yang, Nuo

2016-08-11

Phononic (thermal) devices such as thermal diodes, thermal transistors, thermal logic gates, and thermal memories have been studied intensively. However, tunable thermal resistors have not been demonstrated yet. Here, we propose an instantaneously adjustable thermal resistor based on folded graphene. Through theoretical analysis and molecular dynamics simulations, we study the phonon-folding scattering effect and the dependence of thermal resistivity on the length between two folds and the overall length. Furthermore, we discuss the possibility of realizing instantaneously adjustable thermal resistors in experiment. Our studies bring new insights into designing thermal resistors and understanding the thermal modulation of 2D materials by adjusting basic structure parameters.

Adverse life events increase risk for postpartum psychiatric episodes: A population-based epidemiologic study.

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Meltzer-Brody, S; Larsen, J T; Petersen, L; Guintivano, J; Florio, A Di; Miller, W C; Sullivan, P F; Munk-Olsen, T

2018-02-01

Trauma histories may increase risk of perinatal psychiatric episodes. We designed an epidemiological population-based cohort study to explore if adverse childhood experiences (ACE) in girls increases risk of later postpartum psychiatric episodes. Using Danish registers, we identified women born in Denmark between January 1980 and December 1998 (129,439 childbirths). Exposure variables were ACE between ages 0 and 15 including: (1) family disruption, (2) parental somatic illness, (3) parental labor market exclusion, (4) parental criminality, (5) parental death, (6) placement in out-of-home care, (7) parental psychopathology excluding substance use, and (8) parental substance use disorder. Primary outcome was first occurrence of in- or outpatient contact 0-6 months postpartum at a psychiatric treatment facility with any psychiatric diagnoses, ICD-10, F00-F99 (N = 651). We conducted survival analyses using Cox proportional hazard regressions of postpartum psychiatric episodes. Approximately 52% of the sample experienced ACE, significantly increasing risk of any postpartum psychiatric diagnosis. Highest risks were observed among women who experienced out-of-home placement, hazard ratio (HR) 2.57 (95% CI: 1.90-3.48). Women experiencing two adverse life events had higher risks of postpartum psychiatric diagnosis HR: 1.88 (95% CI: 1.51-2.36), compared to those with one ACE, HR: 1.24 (95% CI: 1.03-49) and no ACE, HR: 1.00 (reference group). ACE primarily due to parental psychopathology and disability contributes to increased risk of postpartum psychiatric episodes; and greater numbers of ACE increases risk for postpartum psychiatric illness with an observed dose-response effect. Future work should explore genetic and environmental factors that increase risk and/or confer resilience. © 2017 Wiley Periodicals, Inc.

Exposure to welding fumes increases lung cancer risk among light smokers but not among heavy smokers: evidence from two case-control studies in Montreal.

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Vallières, Eric; Pintos, Javier; Lavoué, Jérôme; Parent, Marie-Élise; Rachet, Bernard; Siemiatycki, Jack

2012-08-01

We investigated relationships between occupational exposure to gas and arc welding fumes and the risk of lung cancer among workers exposed to these agents throughout the spectrum of industries. Two population-based case-control studies were conducted in Montreal. Study I (1979-1986) included 857 cases and 1066 controls, and Study II (1996-2001) comprised 736 cases and 894 controls. Detailed job histories were obtained by interview and evaluated by an expert team of chemist-hygienists to estimate degree of exposure to approximately 300 substances for each job. Gas and arc welding fumes were among the agents evaluated. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of lung cancer using logistic regression, adjusting for smoking history and other covariates. The two studies provided similar results, so a pooled analysis was conducted. Among all subjects, no significant association was found between lung cancer and gas welding fumes (OR = 1.1; 95% CI = 0.9-1.4) or arc welding fumes (OR = 1.0; 95% CI = 0.8-1.2). However, when restricting attention to light smokers, there was an increased risk of lung cancer in relation to gas welding fumes (OR = 2.9; 95% CI = 1.7-4.8) and arc welding fumes (OR = 2.3; 95% CI = 1.3-3.8), with even higher OR estimates among workers with the highest cumulative exposures. In conclusion, there was no detectable excess risk of lung cancer due to welding fumes among moderate to heavy smokers; but among light smokers we found an excess risk related to both types of welding fumes.

Influence of yarn folding on UV protection properties of hemp knitted fabrics

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Kocić Ana A.

2016-01-01

Full Text Available In the last years the media have highlighted the damage of the ozone layer and the resulting increase of ultraviolet radiation (UVR reaching the earth’s surface. Prolonged and repeated, both occupational and recreational, sun exposure of the population causes some detrimental effects. Clothing is considered to be one of the most important tools for UV protection. It is generally accepted that synthetic fibres provide a high UV protection capability of textiles, while cellulose fibres (cotton, linen, hemp, viscose have a low UV absorption capacity. However, natural pigments, pectin and waxes in natural cellulose fibers, and lignin in hemp fibers, act as UV absorbers having a favorable effect on UPF of grey-state fabrics. Bearing in mind the trend of reintroduction of hemp fibers as a source of eco-friendly textiles, there is a serious lack of study about the potential of hemp materials in terms of UV protection. Folded yarn is a complex yarn composed of two or more component yarns arranged parallel and twisted together to make a “new quality” yarn. Folding of yarns is an operation undertaken in order to modify single-yarn properties to an appreciable degree. There are very few investigations concerning the relationship between the yarn properties and UV protection effectiveness of the fabric made there from. In addition, there is no any result in the scientific literature about the influence of yarn folding on UV protection properties of textile materials. Having this in mind, for our research the idea was to evaluate the effect of yarn folding in this regard. The plain knitted fabrics composed of single or two-folded hemp yarn were compared in terms of UV protection properties. The Ultraviolet Protection Factor (UPF, as the quantitative measurement of the material effectiveness to protect the human skin against UVR, was determined for the textile materials by in vitro test method according to the European standard EN 13758. The knitted

Poor oral health is associated with an increased risk of esophageal squamous cell carcinoma - a population-based case-control study in China.

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Chen, Xingdong; Yuan, Ziyu; Lu, Ming; Zhang, Yuechan; Jin, Li; Ye, Weimin

2017-02-01

To further examine the association between oral hygiene and esophageal squamous cell carcinoma (ESCC) risk and the effect modification of other exposures, we conducted a population-based case-control study between 2010 and 2012 in Taixing, China, a high-risk area for ESCC. Cases were primarily recruited from endoscopy units at local hospitals, supplemented by linkage to the local Cancer Registry. Control subjects were frequency matched to cases by sex and age (5-year groups) and were randomly selected from the Taixing Population Registry. For the current analysis, data from 616 histopathologically confirmed cases and 770 controls with complete information on oral hygiene were analyzed. Unconditional logistic regression models, including oral hygiene indicators and potential behavioral confounders, were used to derive odds ratios (ORs) and 95% confidence intervals (CIs). Tooth loss was only marginally significantly associated with ESCC risk (yes vs. no, OR = 1.29, 95% CI 0.94-1.74). However, the excess risk increased with increasing numbers of lost teeth (more than 6 teeth lost vs. none, OR = 1.48, 95% CI 1.04-2.11). Tooth brushing once or less per day, compared with tooth brushing twice or more per day, was associated with a 1.81-fold increased risk of ESCC. In the stratification analyses, the increased risks associated with these indicators of oral health were more pronounced in older subjects (age ≥ 70 years), women, non-smokers, and non-drinkers. Further studies are warranted to verify these findings and to explore the underlying mechanisms, e.g., changed oral microbiota, associated with poor oral hygiene. © 2016 UICC.

Single-molecule studies of the Im7 folding landscape.

Science.gov (United States)

Pugh, Sara D; Gell, Christopher; Smith, D Alastair; Radford, Sheena E; Brockwell, David J

2010-04-23

Under appropriate conditions, the four-helical Im7 (immunity protein 7) folds from an ensemble of unfolded conformers to a highly compact native state via an on-pathway intermediate. Here, we investigate the unfolded, intermediate, and native states populated during folding using diffusion single-pair fluorescence resonance energy transfer by measuring the efficiency of energy transfer (or proximity or P ratio) between pairs of fluorophores introduced into the side chains of cysteine residues placed in the center of helices 1 and 4, 1 and 3, or 2 and 4. We show that while the native states of each variant give rise to a single narrow distribution with high P values, the distributions of the intermediates trapped at equilibrium (denoted I(eqm)) are fitted by two Gaussian distributions. Modulation of the folding conditions from those that stabilize the intermediate to those that destabilize the intermediate enabled the distribution of lower P value to be assigned to the population of the unfolded ensemble in equilibrium with the intermediate state. The reduced stability of the I(eqm) variants allowed analysis of the effect of denaturant concentration on the compaction and breadth of the unfolded state ensemble to be quantified from 0 to 6 M urea. Significant compaction is observed as the concentration of urea is decreased in both the presence and absence of sodium sulfate, as previously reported for a variety of proteins. In the presence of Na(2)SO(4) in 0 M urea, the P value of the unfolded state ensemble approaches that of the native state. Concurrent with compaction, the ensemble displays increased peak width of P values, possibly reflecting a reduction in the rate of conformational exchange among iso-energetic unfolded, but compact conformations. The results provide new insights into the initial stages of folding of Im7 and suggest that the unfolded state is highly conformationally constrained at the outset of folding. (c) 2010 Elsevier Ltd. All rights reserved.

PAI-1 4G/5G and MTHFR C677T polymorphisms increased the accuracy of two prediction scores for the risk of acute lower extremity deep vein thrombosis.

Science.gov (United States)

Pop, Tudor Radu; Vesa, Ştefan Cristian; Trifa, Adrian Pavel; Crişan, Sorin; Buzoianu, Anca Dana

2014-01-01

This study investigates the accuracy of two scores in predicting the risk of acute lower extremity deep vein thrombosis. The study included 170 patients [85 (50%) women and 85 (50%) men] who were diagnosed with acute lower extremity deep vein thrombosis (DVT) with duplex ultrasonography. Median age was 62 (52.75; 72) years. The control group consisted of 166 subjects [96 (57.8%) women and 70 (42.2%) men], without DVT, matched for age (± one year) to those in the group with DVT. The patients and controls were selected from those admitted to the internal medicine, cardiology and geriatrics wards within the Municipal Hospital of Cluj-Napoca, Romania, between October 2009 and June 2011. Clinical, demographic and lab data were recorded for each patient. For each patient we calculated the prior risk of DVT using two prediction scores: Caprini and Padua. According to the Padua score only 93 (54.7%) patients with DVT had been at high risk of developing DVT, while 48 (28.9%) of controls were at high risk of developing DVT. When Padua score included PAI-1 4G/5G and MTHFR C677T polymorphisms, the sensitivity increased at 71.7%. Using the Caprini score, we determined that 147 (86.4%) patients with DVT had been at high risk of developing DVT, while 103 (62%) controls were at high risk of developing DVT. A Caprini score higher than 5 was the strongest predictor of acute lower extremity DVT risk. The Caprini prediction score was more sensitive than the Padua score in assessing the high risk of DVT in medical patients. PAI-1 4G/5G and MTHFR C677T polymorphisms increased the sensitivity of Padua score.

Increasing The Number of Embryos Transferred from Two to Three, Does not Increase Pregnancy Rates in Good Prognosis Patients

Directory of Open Access Journals (Sweden)

Mahnaz Ashrafi

2015-10-01

Full Text Available Background: To compare the pregnancy outcomes after two embryos versus three embryos transfers (ETs in women undergoing in vitro fertilization (IVF/intracytoplasmic sperm injection (ICSI cycles. Materials and Methods: This retrospective study was performed on three hundred eighty seven women with primary infertility and with at least one fresh embryo in good quality in order to transfer at each IVF/ICSI cycle, from September 2006 to June 2010. Patients were categorized into two groups according to the number of ET as follows: ET2 and ET3 groups, indicating two and three embryos were respectively transferred. Pregnancy outcomes were compared between ET2 and ET3 groups. Chi square and student t tests were used for data analysis. Results: Clinical pregnancy and live birth rates were similar between two groups. The rates of multiple pregnancies were 27 and 45.2% in ET2 and ET3 groups, respectively. The rate of multiple pregnancies in young women was significantly increased when triple instead of double embryos were transferred. Logistic regression analysis indicated two significant prognostic variables for live birth that included number and quality of transferred embryos; it means that the chance of live birth following ICSI treatment increased 3.2-fold when the embryo with top quality (grade A was transferred, but the number of ET had an inverse relationship with live birth rate; it means that probability of live birth in women with transfer of two embryos was three times greater than those who had three ET. Conclusion: Due to the difficulty of implementation of the elective single-ET technique in some infertility centers in the world, we suggest transfer of double instead of triple embryos when at least one good quality embryo is available for transfer in women aged 39 years or younger. However, to reduce the rate of multiple pregnancies, it is recommended to consider the elective single ET strategy.

Topiramate increases the risk of valproic acid-induced encephalopathy.

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Noh, Young; Kim, Dong Wook; Chu, Kon; Lee, Soon-Tae; Jung, Keun-Hwa; Moon, Hye-Jin; Lee, Sang Kun

2013-01-01

Metabolic encephalopathy is a rare but serious complication of valproic acid (VPA) therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that topiramate (TPM) increases the risk of VPA-induced encephalopathy, the additional risk in patients receiving TPM therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA-induced encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA therapy and 1,236 patients who received VPA/TPM combination therapy. We identified 11 patients with VPA-induced encephalopathy (0.13%), 7 of whom received a combination therapy of VPA and TPM. The odds ratio of VPA-induced encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA-induced encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Increased risk of sudden cardiac arrest in obstructive pulmonary disease

DEFF Research Database (Denmark)

Warnier, Miriam Jacoba; Blom, Marieke Tabo; Bardai, Abdennasser

2013-01-01

BACKGROUND: We aimed to determine whether (1) patients with obstructive pulmonary disease (OPD) have an increased risk of sudden cardiac arrest (SCA) due to ventricular tachycardia or fibrillation (VT/VF), and (2) the SCA risk is mediated by cardiovascular risk-profile and/or respiratory drug use...... with electrocardiographic documentation of VT/VF were included. Conditional logistic regression analysis was used to assess the association between SCA and OPD. Pre-specified subgroup analyses were performed regarding age, sex, cardiovascular risk-profile, disease severity, and current use of respiratory drugs. RESULTS...... is associated with an increased observed risk of SCA. The most increased risk was observed in patients with a high cardiovascular risk-profile, and in those who received SABA and, possibly, those who received AC at the time of SCA....

Bactericidal/Permeability-increasing protein fold-containing family member A1 in airway host protection and respiratory disease.

Science.gov (United States)

Britto, Clemente J; Cohn, Lauren

2015-05-01

Bactericidal/permeability-increasing protein fold-containing family member A1 (BPIFA1), formerly known as SPLUNC1, is one of the most abundant proteins in respiratory secretions and has been identified with increasing frequency in studies of pulmonary disease. Its expression is largely restricted to the respiratory tract, being highly concentrated in the upper airways and proximal trachea. BPIFA1 is highly responsive to airborne pathogens, allergens, and irritants. BPIFA1 actively participates in host protection through antimicrobial, surfactant, airway surface liquid regulation, and immunomodulatory properties. Its expression is modulated in multiple lung diseases, including cystic fibrosis, chronic obstructive pulmonary disease, respiratory malignancies, and idiopathic pulmonary fibrosis. However, the role of BPIFA1 in pulmonary pathogenesis remains to be elucidated. This review highlights the versatile properties of BPIFA1 in antimicrobial protection and its roles as a sensor of environmental exposure and regulator of immune cell function. A greater understanding of the contribution of BPIFA1 to disease pathogenesis and activity may clarify if BPIFA1 is a biomarker and potential drug target in pulmonary disease.

Extreme Geohazards: Reducing the Disaster Risk and Increasing Resilience

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Plag, Hans-Peter; Stein, Seth; Brocklebank, Sean; Jules-Plag, Shelley; Marsh, Stuart; Campus, Paola

2013-04-01

Extreme geohazards have the potential to escalate the global sustainability crisis and put us close to the boundaries of the safe operating space for humanity. Exposure of human assets to geohazards has increased dramatically in recent decades, and the sensitivity of the built environment and the embedded socio-economic fabric have changed. We are putting the urban environment, including megacities, in harm's way. Paradoxically, innovation during recent decades, in particular, urban innovation, has increased the disaster risk and coupled this risk to the sustainability crisis. Only more innovation can reduce disaster risk and lead us out of the sustainability crisis. Extreme geohazards (volcanic eruptions, earthquakes, tsunamis) that occurred regularly throughout the last few millennia mostly did not cause major disasters because population density was low and the built environment was not sprawling into hazardous areas to the same extent as today. Similar extreme events today would cause unparalleled damage on a global scale and could worsen the sustainability crisis. Simulation of these extreme hazards under present conditions can help to assess the disaster risk. The Geohazards Community of Practice of the Group on Earth Observations (GEO) with support from the European Science Foundation is preparing a white paper assessing the contemporary disaster risks associated with extreme geohazards and developing a vision for science and society to engage in deliberations addressing this risk (see http://www.geohazcop.org/projects/extgeowp). Risk awareness and monitoring is highly uneven across the world, and this creates two kinds of problems. Firstly, potential hazards are much more closely monitored in wealthy countries than in the developing world. But the largest hazards are global in nature, and it is critical to get as much forewarning as possible to develop an effective response. The disasters and near-misses of the past show that adherence to scientific

Benign Thyroid Conditions Associated with Increased Risk of Thyroid Cancer Later in Life

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In a new study from the National Cancer Institute and Aarhus University Hospital in Denmark, researchers report an association between diagnosis of hyperthyroidism and thyroiditis (inflammation of the thyroid gland), two benign thyroid conditions, and increased risk of differentiated thyroid cancer.

Experimental investigation of protein folding and misfolding.

Science.gov (United States)

Dobson, Christopher M

2004-09-01

Newly synthesised proteins need to fold, often to intricate and close-packed structures, in order to function. The underlying mechanism by which this complex process takes place both in vitro and in vivo is now becoming understood, at least in general terms, as a result of the application of a wide range of biophysical and computational methods used in combination with the techniques of biochemistry and protein engineering. It is increasingly apparent, however, that folding is not only crucial for generating biological activity, but that it is also coupled to a wide range of processes within the cell, ranging from the trafficking of proteins to specific organelles to the regulation of cell growth and differentiation. Not surprisingly, therefore, the failure of proteins to fold appropriately, or to remain correctly folded, is associated with a large number of cellular malfunctions that give rise to disease. Misfolding, and its consequences such as aggregation, can be investigated by extending the types of techniques used to study the normal folding process. Application of these techniques is enabling the development of a unified description of the interconversion and regulation of the different conformational states available to proteins in living systems. Such a description proves a generic basis for understanding the fundamental links between protein misfolding and its associated clinical disorders, such as Alzheimer's disease and Type II diabetes, and for exploring novel therapeutic strategies directed at their prevention and treatment on a rational basis.

Peptide folding in the presence of interacting protein crowders

Energy Technology Data Exchange (ETDEWEB)

Bille, Anna, E-mail: anna.bille@thep.lu.se; Irbäck, Anders, E-mail: anders@thep.lu.se [Computational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund University, Sölvegatan 14A, SE-223 62 Lund (Sweden); Mohanty, Sandipan, E-mail: s.mohanty@fz-juelich.de [Jülich Supercomputing Centre, Institute for Advanced Simulation, Forschungszentrum Jülich, D-52425 Jülich (Germany)

2016-05-07

Using Monte Carlo methods, we explore and compare the effects of two protein crowders, BPTI and GB1, on the folding thermodynamics of two peptides, the compact helical trp-cage and the β-hairpin-forming GB1m3. The thermally highly stable crowder proteins are modeled using a fixed backbone and rotatable side-chains, whereas the peptides are free to fold and unfold. In the simulations, the crowder proteins tend to distort the trp-cage fold, while having a stabilizing effect on GB1m3. The extent of the effects on a given peptide depends on the crowder type. Due to a sticky patch on its surface, BPTI causes larger changes than GB1 in the melting properties of the peptides. The observed effects on the peptides stem largely from attractive and specific interactions with the crowder surfaces, and differ from those seen in reference simulations with purely steric crowder particles.

FRAN and RBF-PSO as two components of a hyper framework to recognize protein folds.

Science.gov (United States)

Abbasi, Elham; Ghatee, Mehdi; Shiri, M E

2013-09-01

In this paper, an intelligent hyper framework is proposed to recognize protein folds from its amino acid sequence which is a fundamental problem in bioinformatics. This framework includes some statistical and intelligent algorithms for proteins classification. The main components of the proposed framework are the Fuzzy Resource-Allocating Network (FRAN) and the Radial Bases Function based on Particle Swarm Optimization (RBF-PSO). FRAN applies a dynamic method to tune up the RBF network parameters. Due to the patterns complexity captured in protein dataset, FRAN classifies the proteins under fuzzy conditions. Also, RBF-PSO applies PSO to tune up the RBF classifier. Experimental results demonstrate that FRAN improves prediction accuracy up to 51% and achieves acceptable multi-class results for protein fold prediction. Although RBF-PSO provides reasonable results for protein fold recognition up to 48%, it is weaker than FRAN in some cases. However the proposed hyper framework provides an opportunity to use a great range of intelligent methods and can learn from previous experiences. Thus it can avoid the weakness of some intelligent methods in terms of memory, computational time and static structure. Furthermore, the performance of this system can be enhanced throughout the system life-cycle. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improvement of high-fold gamma-ray data processing: the spherical gate method

CERN Document Server

Theisen, C; Stezowski, O; Vivien, J P

1999-01-01

A new method for optimizing the processing of events from a highly efficient large array gamma-ray detector is described in this article. The spherical gates technique, developed to project high-fold events, consists of optimizing n-dimensional gate shape as a function of peak width and shape of each detector. Formulas in closed form are proposed for determining the projected statistics from coincidence fold and peak shape and for estimating the increased quality of projected spectra. This procedure has been tested on high-fold, high statistics data sets including superdeformed cascades. Compared to the classical 'square-gate' technique, better peak-to-background ratios as well as a reduction in fluctuations are observed. A quality parameter is defined to characterize the optimal parameter set. This method leads roughly to a gain in spectral quality equivalent of one fold. It is also shown that the efficiency of the method increases with coincidence fold. This should be particularly suited for future higher-f...

Periodic and stochastic thermal modulation of protein folding kinetics.

Science.gov (United States)

Platkov, Max; Gruebele, Martin

2014-07-21

Chemical reactions are usually observed either by relaxation of a bulk sample after applying a sudden external perturbation, or by intrinsic fluctuations of a few molecules. Here we show that the two ideas can be combined to measure protein folding kinetics, either by periodic thermal modulation, or by creating artificial thermal noise that greatly exceeds natural thermal fluctuations. We study the folding reaction of the enzyme phosphoglycerate kinase driven by periodic temperature waveforms. As the temperature waveform unfolds and refolds the protein, its fluorescence color changes due to FRET (Förster resonant Energy Transfer) of two donor/acceptor fluorophores labeling the protein. We adapt a simple model of periodically driven kinetics that nicely fits the data at all temperatures and driving frequencies: The phase shifts of the periodic donor and acceptor fluorescence signals as a function of driving frequency reveal reaction rates. We also drive the reaction with stochastic temperature waveforms that produce thermal fluctuations much greater than natural fluctuations in the bulk. Such artificial thermal noise allows the recovery of weak underlying signals due to protein folding kinetics. This opens up the possibility for future detection of a stochastic resonance for protein folding subject to noise with controllable amplitude.

The influence of running away on the risk of female sexual assault in the subsequent year.

Science.gov (United States)

Thrane, Lisa E; Yoder, Kevin A; Chen, Xiaojin

2011-01-01

This study explores the sexual risk trajectories of female youths and sheds light on the long-term effects of running away. It evaluates whether running away increases the risk of sexual assault in the following year, which is after runaways return home. The sample consists of 5,387 heterosexual females between the ages of 11 and 18 years from the Longitudinal Study of Adolescent Health. Nearly one quarter (23%) of runaways report a previous sexual assault in contrast to 5% of nonrunaways. In a logistic regression model, childhood neglect increases the risk of sexual assault between Waves 1 and 2 by nearly two times. Poor mental health is statistically significant. Alcohol use doubles the odds of sexual assault. The risk of sexual assault is approximately three-fold for girls with a history of sexual onset and sexual touching in a romantic relationship. Running away increases the risk by nearly two and a half times. There is evidence that alcohol use and sexual onset partially mediates the relationship between running away and sexual assault.

Wrinkles, folds, and plasticity in granular rafts

Science.gov (United States)

Jambon-Puillet, Etienne; Josserand, Christophe; Protière, Suzie

2017-09-01

We investigate the mechanical response of a compressed monolayer of large and dense particles at a liquid-fluid interface: a granular raft. Upon compression, rafts first wrinkle; then, as the confinement increases, the deformation localizes in a unique fold. This characteristic buckling pattern is usually associated with floating elastic sheets, and as a result, particle laden interfaces are often modeled as such. Here, we push this analogy to its limits by comparing quantitative measurements of the raft morphology to a theoretical continuous elastic model of the interface. We show that, although powerful to describe the wrinkle wavelength, the wrinkle-to-fold transition, and the fold shape, this elastic description does not capture the finer details of the experiment. We describe an unpredicted secondary wavelength, a compression discrepancy with the model, and a hysteretic behavior during compression cycles, all of which are a signature of the intrinsic discrete and frictional nature of granular rafts. It suggests also that these composite materials exhibit both plastic transition and jamming dynamics.

Exploring the relationship between fall risk-increasing drugs and fall-related fractures.

Science.gov (United States)

De Winter, Sabrina; Vanwynsberghe, Sarah; Foulon, Veerle; Dejaeger, Eddy; Flamaing, Johan; Sermon, An; Van der Linden, Lorenz; Spriet, Isabel

2016-04-01

Hospital admissions due to fall-related fractures are a major problem in the aging population. Several risk factors have been identified, including drug use. Most studies often retrieved prescription-only drugs from national databases. These are associated with some limitations as they do not always reliably reproduce the complete patient's active drug list. To evaluate the association between the number of FRIDs intake identified by a standardised medication reconciliation process and a fall-related fracture leading to a hospital admission in older adults. The first cohort has been recruited from one traumatology ward of a tertiary teaching hospital in Belgium and the second cohort has been recruited from 11 community pharmacies in Belgium. A prospective study with two individually matched cohorts was performed. Adult patients (≥75 years) admitted with an injury due to a fall were included in the first cohort (faller group). The second cohort consisted of patients who did not suffer from a fall within the last 6 months (non-faller group). Matching was performed for age, gender, place of residence and use of a walking aid. In both groups, clinical pharmacists and undergraduate pharmacy students obtained the medication history, using a standardised approach. A list of drugs considered to increase the risk of falling was created. It included cardiovascular drugs and drugs acting on the nervous system. A linear mixed model was used to compare the number of fall risk-increasing drugs between fallers and non-fallers. The number of fall risk-increasing drugs in a faller versus a non-faller group. Sixty-one patients were matched with 121 non-fallers. Patients received on average 3.1 ± 2.1 and 3.2 ± 1.8 fall risk-increasing drugs in the faller and in the non-faller group, respectively. The mean number of fall risk-increasing drugs was comparable in both groups (p = 0.844), even after adjusting for alcohol consumption, fear of falling, vision and foot problems (p = 0

Increased Baseline C-Reactive Protein Concentrations Are Associated with Increased Risk of Infections

DEFF Research Database (Denmark)

Zacho, Jeppe; Benfield, Thomas; Tybjærg-Hansen, Anne

2016-01-01

BACKGROUND: The acute-phase reactant C-reactive protein (CRP) increases rapidly during an infection. We tested the hypothesis that chronic low-level increases in CRP are associated with an increased risk of infectious disease. METHODS: We studied 9660 individuals from a prospective general...... population cohort, including 3592 in whom infectious disease developed, and another 60 896 individuals from a cross-sectional general population study, of whom 13 332 developed infectious disease; 55% were women, and the mean age was 57 years. Hospital diagnoses of infections in 1977-2010 were based....... RESULTS: Individuals with CRP >3 mg/L had 1.2 and 1.7 times increased risk of infectious disease, in the prospective general population cohort and the cross-sectional general population study, respectively, compared with individuals with CRP

Vocal fold contact patterns based on normal modes of vibration.

Science.gov (United States)

Smith, Simeon L; Titze, Ingo R

2018-05-17

The fluid-structure interaction and energy transfer from respiratory airflow to self-sustained vocal fold oscillation continues to be a topic of interest in vocal fold research. Vocal fold vibration is driven by pressures on the vocal fold surface, which are determined by the shape of the glottis and the contact between vocal folds. Characterization of three-dimensional glottal shapes and contact patterns can lead to increased understanding of normal and abnormal physiology of the voice, as well as to development of improved vocal fold models, but a large inventory of shapes has not been directly studied previously. This study aimed to take an initial step toward characterizing vocal fold contact patterns systematically. Vocal fold motion and contact was modeled based on normal mode vibration, as it has been shown that vocal fold vibration can be almost entirely described by only the few lowest order vibrational modes. Symmetric and asymmetric combinations of the four lowest normal modes of vibration were superimposed on left and right vocal fold medial surfaces, for each of three prephonatory glottal configurations, according to a surface wave approach. Contact patterns were generated from the interaction of modal shapes at 16 normalized phases during the vibratory cycle. Eight major contact patterns were identified and characterized by the shape of the flow channel, with the following descriptors assigned: convergent, divergent, convergent-divergent, uniform, split, merged, island, and multichannel. Each of the contact patterns and its variation are described, and future work and applications are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Different secondary structure elements as scaffolds for protein folding transition states of two homologous four-helix bundles.

Science.gov (United States)

Teilum, Kaare; Thormann, Thorsten; Caterer, Nigel R; Poulsen, Heidi I; Jensen, Peter H; Knudsen, Jens; Kragelund, Birthe B; Poulsen, Flemming M

2005-04-01

Comparison of the folding processes for homologue proteins can provide valuable information about details in the interactions leading to the formation of the folding transition state. Here the folding kinetics of 18 variants of yACBP and 3 variants of bACBP have been studied by Phi-value analysis. In combination with Phi-values from previous work, detailed insight into the transition states for folding of both yACBP and bACBP has been obtained. Of the 16 sequence positions that have been studied in both yACBP and bACBP, 5 (V12, I/L27, Y73, V77, and L80) have high Phi-values and appear to be important for the transition state formation in both homologues. Y31, A34, and A69 have high Phi-values only in yACBP, while F5, A9, and I74 have high Phi-values only in bACBP. Thus, additional interactions between helices A2 and A4 appear to be important for the transition state of yACBP, whereas additional interactions between helices A1 and A4 appear to be important for the transition state of bACBP. To examine whether these differences could be assigned to different packing of the residues in the native state, a solution structure of yACBP was determined by NMR. Small changes in the packing of the hydrophobic side-chains, which strengthen the interactions between helices A2 and A4, are observed in yACBP relative to bACBP. It is suggested that different structure elements serve as scaffolds for the folding of the 2 ACBP homologues. (c) 2005 Wiley-Liss, Inc.

Risk of falls after withdrawal of fall-risk-increasing drugs: a prospective cohort study

NARCIS (Netherlands)

van der Velde, Nathalie; Stricker, Bruno H. Ch; Pols, Huib A. P.; van der Cammen, Tischa J. M.

2007-01-01

AIMS: Falling in older persons is a frequent and serious clinical problem. Several drugs have been associated with increased fall risk. The objective of this study was to identify differences in the incidence of falls after withdrawal (discontinuation or dose reduction) of fall-risk-increasing drugs

Optimal fold symmetry of LH2 rings on a photosynthetic membrane.

Science.gov (United States)

Cleary, Liam; Chen, Hang; Chuang, Chern; Silbey, Robert J; Cao, Jianshu

2013-05-21

An intriguing observation of photosynthetic light-harvesting systems is the N-fold symmetry of light-harvesting complex 2 (LH2) of purple bacteria. We calculate the optimal rotational configuration of N-fold rings on a hexagonal lattice and establish two related mechanisms for the promotion of maximum excitation energy transfer (EET). (i) For certain fold numbers, there exist optimal basis cells with rotational symmetry, extendable to the entire lattice for the global optimization of the EET network. (ii) The type of basis cell can reduce or remove the frustration of EET rates across the photosynthetic network. We find that the existence of a basis cell and its type are directly related to the number of matching points S between the fold symmetry and the hexagonal lattice. The two complementary mechanisms provide selection criteria for the fold number and identify groups of consecutive numbers. Remarkably, one such group consists of the naturally occurring 8-, 9-, and 10-fold rings. By considering the inter-ring distance and EET rate, we demonstrate that this group can achieve minimal rotational sensitivity in addition to an optimal packing density, achieving robust and efficient EET. This corroborates our findings i and ii and, through their direct relation to S, suggests the design principle of matching the internal symmetry with the lattice order.

Acute Acrolein Exposure Induces Impairment of Vocal Fold Epithelial Barrier Function.

Directory of Open Access Journals (Sweden)

Xinxin Liu

Full Text Available Acrolein is a ubiquitous pollutant abundant in cigarette smoke, mobile exhaust, and industrial waste. There is limited literature on the effects of acrolein on vocal fold tissue, although there are clinical reports of voice changes after pollutant exposures. Vocal folds are responsible for voice production. The overall objective of this study was to investigate the effects of acrolein exposure on viable, excised vocal fold epithelial tissue and to characterize the mechanism underlying acrolein toxicity. Vocal fold epithelia were studied because they form the outermost layer of the vocal folds and are a primary recipient of inhaled pollutants. Porcine vocal fold epithelia were exposed to 0, 50, 100, 500, 900 or 1300 μM of acrolein for 3 hours; the metabolic activity, epithelial resistance, epithelial permeability, tight junction protein (occludin and claudin 3 expression, cell membrane integrity and lipid peroxidation were investigated. The data demonstrated that acrolein exposure at 500 μM significantly reduced vocal fold epithelial metabolic activity by 27.2% (p≤0.001. Incubation with 100 μM acrolein caused a marked increase in epithelial permeability by 130.5% (p<0.05 and a reduction in transepithelial electrical resistance (TEER by 180.0% (p<0.001. While the expression of tight junctional protein did not change in acrolein-treated samples, the cell membrane integrity was significantly damaged with a 45.6% increase of lipid peroxidation as compared to controls (p<0.05. Taken together, these data provide evidence that acute acrolein exposure impairs vocal fold epithelial barrier integrity. Lipid peroxidation-induced cell membrane damage may play an important role in reducing the barrier function of the epithelium.

Mapping the universe of RNA tetraloop folds

DEFF Research Database (Denmark)

Bottaro, Sandro; Lindorff-Larsen, Kresten

2017-01-01

We report a map of RNA tetraloop conformations constructed by calculating pairwise distances among all experimentally determined four-nucleotide hairpin loops. Tetraloops with similar structures are clustered together and, as expected, the two largest clusters are the canonical GNRA and UNCG fold...

Quantification of fold growth of frontal antiforms in the Zagros fold and thrust belt (Kurdistan, NE Iraq)

Science.gov (United States)

Bretis, Bernhard; Bartl, Nikolaus; Graseman, Bernhard; Lockhart, Duncan

2010-05-01

The Zagros fold and thrust belt is a seismically active orogen, where actual kinematic models based on GPS networks suggest a north-south shortening between Arabian and Eurasian in the order of 1.5-2.5 cm/yr. Most of this deformation is partitioned in south-southwest oriented folding and thrusting with northwest-southeast to north-south trending dextral strike slip faults. The Zagros fold and thrust belt is of great economic interest because it has been estimated that this area contains about 15% of the global recoverable hydrocarbons. Whereas the SE parts of the Zagros have been investigated by detailed geological studies, the NW extent being part of the Republic of Iraq have experienced considerably less attention. In this study we combine field work and remote sensing techniques in order to investigate the interaction of erosion and fold growth in the area NE of Erbil (Kurdistan, Iraq). In particular we focus on the interaction of the transient development of drainage patterns along growing antiforms, which directly reflects the kinematics of progressive fold growth. Detailed geomorphological studies of the Bana Bawi-, Permam- and Safeen fold trains show that these anticlines have not developed from subcylindrical embryonic folds but they have merged from different fold segments that joined laterally during fold amplification. This fold segments with length between 5 and 25 km have been detected by mapping ancient and modern river courses that initially cut the nose of growing folds and eventually got defeated leaving behind a wind gap. Fold segments, propagating in different directions force rivers to join resulting in steep gorges, which dissect the merging fold noses. Along rapidly lateral growing folds (e.g. at the SE end of the Bana Bawi Anticline) we observed "curved wind gaps", a new type of abandoned river course, where form of the wind gap mimics a formed nose of a growing antiform. The inherited curved segments of uplifted curved river courses strongly

Time course of recovery of idiopathic vocal fold paralysis.

Science.gov (United States)

Husain, Solomon; Sadoughi, Babak; Mor, Niv; Levin, Ariana M; Sulica, Lucian

2018-01-01

To clarify the time course of recovery in patients with idiopathic vocal fold paralysis. Retrospective chart review. Medical records for all patients with idiopathic vocal fold paralysis over a 10-year period were reviewed to obtain demographic and clinical information, including onset of disease and recovery of vocal function. Stroboscopic exams of patients who recovered voice were reviewed blindly to assess return of vocal fold motion. Thirty-eight of 55 patients (69%) recovered vocal function. Time course of recovery could be assessed in 34 patients who did not undergo injection augmentation. The mean time to recovery was 152.8 ± 109.3 days (left, 179.8 ± 111.3 days; right, 105.3 ± 93.7 days; P = .088). Two-thirds of patients recovered within 6 months. Probability of recovery declined over time. Five of 22 patients who recovered voice had return of vocal fold motion; 17 did not. The mean time to recovery did not differ between these groups (return of motion, 127.4 ± 132.3 days; no return of motion, 160.1 ± 105.1 days; P = .290). Sixty-nine percent of patients with idiopathic vocal fold paralysis recovered vocal function, two-thirds doing so within 6 months of onset. Age, gender, laterality, use of injection augmentation did not influence recovery rate. Declining probability of recovery over time leads us to consider framework surgery after 6 months in patients with idiopathic paralysis. 4. Laryngoscope, 128:148-152, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Reversible Dual-Image-Based Hiding Scheme Using Block Folding Technique

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Tzu-Chuen Lu

2017-10-01

Full Text Available The concept of a dual-image based scheme in information sharing consists of concealing secret messages in two cover images; only someone who has both stego-images can extract the secret messages. In 2015, Lu et al. proposed a center-folding strategy where each secret symbol is folded into the reduced digit to reduce the distortion of the stego-image. Then, in 2016, Lu et al. used a frequency-based encoding strategy to reduce the distortion of the frequency of occurrence of the maximum absolute value. Because the folding strategy can obviously reduce the value, the proposed scheme includes the folding operation twice to further decrease the reduced digit. We use a frequency-based encoding strategy to encode a secret message and then use the block folding technique by performing the center-folding operation twice to embed secret messages. An indicator is needed to identify the sequence number of the folding operation. The proposed scheme collects several indicators to produce a combined code and hides the code in a pixel to reduce the size of the indicators. The experimental results show that the proposed method can achieve higher image quality under the same embedding rate or higher payload, which is better than other methods.

Birefringence Optical Feedback with a Folded Cavity in HeNe Laser

International Nuclear Information System (INIS)

Wu Yun; Tan Yi-Dong

2013-01-01

The birefringence optical feedback with a folded cavity in HeNe laser is investigated. A theory model based on the equivalent cavity of the Fabry—Perot interferometer is presented. The phase difference between the two intensities in birefringence feedback is twice the retardation of the wave plate. The phase difference is invariable when the length of the feedback cavity changes. With the adoption of a cube corner prism (CCP) to form a folded cavity, the fringe frequency is doubled, and the resolution of the displacement sensor based on birefringence optical feedback with a folded cavity is improved. A resistance chain of 5-fold subdivision and 4-fold logic subdivision is used as further subdivision. The resolution of λ/80 is obtained eventually; for 632.8 nm HeNe laser it is 7.91 nm. The displacement sensor based on birefringence optical feedback with a folded cavity is simple and of high resolution, large measurement range, low cost, and is of great application potential in industry

[Gastro-esophageal Reflux Disease and malignant progression--equal risk for men and women?].

Science.gov (United States)

Pech, O

2015-08-01

Gastroesophageal reflux disease (GERD) is highly prevalent in the Western world. Patients with GERD have a 10 fold increased risk to develop a Barrett's esophagus. Patients with Barrett's esophagus have a higher risk for an esophageal adenocarcinoma. Men have more severe reflux with a higher grade of inflammation and acid reflux. This seems to be the reason why men develop a Barrett's esophagus more frequently--the risk is approximately 2 to 3 fold and the risk for an esophageal adenocarcinoma is even 3 to 6 times higher. © Georg Thieme Verlag KG Stuttgart · New York.

Increasing resilience through participative flood risk map design

Science.gov (United States)

Fuchs, Sven; Spira, Yvonne; Stickler, Therese

2013-04-01

In recent years, an increasing number of flood hazards has shown to the European Commission and the Member States of the European Union the importance of flood risk management strategies in order to reduce losses and to protect the environment and the citizens. Exposure to floods as well as flood vulnerability might increase across Europe due to the ongoing economic development in many EU countries. Thus even without taking climate change into account an increase of flood disasters in Europe might be foreseeable. These circumstances have produced a reaction in the European Commission, and a Directive on the Assessment and Management of Flood Risks was issued as one of the three components of the European Action Programme on Flood Risk Management. Floods have the potential to jeopardise economic development, above all due to an increase of human activities in floodplains and the reduction of natural water retention by land use activities. As a result, an increase in the likelihood and adverse impacts of flood events is expected. Therefore, concentrated action is needed at the European level to avoid severe impacts on human life and property. In order to have an effective tool available for gathering information, as well as a valuable basis for priority setting and further technical, financial and political decisions regarding flood risk mitigation and management, it is necessary to provide for the establishment of flood risk maps which show the potential adverse consequences associated with different flood scenarios. So far, hazard and risk maps are compiled in terms of a top-down linear approach: planning authorities take the responsibility to create and implement these maps on different national and local scales, and the general public will only be informed about the outcomes (EU Floods Directive, Article 10). For the flood risk management plans, however, an "active involvement of interested parties" is required, which means at least some kind of multilateral

Unplanned return to operating room after endovascular repair of abdominal aortic aneurysm (EVAR) is associated with increased risk of hospital readmission.

Science.gov (United States)

Aziz, Faisal; Ferranti, Katelynn; Lehman, Erik B

2018-04-01

Objectives Hospital readmissions after surgical operations are considered serious events. Centers for Medicare and Medicaid (CMS) consider surgical readmissions as preventable and hold hospitals responsible for them. Endovascular abdominal aortic aneurysm (EVAR) has become the first line modality of treatment for suitable patients with abdominal aortic aneurysm (AAA). The purpose of this study is to retrospectively review the factors associated with hospital readmission after EVAR. Methods The 2013 EVAR targeted American College of Surgeons (ACS-NSQIP) database and generalized 2013 general and vascular surgery ACS-NSQIP participant use files were used for this study. Patient, diagnosis, and procedure characteristics of patients undergoing EVAR surgery were assessed. Multivariate logistic regression analysis was used to determine independent risk factors for hospital readmission within 30 days after surgery. Results A total of 2277 patients (81% males, 19% females) underwent EVAR operations in the year 2013. Indications for operations included: asymptomatic large diameter (79%), symptomatic (5.7%), rupture without hypotension (4.3%), and rupture with hypotension (2.8%). Among these patients, 178 (7.8%) were readmitted to the hospital within 30 days after surgery. About 53% of all readmissions were within two weeks after the discharge. Risk factors, associated with readmission included: body mass index (per 5-units, OR 1.23, CI 1.06-1.42, p readmission for patients with presence of all these seven factors was 99.9%. Conclusions Readmission after EVAR is a serious occurrence. Various factors predispose a patient at a high risk for readmission. Unplanned return to operating room after EVAR is associated with a 11-fold increase in hospital readmission.

Exposure to welding fumes increases lung cancer risk among light smokers but not among heavy smokers: evidence from two case–control studies in Montreal

Science.gov (United States)

Vallières, Eric; Pintos, Javier; Lavoué, Jérôme; Parent, Marie-Élise; Rachet, Bernard; Siemiatycki, Jack

2012-01-01

We investigated relationships between occupational exposure to gas and arc welding fumes and the risk of lung cancer among workers exposed to these agents throughout the spectrum of industries. Two population-based case–control studies were conducted in Montreal. Study I (1979–1986) included 857 cases and 1066 controls, and Study II (1996–2001) comprised 736 cases and 894 controls. Detailed job histories were obtained by interview and evaluated by an expert team of chemist–hygienists to estimate degree of exposure to approximately 300 substances for each job. Gas and arc welding fumes were among the agents evaluated. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of lung cancer using logistic regression, adjusting for smoking history and other covariates. The two studies provided similar results, so a pooled analysis was conducted. Among all subjects, no significant association was found between lung cancer and gas welding fumes (OR = 1.1; 95% CI = 0.9–1.4) or arc welding fumes (OR = 1.0; 95% CI = 0.8–1.2). However, when restricting attention to light smokers, there was an increased risk of lung cancer in relation to gas welding fumes (OR = 2.9; 95% CI = 1.7–4.8) and arc welding fumes (OR = 2.3; 95% CI = 1.3–3.8), with even higher OR estimates among workers with the highest cumulative exposures. In conclusion, there was no detectable excess risk of lung cancer due to welding fumes among moderate to heavy smokers; but among light smokers we found an excess risk related to both types of welding fumes. PMID:23342253

Cryptorchidism and increased risk of neurodevelopmental disorders.

Science.gov (United States)

Chen, Jianping; Sørensen, Henrik Toft; Miao, Maohua; Liang, Hong; Ehrenstein, Vera; Wang, Ziliang; Yuan, Wei; Li, Jiong

2018-01-01

Male congenital malformations as cryptorchidism may contribute to the development of neurodevelopmental disorders directly or via shared familial genetic and/or environmental factors, but the evidence is sparse. Using population-based health registries, we conducted a cohort study of all liveborn singleton boys in Denmark during 1979-2008. Boys with a diagnosis of cryptorchidism were categorized into the exposed cohort and the other boys into the unexposed comparison cohort. The outcomes were diagnoses of any neurodevelopmental disorders and their subtypes. We used Cox proportional hazards regression to compute hazard ratios (HRs), taking into consideration several potential confounders. Among 884,083 male infants, 27,505 received a diagnosis of cryptorchidism during follow-up. Boys with cryptorchidism were more likely to be diagnosed with intellectual disability (HR = 1.77; 95%confidence interval [CI]:1.59,1.97), autism spectrum disorders (ASD) (HR = 1.24; 95% CI:1.13,1.35), attention-deficit hyperactivity disorder (ADHD) (HR = 1.17; 95% CI: 1.08,1.26), anxiety (HR = 1.09; 95% CI: 1.01,1.17), and other behavioral/emotional disorders (HR = 1.16; 95% CI: 1.08,1.26) compared to boys without cryptorchidism. The observed risks of intellectual disability, ASD, and ADHD were increased further in boys with bilateral cryptorchidism. Except for anxiety, cryptorchid boys had higher risks of neurodevelopmental disorders than their non-cryptorchid full brothers. The observed increased risks were similar among boys who underwent orchiopexy, as well as among those with shorter waiting times for this surgery. Cryptorchidism may be associated with increased risks of intellectual disability, ASD, ADHD, and other behavioral/emotional disorders. Cryptorchidism and neurodevelopmental disorders may have shared genetic or in-utero/early postnatal risk factors, which need to be further investigated. Copyright © 2017. Published by Elsevier Ltd.

Risk of fracture with thiazolidinediones: an individual patient data meta-analysis

Directory of Open Access Journals (Sweden)

Marloes T Bazelier

2013-02-01

Full Text Available Background: The use of thiazolidinediones (TZDs has been associated with increased fracture risks. Our aim was to estimate the risk of fracture with TZDs in three different healthcare registries, using exactly the same study design, and to perform an individual patient data meta-analysis of these three studies. Methods: Population-based cohort studies were performed utilizing the British General Practice Research Database (GPRD, the Dutch PHARMO Record Linkage System, and the Danish National Health Registers. In all three databases, the exposed cohort consisted of all patients (aged 18+ with at least one prescription of antidiabetic (AD medication. Cox proportional hazards models were used to estimate hazard ratios (HRs of fracture. The total period of follow-up for each patient was divided into periods of current exposure and past exposure, with patients moving between current and past use.Results: In all three registries, the risk of fracture was increased for women who were exposed to TZDs: HR 1.48 [1.37-1.60] in GPRD, HR 1.35 [1.15-1.58] in PHARMO and HR 1.22 [1.03-1.44] in Denmark. Combining the data in an individual patient data meta-analysis resulted, for women, in a 1.4-fold increased risk of any fracture for current TZD users versus other AD drug users (adj. HR 1.44 [1.35-1.53]. For men, there was no increased fracture risk (adj. HR 1.05 [0.96-1.14]. Risks were increased for fractures of the radius/ulna, humerus, tibia/fibula, ankle and foot, but not for hip/femur or vertebral fractures. Current TZD users with more than 25 TZD presciptions ever before had a 1.6-fold increased risk of fracture compared with other AD drug users (HR 1.59 [1.46-1.74].Conclusion: In this study, we consistently found a 1.2- to 1.5-fold increased risk of fractures for women using TZDs, but not for men, across three different healthcare registries. TZD users had an increased risk for fractures of the extremities, and risks further increased for prolonged users

Phi-value analysis of apo-azurin folding: comparison between experiment and theory.

Science.gov (United States)

Zong, Chenghang; Wilson, Corey J; Shen, Tongye; Wolynes, Peter G; Wittung-Stafshede, Pernilla

2006-05-23

Pseudomonas aeruginosa azurin is a 128-residue beta-sandwich metalloprotein; in vitro kinetic experiments have shown that it folds in a two-state reaction. Here, we used a variational free energy functional to calculate the characteristics of the transition state ensemble (TSE) for folding of the apo-form of P. aeruginosa azurin and investigate how it responds to thermal and mutational changes. The variational method directly yields predicted chevron plots for wild-type and mutant apo-forms of azurin. In parallel, we performed in vitro kinetic-folding experiments on the same set of azurin variants using chemical perturbation. Like the wild-type protein, all apo-variants fold in apparent two-state reactions both in calculations and in stopped-flow mixing experiments. Comparisons of phi (phi) values determined from the experimental and theoretical chevron parameters reveal an excellent agreement for most positions, indicating a polarized, highly structured TSE for folding of P. aeruginosa apo-azurin. We also demonstrate that careful analysis of side-chain interactions is necessary for appropriate theoretical description of core mutants.

Autonomously folding protein fragments reveal differences in the energy landscapes of homologous RNases H.

Directory of Open Access Journals (Sweden)

Laura E Rosen

Full Text Available An important approach to understanding how a protein sequence encodes its energy landscape is to compare proteins with different sequences that fold to the same general native structure. In this work, we compare E. coli and T. thermophilus homologs of the protein RNase H. Using protein fragments, we create equilibrium mimics of two different potential partially-folded intermediates (I(core and I(core+1 hypothesized to be present on the energy landscapes of these two proteins. We observe that both T. thermophilus RNase H (ttRNH fragments are folded and have distinct stabilities, indicating that both regions are capable of autonomous folding and that both intermediates are present as local minima on the ttRNH energy landscape. In contrast, the two E. coli RNase H (ecRNH fragments have very similar stabilities, suggesting that the presence of additional residues in the I(core+1 fragment does not affect the folding or structure as compared to I(core. NMR experiments provide additional evidence that only the I(core intermediate is populated by ecRNH. This is one of the biggest differences that has been observed between the energy landscapes of these two proteins. Additionally, we used a FRET experiment in the background of full-length ttRNH to specifically monitor the formation of the I(core+1 intermediate. We determine that the ttRNH I(core+1 intermediate is likely the intermediate populated prior to the rate-limiting barrier to global folding, in contrast to E. coli RNase H for which I(core is the folding intermediate. This result provides new insight into the nature of the rate-limiting barrier for the folding of RNase H.

Solitons and protein folding: An In Silico experiment

Energy Technology Data Exchange (ETDEWEB)

Ilieva, N., E-mail: nevena.ilieva@parallel.bas.bg [Institute of Information and Communication Technologies, Bulgarian Aacademy of Sciences, Sofia (Bulgaria); Dai, J., E-mail: daijing491@gmail.com [School of Physics, Beijing Institute of Technology, Beijing (China); Sieradzan, A., E-mail: adams86@wp.pl [Faculty of Chemistry, University of Gdańsk, Gdańsk (Poland); Niemi, A., E-mail: Antti.Niemi@physics.uu.se [Department of Physics and Astronomy, Uppsala University, Uppsala (Sweden); LMPT–CNRS, Université de Tours, Tours (France)

2015-10-28

Protein folding [1] is the process of formation of a functional 3D structure from a random coil — the shape in which amino-acid chains leave the ribosome. Anfinsen’s dogma states that the native 3D shape of a protein is completely determined by protein’s amino acid sequence. Despite the progress in understanding the process rate and the success in folding prediction for some small proteins, with presently available physics-based methods it is not yet possible to reliably deduce the shape of a biologically active protein from its amino acid sequence. The protein-folding problem endures as one of the most important unresolved problems in science; it addresses the origin of life itself. Furthermore, a wrong fold is a common cause for a protein to lose its function or even endanger the living organism. Soliton solutions of a generalized discrete non-linear Schrödinger equation (GDNLSE) obtained from the energy function in terms of bond and torsion angles κ and τ provide a constructive theoretical framework for describing protein folds and folding patterns [2]. Here we study the dynamics of this process by means of molecular-dynamics simulations. The soliton manifestation is the pattern helix–loop–helix in the secondary structure of the protein, which explains the importance of understanding loop formation in helical proteins. We performed in silico experiments for unfolding one subunit of the core structure of gp41 from the HIV envelope glycoprotein (PDB ID: 1AIK [3]) by molecular-dynamics simulations with the MD package GROMACS. We analyzed 80 ns trajectories, obtained with one united-atom and two different all-atom force fields, to justify the side-chain orientation quantification scheme adopted in the studies and to eliminate force-field based artifacts. Our results are compatible with the soliton model of protein folding and provide first insight into soliton-formation dynamics.

Solitons and protein folding: An In Silico experiment

International Nuclear Information System (INIS)

Ilieva, N.; Dai, J.; Sieradzan, A.; Niemi, A.

2015-01-01

Protein folding [1] is the process of formation of a functional 3D structure from a random coil — the shape in which amino-acid chains leave the ribosome. Anfinsen’s dogma states that the native 3D shape of a protein is completely determined by protein’s amino acid sequence. Despite the progress in understanding the process rate and the success in folding prediction for some small proteins, with presently available physics-based methods it is not yet possible to reliably deduce the shape of a biologically active protein from its amino acid sequence. The protein-folding problem endures as one of the most important unresolved problems in science; it addresses the origin of life itself. Furthermore, a wrong fold is a common cause for a protein to lose its function or even endanger the living organism. Soliton solutions of a generalized discrete non-linear Schrödinger equation (GDNLSE) obtained from the energy function in terms of bond and torsion angles κ and τ provide a constructive theoretical framework for describing protein folds and folding patterns [2]. Here we study the dynamics of this process by means of molecular-dynamics simulations. The soliton manifestation is the pattern helix–loop–helix in the secondary structure of the protein, which explains the importance of understanding loop formation in helical proteins. We performed in silico experiments for unfolding one subunit of the core structure of gp41 from the HIV envelope glycoprotein (PDB ID: 1AIK [3]) by molecular-dynamics simulations with the MD package GROMACS. We analyzed 80 ns trajectories, obtained with one united-atom and two different all-atom force fields, to justify the side-chain orientation quantification scheme adopted in the studies and to eliminate force-field based artifacts. Our results are compatible with the soliton model of protein folding and provide first insight into soliton-formation dynamics

Visualization of protein folding funnels in lattice models.

Directory of Open Access Journals (Sweden)

Antonio B Oliveira

Full Text Available Protein folding occurs in a very high dimensional phase space with an exponentially large number of states, and according to the energy landscape theory it exhibits a topology resembling a funnel. In this statistical approach, the folding mechanism is unveiled by describing the local minima in an effective one-dimensional representation. Other approaches based on potential energy landscapes address the hierarchical structure of local energy minima through disconnectivity graphs. In this paper, we introduce a metric to describe the distance between any two conformations, which also allows us to go beyond the one-dimensional representation and visualize the folding funnel in 2D and 3D. In this way it is possible to assess the folding process in detail, e.g., by identifying the connectivity between conformations and establishing the paths to reach the native state, in addition to regions where trapping may occur. Unlike the disconnectivity maps method, which is based on the kinetic connections between states, our methodology is based on structural similarities inferred from the new metric. The method was developed in a 27-mer protein lattice model, folded into a 3×3×3 cube. Five sequences were studied and distinct funnels were generated in an analysis restricted to conformations from the transition-state to the native configuration. Consistent with the expected results from the energy landscape theory, folding routes can be visualized to probe different regions of the phase space, as well as determine the difficulty in folding of the distinct sequences. Changes in the landscape due to mutations were visualized, with the comparison between wild and mutated local minima in a single map, which serves to identify different trapping regions. The extension of this approach to more realistic models and its use in combination with other approaches are discussed.

The nature of folded states of globular proteins.

Science.gov (United States)

Honeycutt, J D; Thirumalai, D

1992-06-01

We suggest, using dynamical simulations of a simple heteropolymer modelling the alpha-carbon sequence in a protein, that generically the folded states of globular proteins correspond to statistically well-defined metastable states. This hypothesis, called the metastability hypothesis, states that there are several free energy minima separated by barriers of various heights such that the folded conformations of a polypeptide chain in each of the minima have similar structural characteristics but have different energies from one another. The calculated structural characteristics, such as bond angle and dihedral angle distribution functions, are assumed to arise from only those configurations belonging to a given minimum. The validity of this hypothesis is illustrated by simulations of a continuum model of a heteropolymer whose low temperature state is a well-defined beta-barrel structure. The simulations were done using a molecular dynamics algorithm (referred to as the "noisy" molecular dynamics method) containing both friction and noise terms. It is shown that for this model there are several distinct metastable minima in which the structural features are similar. Several new methods of analyzing fluctuations in structures belonging to two distinct minima are introduced. The most notable one is a dynamic measure of compactness that can in principle provide the time required for maximal compactness to be achieved. The analysis shows that for a given metastable state in which the protein has a well-defined folded structure the transition to a state of higher compactness occurs very slowly, lending credence to the notion that the system encounters a late barrier in the process of folding to the most compact structure. The examination of the fluctuations in the structures near the unfolding----folding transition temperature indicates that the transition state for the unfolding to folding process occurs closer to the folded state.

Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population.

Directory of Open Access Journals (Sweden)

Nigam H Shah

Full Text Available Proton pump inhibitors (PPIs have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches.Using a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population.In multiple data sources, we found gastroesophageal reflux disease (GERD patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09-1.24 with myocardial infarction (MI. Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07-3.78; P = 0.031 increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H2 blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000.Consistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.

Significant increase of Echinococcus multilocularis prevalencein foxes, but no increased predicted risk for humans

NARCIS (Netherlands)

Maas, M.; Dam-Deisz, W.D.C.; Roon, van A.M.; Takumi, K.; Giessen, van der J.W.B.

2014-01-01

The emergence of the zoonotic tapeworm Echinococcus multilocularis, causative agent ofalveolar echinococcosis (AE), poses a public health risk. A previously designed risk mapmodel predicted a spread of E. multilocularis and increasing numbers of alveolar echinococ-cosis patients in the province of

In vitro gastrointestinal digestion increases the translocation of polystyrene nanoparticles in an in vitro intestinal co-culture model.

Science.gov (United States)

Walczak, Agata P; Kramer, Evelien; Hendriksen, Peter J M; Helsdingen, Richard; van der Zande, Meike; Rietjens, Ivonne M C M; Bouwmeester, Hans

2015-01-01

The conditions of the gastrointestinal tract may change the physicochemical properties of nanoparticles (NPs) and therewith the bioavailability of orally taken NPs. Therefore, we assessed the impact of in vitro gastrointestinal digestion on the protein corona of polystyrene NPs (PS-NPs) and their subsequent translocation across an in vitro intestinal barrier. A co-culture of intestinal Caco-2 and HT29-MTX cells was exposed to 50 nm PS-NPs of different charges (positive and negative) in two forms: pristine and digested in an in vitro gastrointestinal digestion model. In vitro digestion significantly increased the translocation of all, except the "neutral", PS-NPs. Upon in vitro digestion, translocation was 4-fold higher for positively charged NPs and 80- and 1.7-fold higher for two types of negatively charged NPs. Digestion significantly reduced the amount of protein in the corona of three out of four types of NPs. This reduction of proteins was 4.8-fold for "neutral", 3.5-fold for positively charged and 1.8-fold for one type of negatively charged PS-NPs. In vitro digestion also affected the composition of the protein corona of PS-NPs by decreasing the presence of higher molecular weight proteins and shifting the protein content of the corona to low molecular weight proteins. These findings are the first to report that in vitro gastrointestinal digestion significantly affects the protein corona and significantly increases the in vitro translocation of differently charged PS-NPs. These findings stress the importance of including the in vitro digestion in future in vitro intestinal translocation screening studies for risk assessment of orally taken NPs.

Vulnerability Risk Index Profile for Elder Abuse in Community-Dwelling Population

Science.gov (United States)

Dong, XinQi; Simon, Melissa A.

2013-01-01

Objectives Elder abuse is associated with increased morbidity and mortality. This study aims to develop a vulnerability index for elder abuse in a community-dwelling population. Design Population-based study Setting Geographically defined community in Chicago. Participants A population-based study was conducted in Chicago of community-dwelling older adults who participated in the Chicago Health and Aging Project (CHAP). Of the 8,157 participants in the CHAP study, 213 participants were reported to social services agency for suspected elder abuse. Measurements A vulnerability index for elder abuse was constructed from sociodemographic, health-related, and psychosocial factors. The outcomes of interest were reported and confirmed elder abuse. Logistic regression models were used to determine the accuracy of the index with respect to elder abuse outcomes. Results Out of the selected risk index for elder abuse, every one point increase in the 9 item vulnerability index items, there was a two fold increase in the risk for reported elder abuse (OR, 2.19 (2.00–2.40) and confirmed elder abuse (OR, 2.19 (1.94–2.47). Compared to the reference group, older adults with 3–4 vulnerability index items had increased risk for reported elder abuse (OR, 2.98 (1.98–4.49) and confirmed elder abuse (OR, 3.90, (2.07–7.36); and older adults with 5 or more risk index items, there was an 18 fold increase in risk for reported elder abuse (OR, 18.46 (12.15–28.04) and confirmed elder abuse (OR, 26.79 (14.18–50.61). Receiver Operating Characteristic (ROC) statistically derived curves for identifying reported elder abuse ranged between 0.77–0.84 and for predicting confirmed elder abuse ranged between 0.79–0.86. Conclusion The vulnerability risk index demonstrates value for identifying individuals at risk for elder abuse. Additional studies are needed to validate this index in other community dwelling populations. PMID:25180376

Concept project of joining segment, connecting two folding bridge structures MS-54 and widened DMS-65

Directory of Open Access Journals (Sweden)

Jan Marszałek

2015-09-01

Full Text Available The article includes the concept project of truss segment enabling the constructions of MS-54 and DMS-65 bridges to joint. At the beginning, the basic technical and exploitative characteristics of joined constructions are introduced. On the basis of this data, geometrical analysis of the component is carried out. As a result, the concept project of fitting, enabling the crossing from two types of foldable constructions to be built, is developed. Sequentially, the computer calculations of the bridge including the part of the designed fitting are carried out.The article contains the fragments of M.A. dissertation awarded by the rector of Military University of Technology as the best from the Faculty of Civil Engineering in 2014. The article is summarized with the conclusions.[b]Keywords[/b]: construction, folding bridges, truss segment

Increased risk of hyperthyroidism among patients hospitalized with bipolar disorder

DEFF Research Database (Denmark)

Thomsen, Anders F; Kessing, Lars V

2005-01-01

OBJECTIVES: Hyperthyroidism has been associated with affective disorder in many cross-sectional studies, but longitudinal studies in this connection are scarce. We assessed whether hospitalization with depressive disorder or bipolar disorder was a risk factor for development of hyperthyroidism....... METHODS: We conducted a historical cohort study using the Danish register data. The observational period was 1977--99. Three study cohorts were identified: all patients with a first hospital admission with resulting index discharge diagnoses of depression, bipolar disorder, or osteoarthritis. The risks...... with depressive disorder did not have an increased risk of hyperthyroidism, whereas patients with bipolar disorder had an increased of risk on the margin of statistical significance, when compared to patients with osteoarthritis. Patients with bipolar disorder had a significantly increased risk of hyperthyroidism...

Long-term follow-up of vocal fold movement impairment and feeding after neonatal cardiac surgery.

Science.gov (United States)

Richter, Amy Li; Ongkasuwan, Julina; Ocampo, Elena C

2016-04-01

To determine the long-term prognosis of children with vocal fold mobility impairment (VFMI) after cardiac surgery, with respect to time to normal feeding and incidence of admissions for pneumonia and feeding difficulties. A retrospective chart review was conducted of all neonates who had otolaryngology exam after cardiac surgery at a tertiary children's hospital from May 2007 to May 2008. Charts were reviewed for demographics, type of cardiac surgery, vocal fold mobility, diet at time of discharge and at last follow-up, time to full oral feeding, and hospital admissions. There were a total of 94 patients included in the study, 17 of whom had VFMI. While significantly more patients with VFMI required modified diet at discharge, 48% compared to 19% of patients with normal vocal fold mobility; there was no statistically significant difference in time to regular diet on long-term follow-up, 0.8 years (VFMI) compared to 0.4 years (normal vocal fold mobility). Of the 25 patients with modified diet or gastrostomy tube at discharge, 52% returned to full feeds within a year. There was no difference in hospitalizations for pneumonia in patients with or without VFMI. However in patients with VFMI, 35% required readmission for feeding difficulty or poor weight gain compared to only 5% in the infants with normal vocal fold mobility. After neonatal cardiac surgery, there do not appear to be long-term effects of VFMI with regards to readmission for pneumonia. However, there is an increased risk for hospitalization with respect to feeding difficulties in those neonates with VFMI. The overall prognosis for time to oral feeding is good. Copyright © 2016. Published by Elsevier Ireland Ltd.

The Risk of Venous Thromboembolism with Different Generation of Oral Contraceptives; a Systematic Review and Meta-Analysis

Directory of Open Access Journals (Sweden)

Alireza Baratloo

2014-03-01

Full Text Available Introduction: Oral contraceptives (OCs are considered as one of the most common risk factor of venous thromboembolism (VTE in child bearing age. Some of the recent researches indicate that the odds of VTE may be even higher with newer generations of OCs. The present meta-analysis was designed to evaluate the effect of different generation of OCs on the occurrence of VTE. Methods: Two researchers independently ran a thorough search in Pubmed, ISI Web of Science, EMBASE, CINAHL and Scopus databases regarding study keywords including thromboembolic event, thromboembolism, embolism, thromboembolic, thrombotic and thrombosis, combined with oral contraceptive. The outcomes were the incidence of diagnosed thromboembolism, such as deep vein thrombosis, pulmonary embolism and cerebral venous thrombosis. Based on the heterogeneity of the studies, random effect model was used and pooled odds ratio was reported. Results: Three cohort and 17 case-control studies with 13,265,228 subjects were entered into meta-analysis. Analysis showed that the odds of VTE in women taking OCs are more than three-fold (OR=3.13; 95% CI: 2.61-3.65. The risk of VTE in women taking first-, second- and third-generation OCs are 3.5 fold (OR=3.48; 95% CI: 2.01-4.94, 3 fold (OR=3.08; 95% CI: 2.43-3.74 and 4.3 fold (OR=4.35; CI: 3.69‒5.01, respectively. Conclusion: It seems that the risk of VTE is not same between different generations of OCs, so that third-generation has highest risk. Taking second and third-generation OCs increases the risk of VTE up to 3 and 4.3 fold, respectively. The researchers of the present study suggest that more clinical trials be designed in relation to the effect of newer generations of OCs in different communities. 

Predictions of space radiation fatality risk for exploration missions.

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Cucinotta, Francis A; To, Khiet; Cacao, Eliedonna

2017-05-01

In this paper we describe revisions to the NASA Space Cancer Risk (NSCR) model focusing on updates to probability distribution functions (PDF) representing the uncertainties in the radiation quality factor (QF) model parameters and the dose and dose-rate reduction effectiveness factor (DDREF). We integrate recent heavy ion data on liver, colorectal, intestinal, lung, and Harderian gland tumors with other data from fission neutron experiments into the model analysis. In an earlier work we introduced distinct QFs for leukemia and solid cancer risk predictions, and here we consider liver cancer risks separately because of the higher RBE's reported in mouse experiments compared to other tumors types, and distinct risk factors for liver cancer for astronauts compared to the U.S. The revised model is used to make predictions of fatal cancer and circulatory disease risks for 1-year deep space and International Space Station (ISS) missions, and a 940 day Mars mission. We analyzed the contribution of the various model parameter uncertainties to the overall uncertainty, which shows that the uncertainties in relative biological effectiveness (RBE) factors at high LET due to statistical uncertainties and differences across tissue types and mouse strains are the dominant uncertainty. NASA's exposure limits are approached or exceeded for each mission scenario considered. Two main conclusions are made: 1) Reducing the current estimate of about a 3-fold uncertainty to a 2-fold or lower uncertainty will require much more expansive animal carcinogenesis studies in order to reduce statistical uncertainties and understand tissue, sex and genetic variations. 2) Alternative model assumptions such as non-targeted effects, increased tumor lethality and decreased latency at high LET, and non-cancer mortality risks from circulatory diseases could significantly increase risk estimates to several times higher than the NASA limits. Copyright © 2017 The Committee on Space Research (COSPAR

Increased risk of ischemic stroke in cervical cancer patients: a nationwide population-based study

International Nuclear Information System (INIS)

Tsai, Shiang-Jiun; Su, Yu-Chieh; Hung, Shih-Kai; Huang, Yung-Sung; Tung, Chien-Hsueh; Lee, Ching-Chih; Lee, Moon-Sing; Chiou, Wen-Yen; Lin, Hon-Yi; Hsu, Feng-Chun; Tsai, Chih-Hsin

2013-01-01

Increased risk of ischemic stroke has been validated for several cancers, but limited study evaluated this risk in cervical cancer patients. Our study aimed to evaluate the risk of ischemic stroke in cervical cancer patients. The study analyzed data from the 2003 to 2008 National Health Insurance Research Database (NHIRD) provided by the National Health Research Institutes in Taiwan. Totally, 893 cervical cancer patients after radiotherapy and 1786 appendectomy patients were eligible. The Kaplan-Meier method and the Cox proportional hazards model were used to assess the risk of ischemic stroke. The 5-year cumulative risk of ischemic stroke was significantly higher for the cervical cancer group than for the control group (7.8% vs 5.1%; p <0.005). The risk of stroke was higher in younger (age <51 years) than in older (age ≥51 years) cervical cancer patients (HR = 2.73, p = 0.04; HR = 1.37, p = 0.07) and in patients with more than two comorbid risk factors (5 years cumulative stroke rate of two comorbidities: 15% compared to no comorbidities: 4%). These study demonstrated cervical cancer patients had a higher risk of ischemic stroke than the general population, especially in younger patients. Strategies to reduce this risk should be assessed

Risk of Infections in Patients with Chronic Diseases

DEFF Research Database (Denmark)

Mor, Anil; Thomsen, Reimar W.

2013-01-01

This review provides an update on the risk of several important community-acquired infections seen in patients with diabetes: respiratory tract infections, urinary tract infections, and bacteremia. Respiratory tract infections: Recent epidemiological evidence shows a modest (1.25 to 1.75-fold) ri...... that individuals with diabetes have a substantially increased risk of a number of important infections. Clinicians should remain vigilant for infections in this increasing group of patients....

Acute manic episode is associated with an increased risk of lower limb edema.

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Hochman, Eldar; Krivoy, Amir; Shoval, Gal; Valevski, Avi; Weizman, Abraham; Fischel, Tsvi

2013-12-02

Lower limb edema (LLE) was suggested to be associated with the use of psychotropic drugs among patients suffering from severe mental illnesses; however no direct mechanism was found. Therefore, we examined the association between the occurrence of LLE and acute untreated episode leading to hospitalization. A retrospective cross-sectional study was conducted using medical charts of 2529 patients admitted to Geha Mental Health Center between 2002 and 2012. Incident cases of LLE, demographic and clinical data were retrieved. Admission clinical status was modeled as three non-overlapping groups of patients: (i) Patients with a non-affective psychosis (NAP) episode (n = 1563), (ii) patients with a manic episode (n = 366), and (iii) patients with a depressive episode (n = 600). We performed a logistic regression analysis with LLE as the dependent variable controlling for the demographic and clinical variables that may be associated with LLE. LLE was diagnosed in 3.8% (n = 95) of the study population. The rate of LLE was 3-fold higher (χ(2) = 51.9, df = 2, p<0.001) in patients admitted with a manic episode (n = 38; 10.4%) compared to patients admitted with a NAP episode (n = 41; 2.6%) and patients admitted with a depressive episode (n = 16; 2.7%). Manic episode was associated with an increased risk for LLE compared to depressive episode (OR 8.72, 95% CI: 3.53-21.52, p<0.001) or NAP episode (OR 3.96, 95% CI: 2.16-7.26, p<0.001) after controlling for relevant confounders. Acute manic episode, leading to hospitalization, is associated with an increased risk of LLE, compared to NAP or depressive episode, suggesting causal relationship between mood and fluid imbalance. Yet, future prospective studies are needed to rule out the contribution of physical agitation and lithium treatment. © 2013.

Better consenting for thyroidectomy: who has an increased risk of postoperative hypocalcaemia?

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Harris, Andrew S; Prades, Eduardo; Tkachuk, Olena; Zeitoun, Hisham

2016-12-01

Hypocalcaemia is the most common complication following thyroidectomy. This study aimed to establish the factors associated with increased risk of hypocalcaemia on day 1 following thyroidectomy. All patients who underwent thyroidectomy under a single consultant during a 5-year period were included. A multivariate analysis was undertaken to ascertain which variables had the most effect on the risk of hypocalcaemia. A prognosis table was constructed to allow risk to be predicted for individual patients based on these factors. Included in the analysis were 210 procedures and 194 patients. Eighty-two percent of patients had no calcium derangement postoperatively. Fourteen point nine percent were categorised as early hypocalcaemia, 1 % had protracted hypocalcaemia and 2.1 % had permanent hypocalcaemia. For hemi-thyroidectomies 2.8 % had postoperative hypocalcaemia and 0.9 % had permanent hypocalcaemia. The multivariate analysis revealed total thyroidectomy (risk ratio 26.5, p < 0.0001), diabetes (risk ratio 4.8, p = 0.07) and thyrotoxicosis (risk ratio 3.1, p = 0.04) as statistically significant variables for early postoperative hypocalcaemia. Gender as an isolated factor did not reach significance but was included in the model. The p value for the model was p < 1 × 10 -12 . Total thyroidectomy increases risk of early hypocalcaemia when compared to hemithyroidectomy. Gender, diabetes and thyrotoxicosis were also been found to influence the risk. All of these factors are available pre-operatively and can therefore be used to predict a more specific risk for individual patients. It is hoped that this can lead to better informed consent, prevention and better resource allocation.

Is there an increased risk of second primaries following prostate irradiation?

International Nuclear Information System (INIS)

Movsas, Benjamin; Hanlon, Alexandra L.; Pinover, Wayne; Hanks, Gerald E.

1998-01-01

Purpose: To assess the risk of developing a second primary cancer following prostate irradiation compared to the underlying risk in patients with prostate cancer. Methods and Materials: The baseline rate of secondary cancers following prostate cancer was obtained from a study of 18,135 patients from the Connecticut Tumor Registry, of whom only 12.5% received radiotherapy. These patients, with a mean age of 72 and a mean follow-up of 3.9 years, were compared to a cohort of 543 patients (median age 70) with similar follow-up (median 3.9 years), all of whom were treated with definitive radiotherapy at Fox Chase Cancer Center. The possible association between various covariates (age, dose, palpation stage, field size, Gleason score, pretreatment PSA) and the development of a secondary cancer was assessed. Results: 1,053 of 18,135 patients (5.8%) in the Connecticut Tumor Registry developed a second primary cancer compared with 31 of 543 (5.7%) patients treated with prostate radiation (p = 0.99). Although this risk increases gradually over time, it is not significantly different, at any time period, between the two groups of patients. Of the 31 secondary primaries in the irradiated group, 82% had a history of tobacco and/or alcohol use. Only melanomas were significantly increased compared to the expected rate in an age-matched population (p <0.001). Five of the 31 secondary cancers occurred within the radiation field (four bladder, one colon), four within 3 years and only one occurred 9 years after radiotherapy. No association was found between age (<70 vs. ≥70 and as a continuous variable), dose (<74 vs. ≥74 Gy), palpation stage (< T2C vs. ≥T2C), field size (prostate vs. pelvic), radiation technique (conventional vs. conformal), Gleason score (2-6 vs. 7-10), or pretreatment PSA (<15 vs. ≥15 and as a continuous variable) and the risk of developing a second primary. Although a lower radiation dose (as a continuous variable) correlated with an increased risk of

Family history of skin cancer is associated with increased risk of cutaneous squamous cell carcinoma.

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Asgari, Maryam M; Warton, E Margaret; Whittemore, Alice S

2015-04-01

The contribution of family history to cutaneous squamous cell carcinoma (SCC) risk has not been systematically quantified. To examine the association between self-reported family history of skin cancer and SCC risk. Cases (n = 415) with a pathology-verified SCC and 415 age-, gender-, and race-matched controls were identified within a large integrated health care delivery system. Family history and skin cancer risk factors were ascertained by survey. Odds ratios (ORs) for associations of SCC with family history of skin cancer were estimated using conditional logistic regression adjusted for environmental and innate SCC risk factors. Any known family history of skin cancer was associated with a four-fold higher risk of SCC, adjusting for known environmental and innate SCC risk factors (OR, 4.0; confidence interval [CI]: 2.5-6.5). An unknown family history of skin cancer showed similar risk for SCC (OR, 3.9; CI: 2.4-6.5). In models including skin cancer type, the strongest association was for family history of basal cell carcinoma (OR, 9.8; CI: 2.6-36.8) and for multiple skin cancer types (OR, 10.5; CI: 3.7-29.6). Family history of skin cancer is an important independent risk factor for cutaneous SCCs.

Erbium:YAG laser resurfacing increases skin permeability and the risk of excessive absorption of antibiotics and sunscreens: the influence of skin recovery on drug absorption.

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Lee, Woan-Ruoh; Shen, Shing-Chuan; Al-Suwayeh, Saleh A; Li, Yi-Ching; Fang, Jia-You

2012-06-01

While laser skin resurfacing is expected to result in reduced barrier function and increased risk of drug absorption, the extent of the increment has not yet been systematically investigated. We aimed to establish the skin permeation profiles of tetracycline and sunscreens after exposure to the erbium:yttrium-aluminum-garnet (Er:YAG) laser during postoperative periods. Physiological and histopathological examinations were carried out for 5 days after laser treatment on nude mice. Percutaneous absorption of the permeants was determined by an in vitro Franz cell. Ablation depths varied in reaching the stratum corneum (10 μm, 2.5 J/cm²) to approach the epidermis (25 μm, 6.25 J/cm²) and upper dermis (40 μm, 10 J/cm²). Reepithelialization evaluated by transepidermal water loss was complete within 2-4 days and depended on the ablation depth. Epidermal hyperplasia was observed in the 40-μm-treated group. The laser was sufficient to disrupt the skin barrier and allow the transport of the permeants into and across the skin. The laser fluence was found to play an important role in modulating skin absorption. A 25-μm ablation depth increased tetracycline flux 84-fold. A much smaller enhancement (3.3-fold) was detected for tetracycline accumulation within the skin. The laser with different fluences produced enhancement of oxybenzone skin deposition of 3.4-6.4-fold relative to the untreated group. No penetration across the skin was shown regardless of whether titanium dioxide was applied to intact or laser-treated skin. However, laser resurfacing increased the skin deposition of titanium dioxide from 46 to 109-188 ng/g. Tetracycline absorption had recovered to the level of intact skin after 5 days, while more time was required for oxybenzone absorption. The in vivo skin accumulation and plasma concentration revealed that the laser could increase tetracycline absorption 2-3-fold. The experimental results indicated that clinicians should be cautious when determining the

High neonatal blood iron content is associated with the risk of childhood type 1 diabetes mellitus

DEFF Research Database (Denmark)

Kyvsgaard, Julie Nyholm; Overgaard, Anne Julie; Thorsen, Steffen Ullitz

2017-01-01

with the risk of developing type 1 diabetes mellitus (T1D) in childhood; (2) Methods: A case-control study was conducted, including 199 children diagnosed with T1D before the age of 16 years from 1991 to 2005 and 199 controls matched on date of birth. Information on confounders was available in 181 cases......: A doubling of iron content increased the odds of developing T1D more than two-fold (odds ratio (95% CI), 2.55 (1.04; 6.24)). Iron content increased with maternal age (p = 0.04) and girls had higher content than boys (p = 0.01); (4) Conclusions: Higher neonatal iron content associates to an increased risk...

Comparison of accuracy of diabetes risk score and components of the metabolic syndrome in assessing risk of incident type 2 diabetes in Inter99 cohort.

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Tracy B Shafizadeh

Full Text Available BACKGROUND: Given the increasing worldwide incidence of diabetes, methods to assess diabetes risk which would identify those at highest risk are needed. We compared two risk-stratification approaches for incident type 2 diabetes mellitus (T2DM; factors of metabolic syndrome (MetS and a previously developed diabetes risk score, PreDx® Diabetes Risk Score (DRS. DRS assesses 5 yr risk of incident T2DM based on the measurement of 7 biomarkers in fasting blood. METHODOLOGY/PRINCIPAL FINDINGS: DRS was evaluated in baseline serum samples from 4,128 non-diabetic subjects in the Inter99 cohort (Danes aged 30-60 for whom diabetes outcomes at 5 years were known. Subjects were classified as having MetS based on the presence of at least 3 MetS risk factors in baseline clinical data. The sensitivity and false positive rate for predicting diabetes using MetS was compared to DRS. When the sensitivity was fixed to match MetS, DRS had a significantly lower false positive rate. Similarly, when the false positive rate was fixed to match MetS, DRS had a significantly higher specificity. In further analyses, subjects were classified by presence of 0-2, 3 or 4-5 risk factors with matching proportions of subjects distributed among three DRS groups. Comparison between the two risk stratification schemes, MetS risk factors and DRS, were evaluated using Net Reclassification Improvement (NRI. Comparing risk stratification by DRS to MetS factors in the total population, the NRI was 0.146 (p = 0.008 demonstrating DRS provides significantly improved stratification. Additionally, the relative risk of T2DM differed by 15 fold between the low and high DRS risk groups, but only 8-fold between the low and high risk MetS groups. CONCLUSIONS/SIGNIFICANCE: DRS provides a more accurate assessment of risk for diabetes than MetS. This improved performance may allow clinicians to focus preventive strategies on those most in need of urgent intervention.

Increased colon cancer risk after severe Salmonella infection

Science.gov (United States)

Mooij, Sofie; Neefjes-Borst, E. Andra; van Pelt, Wilfrid; Neefjes, Jacques

2018-01-01

Background Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans. Methods and findings We performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999–2015) for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264) were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1–2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite) among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA) and Statistics Netherlands (CBS) allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD), and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09–2.10) among patients with Salmonella infection diagnosed transverse colon (SIR 2.12; 95%CI 1.38–3.09) after S. Enteritidis infection (SIR 2.97; 95%CI 1.73–4.76). Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade. Conclusions Patients diagnosed with severe

Increased mortality risk in women with depression and diabetes mellitus

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Pan, An; Lucas, Michel; Sun, Qi; van Dam, Rob M.; Franco, Oscar H.; Willett, Walter C.; Manson, JoAnn E.; Rexrode, Kathryn M.; Ascherio, Alberto; Hu, Frank B.

2011-01-01

Context Both depression and diabetes have been associated with an increased risk of all-cause and cardiovascular diseases (CVD) mortality. However, data evaluating the joint effects of these two conditions on mortality are sparse. Objectives To evaluate the individual and joint effects of depression and diabetes on all-cause and CVD mortality in a prospective cohort study. Design, Settings and Participants A total of 78282 female participants in the Nurses' Health Study aged 54-79 years at baseline in 2000 were followed until 2006. Depression was defined as having self-reported diagnosed depression, treatment with antidepressant medications, or a score indicating severe depressive symptomatology, i.e., a five-item Mental Health Index score ≤52. Self-reported type 2 diabetes was confirmed using a supplementary questionnaire. Main outcome measures All-cause and CVD-specific mortality. Results During 6 years of follow-up (433066 person-years), 4654 deaths were documented, including 979 deaths from CVD. Compared to participants without either condition, the age-adjusted relative risks (95% confidence interval, CI) for all-cause mortality were 1.76 (1.64-1.89) for women with depression only, 1.71 (1.54-1.89) for individuals with diabetes only, and 3.11 (2.70-3.58) for those with both conditions. The corresponding age-adjusted relative risks of CVD mortality were 1.81 (1.54-2.13), 2.67 (2.20-3.23), and 5.38 (4.19-6.91), respectively. These associations were attenuated after multivariate adjustment for other demographic variables, body mass index, smoking status, alcohol intake, physical activity, and major comorbidities (including hypertension, hypercholesterolemia, heart diseases, stroke and cancer) but remained significant, with the highest relative risks for all-cause and CVD mortality found in those with both conditions (2.07 [95% CI, 1.79-2.40] and 2.72 [95% CI, 2.09-3.54], respectively). Furthermore, the combination of depression with a long duration of diabetes

Folding Membrane Proteins by Deep Transfer Learning

KAUST Repository

Wang, Sheng

2017-08-29

Computational elucidation of membrane protein (MP) structures is challenging partially due to lack of sufficient solved structures for homology modeling. Here, we describe a high-throughput deep transfer learning method that first predicts MP contacts by learning from non-MPs and then predicts 3D structure models using the predicted contacts as distance restraints. Tested on 510 non-redundant MPs, our method has contact prediction accuracy at least 0.18 better than existing methods, predicts correct folds for 218 MPs, and generates 3D models with root-mean-square deviation (RMSD) less than 4 and 5 Å for 57 and 108 MPs, respectively. A rigorous blind test in the continuous automated model evaluation project shows that our method predicted high-resolution 3D models for two recent test MPs of 210 residues with RMSD ∼2 Å. We estimated that our method could predict correct folds for 1,345–1,871 reviewed human multi-pass MPs including a few hundred new folds, which shall facilitate the discovery of drugs targeting at MPs.

Human Adipose Tissue Derived Extracellular Matrix and Methylcellulose Hydrogels Augments and Regenerates the Paralyzed Vocal Fold.

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Kim, Dong Wook; Kim, Eun Ji; Kim, Eun Na; Sung, Myung Whun; Kwon, Tack-Kyun; Cho, Yong Woo; Kwon, Seong Keun

2016-01-01

Vocal fold paralysis results from various etiologies and can induce voice changes, swallowing complications, and issues with aspiration. Vocal fold paralysis is typically managed using injection laryngoplasty with fat or synthetic polymers. Injection with autologous fat has shown excellent biocompatibility. However, it has several disadvantages such as unpredictable resorption rate, morbidities associated with liposuction procedure which has to be done in operating room under general anesthesia. Human adipose-derived extracellular matrix (ECM) grafts have been reported to form new adipose tissue and have greater biostability than autologous fat graft. Here, we present an injectable hydrogel that is constructed from adipose tissue derived soluble extracellular matrix (sECM) and methylcellulose (MC) for use in vocal fold augmentation. Human sECM derived from adipose tissue was extracted using two major steps-ECM was isolated from human adipose tissue and was subsequently solubilized. Injectable sECM/MC hydrogels were prepared by blending of sECM and MC. Sustained vocal fold augmentation and symmetric vocal fold vibration were accomplished by the sECM/MC hydrogel in paralyzed vocal fold which were confirmed by laryngoscope, histology and a high-speed imaging system. There were increased number of collagen fibers and fatty granules at the injection site without significant inflammation or fibrosis. Overall, these results indicate that the sECM/MC hydrogel can enhance vocal function in paralyzed vocal folds without early resorption and has potential as a promising material for injection laryngoplasty for stable vocal fold augmentation which can overcome the shortcomings of autologous fat such as unpredictable duration and morbidity associated with the fat harvest.

Targeting the OB-Folds of Replication Protein A with Small Molecules

Directory of Open Access Journals (Sweden)

Victor J. Anciano Granadillo

2010-01-01

Full Text Available Replication protein A (RPA is the main eukaryotic single-strand (ss DNA-binding protein involved in DNA replication and repair. We have identified and developed two classes of small molecule inhibitors (SMIs that show in vitro inhibition of the RPA-DNA interaction. We present further characterization of these SMIs with respect to their target binding, mechanism of action, and specificity. Both reversible and irreversible modes of inhibition are observed for the different classes of SMIs with one class found to specifically interact with DNA-binding domains A and B (DBD-A/B of RPA. In comparison with other oligonucleotide/oligosaccharide binding-fold (OB-fold containing ssDNA-binding proteins, one class of SMIs displayed specificity for the RPA protein. Together these data demonstrate that the specific targeting of a protein-DNA interaction can be exploited towards interrogating the cellular activity of RPA as well as increasing the efficacy of DNA-damaging chemotherapeutics used in cancer treatment.

BiP clustering facilitates protein folding in the endoplasmic reticulum.

Directory of Open Access Journals (Sweden)

Marc Griesemer

2014-07-01

Full Text Available The chaperone BiP participates in several regulatory processes within the endoplasmic reticulum (ER: translocation, protein folding, and ER-associated degradation. To facilitate protein folding, a cooperative mechanism known as entropic pulling has been proposed to demonstrate the molecular-level understanding of how multiple BiP molecules bind to nascent and unfolded proteins. Recently, experimental evidence revealed the spatial heterogeneity of BiP within the nuclear and peripheral ER of S. cerevisiae (commonly referred to as 'clusters'. Here, we developed a model to evaluate the potential advantages of accounting for multiple BiP molecules binding to peptides, while proposing that BiP's spatial heterogeneity may enhance protein folding and maturation. Scenarios were simulated to gauge the effectiveness of binding multiple chaperone molecules to peptides. Using two metrics: folding efficiency and chaperone cost, we determined that the single binding site model achieves a higher efficiency than models characterized by multiple binding sites, in the absence of cooperativity. Due to entropic pulling, however, multiple chaperones perform in concert to facilitate the resolubilization and ultimate yield of folded proteins. As a result of cooperativity, multiple binding site models used fewer BiP molecules and maintained a higher folding efficiency than the single binding site model. These insilico investigations reveal that clusters of BiP molecules bound to unfolded proteins may enhance folding efficiency through cooperative action via entropic pulling.

The functional polymorphism of NBS1 p.Glu185Gln is associated with an increased risk of lung cancer in Chinese populations: Case–control and a meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Fang, Wenxiang; Qiu, Fuman; Zhang, Lisha [The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182 (China); Deng, Jieqiong [Soochow University Laboratory of Cancer Molecular Genetics, Collaborative Innovation Center for Environmental Toxicity, Medical College of Soochow University, Suzhou 215123 (China); Zhang, Haibo [Department of Cardio-thoracic Surgery, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080 (China); Yang, Lei [The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182 (China); Zhou, Yifeng [Soochow University Laboratory of Cancer Molecular Genetics, Collaborative Innovation Center for Environmental Toxicity, Medical College of Soochow University, Suzhou 215123 (China); Lu, Jiachun, E-mail: jcLu@gzhmu.edu.cn [The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182 (China)

2014-12-15

Highlights: • NBS1 rs1805794G>C polymorphism conferred an adverse role on lung cancer risk in a two centers case–control study. • Rs1805794C variants had more chromatid breaks and higher DNA damage induced by X-ray radiation. • Meta analysis result confirmed the association between the variant rs1805794G>C and lung cancer risk. - Abstract: NBS1 plays pivotal roles in maintaining genomic stability and cancer development. The exon variant rs1805794G>C (p.Glu185Gln) of NBS1 has been frequently studied in several association studies. However, the results were conflicting. Also, the function of this variant has never been well studied. In the current study, we performed a two centers case–control study and function assays to investigate the effect of the variant rs1805794G>C on lung cancer risk in Chinese, and a meta-analysis to summarize the data on the association between rs1805794G>C and cancer risk. We found that compared with the rs1805794GG genotype, the C genotypes (CG/CC) conferred a significantly increased risk of lung cancer in Chinese (OR = 1.40, 95% CI = 1.21–1.62) and interacted with medical ionizing radiation exposure on increasing cancer risk (P{sub interaction} = 0.015). The lymphocyte cells from the C genotype individuals developed more chromatid breaks than those from the GG genotype carriers after the X-ray radiation (P = 0.036). Moreover, the rs1805794C allele encoding p.185Gln attenuated NBS1's ability to repair DNA damage as the cell lines transfected with NBS1 cDNA expression vector carrying rs1805794C allele had significantly higher DNA breaks than those transfected with NBS1 cDNA expression vector carrying rs1805794G allele (P < 0.05). The meta-analysis further confirmed the association between the variant rs1805794G>C and lung cancer risk, that compared with the GG genotype, the carriers of C genotypes had a 1.30-fold risk of cancer (95% CI = 1.14–1.49, P = 8.49 × 10{sup −5}). These findings suggest that the rs1805794G

Regeneration of Vocal Fold Mucosa Using Tissue-Engineered Structures with Oral Mucosal Cells

Science.gov (United States)

Fukahori, Mioko; Chitose, Shun-ichi; Sato, Kiminori; Sueyoshi, Shintaro; Kurita, Takashi; Umeno, Hirohito; Monden, Yu; Yamakawa, Ryoji

2016-01-01

Objectives Scarred vocal folds result in irregular vibrations during phonation due to stiffness of the vocal fold mucosa. To date, a completely satisfactory corrective procedure has yet to be achieved. We hypothesize that a potential treatment option for this disease is to replace scarred vocal folds with organotypic mucosa. The purpose of this study is to regenerate vocal fold mucosa using a tissue-engineered structure with autologous oral mucosal cells. Study Design Animal experiment using eight beagles (including three controls). Methods A 3 mm by 3 mm specimen of canine oral mucosa was surgically excised and divided into epithelial and subepithelial tissues. Epithelial cells and fibroblasts were isolated and cultured separately. The proliferated epithelial cells were co-cultured on oriented collagen gels containing the proliferated fibroblasts for an additional two weeks. The organotypic cultured tissues were transplanted to the mucosa-deficient vocal folds. Two months after transplantation, vocal fold vibrations and morphological characteristics were observed. Results A tissue-engineered vocal fold mucosa, consisting of stratified epithelium and lamina propria, was successfully fabricated to closely resemble the normal layered vocal fold mucosa. Laryngeal stroboscopy revealed regular but slightly small mucosal waves at the transplanted site. Immunohistochemically, stratified epithelium expressed cytokeratin, and the distributed cells in the lamina propria expressed vimentin. Elastic Van Gieson staining revealed a decreased number of elastic fibers in the lamina propria of the transplanted site. Conclusion The fabricated mucosa with autologous oral mucosal cells successfully restored the vocal fold mucosa. This reconstruction technique could offer substantial clinical advantages for treating intractable diseases such as scarring of the vocal folds. PMID:26730600

Evaluation of Vocal Fold Motion Abnormalities: Are We All Seeing the Same Thing?

Science.gov (United States)

Madden, Lyndsay L; Rosen, Clark A

2017-01-01

Flexible laryngoscopy is the principle tool for the evaluation of vocal fold motion. As of yet, no consistent, unified outcome metric has been developed for vocal fold paralysis/immobility research. The goal of this study was to evaluate vocal fold motion assessment (inter- and intra-rater reliability) among general otolaryngologists and fellowship-trained laryngologists. Prospective video perceptual analysis study. Flexible laryngoscopic examinations, with sound, of 15 unique patient cases (20 seconds each) were sent to 10 general otolaryngologists and 10 fellowship-trained laryngologists blinded to clinical history. Reviewers were given written definitions of vocal fold mobility and immobility and two video examples. The cases included bilateral vocal fold mobility (six), unilateral vocal fold immobility (five), and unilateral vocal fold hypomobility (four). Five examinations were repeated to determine intra-rater reliability. Participants were asked to judge if there was or there was no purposeful motion, as described by written definitions, for each vocal fold (800 tokens in total). Twenty reviewers (100%) replied. Both general otolaryngologists and fellowship-trained laryngologists had an overall inter-rater reliability of 95%. Difference in inter-rater reliability between the two groups of raters was negligible: 95% for general otolaryngologists and 97.5% for fellowship-trained laryngologists. There was no variability in intra-rater reliability within either rater group (99%). Intra- and inter-rater agreement in determining whether the patient had purposeful vocal fold motion on flexible laryngoscopic examination was excellent in both groups. This study demonstrates that otolaryngologists can consistently and accurately judge the presence and the absence of vocal fold motion. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Thrombocytopenia is associated with an increased risk of cancer during treated HIV disease.

Science.gov (United States)

Borges, Álvaro H; Lundgren, Jens D; Ridolfo, Annalisa; Katlama, Christine; Antunes, Francisco; Grzeszczuk, Anna; Blaxhult, Anders; Mitsura, Viktar M; Doroana, Manuela; Battegay, Manuel; Gargalianos, Panagiotis; Mocroft, Amanda

2014-11-13

To assess the relationship between platelet counts and risk of AIDS and non-AIDS-defining events. Prospective cohort. EuroSIDA patients with at least one platelet count were followed from baseline (first platelet ≥ 1 January 2005) until last visit or death. Multivariate Poisson regression was used to assess the relationship between current platelet counts and the incidence of non-AIDS-defining (pancreatitis, end-stage liver/renal disease, cancer, cardiovascular disease) and AIDS-defining events. There were 62 898 person-years of follow-up (PYFU) among 12 279 patients, including 1168 non-AIDS-defining events [crude incidence 18.6/1000 PYFU, 95% confidence interval (CI) 17.5-19.6] and 735 AIDS-defining events (crude incidence 11.7/1000 PYFU, 95% CI 10.8-12.5). Patients with thrombocytopenia (platelet count ≤100 × 10/l) had a slightly increased incidence of AIDS-defining events [adjusted incidence rate ratio (aIRR) 1.42, 95% CI 1.07-1.86], when compared to those with platelet counts 101-200 × 10/l, whereas the incidence of non-AIDS-defining events was more than two-fold higher (aIRR 2.66, 95% CI 2.17-3.26). Among non-AIDS-defining events, the adjusted incidence of cancer (aIRR 2.20, 95% CI 1.61-3.01), but not cardiovascular disease (aIRR 0.66, 95% CI 0.32-1.34), was significantly higher in patients with thrombocytopenia. The association between thrombocytopenia and cancer remained unaltered in sensitivity analyses requiring repeated platelet counts to confirm thrombocytopenia and lagging platelets by 1 year prior to clinical events. Patients with thrombocytopenia had increased incidence of AIDS-defining and non-AIDS-defining events, but the association with the latter, in particular cancer, was stronger. Future studies should investigate whether the pathophysiological processes underlying thrombocytopenia are associated with the development of cancer during treated HIV disease.

Quantification of change in vocal fold tissue stiffness relative to depth of artificial damage.

Science.gov (United States)

Rohlfs, Anna-Katharina; Schmolke, Sebastian; Clauditz, Till; Hess, Markus; Müller, Frank; Püschel, Klaus; Roemer, Frank W; Schumacher, Udo; Goodyer, Eric

2017-10-01

To quantify changes in the biomechanical properties of human excised vocal folds with defined artificial damage. The linear skin rheometer (LSR) was used to obtain a series of rheological measurements of shear modulus from the surface of 30 human cadaver vocal folds. The tissue samples were initially measured in a native condition and then following varying intensities of thermal damage. Histological examination of each vocal fold was used to determine the depth of artificial alteration. The measured changes in stiffness were correlated with the depth of cell damage. For vocal folds in a pre-damage state the shear modulus values ranged from 537 Pa to 1,651 Pa (female) and from 583 Pa to 1,193 Pa (male). With increasing depth of damage from the intermediate layer of the lamina propria (LP), tissue stiffness increased consistently (compared with native values) following application of thermal damage to the vocal folds. The measurement showed an increase of tissue stiffness when the depth of tissue damage was extending from the intermediate LP layer downwards. Changes in the elastic characteristics of human vocal fold tissue following damage at defined depths were demonstrated in an in vitro experiment. In future, reproducible in vivo measurements of elastic vocal fold tissue alterations may enable phonosurgeons to infer the extent of subepithelial damage from changes in surface elasticity.

Side chain and backbone contributions of Phe508 to CFTR folding

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Thibodeau, Patrick H.; Brautigam, Chad A.; Machius, Mischa; Thomas, Philip J. (U. of Texas-SMED)

2010-12-07

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an integral membrane protein, cause cystic fibrosis (CF). The most common CF-causing mutant, deletion of Phe508, fails to properly fold. To elucidate the role Phe508 plays in the folding of CFTR, missense mutations at this position were generated. Only one missense mutation had a pronounced effect on the stability and folding of the isolated domain in vitro. In contrast, many substitutions, including those of charged and bulky residues, disrupted folding of full-length CFTR in cells. Structures of two mutant nucleotide-binding domains (NBDs) reveal only local alterations of the surface near position 508. These results suggest that the peptide backbone plays a role in the proper folding of the domain, whereas the side chain plays a role in defining a surface of NBD1 that potentially interacts with other domains during the maturation of intact CFTR.

Alcoholic Cirrhosis Increases Risk for Autoimmune Diseases

DEFF Research Database (Denmark)

Grønbæk, Lisbet; Vilstrup, Hendrik; Deleuran, Bent

2015-01-01

IRR, 1.56; 95% CI, 1.26-1.92), celiac disease (aIRR, 5.12; 95% CI, 2.58-10.16), pernicious anemia (aIRR, 2.35; 95% CI, 1.50-3.68), and psoriasis (aIRR, 4.06; 95% CI, 3.32-4.97). There was no increase in the incidence rate for rheumatoid arthritis (aIRR, 0.89; 95% CI, 0.69-1.15); the incidence rate......BACKGROUND & AIMS: Alcoholic cirrhosis is associated with hyperactivation and dysregulation of the immune system. In addition to its ability to increase risk for infections, it also may increase the risk for autoimmune diseases. We studied the incidence of autoimmune diseases among patients...... (controls) of the same sex and age. The incidence rates of various autoimmune diseases were compared between patients with cirrhosis and controls and adjusted for the number of hospitalizations in the previous year (a marker for the frequency of clinical examination). RESULTS: Of the 24,679 patients...

The increased risk of globus pharyngeus in patients with chronic thyroiditis: a case control study.

Science.gov (United States)

Karahatay, S; Ayan, A; Aydin, U; Ince, S; Emer, O; Alagoz, E

2015-12-01

A correlation between globus pharyngeus and thyroid gland inflammation has been mentioned in previous studies. However, the potential risk of globus pharyngeus in chronic thyroiditis patients has not been shown so far. The aim of this study is to investigate a possible association between chronic thyroiditis and globus pharyngeus. The study was performed in an ultrasound (US) center of a tertiary health care institution. Ninety-two patients who were under examination for suspected thyroid pathologies or undergoing follow-up for a previously diagnosed thyroid disease were enrolled in the study. The patients were divided into two groups according to the existence of globus symptoms. Subsequently, all patients underwent high-resolution thyroid ultrasounds. The patients whose ultrasound findings were suggestive of chronic thyroiditis constituted the second subgroup. The demographic data of the patients and other ultrasound findings including the volume of the thyroid glands and nodules, if any, were noted as well. Sixty-seven female (73%) and 25 male (27%) patients were enrolled in the study. Thirty-two (35%) of the 92 patients constituted the globus pharyngeus group according to their responses to the questionnaire and the US findings were concordant with chronic thyroiditis in 36 (39%) patients. The correlation between chronic thyroiditis and globus sensation was significant (p = 0.004), and the odds ratio was calculated as 3.7 (95% CI = 1.5-9.11). Other parameters including age, sex, thyroid volume and nodule status were not significantly related to globus pharyngeus in this particular patient series. In the presented study, the risk of globus pharyngeus occurrence was calculated as 3.7-fold higher in patients with chronic thyroiditis. Being a preliminary report, it is necessary to confirm this finding and understand the pathophysiological mechanism via further investigations with a larger patient series.

Does high sugar consumption exacerbate cardiometabolic risk factors and increase the risk of type 2 diabetes and cardiovascular disease?

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David E. Laaksonen

2012-07-01

Full Text Available Consumption of sugar has been relatively high in the Nordic countries; the impact of sugar intake on metabolic risk factors and related diseases has been debated. The objectives were to assess the effect of sugar intake (sugar-sweetened beverages, sucrose and fructose on association with type 2 diabetes, cardiovascular disease and related metabolic risk factors (impaired glucose tolerance, insulin sensitivity, dyslipidemia, blood pressure, uric acid, inflammation markers, and on all-cause mortality, through a systematic review of prospective cohort studies and randomised controlled intervention studies published between January 2000 and search dates. The methods adopted were as follows: the first search was run in PubMed in October 2010. A second search with uric acid as risk marker was run in April 2011. The total search strategy was rerun in April 2011 in SveMed+. An update was run in PubMed in January 2012. Two authors independently selected studies for inclusion from the 2,743 abstracts according to predefined eligibility criteria. The outcome was that out of the 17 studies extracted, 15 were prospective cohort studies and two were randomised controlled crossover trials. All of the studies included only adults. With respect to incident type 2 diabetes (nine studies, four of six prospective cohort studies found a significant positive association for sugar-sweetened beverage intake. In general, larger cohort studies with longer follow-up more often reported positive associations, and BMI seemed to mediate part of the increased risk. For other metabolic or cardiovascular risk factors or outcomes, too few studies have been published to draw conclusions. In conclusion, data from prospective cohort studies published in the years 2000–2011 suggest that sugar-sweetened beverages probably increase the risk of type 2 diabetes. For related metabolic risk factors, cardiovascular disease or all-cause mortality and other types of sugars, too few studies

Effects of two mutations detected in medium chain acyl-CoA dehydrogenase (MCAD)-deficient patients on folding, oligomer assembly, and stability of MCAD enzyme

DEFF Research Database (Denmark)

Bross, P; Jespersen, C; Jensen, T G

1995-01-01

We have used expression of human medium chain acyl-CoA dehydrogenase (MCAD) in Escherichia coli as a model system for dissecting the molecular effects of two mutations detected in patients with MCAD deficiency. We demonstrate that the R28C mutation predominantly affects polypeptide folding...

Araguaia fold belt, new geochronological data

International Nuclear Information System (INIS)

Lafon, J.M.; Macambira, J.B.; Macambira, M.J.B.; Moura, C.A.V.; Souza, A.C.C.

1990-01-01

The northern part of the Araguaia Fold Belt (AFB) outcrops in a N-S direction for about 400 km in the state of Tocantins. Dome-like structures occur in this fold belt also in a N-S direction. Both deformation and metamorphism increase from the West to the East. The basement of the AFB consist of Colmeia complex and Cantao gneiss, which crop out mainly in the core of the dome-like structures. The supracrustals rocks of the fold belt belongs to the Baixo Araguaia supergroup which is divided into the lower Estrondo group and the upper Tocantins group. Preliminary Sm-Nd data from the Colmeia complex (Grota Rica dome) gave Archean model ages of 2.8 Ga (TNd sub(DM)) while Rb-Sr data in the same rocks give an age of 2530 ± 200 Ma. In the others dome-like structures, the Rb-Sr systematics gave ages for the Colmeia a complex of 2239 ± 47 Ma (Colmeia structure) and 1972 ± 46 Ma (Lontra structure). These younger ages are believed to represent partial to total isotopic resetting of the Rb-Sr system during the Transamazonian Event. The Rb-Sr studies of the Cantao gneiss gave an age of 1774 ± 31 Ma. (author)

Animated graphics for comparing two risks: a cautionary tale.

Science.gov (United States)

Zikmund-Fisher, Brian J; Witteman, Holly O; Fuhrel-Forbis, Andrea; Exe, Nicole L; Kahn, Valerie C; Dickson, Mark

2012-07-25

The increasing use of computer-administered risk communications affords the potential to replace static risk graphics with animations that use motion cues to reinforce key risk messages. Research on the use of animated graphics, however, has yielded mixed findings, and little research exists to identify the specific animations that might improve risk knowledge and patients' decision making. To test whether viewing animated forms of standard pictograph (icon array) risk graphics displaying risks of side effects would improve people's ability to select the treatment with the lowest risk profile, as compared with viewing static images of the same risks. A total of 4198 members of a demographically diverse Internet panel read a scenario about two hypothetical treatments for thyroid cancer. Each treatment was described as equally effective but varied in side effects (with one option slightly better than the other). Participants were randomly assigned to receive all risk information in 1 of 10 pictograph formats in a quasi-factorial design. We compared a control condition of static grouped icons with a static scattered icon display and with 8 Flash-based animated versions that incorporated different combinations of (1) building the risk 1 icon at a time, (2) having scattered risk icons settle into a group, or (3) having scattered risk icons shuffle themselves (either automatically or by user control). We assessed participants' ability to choose the better treatment (choice accuracy), their gist knowledge of side effects (knowledge accuracy), and their graph evaluation ratings, controlling for subjective numeracy and need for cognition. When compared against static grouped-icon arrays, no animations significantly improved any outcomes, and most showed significant performance degradations. However, participants who received animations of grouped icons in which at-risk icons appeared 1 at a time performed as well on all outcomes as the static grouped-icon control group

Increased risk for diabetes mellitus in patients with carbon monoxide poisoning

Science.gov (United States)

Huang, Chien-Cheng; Ho, Chung-Han; Chen, Yi-Chen; Lin, Hung-Jung; Hsu, Chien-Chin; Wang, Jhi-Joung; Su, Shih-Bin; Guo, How-Ran

2017-01-01

Carbon monoxide poisoning (COP) causes hypoxic injury and inflammatory and immunological reactions in the brain and local organs including the pancreas. Therefore, it is plausible that COP may increase the risk for developing diabetes mellitus (DM), but studies on this possible association are limited. We conducted a nationwide study in Taiwan to fill the data gap. We used the Nationwide Poisoning Database and the Longitudinal Health Insurance Database 2000 to identify all COP patients diagnosed between 1999 and 2012 (the study cohort) and then construct a comparison cohort of patients without COP through matching at 1:3 by the index date and age. The risk for DM between the two cohorts was compared by following up until 2013. We also investigated the independent predictors for DM in all the patients. During the study period, 22,308 COP patients were identified, and 66,924 non-COP patients were included in the comparison cohort accordingly. Patients with COP had an increased risk for DM with an adjusted hazard ratio (AHR) of 1.92 (95% confidence interval [CI]: 1.79–2.06) after adjusting for age, sex, comorbidities, and monthly income, especially in the subgroups of age increased risk for DM was highest in the first month after COP (AHR= 3.38; 95% CI: 2.29–4.99) and lasted even after 4 years (AHR= 1.82; 95% CI: 1.62–2.04). We found that COP, older age, male sex, hypertension, hyperlipidemia, hyperuricemia, and low monthly income were independent predictors for DM. Intervention studies are needed to validate the results and delineate the detailed mechanisms. PMID:28969020

Relation of Structural and Vibratory Kinematics of the Vocal Folds to Two Acoustic Measures of Breathy Voice Based on Computational Modeling

Science.gov (United States)

Samlan, Robin A.; Story, Brad H.

2011-01-01

Purpose: To relate vocal fold structure and kinematics to 2 acoustic measures: cepstral peak prominence (CPP) and the amplitude of the first harmonic relative to the second (H1-H2). Method: The authors used a computational, kinematic model of the medial surfaces of the vocal folds to specify features of vocal fold structure and vibration in a…

SVM-Fold: a tool for discriminative multi-class protein fold and superfamily recognition.

Science.gov (United States)

Melvin, Iain; Ie, Eugene; Kuang, Rui; Weston, Jason; Stafford, William Noble; Leslie, Christina

2007-05-22

Predicting a protein's structural class from its amino acid sequence is a fundamental problem in computational biology. Much recent work has focused on developing new representations for protein sequences, called string kernels, for use with support vector machine (SVM) classifiers. However, while some of these approaches exhibit state-of-the-art performance at the binary protein classification problem, i.e. discriminating between a particular protein class and all other classes, few of these studies have addressed the real problem of multi-class superfamily or fold recognition. Moreover, there are only limited software tools and systems for SVM-based protein classification available to the bioinformatics community. We present a new multi-class SVM-based protein fold and superfamily recognition system and web server called SVM-Fold, which can be found at http://svm-fold.c2b2.columbia.edu. Our system uses an efficient implementation of a state-of-the-art string kernel for sequence profiles, called the profile kernel, where the underlying feature representation is a histogram of inexact matching k-mer frequencies. We also employ a novel machine learning approach to solve the difficult multi-class problem of classifying a sequence of amino acids into one of many known protein structural classes. Binary one-vs-the-rest SVM classifiers that are trained to recognize individual structural classes yield prediction scores that are not comparable, so that standard "one-vs-all" classification fails to perform well. Moreover, SVMs for classes at different levels of the protein structural hierarchy may make useful predictions, but one-vs-all does not try to combine these multiple predictions. To deal with these problems, our method learns relative weights between one-vs-the-rest classifiers and encodes information about the protein structural hierarchy for multi-class prediction. In large-scale benchmark results based on the SCOP database, our code weighting approach

Quantification of Porcine Vocal Fold Geometry.

Science.gov (United States)

Stevens, Kimberly A; Thomson, Scott L; Jetté, Marie E; Thibeault, Susan L

2016-07-01

The aim of this study was to quantify porcine vocal fold medial surface geometry and three-dimensional geometric distortion induced by freezing the larynx, especially in the region of the vocal folds. The medial surface geometries of five excised porcine larynges were quantified and reported. Five porcine larynges were imaged in a micro-CT scanner, frozen, and rescanned. Segmentations and three-dimensional reconstructions were used to quantify and characterize geometric features. Comparisons were made with geometry data previously obtained using canine and human vocal folds as well as geometries of selected synthetic vocal fold models. Freezing induced an overall expansion of approximately 5% in the transverse plane and comparable levels of nonuniform distortion in sagittal and coronal planes. The medial surface of the porcine vocal folds was found to compare reasonably well with other geometries, although the compared geometries exhibited a notable discrepancy with one set of published human female vocal fold geometry. Porcine vocal folds are qualitatively geometrically similar to data available for canine and human vocal folds, as well as commonly used models. Freezing of tissue in the larynx causes distortion of around 5%. The data can provide direction in estimating uncertainty due to bulk distortion of tissue caused by freezing, as well as quantitative geometric data that can be directly used in developing vocal fold models. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Graph-representation of oxidative folding pathways

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Kaján László

2005-01-01

Full Text Available Abstract Background The process of oxidative folding combines the formation of native disulfide bond with conformational folding resulting in the native three-dimensional fold. Oxidative folding pathways can be described in terms of disulfide intermediate species (DIS which can also be isolated and characterized. Each DIS corresponds to a family of folding states (conformations that the given DIS can adopt in three dimensions. Results The oxidative folding space can be represented as a network of DIS states interconnected by disulfide interchange reactions that can either create/abolish or rearrange disulfide bridges. We propose a simple 3D representation wherein the states having the same number of disulfide bridges are placed on separate planes. In this representation, the shuffling transitions are within the planes, and the redox edges connect adjacent planes. In a number of experimentally studied cases (bovine pancreatic trypsin inhibitor, insulin-like growth factor and epidermal growth factor, the observed intermediates appear as part of contiguous oxidative folding pathways. Conclusions Such networks can be used to visualize folding pathways in terms of the experimentally observed intermediates. A simple visualization template written for the Tulip package http://www.tulip-software.org/ can be obtained from V.A.

Nutrition deficiency increases the risk of stomach cancer mortality

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Da Li Qing

2012-07-01

Full Text Available Abstract Background The purpose of the study is to determine whether exposure to malnutrition during early life is associated with increased risk of stomach cancer in later life. Methods The design protocol included analyzing the trend of gastric cancer mortality and nutrition and evaluating the association between nutrient deficiency in early life and the risk of gastric cancer by hierarchical age–period–birth cohort (APC analysis using general log-linear Poisson models and to compare the difference between birth cohorts who were exposed to the 1959–1961 Chinese famine and those who were not exposed to the famine. Data on stomach cancer mortality from 1970 to 2009 and the dietary patterns from 1955 to 1985 which included the 1959–1961 Chinese famine period in the Zhaoyuan County population were obtained. The nutrition information was collected 15 years prior to the mortality data as based on the latest reference of disease incubation. Results APC analysis revealed that severe nutrition deficiency during early life may increase the risk of stomach cancer. Compared with the 1960–1964 birth cohort, the risk for stomach cancer in all birth cohorts from 1900 to 1959 significantly increased; compared with the 1970–1974 cohort, the risk for stomach cancer in the 1975–1979 cohort significantly increased, whereas the others had a steadily decreased risk; compared with 85–89 age group in the 2005–2009 death survey, the ORs decreased with younger age and reached significant levels for the 50–54 age group after adjusting the confounding factors. The 1930 to 1964 group (exposed to famine had a higher mortality rate than the 1965 to 1999 group (not exposed to famine. For males, the relative risk (RR was 2.39 and the 95% confidence interval (CI was 1.51 to 3.77. For females, RR was 1.64 and 95% CI was 1.02 to 2.62. Conclusion The results of the present study suggested that prolonged malnutrition during early life may increase the risk of

THE INFLUENCE OF FOLD AND FRACTURE DEVELOPMENT ON RESERVOIR BEHAVIOR OF THE LISBURNE GROUP OF NORTHERN ALASKA

Energy Technology Data Exchange (ETDEWEB)

Wesley K. Wallace; Catherine L. Hanks; Jerry Jensen; Michael T. Whalen

2002-01-01

increases in resistance upward. The Alapah consists of a lower resistant member (100 m) of alternating limestone and chert, a middle recessive member (100 m), and an upper resistant member (260 m) that is similar to Wahoo in the northeastern Brooks Range. The Wahoo is recessive and is thin (30 m) due either to non-deposition or erosion beneath the sub-Permian unconformity. The Lisburne of the area records two major episodes of transgression and shallowing-upward on a carbonate ramp. Thicknesses and facies vary along depositional strike. Asymmetrical folds, mostly truncated by thrust faults, were studied in and south of the local range front. Fold geometry was documented by surveys of four thrust-truncated folds and two folds not visibly cut by thrusts. A portion of the local range front was mapped to document changes in fold geometry along strike in three dimensions. The folds typically display a long, non-folded gently to moderately dipping backlimbs and steep to overturned forelimbs, commonly including parasitic anticline-syncline pairs. Thrusts commonly cut through the anticlinal forelimb or the forward synclinal hinge. These folds probably originated as detachment folds based on their mechanical stratigraphy and the transition to detachment folds to the north. Their geometry indicates that they were asymmetrical prior to thrust truncation. This asymmetry may have favored accommodation of increasing shortening by thrust breakthrough rather than continued folding. Fracture patterns were documented in the gently dipping panel of Lisburne and the asymmetrical folds within it. Four sets of steeply dipping extension fractures were identified, with strikes to the (1) N, (2) E, (3) N to NW, and (4) NE. The relative timing of these fracture sets is complex and unclear. En echelon sets of fractures are common, and display normal or strike-slip sense. Mesoscopic and penetrative structures are locally well developed, and indicate bed-parallel shear within the flat panel and strain

Interaction between Red Meat Intake and NAT2 Genotype in Increasing the Risk of Colorectal Cancer in Japanese and African Americans.

Directory of Open Access Journals (Sweden)

Hansong Wang

Full Text Available Heterocyclic aromatic amines formed in cooked meat may be an underlying mechanism for the red meat-colorectal cancer (CRC association. These compounds require bioactivaction by N-acetyltransferase 2 (NAT2. An interaction effect between red meat consumption and NAT2 in increasing CRC risk has been inconsistently reported in whites. We investigated this interaction in two populations in which the high-activity rapid NAT2 phenotype is 10- and 2-fold more common than in whites. We meta-analyzed four studies of Japanese (2,217 cases, 3,788 controls and three studies of African Americans (527 cases, 4,527 controls. NAT2 phenotype was inferred from an optimized seven-SNP genotyping panel. Processed and total red meat intakes were associated with an increased CRC risk in Japanese and in both ethnic groups combined (P's ≤ 0.002. We observed an interaction between processed meat intake and NAT2 in Japanese (P = 0.04, African Americans (P = 0.02, and in both groups combined (P = 0.006. The association of processed meat with CRC was strongest among individuals with the rapid NAT2 phenotype (combined analysis, OR for highest vs. lowest quartile: 1.62, 95% CI: 1.28-2.05; Ptrend = 8.0×10-5, intermediate among those with the intermediate NAT2 phenotype (1.29, 95% CI: 1.05-1.59; Ptrend = 0.05 and null among those with the slow phenotype (Ptrend = 0.45. A similar interaction was found for NAT2 and total red meat (Pinteraction = 0.03. Our findings support a role for NAT2 in modifying the association between red meat consumption and CRC in Japanese and African Americans.

Understanding ensemble protein folding at atomic detail

International Nuclear Information System (INIS)

Wallin, Stefan; Shakhnovich, Eugene I

2008-01-01

Although far from routine, simulating the folding of specific short protein chains on the computer, at a detailed atomic level, is starting to become a reality. This remarkable progress, which has been made over the last decade or so, allows a fundamental aspect of the protein folding process to be addressed, namely its statistical nature. In order to make quantitative comparisons with experimental kinetic data a complete ensemble view of folding must be achieved, with key observables averaged over the large number of microscopically different folding trajectories available to a protein chain. Here we review recent advances in atomic-level protein folding simulations and the new insight provided by them into the protein folding process. An important element in understanding ensemble folding kinetics are methods for analyzing many separate folding trajectories, and we discuss techniques developed to condense the large amount of information contained in an ensemble of trajectories into a manageable picture of the folding process. (topical review)

Hypospadias and increased risk for neurodevelopmental disorders.

Science.gov (United States)

Butwicka, Agnieszka; Lichtenstein, Paul; Landén, Mikael; Nordenvall, Anna S; Nordenström, Anna; Nordenskjöld, Agneta; Frisén, Louise

2015-02-01

Hypospadias (aberrant opening of the urethra on the underside of the penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether this common malformation is associated with increased psychiatric morbidity later in life. Studies of individuals with hypospadias also provide an opportunity to examine whether difference in androgen signaling is related to neurodevelopmental disorders. To elucidate the mechanisms behind a possible association, we also studied psychiatric outcomes among brothers of the hypospadias patients. Registry study within a national cohort of all 9,262 males with hypospadias and their 4,936 healthy brothers born in Sweden between 1973 and 2009. Patients with hypospadias and their brothers were matched with controls by year of birth and county. The following outcomes were evaluated (1) any psychiatric (2) psychotic, (3) mood, (4) anxiety, (5) eating, and (6) personality disorders, (7) substance misuse, (8) attention-deficit hyperactivity disorder (ADHD), (9) autism spectrum disorders (ASD), (10) intellectual disability, and (11) other behavioral/emotional disorders with onset in childhood. Patients with hypospadias were more likely to be diagnosed with intellectual disability (OR 3.2; 95% CI 2.8-3.8), ASD (1.4; 1.2-1.7), ADHD (1.5; 1.3-1.9), and behavioral/emotional disorders (1.4; 1.2-1.6) compared with the controls. Brothers of patients with hypospadias had an increased risk of ASD (1.6; 1.3-2.1) and other behavioral/emotional disorders with onset in childhood (1.2; 0.9-1.5) in comparison to siblings of healthy individuals. A slightly higher, although not statistically significant, risk was found for intellectual disability (1.3; 1.0-1.9). No relation between other psychiatric diagnosis and hypospadias was found. This is the first study to identify an increased risk for neurodevelopmental disorders in patients with hypospadias, as well as an increased risk for ASD in their brothers, suggesting a common familial (genetic and

Vocal fold injection medialization laryngoplasty.

Science.gov (United States)

Modi, Vikash K

2012-01-01

Unilateral vocal fold paralysis (UVFP) can cause glottic insufficiency that can result in hoarseness, chronic cough, dysphagia, and/or aspiration. In rare circumstances, UVFP can cause airway obstruction necessitating a tracheostomy. The treatment options for UVFP include observation, speech therapy, vocal fold injection medialization laryngoplasty, thyroplasty, and laryngeal reinnervation. In this chapter, the author will discuss the technique of vocal fold injection for medialization of a UVFP. Copyright © 2012 S. Karger AG, Basel.

Thermal analysis for folded solar array of spacecraft in orbit

International Nuclear Information System (INIS)

Yang, W.H.; Cheng, H.E.; Cai, A.

2004-01-01

The combined radiation-conduction heat transfer in folded solar array was considered as a three-dimensional anisotropic conduction without inner heat source. The three-dimensional equivalent conductivity in cell plate were obtained. The especially discrete equation coefficients of the nodes on the surfaces of adjacent cell plates were deduced by utilizing the simplified radiation network among the two adjacent cell plate surfaces and the deep cold space. All the thermal influence factors on the temperature response of the folded solar array were considered carefully. SIP method was used to solve the discrete equation. By comparing the calculation results under three cases, the temperature response and the maximum average difference of the folded solar array was obtained during the period of throw-radome of the launch vehicle and spread of the folded solar array. The obtained result is a valuable reference for the selection of the launch time of the spacecraft

NR4A1 is an endogenous inhibitor of vocal fold fibrosis.

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Hiwatashi, Nao; Bing, Renjie; Kraja, Iv; Branski, Ryan C

2017-09-01

NR4A1 was recently identified as an endogenous inhibitor of transforming growth factor (TGF)-β-induced fibrosis, and the role of this nuclear receptor has not been elucidated in tissue health or the response to injury in the vocal folds. Given the clinical implications of vocal fold fibrosis, we investigated NR4A1 expression during vocal fold wound healing in vivo and the regulatory roles of NR4A1 on vocal fold fibroblasts (VFFs) in vitro with the ultimate goal of developing targeted therapies for this challenging patient population. In vivo and in vitro. In vivo, the temporal pattern of NR4A1 mRNA expression was quantified following rat vocal fold injury. In vitro, the role of NR4A1 on TGF-β1-mediated transcription of genes underlying fibrosis as well as myofibroblast differentiation and collagen gel contraction was quantified in our human VFF line. Small interfering RNA was employed to alter NR4A1 expression to further elucidate this complex system. Nr4a1 mRNA increased 1 day after injury and peaked at 7 days. Knockdown of NR4A1 resulted in upregulation of COL1A1 and TGF-β1, with TGF-β1 stimulation (both P vocal fold health or disease. Upregulation of TGF-β following vocal fold injury was concurrent with increased NR4A1 expression. These data provide a foundation for the development of therapeutic strategies given persistent TGF-β signaling in vocal fold fibrosis. N/A Laryngoscope, 127:E317-E323, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Recovery of Vocal Fold Epithelium after Acute Phonotrauma.

Science.gov (United States)

Rousseau, Bernard; Kojima, Tsuyoshi; Novaleski, Carolyn K; Kimball, Emily E; Valenzuela, Carla V; Mizuta, Masanobu; Daniero, James J; Garrett, C Gaelyn; Sivasankar, M Preeti

2017-01-01

We investigated the timeline of tissue repair of vocal fold epithelium after acute vibration exposure using an in vivo rabbit model. Sixty-five New Zealand white breeder rabbits were randomized to 120 min of modal- or raised-intensity phonation. After the larynges were harvested at 0, 4, 8, and 24 h, and at 3 and 7 days, the vocal fold tissue was evaluated using electron microscopy and quantitative real-time polymerase chain reaction. There was an immediate decrease in the microprojection depth and height following raised-intensity phonation, paired with upregulation of cyclooxygenase-2. This initial 24-h period was also characterized by the significant downregulation of junction proteins. Interleukin 1β and transforming growth factor β1 were upregulated for 3 and 7 days, respectively, followed by an increase in epithelial cell surface depth at 3 and 7 days. These data appear to demonstrate a shift from inflammatory response to the initiation of a restorative process in the vocal fold epithelium between 24 h and 3 days. Despite the initial damage from raised-intensity phonation, the vocal fold epithelium demonstrates a remarkable capacity for the expeditious recovery of structural changes from transient episodes of acute phonotrauma. While structurally intact, the return of functional barrier integrity may be delayed by repeated episodes of phonotrauma and may also play an important role in the pathophysiology of vocal fold lesions. © 2017 S. Karger AG, Basel.

Increased incidence of preeclampsia in mothers of advanced age conceiving by oocyte donation.

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Dior, Uri P; Laufer, Neri; Chill, Henry H; Granovsky-Grisaru, Sorina; Yagel, Simcha; Yaffe, Haim; Gielchinsky, Yuval

2018-05-01

The aim of this study was to evaluate the risk of preeclampsia in women of advanced age who conceived through donated oocytes as compared with natural conceptions. A historical prospective study of singleton live births of parturients ≥ 45 years of age at four university hospitals was conducted. For the purpose of the study, the population was divided by the mode of conception into two groups: oocyte donation and natural conception. The main outcome variable in this study was preeclampsia. Secondary outcomes included pregnancy-induced hypertension and Small for Gestational Age. Two hundred and seventy pregnancies were achieved naturally and 135 women conceived by oocyte donation. Mean age at delivery for the natural conception and oocyte donation groups was 45.7 and 47.8, respectively. Preeclampsia complicated 3 out of 270 (1.1%) natural conception pregnancies and 17 out of 135 (12.6%) oocyte donation conceptions. After adjusting for confounders, oocyte donation pregnancies were found to be associated with a 12-fold increased risk for preeclampsia (P = 0.001). Among oocyte donation pregnancies, the risk of preeclampsia was not affected by parity or age. A substantially increased risk for preeclampsia was found in oocyte donation pregnancies, suggesting that the foreign oocyte may play a specific biologic role in the development of preeclampsia after the age of 45.

Structure and activity of the Pseudomonas aeruginosa hotdog-fold thioesterases PA5202 and PA2801.

Science.gov (United States)

Gonzalez, Claudio F; Tchigvintsev, Anatoli; Brown, Greg; Flick, Robert; Evdokimova, Elena; Xu, Xiaohui; Osipiuk, Jerzy; Cuff, Marianne E; Lynch, Susan; Joachimiak, Andrzej; Savchenko, Alexei; Yakunin, Alexander F

2012-06-15

The hotdog fold is one of the basic protein folds widely present in bacteria, archaea and eukaryotes. Many of these proteins exhibit thioesterase activity against fatty acyl-CoAs and play important roles in lipid metabolism, cellular signalling and degradation of xenobiotics. The genome of the opportunistic pathogen Pseudomonas aeruginosa contains over 20 genes encoding predicted hotdog-fold proteins, none of which have been experimentally characterized. We have found that two P. aeruginosa hotdog proteins display high thioesterase activity against 3-hydroxy-3-methylglutaryl-CoA and glutaryl-CoA (PA5202), and octanoyl-CoA (PA2801). Crystal structures of these proteins were solved (at 1.70 and 1.75 Å for PA5202 and PA2801 respectively) and revealed a hotdog fold with a potential catalytic carboxylate residue located on the long α-helix (Asp(57) in PA5202 and Glu(35) in PA2801). Alanine residue replacement mutagenesis of PA5202 identified four residues (Asn(42), Arg(43), Asp(57) and Thr(76)) that are critical for its activity and are located in the active site. A P. aeruginosa PA5202 deletion strain showed an increased secretion of the antimicrobial pigment pyocyanine and an increased expression of genes involved in pyocyanin biosynthesis, suggesting a functional link between PA5202 activity and pyocyanin production. Thus the P. aeruginosa hotdog thioesterases PA5202 and PA2801 have similar structures, but exhibit different substrate preferences and functions.

Social and economic factors of the natural risk increasing: estimation of the Russian regions

Directory of Open Access Journals (Sweden)

E. Petrova

2004-01-01

Full Text Available This study is an attempt to assess quantitatively social and economic factors that determine vulnerability of Russian regions to natural risk, to trace the space differences of the considered factors, and to group the regions by their similarity. In order to indicate the regional differences in social and economic development, equipment condition, dangerous substances accumulation, and social trouble four the most suitable parameters were estimated, including the per capita production of Gross Regional Product (GRP, capital consumption, volume of total toxic waste, and crime rate. Increase of the first parameter causes vulnerability reducing, the increase of the last three causes its increasing. Using multidimensional cluster analysis five types of regions were found for Russia according to similarity of the considered parameters. These types are characterized with higher value of a single (rarely two chosen parameter, which seems to be sufficient enough to affect natural risks increasing in these regions in near future. Only few regions belonging to the fifth type proved to have rather high value of GRP and relatively low values of the other parameters. The negative correlation was found between a number of natural disasters (ND and the per capita GRP in case when some parameters reached anomalously high value. The distinctions between regions by prevailing different parameters, which result in natural risk increasing, help risk management to find directions where to focus on.

Analysis of transitions at two-fold redundant sites in mammalian genomes. Transition redundant approach-to-equilibrium (TREx distance metrics

Directory of Open Access Journals (Sweden)

Liberles David A

2006-03-01

Full Text Available Abstract Background The exchange of nucleotides at synonymous sites in a gene encoding a protein is believed to have little impact on the fitness of a host organism. This should be especially true for synonymous transitions, where a pyrimidine nucleotide is replaced by another pyrimidine, or a purine is replaced by another purine. This suggests that transition redundant exchange (TREx processes at the third position of conserved two-fold codon systems might offer the best approximation for a neutral molecular clock, serving to examine, within coding regions, theories that require neutrality, determine whether transition rate constants differ within genes in a single lineage, and correlate dates of events recorded in genomes with dates in the geological and paleontological records. To date, TREx analysis of the yeast genome has recognized correlated duplications that established a new metabolic strategies in fungi, and supported analyses of functional change in aromatases in pigs. TREx dating has limitations, however. Multiple transitions at synonymous sites may cause equilibration and loss of information. Further, to be useful to correlate events in the genomic record, different genes within a genome must suffer transitions at similar rates. Results A formalism to analyze divergence at two fold redundant codon systems is presented. This formalism exploits two-state approach-to-equilibrium kinetics from chemistry. This formalism captures, in a single equation, the possibility of multiple substitutions at individual sites, avoiding any need to "correct" for these. The formalism also connects specific rate constants for transitions to specific approximations in an underlying evolutionary model, including assumptions that transition rate constants are invariant at different sites, in different genes, in different lineages, and at different times. Therefore, the formalism supports analyses that evaluate these approximations. Transitions at synonymous

Chronic kidney disease and bleeding risk in patients at high cardiovascular risk: a cohort study.

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Ocak, G; Rookmaaker, M B; Algra, A; de Borst, G J; Doevendans, P A; Kappelle, L J; Verhaar, M C; Visseren, F L

2018-01-01

Essentials The association between chronic kidney disease and bleeding is unknown. We followed 10 347 subjects at high cardiovascular risk for bleeding events. Chronic kidney disease was associated with a 1.5-fold increased bleeding risk. Especially albuminuria rather than decreased kidney function was associated with bleeding events. Background There are indications that patients with chronic kidney disease have an increased bleeding risk. Objectives To investigate the association between chronic kidney disease and bleeding in patients at high cardiovascular risk. Methods We included 10 347 subjects referred to the University Medical Center Utrecht (the Netherlands) from September 1996 to February 2015 for an outpatient visit with classic risk factors for arterial disease or with symptomatic arterial disease (Second Manifestation of Arterial disease [SMART] cohort). Patients were staged according to the KDIGO guidelines, on the basis of estimated glomerular filtration rate (eGFR) and albuminuria, and were followed for the occurrence of major hemorrhagic events until March 2015. Hazard ratios (HRs) with 95% confidence intervals (CIs) for bleeding were calculated with Cox proportional hazards analyses. Results The incidence rate for bleeding in subjects with chronic kidney disease was 8.0 per 1000 person-years and that for subjects without chronic kidney disease was 3.5 per 1000 person-years. Patients with chronic kidney disease (n = 2443) had a 1.5-fold (95% CI 1.2-1.9) increased risk of bleeding as compared with subjects without chronic kidney disease (n = 7904) after adjustment. Subjects with an eGFR of Chronic kidney disease is a risk factor for bleeding in patients with classic risk factors for arterial disease or with symptomatic arterial disease, especially in the presence of albuminuria. © 2017 University Medical Center Utrecht. Journal of Thrombosis and Haemostasis © 2017 International Society on Thrombosis and Haemostasis.

Prevention of vocal fold scarring by local application of basic fibroblast growth factor in a rat vocal fold injury model.

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Suzuki, Ryo; Kawai, Yoshitaka; Tsuji, Takuya; Hiwatashi, Nao; Kishimoto, Yo; Tateya, Ichiro; Nakamura, Tatsuo; Hirano, Shigeru

2017-02-01

Vocal fold scarring, which causes severe hoarseness, is intractable. The optimal treatment for vocal fold scarring has not been established; therefore, prevention of scarring is important. The aim of this study was to clarify the effectiveness of basic fibroblast growth factor (bFGF) for prevention of postsurgical vocal fold scarring. Prospective animal experiments with controls. The vocal folds of Sprague-Dawley rats were injured unilaterally or bilaterally after local application of a 10 μL solution of bFGF. Larynges ware harvested for histological and immunohistochemical examination 2 months postoperation and for quantitative real-time polymerase chain reaction (qRT-PCR) analysis 1 week postoperation. Histological examination showed significantly increased hyaluronic acid and decreased deposition of dense collagen in the bFGF-treated group at 100 ng/10 μL compared with the sham-treated group. Immunohistochemical examination showed significantly decreased collagen type III deposition in the bFGF-treated group at 100 ng/10 μL compared with the sham-treated group. qRT-PCR revealed that hyaluronan synthase 2 (Has2), Has3, and hepatocyte growth factor were upregulated in bFGF-treated groups compared with sham-treated group. The current results suggest that local application of bFGF at the time of injury has the potential to prevent vocal fold scarring. Preventive injection of bFGF could be applied at the time of phonomicrosurgery to avoid postoperative scar formation. N/A. Laryngoscope, 2016 127:E67-E74, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Occupational Exposure to Pesticides With Occupational Sun Exposure Increases the Risk for Cutaneous Melanoma.

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Fortes, Cristina; Mastroeni, Simona; Segatto M, Marjorie; Hohmann, Clarissa; Miligi, Lucia; Bakos, Lucio; Bonamigo, Renan

2016-04-01

The objective of the study was to examine the association between occupational exposure to pesticides and cutaneous melanoma, controlling for all possible confounders. A pooled analysis of two case-control studies was conducted in two different geographic areas (Italy and Brazil). Detailed pesticides exposure histories were obtained. Ever use of any pesticide was associated with a high risk of cutaneous melanoma (odds ratio 2.58; 95% confidence interval 1.18-5.65) in particular exposure to herbicides (glyphosate) and fungicides (mancozeb, maneb), after controlling for confounding factors. When subjects were exposed to both pesticides and occupational sun exposure, the risk increased even more (odds ratio 4.68; 95% confidence interval 1.29-17.0). The study suggests an augmented risk of cutaneous melanoma among subjects with exposure to pesticides, in particular among those exposed to occupational sun exposure.

Radiation, Atherosclerotic Risk Factors, and Stroke Risk in Survivors of Pediatric Cancer: A Report From the Childhood Cancer Survivor Study

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Mueller, Sabine, E-mail: muellers@neuropeds.ucsf.edu [Department of Neurology, Pediatrics and Neurosurgery, University of California, San Francisco, San Francisco, California (United States); Fullerton, Heather J. [Department of Neurology and Pediatrics, University of California, San Francisco, San Francisco, California (United States); Stratton, Kayla; Leisenring, Wendy [Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Weathers, Rita E.; Stovall, Marilyn [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Armstrong, Gregory T. [St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Goldsby, Robert E. [Department of Pediatrics, University of California, San Francisco, San Francisco, California (United States); Packer, Roger J. [Children' s National Medical Center, Washington, District of Columbia (United States); Sklar, Charles A. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bowers, Daniel C. [University of Texas Southwestern Medical School, Dallas, Texas (United States); Robison, Leslie L.; Krull, Kevin R. [St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

2013-07-15

Purpose: To test the hypotheses that (1) the increased risk of stroke conferred by childhood cranial radiation therapy (CRT) persists into adulthood; and (2) atherosclerotic risk factors further increase the stroke risk in cancer survivors. Methods and Materials: The Childhood Cancer Survivor Study is a multi-institutional retrospective cohort study of 14,358 5-year survivors of childhood cancer and 4023 randomly selected sibling controls with longitudinal follow-up. Age-adjusted incidence rates of self-reported late-occurring (≥5 years after diagnosis) first stroke were calculated. Multivariable Cox proportional hazards models were used to identify independent stroke predictors. Results: During a mean follow-up of 23.3 years, 292 survivors reported a late-occurring stroke. The age-adjusted stroke rate per 100,000 person-years was 77 (95% confidence interval [CI] 62-96), compared with 9.3 (95% CI 4-23) for siblings. Treatment with CRT increased stroke risk in a dose-dependent manner: hazard ratio 5.9 (95% CI 3.5-9.9) for 30-49 Gy CRT and 11.0 (7.4-17.0) for 50+ Gy CRT. The cumulative stroke incidence in survivors treated with 50+ Gy CRT was 1.1% (95% CI 0.4-1.8%) at 10 years after diagnosis and 12% (95% CI 8.9-15.0%) at 30 years. Hypertension increased stroke hazard by 4-fold (95% CI 2.8-5.5) and in black survivors by 16-fold (95% CI 6.9-36.6). Conclusion: Young adult pediatric cancer survivors have an increased stroke risk that is associated with CRT in a dose-dependent manner. Atherosclerotic risk factors enhanced this risk and should be treated aggressively.

Radiation, Atherosclerotic Risk Factors, and Stroke Risk in Survivors of Pediatric Cancer: A Report From the Childhood Cancer Survivor Study

International Nuclear Information System (INIS)

Mueller, Sabine; Fullerton, Heather J.; Stratton, Kayla; Leisenring, Wendy; Weathers, Rita E.; Stovall, Marilyn; Armstrong, Gregory T.; Goldsby, Robert E.; Packer, Roger J.; Sklar, Charles A.; Bowers, Daniel C.; Robison, Leslie L.; Krull, Kevin R.

2013-01-01

Purpose: To test the hypotheses that (1) the increased risk of stroke conferred by childhood cranial radiation therapy (CRT) persists into adulthood; and (2) atherosclerotic risk factors further increase the stroke risk in cancer survivors. Methods and Materials: The Childhood Cancer Survivor Study is a multi-institutional retrospective cohort study of 14,358 5-year survivors of childhood cancer and 4023 randomly selected sibling controls with longitudinal follow-up. Age-adjusted incidence rates of self-reported late-occurring (≥5 years after diagnosis) first stroke were calculated. Multivariable Cox proportional hazards models were used to identify independent stroke predictors. Results: During a mean follow-up of 23.3 years, 292 survivors reported a late-occurring stroke. The age-adjusted stroke rate per 100,000 person-years was 77 (95% confidence interval [CI] 62-96), compared with 9.3 (95% CI 4-23) for siblings. Treatment with CRT increased stroke risk in a dose-dependent manner: hazard ratio 5.9 (95% CI 3.5-9.9) for 30-49 Gy CRT and 11.0 (7.4-17.0) for 50+ Gy CRT. The cumulative stroke incidence in survivors treated with 50+ Gy CRT was 1.1% (95% CI 0.4-1.8%) at 10 years after diagnosis and 12% (95% CI 8.9-15.0%) at 30 years. Hypertension increased stroke hazard by 4-fold (95% CI 2.8-5.5) and in black survivors by 16-fold (95% CI 6.9-36.6). Conclusion: Young adult pediatric cancer survivors have an increased stroke risk that is associated with CRT in a dose-dependent manner. Atherosclerotic risk factors enhanced this risk and should be treated aggressively

Hemorrhagic and Ischemic Strokes Compared Stroke Severity, Mortality, and Risk Factors

DEFF Research Database (Denmark)

Andersen, Klaus Kaae; Olsen, T. S.; Dehlendorff, Christian

2009-01-01

were diabetes, atrial fibrillation, previous myocardial infarction, previous stroke, and intermittent arterial claudication. Smoking and alcohol consumption favored HS, whereas age, sex, and hypertension did not herald stroke type. Compared with ischemic strokes, HS was associated with an overall...... higher mortality risk (HR, 1.564; 95% CI, 1.441-1.696). The increased risk was, however, time-dependent; initially, risk was 4-fold, after 1 week it was 2.5-fold, and after 3 weeks it was 1.5-fold. After 3 months stroke type did not correlate to mortality. Conclusion-Strokes are generally more severe...... based on 25 123 individuals with a complete data set. Results-Of the patients 3993 (10.1%) had HS. Stroke severity was almost linearly related to the probability of having HS (2% in patients with the mildest stroke and 30% in those with the most severe strokes). Factors favoring ischemic strokes vs HS...

Cancer and the risk for taking early retirement pension: a Danish cohort study

DEFF Research Database (Denmark)

Carlsen, Kathrine; Oksbjerg Dalton, Susanne; Frederiksen, Kirsten

2008-01-01

, physical and psychological comorbidity, low education and low income. Three risk categories were identified (high, medium and low) by cancer site and we found that in the high risk category, people diagnosed with leukemia, prostate cancer or ovary cancer had a more than two-fold increased risk for ERP......AIMS: The purpose of this study was to determine the risk for taking early retirement pension (ERP) in cancer survivors who were working at the time of diagnosis. METHODS: We conducted a nationwide and population based cohort study including 44,905 persons aged 30-60 years diagnosed with selected...... cancers in the period 1981-2000 and 211,562 randomly sampled cancer-free controls. Information on socioeconomic status, demography and physical and psychiatric comorbidity was obtained from Danish administrative registries. RESULTS: We analyzed the risk for ERP adjusted for known risk factors and found...