bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and tolerability of paritaprevir, a direct acting antiviral agent for hepatitis C virus treatment, with and without ritonavir in healthy volunteers
Authors: Menon R. M. , Klein C. E. , Podsadecki T. J. , Chiu Y.‐L. , Dutta S. , Awni W. M. 
Published: December 2015

AimsParitaprevir is a direct acting antiviral agent for use as part of a multidrug hepatitis C virus infection treatment regimen. To characterize the pharmacokinetics, safety, and tolerability of paritaprevir and determine an optimal dosing regimen for subsequent evaluations, clinical studies were conducted with paritaprevir alone or with ritonavir, a cytochrome P450 3A4 inhibitor anticipated to increase paritaprevir exposure.MethodsTwo phase 1, double‐blind, placebo‐controlled, parallel group studies were conducted in healthy volunteers (NCT00850044 and NCT00931281). Single dose study participants (n = 87) were randomized to one time administration of either paritaprevir or placebo, or paritaprevir with ritonavir or placebo. Participants (n = 38) enrolled in the multiple dose study received paritaprevir with ritonavir or placebo once or twice daily for 14 days. Pharmacokinetics, safety and tolerability were assessed throughout the study treatment periods.ResultsAfter single or multiple dose administration, paritaprevir displayed non‐linear pharmacokinetics, with maximum plasma concentration and area under the plasma concentration–time curve increasing in a greater than dose proportional manner. Concomitant administration of 100 mg ritonavir increased paritaprevir exposure from a 300 mg dose approximately 30‐ to 50‐fold and extended paritaprevir half‐life. The tolerability of paritaprevir was similar with or without ritonavir. Asymptomatic, transient increases in bilirubin were observed but were not associated with abnormalities in other liver function tests.ConclusionsParitaprevir exhibits non‐linear pharmacokinetics with greater than dose proportional increases in exposure after single or multiple dosing. Co‐administration with ritonavir increases paritaprevir exposure and half‐life without adversely influencing tolerability.
Caries experience in 7‐, 12‐, and 15‐year‐old schoolchildren in the canton of Basel‐Landschaft, Switzerland, from 1992 to 2011
Authors: Waltimo Tuomas , Menghini Giorgio , Weber Catherine , Kulik Eva M. , Schild Samuel , Meyer Jürg 
Published: December 2015

AbstractObjectivesTo investigate the changes in caries experience and prevalence among schoolchildren of the canton of Basel‐Landschaft, Switzerland, over the course of 20 years.MethodsA random sample of either schoolchildren aged 7, 12, and 15 years (in 1992) or aged 12 and 15 years (in 1997) or their respective school classes (2001, 2006 and 2011) was selected so that approximately 10% of schoolchildren could be examined. The children's dmft and DMFT scores were determined according to the WHO methodology and analyzed using cluster‐adjusted ordinary multiple linear regression modeling.ResultsFor all age groups, the respective dmft/DMFT values decreased steadily from 1992 to 2006 but increased again in 2011. However, the observed differences were not statistically significant over the examination years from 2001 to 2011. Schoolchildren with a migrant background had approximately two‐ to threefold higher dmft/DMFT values.ConclusionsIn the years from 1992 to 2001, a steady decline in caries was observed in all age groups of schoolchildren examined in the canton of Basel‐Landschaft. However, in the subsequent 10 years, this decline has leveled off. The mean dmft/DMFT values are comparable to those in other parts of Switzerland. Migrants are a caries‐risk group; the mean dmft/DMFT values were higher in schoolchildren with a migrant background than in the comparable Swiss children.
A comparison of tooth retention and replacement across 15 countries in the over‐50s
Authors: Stock Christian , Jürges Hendrik , Shen Jing , Bozorgmehr Kayvan , Listl Stefan 
Published: December 2015

AbstractObjectivesOral diseases are still among the most common chronic diseases globally with substantial detrimental impact especially on elderly people's health and well‐being. However, limited evidence exists on international variation in the oral health status of the older population. We aimed to examine international variation in tooth loss and tooth replacement in the general population aged between 50 and 90 years.MethodsA cross‐sectional analysis of data from the fifth wave of the Survey of Health, Ageing and Retirement in Europe (SHARE) was conducted. The data cover 14 European countries (Austria, Belgium, Czech Republic, Denmark, Estonia, France, Germany, Italy, Luxembourg, the Netherlands, Slovenia, Spain, Sweden, and Switzerland) and Israel, and they were collected during the year 2013. Age‐specific percentages of the population having all natural teeth, the age‐specific numbers of natural (and artificial) teeth, and the age‐specific percentages of full, partial, or no replacement of missing teeth were assessed with stratification by country. It was further evaluated to which extent proposed oral health goals concerning tooth loss at higher ages had been achieved.ResultsIn total, 62 763 individuals were included in the study. Age‐standardized mean numbers of natural teeth exhibited substantial variation, ranging from 14.3 (Estonia) to 24.5 (Sweden). The oral health goal of retaining at least 20 teeth at age 80 years was achieved by 25% of the population or less in most countries. A target concerning edentulism (≤15% in population aged 65–74 years) was reached in Sweden, Switzerland, Denmark, France, and Germany. Tooth replacement practices varied especially for a number of up to five missing teeth which were more likely to be replaced in Austria, Germany, Luxembourg, and Switzerland than in Israel, Denmark, Estonia, Spain, and Sweden.ConclusionsThis study suggests that the age‐specific number of natural teeth and the practice of tooth replacement in the over 50s differ substantially among the included countries. The present results may be helpful in the formulation and evaluation of oral health goals in the older population.
Association between lung capacity and abnormal glucose metabolism: findings from China and Australia
Authors: Yu Dahai , Chen Tao , Qin Rui , Cai Yamei , Jiang Zhixin , Zhao Zhanzheng , Simmons David 
Published: December 2015

SummaryObjectiveRestricted pulmonary function is found among people with diabetes. This study aimed to investigate the dose–response relationship between pulmonary function measurements [forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)] and risk of metabolic syndrome (MS)/type 2 diabetes.MethodsA total of 1454 adults in rural Victoria, Australia, and 5824 adults in Nanjing, China, from randomly selected households provided clinical history, oral glucose tolerance test, lipids, anthropometric, blood pressure and spirometric measurements. MS was defined by International Diabetes Federation criteria. Adjusted odds ratios for MS and type 2 diabetes with lung capacity measurements were estimated using logistic regression. Dose–response relationships were explored using the restricted cubic spline models.ResultsThere was a nonlinear relationship between FEV1 and the risk of type 2 diabetes and MS (both P < 0·0001) in both the Australian and Chinese populations. The FEV1 associated with the lowest risk of type 2 diabetes and MS was above 2·70 l (95%CI: 2·68 to 2·72 l and 2·65 to 2·76 l in Chinese and Australian populations, respectively). The discrimination of the model could be significantly improved using the FEV1 threshold in both the Australian and Chinese populations.ConclusionsIn both the Australian and Chinese populations, the risk of type 2 diabetes and MS is lowest with a FEV1 of 2·65–2·76 l. This might be used in clinical practice in different countries as a prompt to screen for type 2 diabetes and MS in patients with obstructive lung disease and to ensure there was no abnormal glucose metabolism before the commencement of steroids if indicated.
SOS1 frameshift mutations cause pure mucosal neuroma syndrome, a clinical phenotype distinct from multiple endocrine neoplasia type 2B
Authors: Owens Martina , Kivuva Emma , Quinn Anthony , Brennan Paul , Caswell Richard , Allen Hana Lango , Vaidya Bijay , Ellard Sian 
Published: December 2015

SummaryBackgroundMucosal neuromas, thickened corneal nerves and marfanoid body habitus are characteristic phenotypic features of multiple endocrine neoplasia type 2B (MEN2B) and often provide an early clue to the diagnosis of the syndrome. Rarely, patients present with typical physical features of MEN2B but without associated endocrinopathies (medullary thyroid carcinoma or pheochromocytoma) or a RET gene mutation; this clinical presentation is thought to represent a distinct condition termed ‘pure mucosal neuroma syndrome’.MethodsExome sequencing was performed in two unrelated probands with mucosal neuromas, thickened corneal nerves and marfanoid body habitus, but no MEN2B‐associated endocrinopathy or RET gene mutation. Sanger sequencing was performed to confirm mutations detected by exome sequencing and to test in family members and 3 additional unrelated index patients with mucosal neuromas or thickened corneal nerves.ResultsA heterozygous SOS1 gene frameshift mutation (c.3266dup or c.3248dup) was identified in each proband. Sanger sequencing showed that proband 1 inherited the c.3266dup mutation from his affected mother, while the c.3248dup mutation had arisen de novo in proband 2. Sanger sequencing also identified one further novel SOS1 mutation (c.3254dup) in one of the 3 additional index patients.ConclusionOur results demonstrate the existence of pure mucosal neuroma syndrome as a clinical entity distinct from MEN2B that can now be diagnosed by genetic testing.
Understanding the genetic and environmental specificity and overlap between well‐being and internalizing symptoms in adolescence
Authors: Haworth Claire M.A. , Carter Kathryn , Eley Thalia C. , Plomin Robert 
Published: December 2015

AbstractModerate inverse correlations are typically found between well‐being and mental illness. We aimed to investigate the role of genes and environments in explaining the relationships between two aspects of well‐being and two measures of internalizing symptoms. Altogether, 4700 pairs of 16‐year‐old twins contributed data on subjective happiness and life satisfaction, as well as symptoms of depression and emotional problems. Well‐being was moderately correlated with internalizing symptoms (range = −0.45, −0.58). Multivariate twin model‐fitting indicated both genetic and environmental overlap. Life satisfaction and happiness demonstrated different patterns of overlap, with stronger genetic links between life satisfaction and depression. Non‐shared environmental influences were largely specific to each trait. This study supports the theory of mental health and illness being partly (but not entirely) correlated dimensions. There are also significant genetic and environmental factors to identify for well‐being that go beyond the absence of mental illness. It is therefore possible that different interventions are needed for treating mental illness and promoting mental health.
Red cell distribution width and mortality in carotid atherosclerosis
Authors: Wonnerth Anna , Krychtiuk Konstantin A. , Mayer Florian J. , Minar Erich , Wojta Johann , Schillinger Martin , Koppensteiner Renate , Hoke Matthias 
Published: December 2015

AbstractBackgroundRed cell distribution width (RDW) is associated with morbidity and mortality in chronic cardiac disease. The aim of the present study was to investigate the role of RDW as a predictor of adverse outcome in patients with carotid atherosclerosis.Materials and methodsWe prospectively studied 1065 of 1286 consecutive patients with neurological asymptomatic carotid artery stenosis as assessed by duplex Doppler sonography. The study end points were all‐cause mortality and cardiovascular mortality respectively.ResultsDuring a median follow‐up time of 6·2 years (interquartile range 5·9–6·6), corresponding to 5551 overall person‐years, 275 patients (25·8%) died. Of them, 182 patients (66·2%) died due to cardiovascular causes. RDW was significantly associated with adverse outcome. In a continuous multivariate Cox regression analysis, the adjusted hazard ratio for each per cent increase in RDW was 1·39 (95% CI 1·27–1·53; P < 0·001) for all‐cause and 1·43 (95% CI 1·28–1·60; P < 0·001) for cardiovascular mortality respectively. Kaplan–Meier estimates showed a gradual relationship between increasing quartiles of RDW and death (log rank P < 0·001). Adjusted hazard ratios for all‐cause death ranged from 0·89 to 1·94 for the highest vs. the lowest quartile (P < 0·001 for trend) and for cardiovascular death from 1·08 to 2·34 for the highest vs. the lowest quartile (P < 0·001 for trend) respectively.ConclusionsRed cell distribution width was significantly and independently associated with all‐cause and cardiovascular death in patients with asymptomatic carotid atherosclerosis.
Renal microRNA‐ and RNA‐profiles in progressive chronic kidney disease
Authors: Rudnicki Michael , Perco Paul , D′haene Barbara , Leierer Johannes , Heinzel Andreas , Mühlberger Irmgard , Schweibert Ninella , Sunzenauer Judith , Regele Heinz , Kronbichler Andreas , Mestdagh Pieter , Vandesompele Jo , Mayer Bernd , Mayer Gert 
Published: December 2015

AbstractBackgroundMicroRNAs (miRNAs) contribute to chronic kidney disease (CKD) progression via regulating mRNAs involved in renal homeostasis. However, their association with clinical outcome remains poorly understood.Materials and methodsWe performed miRNA and mRNA expression profiling on renal biopsy sections by qPCR (miRNA) and microarrays (mRNA) in a discovery (n = 43) and in a validation (n = 29) cohort. miRNAs differentiating stable and progressive cases were inversely correlated with putative target mRNAs, which were further characterized by pathway analysis using KEGG pathways.ResultsmiR‐30d, miR‐140‐3p, miR‐532‐3p, miR‐194, miR‐190, miR‐204 and miR‐206 were downregulated in progressive cases. These seven miRNAs correlated with upregulated 29 target mRNAs involved in inflammatory response, cell–cell interaction, apoptosis and intra‐cellular signalling. In particular, miR‐206 and miR‐532‐3p were associated with distinct biological processes via the expression of their target mRNAs: Reduced expression of miR‐206 in progressive disease correlated with the upregulation of target mRNAs participating in inflammatory pathways (CCL19, CXCL1, IFNAR2, NCK2, PTK2B, PTPRC, RASGRP1 and TNFRSF25). Progressive cases also showed a lower expression of miR‐532‐3p and an increased expression of target transcripts involved in apoptosis pathways (MAP3K14, TNFRSF10B/TRAIL‐R2, TRADD and TRAF2). In the validation cohort, we confirmed the decreased expression of miR‐206 and miR‐532‐3p, and the inverse correlation of these miRNAs with the expression of nine of the 12 target genes. The levels of the identified miRNAs and the target mRNAs correlated with clinical parameters and histological damage indices.ConclusionsThese results suggest the involvement of specific miRNAs and mRNAs in biological pathways associated with the progression of CKD.
Aquaporin‐1 and 8 expression in the gallbladder mucosa might not be associated with the development of gallbladder stones in humans
Authors: Ambe Peter C. , Gödde Daniel , Zirngibl Hubert , Störkel Stephan 
Published: December 2015

AbstractBackgroundCholecystolithiasis is a highly prevalent condition in the Western world. Gallbladder stone‐related conditions represent the second most common gastrointestinal pathology. Cholesterol stones represent over 80% of gallstones. Cholesterol stones develop secondary to crystallization of bile cholesterol. Water resorption from gallbladder bile via aquaporin in the gallbladder mucosa might play a role in the development of cholesterol stones. This study investigated the expression of Aquaporin‐1 (AQP1) and Aquaporin‐8 (AQP8) in the human gallbladder mucosa and their possible association with the formation of gallbladder stones.MethodsThe expression of AQP1 and AQP8 in the gallbladder mucosa was examined via immunohistochemical staining. The expression of both AQP1 and AQP8 in the gallbladder mucosa of stone carriers (study group) was compared to that of nonstone carriers (control group).ResultsEighty‐four gallbladder specimens from 44 male (52·2%) and 40 female (47·6%) patients were analysed. The study group included 47 specimens from stone carriers, while 37 specimens from stone‐free gallbladders were included in the control group. Immunostaining for both AQP1 and AQP8 was positive in 80 cases. AQP1 was expressed both over the apical and intercellular membrane, while AQP8 was expressed only over the apical membrane. A similar distribution was recorded in specimens from the cystic duct. Immunostaining with AQP1 was generally stronger in comparison with AQP8. No significant (P > 0·05) relationship was found between aquaporin expression and the presence or absence of gallbladder stones.ConclusionAQP1 and AQP8 are both expressed in the gallbladder and cystic duct mucosa. However, their role in the development of gallbladder stones is still to be proven.
Eltrombopag safety and efficacy for primary chronic immune thrombocytopenia in clinical practice
Authors: González‐López Tomás José , Alvarez‐Román María Teresa , Pascual Cristina , Sánchez‐González Blanca , Fernández‐Fuentes Fernando , Jarque Isidro , Pérez‐Rus Gloria , Pérez‐Crespo Susana , Bernat Silvia , Hernández‐Rivas José Angel , Andrade Marcio M. , Cortés Montserrat , Gómez‐Nuñez Marta , Olivera Pavel , Martínez‐Robles Violeta , Fernández‐Rodríguez Angeles , Fuertes‐Palacio Miguel Angel , Fernández‐Miñano Carmen , de Cabo Erik , Fisac Rosa , Aguilar Carlos , Bárez Abelardo , Peñarrubia María Jesús , García‐Frade Luis Javier , González‐Porras José Ramón 
Published: December 2015

AbstractBackgroundEltrombopag is effective and safe in chronic immune thrombocytopenia (ITP). However, clinical trials may not accurately reflect what happens in clinical practice. We evaluated the efficacy and safety of eltrombopag in primary chronic ITP in a real‐world setting.MethodsA total of 164 primary patients with chronic ITP from 40 Spanish centers, who had been treated with eltrombopag, were retrospectively evaluated.ResultsThe median age of our cohort (72% women) was 63 yr (interquartile range, IQR, 45–75 yr). The median time with ITP diagnosis was 81 months (IQR, 30–192 months). The median number of therapies prior to eltrombopag was 3 (IQR, 2–4). At the time of eltrombopag start, 45 patients (30%) were receiving concomitant treatment for ITP. Forty‐six patients (30%) had bleeding signs/symptoms the month before the treatment started. The median platelet count at eltrombopag initiation was 22 × 109/L (IQR, 8–39 × 109/L). A total of 135 patients (88.8%) achieved a platelet response. The median time to platelet response was 12 d (95% CI, 9–13 d). Maintained platelet response rate during the 15‐month period under examination was 75.2%. Twenty‐eight patients (18.4%) experienced adverse events, mainly grades 1–2.ConclusionEltrombopag is highly effective and well tolerated in unselected patients with primary chronic ITP.
Not for Parents Only: Begging Calls Allow Nest‐Mate Discrimination in Juvenile Zebra Finches
Authors: Ligout Séverine , Dentressangle Fabrice , Mathevon Nicolas , Vignal Clémentine 
Published: December 2015

AbstractThe benefits of recognition of family members may range from inbreeding avoidance to cooperative and coordinated behaviors within the family group. In birds, recognition of family members has almost exclusively been studied between parents and offspring or within cooperatively breeding societies. Yet, recognition of nest‐mates could be of special importance in recently fledged birds of colonial species by helping in locating the nest, maintaining family group cohesion, or allowing detection of feeding opportunities by recognizing the begging calls nest‐mates produced on the return of a parent. Here we study nest‐mate discrimination based on begging calls in fledglings of domesticated zebra finches (Taeniopygia guttata), a gregarious songbird living in loose colonies in which juveniles may gather in crèches and are fed by parents up to 20 d after fledging. Using playback tests, we show that fledglings called more and spent more time near the loudspeaker in response to the begging calls of their nest‐mates than to the calls of other familiar individuals. Because each fledgling was exposed to the repeated association of the begging calls of its nest‐mates and the subsequent feeding of its parents, this preferential response to the nest‐mates' calls could be a conditioned response to the food reward. Whereas fledglings answered more to male fledgling calls than to female fledgling calls, response to playback was influenced neither by the sex of the subject nor by its brood size. Discriminant function analysis based on acoustic parameters showed that begging calls carried an individual signature as well as a brood signature which might account for such nest‐mate discrimination. Begging signals are major study systems of the evolution of communication in the face of conflicts of interest between signalers and receivers. Our results suggest that eavesdropping and communication networks may be other informative frameworks to understand the design of offspring solicitation signals.
Algal Turbidity Hampers Ornament Perception, but Not Expression, in a Sex‐Role‐Reversed Pipefish
Authors: Sundin Josefin , Rosenqvist Gunilla , Myhren Siri , Berglund Anders 
Published: December 2015

AbstractSexual ornaments are used both in intra‐ and intersexual contexts, and these signals have evolved to function in the particular habitat the animal is adapted to. Habitat characteristics may, however, change rapidly due to anthropogenic effects, sometimes at rates too fast for many organisms to adaptively respond. In aquatic ecosystems, eutrophication is currently changing chemical as well as visual properties of the environment. Algae blooms increase water turbidity, and the reduction of water transparency thus has the potential to alter visual ornaments and their perception. However, results are not congruent. Rather, algae turbidity may decrease, increase, or leave ornaments unaffected. The effect seems to depend on exposure time, condition, population and species. Here, we found that the perception of sexual signals, but not their expression, was hampered by turbidity in the sex‐role‐reversed pipefish Nerophis ophidion. In a laboratory experiment we found that female sexual ornaments (i.e., blue color markings and a skinfold) and fecundity was unaffected by turbidity. Male adaptive mate choice for larger females with large ornament was, however, hampered under turbid conditions, whereas in clear water males choose larger, more ornamented females. Thus, we show that water turbidity had no effect on signal expression but did hamper ornament perception and consequently randomized mate choice.