bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative study shows differences in screen exposure, sleep patterns and sleep disturbances between Jewish and Muslim children in Israel
Authors: Tzischinsky Orna , Haimov Iris 
Published: June 2017

AbstractAimThis study determined the differences in screen exposure, sleep patterns and sleep disturbances, and the associations between these factors, among Jewish and Muslim children in Israel.MethodsThe participants were 1049 school children – 499 Jewish and 550 Muslim – with a mean age of 9.2 ± 0.7 years, who attended public schools in both urban and rural residential settings in 2014. They all completed the Sleep Self‐Report questionnaire and the Screen Exposure Questionnaire.ResultsMuslim children reported increased screen time, despite having fewer televisions and computers in their bedroom than Jewish children. Muslim children also reported earlier bedtimes and longer sleep duration, but greater sleep disturbances. Having screens in bedrooms and non‐school days were related to later bedtimes and later wake‐up times for all children. Children who spent four or more hours watching television or using a computer on school days reported significantly more sleep disturbances than children with lower usage.ConclusionMuslim children with a mean age of nine years reported longer screen exposure, earlier bedtimes and longer sleep duration, but more sleep disturbances, than Jewish children. Cultural sleep practices may contribute to the differences in sleep patterns and sleep disturbances of Jewish and Muslim children in Israel.
Comparison of effect sizes between enriched and nonenriched trials of analgesics for chronic musculoskeletal pain: a systematic review
Authors: Yamato Tie P. , Maher Chris G. , Saragiotto Bruno T. , Shaheed Christina Abdel , Moseley Anne M. , Lin Chung‐Wei Christine , Koes Bart , McLachlan Andrew J. 
Published: June 2017

AIMSTo investigate the use of an enriched study design on the estimates of treatment effect in analgesic trials for chronic musculoskeletal pain.MethodsDatabase searches were conducted from 2004 to 2014. We included randomized placebo‐controlled trials evaluating pain medications for chronic musculoskeletal pain. Methodological quality was assessed using the PEDro scale. The estimates of treatment effect on pain and adverse events were compared between enriched and nonenriched designs. Metaregression was used to assess the association between the effect size estimate and the study design controlling for analgesic dose and methodological quality.ResultsWe included 108 trials, of which 99 were included in the meta‐analysis (n = 44 171). There were no overall differences in effect sizes between enriched and nonenriched designs for pain intensity. There was a significant difference for a reduction in any adverse events favouring enriched designs for opioids, but not for other analgesics or the outcome serious adverse events. There was an association between effect size and methodological quality, with failure to blind the outcome assessor and failure to use intention‐to‐treat analysis being associated with larger effect sizes.ConclusionsThere is no evidence that the use of an enriched study design changes the treatment effect size estimate for pain. There is some evidence that clinical trials that employ enriched designs report a reduced risk of adverse events in trials for chronic musculoskeletal pain, but it is unclear whether enriched designs influence estimates of serious adverse events. Features of trial design and study quality were associated with treatment effect estimates.
Molecular regulation and pharmacological targeting of the β‐catenin destruction complex
Authors: van Kappel Eline C , Maurice Madelon M 
Published: June 2017

The β‐catenin destruction complex is a dynamic cytosolic multiprotein assembly that provides a key node in Wnt signalling regulation. The core components of the destruction complex comprise the scaffold proteins axin and adenomatous polyposis coli and the Ser/Thr kinases casein kinase 1 and glycogen synthase kinase 3. In unstimulated cells, the destruction complex efficiently drives degradation of the transcriptional coactivator β‐catenin, thereby preventing the activation of the Wnt/β‐catenin pathway. Mutational inactivation of the destruction complex is a major pathway in the pathogenesis of cancer. Here, we review recent insights in the regulation of the β‐catenin destruction complex, including newly identified interaction interfaces, regulatory elements and post‐translationally controlled mechanisms. In addition, we discuss how mutations in core destruction complex components deregulate Wnt signalling via distinct mechanisms and how these findings open up potential therapeutic approaches to restore destruction complex activity in cancer cells.Linked ArticlesThis article is part of a themed section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc
Neuroadaptations of presynaptic and postsynaptic GABAB receptor function in the paraventricular nucleus in response to chronic unpredictable stress
Authors: Gao Yonggang , Zhou Jing‐Jing , Zhu Yun , Wang Li , Kosten Therese A , Zhang Xiangjian , Li De‐Pei 
Published: June 2017

Background and purposeChronic stress impairs GABAA (GABA type A) receptor‐mediated inhibition in the hypothalamic paraventricular nucleus (PVN). It is not clear whether GABAB receptor function is also altered. We hypothesize that chronic stress alters GABAB receptor function in PVN corticotrophin‐releasing hormone (CRH) neurons to control hypothalamus‐pituitary–adrenal axis activity.Experimental ApproachWhole‐cell patch clamp recordings were made of PVN‐CRH neurons expressing eGFP driven by CRH promoter in brain slices from unstressed rats and rats exposed to chronic unpredictable mild stress (CUMS).Key ResultsCUMS elevated the basal circulating corticosterone levels and increased the basal firing activity of PVN‐CRH neurons. Microinjection of GABAB receptor agonist baclofen into the PVN suppressed the increased corticosterone levels in CUMS rats compared with unstressed rats. CUMS blunted the baclofen‐induced inhibition on PVN‐CRH neurons and outward currents in these neurons. Furthermore, CUMS reduced expression of GABAB1 (GABABR1) protein in the PVN. Blocking NMDA receptors with AP5 restored the reduced baclofen‐induced currents in CUMS rats but had no effect on GABAB1 expression. Furthermore, CUMS treatment augmented the baclofen‐induced decrease in the frequency of glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitor postsynaptic currents in PVN‐CRH neurons. The GABAB receptor antagonist CGP55845 increased the firing activity of PVN‐CRH neurons only in CUMS‐treated rats and not in unstressed rats.Conclusions and ImplicationsThese findings suggest that chronic stress impairs postsynaptic GABAB receptor function but augments presynaptic GABAB receptor function in controlling glutamatergic and GABAergic synaptic inputs in PVN‐CRH neurons.
Diversity and stability of egg‐bacterial assemblages: The role of paternal care in the glassfrog Hyalinobatrachium colymbiphyllum
Authors: Hughey Myra C. , Delia Jesse , Belden Lisa K. 
Published: June 2017

AbstractEmbryos of oviparous organisms must cope with harsh environments and are especially susceptible to disease, considering that many immune mechanisms do not develop until later in life. Parents may transmit symbiotic microflora to eggs, which can contribute to embryo immune defense. Despite the importance of symbiotic microbes for immune function and survival of adult amphibians, vertical transfer of symbionts in amphibians has received less attention than in other taxa. Here, we test the role of male‐only parental care in establishing and maintaining the diversity of egg‐bacterial assemblages in a Neotropical glassfrog (Centrolenidae). Previous research suggests that father Hyalinobatrachium colymbiphyllum may transfer bacterial symbionts to their eggs. We combined a male‐removal experiment in situ with 16S rRNA gene amplicon sequencing to determine whether egg attendance by father H. colymbiphyllum influences the bacterial community and survival of eggs. We found that eggs harbor a diverse and stable bacterial assemblage. Despite different host environments, we found that adult skin and eggs supported very similar bacterial assemblages—even after removing fathers. While we found overlap in the bacteria present on eggs and their fathers, our experiment reveals that extended male care does not contribute to the maintenance of egg‐bacterial communities, so there may be other potential routes of transfer. This study contributes to our understanding of the diversity and maintenance of egg microbiomes, and motivates further research on how initial bacteria are acquired and the ontogenetic development of host–symbiont communities.
Annual direct medical costs associated with diabetes‐related complications in the event year and in subsequent years in Hong Kong
Authors: Jiao F. , Wong C. K. H. , Tang S. C. W. , Fung C. S. C. , Tan K. C. B. , McGhee S. , Gangwani R. , Lam C. L. K. 
Published: June 2017

AbstractAimTo develop models to estimate the direct medical costs associated with diabetes‐related complications in the event year and in subsequent years.MethodsThe public direct medical costs associated with 13 diabetes‐related complications were estimated among a cohort of 128 353 people with diabetes over 5 years. Private direct medical costs were estimated from a cross‐sectional survey among 1825 people with diabetes. We used panel data regression with fixed effects to investigate the impact of each complication on direct medical costs in the event year and subsequent years, adjusting for age and co‐existing complications.ResultsThe expected annual public direct medical cost for the baseline case was US$1,521 (95% CI 1,518 to 1,525) or a 65‐year‐old person with diabetes without complications. A new lower limb ulcer was associated with the biggest increase, with a multiplier of 9.38 (95% CI 8.49 to 10.37). New end‐stage renal disease and stroke increased the annual medical cost by 5.23 (95% CI 4.70 to 5.82) and 5.94 (95% CI 5.79 to 6.10) times, respectively. History of acute myocardial infarction, congestive heart failure, stroke, end‐stage renal disease and lower limb ulcer increased the cost by 2–3 times. The expected annual private direct medical cost of the baseline case was US$187 (95% CI 135 to 258) for a 65‐year‐old man without complications. Heart disease, stroke, sight‐threatening diabetic retinopathy and end‐stage renal disease increased the private medical costs by 1.5 to 2.5 times.ConclusionsWide variations in direct medical cost in event year and subsequent years across different major complications were observed. Input of these data would be essential for economic evaluations of diabetes management programmes.
Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: the randomized MARLINA‐T2D trial
Authors: Groop Per‐Henrik , Cooper Mark E. , Perkovic Vlado , Hocher Berthold , Kanasaki Keizo , Haneda Masakazu , Schernthaner Guntram , Sharma Kumar , Stanton Robert C. , Toto Robert , Cescutti Jessica , Gordat Maud , Meinicke Thomas , Koitka‐Weber Audrey , Thiemann Sandra , von Eynatten Maximilian 
Published: June 2017

AimsThe MARLINA‐T2D study (ClinicalTrials.gov, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard‐of‐care in individuals with type 2 diabetes and albuminuria.MethodsA total of 360 individuals with type 2 diabetes, HbA1c 6.5% to 10.0% (48–86 mmol/mol), estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 and urinary albumin‐to‐creatinine ratio (UACR) 30–3000 mg/g despite single agent renin‐angiotensin‐system blockade were randomized to double‐blind linagliptin (n = 182) or placebo (n = 178) for 24 weeks. The primary and key secondary endpoints were change from baseline in HbA1c at week 24 and time‐weighted average of percentage change from baseline in UACR over 24 weeks, respectively.ResultsBaseline mean HbA1c and geometric mean (gMean) UACR were 7.8% ± 0.9% (62.2 ± 9.6 mmol/mol) and 126 mg/g, respectively; 73.7% and 20.3% of participants had microalbuminuria or macroalbuminuria, respectively. After 24 weeks, the placebo‐adjusted mean change in HbA1c from baseline was −0.60% (−6.6 mmol/mol) (95% confidence interval [CI], −0.78 to −0.43 [−8.5 to −4.7 mmol/mol]; P < .0001). The placebo‐adjusted gMean for time‐weighted average of percentage change in UACR from baseline was −6.0% (95% CI, −15.0 to 3.0; P = .1954). The adverse‐event profile, including renal safety and change in eGFR, was similar between the linagliptin and placebo groups.ConclusionsIn individuals at early stages of diabetic kidney disease, linagliptin significantly improved glycaemic control but did not significantly lower albuminuria. There was no significant change in placebo‐adjusted eGFR. Detection of clinically relevant renal effects of linagliptin may require longer treatment, as its main experimental effects in animal studies have been to reduce interstitial fibrosis rather than alter glomerular haemodynamics.
Dietary map of Nile tilapia using stable isotopes in three tropical lakes, Ethiopia
Authors: Fetahi Tadesse , Rothhaupt Karl‐Otto , Peeters Frank 
Published: June 2017

AbstractComprehensive analysis of food webs requires identifying dietary sources that support the production of all major organisms within the food web/food chain. Here, we use stable isotope ratios (δ13C, δ34S and δ15N) to assess the relative contribution of different basal carbon sources to the diet of Nile tilapia (Oreochromis niloticusL.) in three tropical lakes Hawassa (also Awasa in literature), Ziway and Koka (Ethiopia). Computations were carried out with Stable Isotope Analysis in R (SIAR) model to quantify the dietary proportion of each prey for the tilapia fish. Basal food sources were distinguishable based on their δ13C, δ34S and δ15N values. In Lake Ziway, macrophytes (64%) were the dominant assimilated diet of tilapia while particulate organic matter (POM) and zooplankton contributed only 20% and 16%, respectively. In parallel, Nile tilapia in Lake Hawassa assimilated macrophytes (35%),POM(33%) and zooplankton (32%) at comparatively equal proportion. The dietary sources of the fish in Lake Koka werePOM(49%) and zooplankton (51%). In contrast with earlier studies based on gut content analysis, the present results reveal that macrophytes contributed more and phytoplankton less than previously reported especially in macrophyte‐dominated lakes Ziway and Hawassa. The ecological condition of the lakes might have been predominantly accountable for the diet change of the tilapia. As dietary data are prerequisite for food web/food chain analysis and aquaculture industry, re‐evaluating the diet of aquatic organisms appear relevant.
A small molecule activator of Nav1.1 channels increases fast‐spiking interneuron excitability and GABAergic transmission in vitro and has anti‐convulsive effects in vivo
Authors: Frederiksen Kristen , Lu Dunguo , Yang Jinhui , Jensen Henrik Sindal , Bastlund Jesper Frank , Larsen Peter Hjørringgaard , Liu Henry , Crestey François , Dekermendjian Kim , Badolo Lassina , Laursen Morten , Hougaard Charlotte , Yang Charles , Svenstrup Niels , Grunnet Morten 
Published: June 2017

AbstractNav1.1 (SCN1A) channels primarily located in gamma‐aminobutyric acid (GABA)ergic fast‐spiking interneurons are pivotal for action potential generation and propagation in these neurons. Inappropriate function of fast‐spiking interneurons, leading to disinhibition of pyramidal cells and network desynchronization, correlates with decreased cognitive capability. Further, reduced functionality of Nav1.1 channels is linked to various diseases in the central nervous system. There is, at present, however no subtype selective pharmacological activators of Nav1.1 channels available for studying pharmacological modulation of interneuron function. In the current study, we identified a small molecule Nav1.1 activator, 3‐amino‐5‐(4‐methoxyphenyl)thiophene‐2‐carboxamide, named AA43279, and provided an in vitro to in vivo characterization of the compound. In HEK‐293 cells expressing human Nav1.1 channels, AA43279 increased the Nav1.1‐mediated current in a concentration‐dependent manner mainly by impairing the fast inactivation kinetics of the channels. In rat hippocampal brain slices, AA43279 increased the firing activity of parvalbumin‐expressing, fast‐spiking GABAergic interneurons and increased the spontaneous inhibitory post‐synaptic currents (sIPSCs) recorded from pyramidal neurons. When tested in vivo, AA43279 had anti‐convulsive properties in the maximal electroshock seizure threshold test. AA43279 was tested for off‐target effects on 72 different proteins, including Nav1.2, Nav1.4, Nav1.5, Nav1.6 and Nav1.7 and exhibited reasonable selectivity. Taken together, AA43279 might constitute a valuable tool compound for revealing biological functions of Nav1.1 channels.
E‐cadherin mediates ultraviolet radiation‐ and calcium‐induced melanin transfer in human skin cells
Authors: Singh Suman K. , Baker Richard , Sikkink Stephen K. , Nizard Carine , Schnebert Sylvianne , Kurfurst Robin , Tobin Desmond J. 
Published: June 2017

AbstractSkin pigmentation is directed by epidermal melanin units, characterized by long‐lived and dendritic epidermal melanocytes (MC) that interact with viable keratinocytes (KC) to contribute melanin to the epidermis. Previously, we reported that MC:KC contact is required for melanosome transfer that can be enhanced by filopodi, and by UVR/UVA irradiation, which can upregulate melanosome transfer via Myosin X‐mediated control of MC filopodia. Both MC and KC express Ca2+‐dependent E‐cadherins. These homophilic adhesion contacts induce transient increases in intra‐KC Ca2+, while ultraviolet radiation (UVR) raises intra‐MC Ca2+ via calcium‐selective ORAI1 ion channels; both are associated with regulating melanogenesis. However, how Ca2+ triggers melanin transfer remains unclear. Here we evaluated the role of E‐cadherin in UVR‐mediated melanin transfer in human skin cells. MC and KC in human epidermis variably express filopodia‐associated E‐cadherin, Cdc42, VASP and β‐catenin, all of which were upregulated by UVR in human MC in vitro. Knockdown of E‐cadherin revealed that this cadherin is essential for UVR‐induced MC filopodia formation and melanin transfer. Moreover, Ca2+ induced a dose‐dependent increase in filopodia formation and melanin transfer, as well as increased β‐catenin, Cdc42, Myosin X and E‐cadherin expression in these skin cells. Together, these data suggest that filopodial proteins and E‐cadherin, which are upregulated by intracellular (UVR‐stimulated) and extracellular Ca2+ availability, are required for filopodia formation and melanin transfer. This may open new avenues to explore how Ca2+ signalling influences human pigmentation.
The Sox2: GFP+/− knock‐in mouse model does not faithfully recapitulate Sox2 expression in skin
Authors: Salz Lucia , Driskell Ryan R. 
Published: June 2017

AbstractHair follicle heterogeneity may be regulated by distinct dermal papillae (DP) that represent mesenchymal lineages, which can be defined by Sox2 expression. However, it was recently shown that GFP expression in the Sox2: GFP+/− mouse model occurs in the DPs of all hair follicle types, challenging the idea that hair follicle heterogeneity can be defined by DP heterogeneity. Here, we investigated whether the knock‐in mouse model faithfully expresses GFP when compared to endogenous Sox2 expression. The results reveal that GFP expression is aberrant in both the infundibulum of hair follicles and in the DPs. Consequently, we provide an explanation for the aberrant expression of the knock‐in gene based on the original cloning strategy for the mouse model in the context of a newly identified regulatory element associated within the coding region of Sox2.
Recent climatic drying leads to age‐independent growth reductions of white spruce stands in western Canada
Authors: Hogg Edward H. , Michaelian Michael , Hook Trisha I. , Undershultz Michael E. 
Published: June 2017

AbstractSince 2001, climatic conditions have been notably drier than normal across large areas of the western Canadian interior, leading to widespread impacts on the forests of this region. This poses a major concern for the future, given climate change projections for continued warming and drying. We conducted tree‐ring analysis in 75 pure stands of white spruce (Picea glauca) across Alberta and west‐central Saskatchewan to examine the effects of recent climatic drying on the growth of this important boreal tree species. Allometric equations were used to calculate annual growth in aboveground tree biomass (GBM) from ring width measurements. Results showed an increasing trend in GBM from the 1960s to the 1990s, followed by a sharp decline during the severe drought of 2001–2002. Of the 75 stands, only 18 recovered sufficiently to cause an increase in mean GBM from the predrought decade of 1991–2000 to the subsequent decade of 2001–2010. The remaining 57 stands exhibited a decline in mean GBM between these decades. Climatic drying was a major cause of the growth decline, as shown by the significant stand‐level relationship between percentage change in decadal mean GBM and the change in decadal mean values of a climate moisture index from 1991–2000 to 2001–2010. Subsequent analyses of boreal stands sampled across Alberta during 2015 revealed that white spruce growth had declined even further as drought conditions intensified during 2014–2015. Overall, there was a 38% decrease in mean GBM between 1997 and 2015, but surprisingly, the percentage decrease was not significantly different for young, productive stands compared with older, less productive stands. Thus, stand ageing cannot explain the observed decline in white spruce growth during the past quarter century, suggesting that these forests are at risk if the trend towards more frequent, severe drought continues in the region.
Potential drug–drug interactions in older adults: A population‐based study
Authors: Santos Thalyta Renata Araújo , Silveira Erika Aparecida , Pereira Lílian Varanda , Provin Mércia Pandolfo , Lima Dione Marçal , Amaral Rita Goreti 
Published: June 2017

AimTo evaluate the potential drug–drug interactions (PDDI) between drugs used by older adults, any associated factors and recommended clinical management.MethodsA cross‐sectional, population‐based study was carried out through a home survey of 934 older adults (from December 2009 to April 2010). A questionnaire was applied, and the participants were asked to show all the drugs used and their respective prescriptions, thus providing data to identify polypharmacy, self‐medication and PDDI. PDDI, their consequences, severity and clinical management were identified using Micromedex.ResultsOverall, 2846 drugs and 665 PDDI were identified, 71.0% of which were moderate and 22.4% serious. The prevalence of PDDI was 36.9%. Drugs with a narrow therapeutic index were involved in 17.0% of the PDDI. The variables female sex (PR = 1.11, 95% CI 1.02–1.20), age ≥80 years (PR = 1.15, 95% CI 1.03–1.28), no polypharmacy (PR = 0.72, 95% CI 0.67–0.78) and no hospitalization in the past year (PR = 0.90, 95% CI 0.82–0.97) remained associated with the presence of three or more PDDI in the final multivariate analysis model.ConclusionsMost PDDI were related to routinely used drugs (enalapril, hydrochlorothiazide, calcium, captopril, levothyroxine and simvastatin), and more than one‐third of the older adults were exposed to PDDI with the possible risk of serious health consequences. Drugs with a narrow therapeutic index were involved in several PDDI, with increased risk of toxicity. The clinical management procedures most recommended are dose adjustment and dosing changes, control of the drugs’ serum levels, and monitoring of the clinical conditions.Geriatr Gerontol Int 2017; 17: 2336–2346.