bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased plasma chemerin levels in women with gestational diabetes mellitus
Authors: Hare K. J. , Bonde L. , Svare J. A. , Randeva H. S. , Asmar M. , Larsen S. , Vilsbøll T. , Knop F. K. 
Published: March 2014

AbstractAimsTo evaluate fasting and post‐prandial serum chemerin levels in pregnant women with and without gestational diabetes, and again following delivery when normal glucose homeostasis is re‐established.MethodsChemerin levels were measured in serum from nine women with gestational diabetes, and from eight age‐ and BMI‐matched pregnant women with normal glucose tolerance during two meal tests: in the third trimester and 3–4 months post partum. All women with gestational diabetes re‐established normal glucose tolerance after delivery.ResultsMeal intake did not affect serum chemerin levels. The group with gestational diabetes had lower mean serum chemerin levels during the third trimester compared with the group with normal glucose tolerance (28 ± 1.3 vs. 88 ± 3.5 ng/ml, P < 0.0001). In the group with normal glucose tolerance, mean serum chemerin levels decreased significantly post partum to 57 ± 2.8 ng/ml (P = 0.0001), but remained significantly (P = 0.0003) higher than post‐partum levels in the group with gestational diabetes (31 ± 1.9 ng/ml), which did not differ significantly from third trimester levels (P = 0.31).ConclusionsNormal pregnancy is associated with increased circulating chemerin levels, which may act to reduce pregnancy‐induced insulin resistance and prevent glucose intolerance. Women with gestational diabetes, however, have severely reduced chemerin levels that remain low after delivery, which may contribute to the insulin resistance, glucose intolerance and high Type 2 diabetes risk associated with gestational diabetes.
Effectiveness and cost‐effectiveness of 3‐monthly versus 6‐monthly monitoring of well‐controlled type 2 diabetes patients: a pragmatic randomised controlled patient‐preference equivalence trial in primary care (EFFIMODI study)
Authors: Wermeling P. R. , Gorter K. J. , Stellato R. K. , de Wit G. A. , Beulens J. W. J. , Rutten G. E. H. M. 
Published: March 2014

AimTo investigate effectiveness and cost‐effectiveness of 6‐monthly monitoring compared with 3‐monthly monitoring of well‐controlled type 2 diabetes patients in primary care.MethodsA pragmatic randomised controlled patient‐preference equivalence trial was performed. From April 2009 to August 2010, 2215 patients from 233 general practitioners across the Netherlands were included. Patients were eligible if between 40‐ and 80‐years‐old, diagnosed with type 2 diabetes for more than a year, treated by their general practitioner, not on insulin treatment and well‐controlled during the last year (HbA1c ≤58 mmol/mol, systolic blood pressure ≤145 mmHg and total cholesterol ≤5.2 mmol/l). Patients without a strong preference for their monitoring frequency were randomised to 3‐monthly or 6‐monthly monitoring. Follow‐up was 18 months. The primary outcome is the percentage of patients remaining under: HbA1c ≤58 mmol/mol, systolic blood pressure ≤145 mmHg and total cholesterol ≤5.2 mmol/l. Equivalence was assumed if the two‐sided 95% confidence interval (CI) was between −5 and 5%. Cost‐effectiveness was determined using a cost‐minimisation analysis.ResultsIn the 3‐monthly group 69.5% remained under good cardiometabolic control, versus 69.8% in the 6‐monthly group (difference: 0.3%; 95%CI: −6.2–6.7%). All secondary outcomes were equivalent for 3‐monthly and 6‐monthly monitoring, except the systolic blood pressure target, physical activity and antihypertensive drug use. Six‐monthly monitoring was €387 (£333) cheaper per patient compared to 3‐monthly monitoring during the study period.ConclusionsPatients with good cardiometabolic control and without preference for their monitoring frequency can visit the primary care physician less often. The cost‐savings can be considerable.
FDI into transition economies
Authors: Estrin S. , Uvalic M. 
Published: March 2014

AbstractThe article explores the determination of foreign direct investment (FDI) into the Balkan transition economies – Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Macedonia, Montenegro, Romania and Serbia. Detailed FDI inflows to Southeast Europe are analysed to determine the main differences in the volume, timing and sectoral structure of FDI within the region and in comparison to the Central East European countries. A gravity model for all transition economies during 1990–2011 is then estimated to assess whether the factors driving FDI to the Western Balkans are different. They are found to be so; even when the size of their economies, distance from the source economies, institutional quality and prospects of EU membership are taken into account, Western Balkans countries receive less FDI than other transition countries. These issues are of policy relevance for the Balkan economies and ought to contribute to the current debate on the ‘new growth model’.
GABAA receptors and plasticity of inhibitory neurotransmission in the central nervous system
Authors: Fritschy Jean‐Marc , Panzanelli Patrizia 
Published: March 2014

AbstractGABAA receptors (GABAARs) are ligand‐gated Cl− channels that mediate most of the fast inhibitory neurotransmission in the central nervous system (CNS). Multiple GABAAR subtypes are assembled from a family of 19 subunit genes, raising the question of the significance of this heterogeneity. In this review, we discuss the evidence that GABAAR subtypes represent distinct receptor populations with a specific spatio‐temporal expression pattern in the developing and adult CNS, being endowed with unique functional and pharmacological properties, as well as being differentially regulated at the transcriptional, post‐transcriptional and translational levels. GABAAR subtypes are targeted to specific subcellular domains to mediate either synaptic or extrasynaptic transmission, and their action is dynamically regulated by a vast array of molecular mechanisms to adjust the strength of inhibition to the changing needs of neuronal networks. These adaptations involve not only changing the gating or kinetic properties of GABAARs, but also modifying the postsynaptic scaffold organised by gephyrin to anchor specific receptor subtypes at postsynaptic sites. The significance of GABAAR heterogeneity is particularly evident during CNS development and adult neurogenesis, with different receptor subtypes fulfilling distinct steps of neuronal differentiation and maturation. Finally, analysis of the specific roles of GABAAR subtypes reveals their involvement in the pathophysiology of major CNS disorders, and opens novel perspectives for therapeutic intervention. In conclusion, GABAAR subtypes represent the substrate of a multifaceted inhibitory neurotransmission system that is dynamically regulated and performs multiple operations, contributing globally to the proper development, function and plasticity of the CNS.
SynCAMs extend their functions beyond the synapse
Authors: Frei Jeannine A. , Stoeckli Esther T. 
Published: March 2014

AbstractSynaptic cell adhesion molecules are characterized by their potential to trigger synaptogenesis in vitro, even when expressed in non‐neuronal cell lines. In addition to the prototypic synaptic cell adhesion molecules (SynCAMs), other structurally unrelated families of synaptic cell adhesion molecules have been identified: neurexins and neuroligins, as well as the leucine‐rich repeat transmembrane neuronal protein family. Although in vivo the absence of individual synaptic cell adhesion molecules does not necessarily reduce the number of synapses, it does affect the function of synapses. Not surprisingly, mutations in synaptic cell adhesion molecules have been identified in patients suffering from neurodevelopmental disorders, such as autism spectrum disorders, intellectual disability or schizophrenia. In line with the major function of these genes at the synapse, their role in the pathogenesis of neurodevelopmental diseases has been attributed to synaptogenesis, synapse maintenance and synaptic plasticity. However, one family of synaptic cell adhesion molecules, the SynCAMs, have also been implicated in axon guidance, that is, an earlier step in neural circuit formation. These findings suggest that SynCAMs, and maybe other families of synaptic cell adhesion molecules as well, could contribute to the pathogenesis of neurodevelopmental disorders at multiple steps of neural circuit formation and, thus, shape the distinct symptoms associated with different disease variants or distinct neurodevelopmental disorders in addition to their effect on synaptic function. In this review, we summarize the roles of one family of synaptic cell adhesion molecules, the SynCAMs, at the synapse and beyond in axon guidance and myelination.
Microbial community dynamics alleviate stoichiometric constraints during litter decay
Authors: Kaiser Christina , Franklin Oskar , Dieckmann Ulf , Richter Andreas 
Published: March 2014

AbstractUnder the current paradigm, organic matter decomposition and nutrient cycling rates are a function of the imbalance between substrate and microbial biomass stoichiometry. Challenging this view, we demonstrate that in an individual‐based model, microbial community dynamics alter relative C and N limitation during litter decomposition, leading to a system behaviour not predictable from stoichiometric theory alone. Rather, the dynamics of interacting functional groups lead to an adaptation at the community level, which accelerates nitrogen recycling in litter with high initial C : N ratios and thus alleviates microbial N limitation. This mechanism allows microbial decomposers to overcome large imbalances between resource and biomass stoichiometry without the need to decrease carbon use efficiency (CUE), which is in contrast to predictions of traditional stoichiometric mass balance equations. We conclude that identifying and implementing microbial community‐driven mechanisms in biogeochemical models are necessary for accurately predicting terrestrial C fluxes in response to changing environmental conditions.
Pooled analysis of the safety and tolerability of onabotulinumtoxinA in the treatment of chronic migraine
Authors: Diener H.‐C. , Dodick D. W. , Turkel C. C. , Demos G. , DeGryse R. E. , Earl N. L. , Brin M. F. 
Published: March 2014

Background and purposeOnabotulinumtoxinA was effective and well tolerated for prophylaxis of headache in patients with chronic migraine (CM) in two randomized, double‐blind, placebo‐controlled, phase 3 trials. To further assess the safety and tolerability of onabotulinumtoxinA in CM prophylaxis in adults, the pooled safety data from four double‐blind, placebo‐controlled trials were analyzed.MethodsThe pooled analysis included two phase 2 and two phase 3 double‐blind, placebo‐controlled trials. The safety population was 2436 patients, 1997 of whom received ≥1 dose of onabotulinumtoxinA. The studies shared similar dosing intervals (approximately 12 weeks) with doses between 75 and 260 U. Safety assessments included adverse events (AEs), physical examination and clinical laboratory tests.ResultsOnabotulinumtoxinA was safe and well tolerated, with a low discontinuation rate (3.4%) due to AEs. The majority of patients in this pooled analysis received doses between 150 and 200 U, with an average of 163 U per treatment cycle. Of the 1997 patients who received any onabotulinumtoxinA injections, 1455 patients (72.9%) reported at least one AE. Neck pain (12.6%) was the most common onabotulinumtoxinA‐associated AE, followed by muscle weakness (8.0%), musculoskeletal stiffness (6.1%) and eyelid ptosis (4.6%). Serious AEs were infrequent, occurring in 5.4% of patients who received any onabotulinumtoxinA treatment and 3.0% of patients receiving placebo. AEs were consistent with the known tolerability profile of onabotulinumtoxinA.ConclusionsMultiple treatments with onabotulinumtoxinA at doses of 75–260 U administered every 12 weeks, and up to five treatment cycles, were well tolerated for the prophylaxis of headache in adults with CM.
Paroxysmal atrial fibrillation occurs often in cryptogenic ischaemic stroke. Final results from the SURPRISE study
Authors: Christensen L. M. , Krieger D. W. , Højberg S. , Pedersen O. D. , Karlsen F. M. , Jacobsen M. D. , Worck R. , Nielsen H. , Ægidius K. , Jeppesen L. L. , Rosenbaum S. , Marstrand J. , Christensen H. 
Published: March 2014

Background and purposeAtrial fibrillation (AF) increases the risk of stroke fourfold and is associated with a poor clinical outcome. Despite work‐up in compliance with guidelines, up to one‐third of patients have cryptogenic stroke (CS). The prevalence of asymptomatic paroxysmal atrial fibrillation (PAF) in CS remains unknown. The SURPRISE project aimed at determining this rate using long‐term cardiac monitoring.MethodsPatients with CS after protocolled work‐up including electrocardiography (ECG) and telemetry were included after informed consent. An implantable loop recorder (ILR) was implanted subcutaneously. PAF was defined by events of atrial arrhythmia >2 min with a correlating one‐lead ECG confirming the diagnosis.ResultsEighty‐five patients were monitored for a mean of 569 days (SD ±310). PAF was documented in 18 patients (20.7%) during the study period and detected by ILR in 14 patients (16.1%). In three patients PAF was detected by other methods before or after monitoring and was undiscovered due to device sensitivity in one case. The first event of PAF was documented at a mean of 109 days (SD ±48) after stroke onset. PAF was asymptomatic in all cases and occurred in episodes lasting predominantly between 1 and 4 h. Four recurrent strokes were observed, three in patients with PAF; all three patients were on oral anticoagulation (OAC).ConclusionsOne in five patients with CS had PAF, which occurred at low burden and long after stroke. Future studies should determine the role of implantable cardiac monitors after stroke and determine the potential therapeutic benefit of OAC treatment of patients with PAF.
Anosognosia, neglect and quality of life of right hemisphere stroke survivors
Authors: Dai C.‐Y. , Liu W.‐M. , Chen S.‐W. , Yang C.‐A. , Tung Y.‐C. , Chou L.‐W. , Lin L.‐C. 
Published: March 2014

Background and purposeAnosognosia and neglect may coexist in stroke patients. Neglect patients often report poor quality of life (QOL), whereas patients suffering from other cognition disorders with poor insight report better QOL. This study investigates the relationship between anosognosia, neglect and QOL amongst stroke survivors.MethodsStroke survivors who met the criteria were used as a sampling pool. Sixty stroke patients were observed in this study, amongst whom 20 patients with anosognosia and neglect (A+N+), 20 patients with neglect but not anosognosia (A−N+) and 20 patients with neither anosognosia nor neglect (A−N−) were selected from the sampling pool based on demographic characteristics matched with the A+N+ group. A questionnaire (SS‐QOL) was used to collect the QOL perceived by the stroke survivors.ResultsThe perceived QOL of the A+N+ group was significantly better than those of the other groups, including the subscales of self‐care, mobility, work/productivity, upper extremity, mood, family role and social role. However, the A+N+ group had poor balance level and more fall incidents were reported.ConclusionThe A+N+ group perceived better QOL but had more falls and poorer balance than the other groups. Health providers should work with caregivers aggressively in preventing accidents.
Risk factors in patients with perimesencephalic hemorrhage
Authors: Mensing L. A. , Ruigrok Y. M. , Greebe P. , Vlak M. H. M. , Algra A. , Rinkel G. J. E. 
Published: March 2014

Background and purposeSmoking and hypertension are risk factors for aneurysmal subarachnoid hemorrhage (aSAH), whilst excessive alcohol consumption is less consistently linked with aSAH. Perimesencephalic hemorrhage (PMH) is a benign subset of non‐aneurysmal subarachnoid hemorrhage. The exact cause of PMH is unknown, and its risk factor profile may help to elucidate the pathogenesis. The influence of smoking, hypertension and excessive alcohol consumption on the occurrence of PMH was studied.MethodsSeventy‐nine patients admitted with a PMH to the University Medical Center Utrecht were studied. As controls 574 persons were selected from five different general practices in the referral region of the University Medical Center Utrecht. All participants filled in a questionnaire about smoking habits, the presence of hypertension and alcohol consumption before their hemorrhage. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to assess the association of risk factors and PMH, and multivariable logistic regression was used to adjust for possible confounding by age and sex.ResultsAdjusted ORs for the occurrence of PMH were 1.7 (95% CI 1.0–2.8) for smoking cigarettes, cigars, pipes or any combination of these, 1.1 (95% CI 0.6–2.0) for hypertension and 1.1 (95% CI 0.5–2.1) for excessive alcohol consumption.ConclusionsSimilar to aSAH, smoking is a risk factor for PMH and excessive alcohol consumption is not. In contrast to aSAH, hypertension is not a risk factor for PMH. This implies that the pathophysiological mechanisms causing PMH might be slightly different from those causing aSAH.
A novel cryptochrome in the diatom Phaeodactylum tricornutum influences the regulation of light‐harvesting protein levels
Authors: Juhas Matthias , von Zadow Andrea , Spexard Meike , Schmidt Matthias , Kottke Tilman , Büchel Claudia 
Published: March 2014

Diatoms possess several genes for proteins of the cryptochrome/photolyase family. A typical sequence for a plant cryptochrome was not found in our analysis of the Phaeodactylum tricornutum genome, but one protein grouped with higher plant and green algal cryptochromes. This protein, CryP, binds FAD and 5,10‐methenyltetrahydrofolate, according to our spectroscopic studies on heterologously expressed protein. 5,10‐Methenyltetrahydrofolate binding is a feature common to both cyclobutane pyrimidine dimer photolyases and DASH cryptochromes. In recombinant CryP, however, the FAD chromophore was present in its neutral radical state and had a red‐shifted absorption maximum at 637 nm, which is more characteristic for a DASH cryptochrome than a cyclobutane pyrimidine dimer photolyase. Upon illumination with blue light, the fully reduced state of FAD was formed in the presence of reductant. Expression of CryP was silenced by antisense approaches, and the resulting cell lines showed increased levels of proteins of light‐harvesting complexes, the Lhcf proteins, in vivo. In contrast, the levels of proteins active in light protection, the Lhcx proteins, were reduced. Thus, CryP cannot be directly grouped with known members of the cryptochrome/photolyase family. Of all P. tricornutum proteins, it is the most similar in sequence to a plant cryptochrome, and is involved in the regulation of light‐harvesting protein expression, but shows spectroscopic features and a chromophore composition that are most typical of a DASH cryptochrome.
Diphtheria toxin conformational switching at acidic pH
Authors: Leka Oneda , Vallese Francesca , Pirazzini Marco , Berto Paola , Montecucco Cesare , Zanotti Giuseppe 
Published: March 2014

Diphtheria toxin (DT), the etiological agent of the homonymous disease, like other bacterial toxins, has to undergo a dramatic structural change in order to be internalized into the cytosol, where it finally performs its function. The molecular mechanism of toxin transit across the membrane is not well known, but the available experimental evidence indicates that one of the three domains of the toxin, called the central α‐helical domain, inserts into the lipid bilayer, so favoring the translocation of the catalytic domain. This process is driven by the acidic pH of the endosomal lumen. Here, we describe the crystal structure of DT grown at acidic pH in the presence of bicelles. We were unable to freeze the moment of DT insertion into the lipid bilayer, but our crystal structure indicates that the low pH causes the unfolding of the TH2, TH3 and TH4 α‐helices. This event gives rise to the exposure of a hydrophobic surface that includes the TH5 and TH8 α‐helices, and the loop region connecting the TH8 and TH9 α‐helices. Their exposure is probably favored by the presence of lipid bilayers in the crystallization solution, and they appear to be ready to insert into the membrane.DatabaseCoordinates and structure factors have been deposited in the Protein Data Bank under accession number 4OW6.
Patterns of dental services and factors that influence dental services among 64–65‐year‐old regular users of dental care in Denmark
Authors: Christensen Lisa B. , Rosing Kasper , Lempert Susanne M. , Hede Børge 
Published: March 2014

ObjectivesTo describe the pattern of dental services provided to 64–65‐year‐old Danes who are regular users of dental care over a 5‐year period, to analyse whether this pattern is associated with socio‐demographic and/or socioeconomic factors, and if different uses of dental services are related to dental status and caries experience. Finally, to discuss the future planning of dental services aimed at the increasing population of elderly citizens. [Correction made on 21 March 2014, after first online publication: The sentence ‘Data on elderly's dental service are scarce, although increased use is seen and more teeth are present in this age group.’ was removed.]MethodsA cross‐sectional study of all aged 64–65 (n = 37 234) who received a dental examination in 2009 was conducted. Clinical data comprised dental services received under the National Health Insurance reimbursement scheme, dental status and DMFT. Geographical, socio‐demographic and socioeconomic data derived from public registers.ResultsAlmost all received restorations, while periodontal treatment was received by <50% during 5 years. Heavy use of dental services was dominated by periodontal services. Periodontal services were most prevalent in the capital and the most affluent areas. Relatively more extractions were related to low income and persons in least affluent areas. Total number of services was highest among women, persons with ≥20 teeth, persons living in the capital, and where the ratio user per dentist was low.ConclusionFor future planning of dental care for elderly, dental status, geographical and social area‐based factors and to some degree gender, income, and education must be taken into consideration as all these factors seem to influence the future demand for dental services.