bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inappropriate prescribing in elderly people with diabetes admitted to hospital
Authors: Formiga F. , Vidal X. , Agustí A. , Chivite D. , Rosón B. , Barbé J. , López‐Soto A. , Torres O. H. , Fernández‐Moyano A. , García J. , Ramírez‐Duque N. , San José A. ,   Potentially Inappropriate Prescription in Older Patients in Spain (PIPOPS) Investigators' Project
Published: September 2015

AbstractAimsTo assess inappropriate prescribing in older people with diabetes mellitus during the month prior to a hospitalization, using tools on potentially inappropriate medicines (PIMs) and potential prescribing omissions (PPOs) and comparing inappropriate prescribing in patients with without diabetes.MethodsIn an observational, prospective multicentric study, we assessed inappropriate prescribing in 672 patients aged 75 years and older during hospital admission. The Beers, Screening Tool of Older Person's Prescriptions (STOPP) and Screening Tool to Alert Doctors to Right Treatment (START) criteria and Assessing Care of Vulnerable Elders (ACOVE‐3) medicine quality indicators were used. We analysed demographic and clinical factors associated with inappropriate prescribing.ResultsOf 672 patients, 249 (mean age 82.4 years, 62.9% female) had a diagnosis of diabetes mellitus. The mean number of prescribing drugs per patient with diabetes was 12.6 (4.5) vs. 9.4 (4.3) in patients without diabetes (P < 0.001). Of those patients with diabetes, 74.2% used 10 or more medications; 54.5% of patients with diabetes had at least one Beers‐listed PIM, 68.1% had at least one STOPP‐listed PIM, 64.6% had at least one START‐listed PPO and 62.8% had at least one ACOVE‐3‐listed PPO. Except for the Beers criteria, these prevalences were significantly higher in patients with diabetes than in those without. After excluding diabetes‐related items from these tools, only STOPP‐listed PIMs remained significantly higher among patients with diabetes (P = 0.04).ConclusionsPolypharmacy is common among older patients with diabetes mellitus. Inappropriate prescribing is higher in older patients with diabetes, even when diabetes‐related treatment is excluded from the inappropriate prescribing evaluation.
Poor structural social support is associated with an increased risk of Type 2 diabetes mellitus: findings from the MONICA/KORA Augsburg cohort study
Authors: Altevers J. , Lukaschek K. , Baumert J. , Kruse J. , Meisinger C. , Emeny R. T. , Ladwig K. H. 
Published: September 2015

AbstractAimsSeveral psychosocial factors have been shown to increase the risk of Type 2 diabetes mellitus. This study investigated the association between structural social support and incidence of Type 2 diabetes mellitus in men and women.MethodsData were derived from three population‐based MONICA/KORA surveys conducted in 1984–1995 in the Augsburg region (southern Germany) and followed up by 2009. The study population comprised 8952 participants (4669 men/4283 women) aged 30–74 years without diabetes at baseline. Structural social support was assessed using the Social Network Index. Sex‐specific hazard ratios were estimated from Cox proportional hazard models.ResultsWithin follow‐up, 904 incident Type 2 diabetes mellitus cases (558 men, 346 women) were observed. Crude incidence rates for Type 2 diabetes mellitus per 10 000 person‐years were substantially higher in poor compared with good structural social support (men: 94 vs. 69, women: 58 vs. 43). After adjustment for age, survey, parental history of diabetes, smoking status, alcohol intake, physical activity, hypertension, dyslipidaemia, BMI, education, sleep complaints and depressed mood, risk of Type 2 diabetes mellitus for participants with poor compared with good structural social support was 1.31 [95% confidence interval (CI) = 1.11–1.55] in men and 1.10 (95% CI = 0.88–1.37) in women. Stratified analyses revealed a hazard ratio of 1.50 (95% CI = 1.23–1.83) in men with a low level of education and 0.87 (95% CI = 0.62–1.22) in men with a high level of education (P for interaction: 0.0082).ConclusionsPoor structural social support is associated with Type 2 diabetes mellitus in men. This association is independent of risk factors at baseline and is particularly pronounced in men with a low level of education.
Molecular components of the circadian clock in mammals
Authors: Takahashi J. S. 
Published: September 2015

AbstractThe circadian clock mechanism in animals involves a transcriptional feedback loop in which the bHLH‐PAS proteins CLOCK and BMAL1 form a transcriptional activator complex to activate the transcription of the Period and Cryptochrome genes, which in turn feed back to repress their own transcription. In the mouse liver, CLOCK and BMAL1 interact with the regulatory regions of thousands of genes, which are both cyclically and constitutively expressed. The circadian transcription in the liver is clustered in phase and this is accompanied by circadian occupancy of RNA polymerase II recruitment and initiation. These changes also lead to circadian fluctuations in histone H3 lysine4 trimethylation (H3K4me3) as well as H3 lysine9 acetylation (H3K9ac) and H3 lysine27 acetylation (H3K27ac). Thus, the circadian clock regulates global transcriptional poise and chromatin state by regulation of RNA polymerase II.
Sleep efficiency as a determinant of insulin sensitivity in overweight and obese adolescents
Authors: Dorenbos E. , Rijks J. M. , Adam T. C. , Westerterp‐Plantenga M. S. , Vreugdenhil A. C. E. 
Published: September 2015

AbstractInsulin resistance (IR) occurs in a transient manner during puberty. Obese adolescents may be at risk for persistent IR during puberty. The objective of the study is to review the literature on the association of the anthropometry and lifestyle characteristics with insulin sensitivity in overweight and obese adolescents, and include data from a new study. Relevant papers were selected and reviewed. In addition, 137 overweight and obese adolescents (42 male/95 female, age 14.4 ± 2.3 years, BMI z‐score +3.3 ± 0.7, HOMA‐IR 3.4 ± 1.8) from the Centre for Overweight Adolescent and Children's Healthcare (MUMC+) were included in this study. Anthropometrics, Tanner stages, sleep characteristics, food intake behaviour and physical activity were determined, and possible associations with homeostasis model assessment of insulin resistance (HOMA‐IR) were tested. Results: Overweight and obese adolescents with unfavourable fat partitioning and family history of NIDDM are at risk for persistent IR. Overweight and obese adolescents from the new cohort showed a higher HOMA‐IR postpubertally. BMI z‐score, age, pubertal stage and prepubertally total sleeping time (TST) and sleep efficiency (SE) were identified as significant contributors. Overweight and obese adolescents showed a persistently higher instead of transiently higher HOMA‐IR during puberty, associated with BMI z‐score, age, pubertal stage and prepubertally less TST and SE.
Effects of plant diversity and structural complexity on parasitoid behaviour in a field experiment
Authors: KOSTENKO OLGA , LAMMERS MARK , GROOTEMAAT SASKIA , KROON THOMAS , HARVEY JEFFREY A. , VAN GEEM MONIEK , BEZEMER T. MARTIJN 
Published: September 2015

1. In natural ecosystems, plants containing hosts for parasitoids are often embedded within heterogeneous plant communities. These plant communities surrounding host‐infested plants may influence the host‐finding ability of parasitoids.2. A release‐recapture‐approach was used to examine whether the diversity and structural complexity of the community surrounding a host‐infested plant influences the aggregation behaviour of the leaf‐miner parasitoidDacnusa sibiricaTelenga and naturally occurring local leaf‐miner parasitoids. Released and locally present parasitoids were collected on pottedJacobaea vulgarisGaertn.plants infested with the generalist leaf‐minerChromatomyia syngenesiaeHardy. The plants were placed in experimentally established plant communities differing in plant diversity (1–9 species) and habitat complexity (bare ground, mown vegetation, and tall vegetation). Additionally, parasitoids were reared out from host mines on the trap plants.3. Plant diversity did not influence the mean number of recapturedD. sibiricaor captures of other locally present parasitoids but the number of recaptured parasitoids was influenced by habitat complexity. NoD. sibiricaparasitoids were recaptured in the bare ground plots or plots with mown vegetation. The mean number of recapturedD. sibiricagenerally increased with increasing complexity of the plant community, whereas locally present parasitoids were captured more frequently in communities with more bare ground. There was a unimodal relationship between the number of reared out parasitoids and diversity of the surrounding vegetation with the highest density of emerged parasitoids at intermediate diversity levels.4. The present study adds to the thus far limited body of literature examining the aggregation behaviour of parasitoids in the field and suggests that the preference of parasitoids to aggregate in complex versus simple vegetation is association specific and thus depends on the parasitoid species as well as the identity of the plant community.
The role of youth mental health services in the treatment of young people with serious mental illness: 2‐year outcomes and economic implications
Authors: Brimblecombe Nicola , Knapp Martin , Murguia Silvia , Mbeah‐Bankas Henrietta , Crane Steve , Harris Abi , Evans‐Lacko Sara , Ardino Vittoria , Iemmi Valentina , King Derek 
Published: September 2015

AbstractAimThis study aims to evaluate the outcomes and economic case for a UK innovative youth‐specific mental health service for 16–25 year olds.MethodsA pre‐, during‐ and post‐treatment comparative design for 20 young people at high risk of developing psychosis who received 2 years' treatment with the service, using outcomes that concurred with the service aims: changes in mental health, employment rates and service use.ResultsForty‐five percent of those at risk and with symptoms of serious mental illness commencing treatment were not receiving mental health services at baseline. Compared with service use prior to treatment at the youth‐specific service, hospital admissions, Accident and Emergency, and criminal justice system use appear to decrease over the 2 years of treatment and the year after treatment, with potential cost differences of £473 000. Mental health improved or stayed the same, compared with baseline. Employment rates improved, although the sample size for this is very small. Potential cost differences associated with service users moving into employment over the 2 years are £148 000. The estimated cost over 2 years of providing the youth‐specific mental health service to these young people was £106 000.ConclusionsGiven the extensive long‐term negative consequences and high costs of untreated mental illness in the 16–25 age group and the documented problems young people have in receiving appropriate services, this youth‐specific, age‐appropriate service model appears to be successful, with improved outcomes and cost differences in the short‐term, and with encouraging implications for the longer term.
‘Real‐life’ experience of preapproval carfilzomib‐based therapy in myeloma – analysis of cardiac toxicity and predisposing factors
Authors: Danhof Sophia , Schreder Martin , Rasche Leo , Strifler Susanne , Einsele Hermann , Knop Stefan 
Published: September 2015

AbstractBackgroundCarfilzomib, the second‐generation proteasome inhibitor, is still awaiting approval for the treatment of multiple myeloma in Europe. Results from clinical trials have demonstrated favorable efficacy in advanced disease but have opened an ongoing debate on cardiac complications related to carfilzomib treatment. ‘Real‐life’ data are scarce.Methods/PatientsAt our institution, 22 patients were registered within the European Carfilzomib Access Program for treatment with carfilzomib, dexamethasone, and a third combination partner depending on patient characteristics and prior treatment. Patients had received a median of six previous lines of therapy, and most were refractory to bortezomib (77%) and immunomodulatory drugs (95%).ResultsOverall response rate was 65% with a median progression‐free survival of 6.0 months and a median duration of response of 6.8 months. Median overall survival was 14.9 months. Grade 3/4 adverse events (AEs) occurred in 50% of patients with 23% experiencing left ventricular failure. The risk of cardiac AEs was markedly increased after previous radiotherapy of the thoracic spine and concomitant administration of doxorubicin.ConclusionCarfilzomib‐based treatment is efficient in advanced multiple myeloma. In our ‘real‐life’ patients, we found considerable cardiotoxic effects in some cases, indicating a need for careful patient selection and close monitoring of the at‐risk population.
Oligomeric α‐synuclein and β‐amyloid variants as potential biomarkers for Parkinson's and Alzheimer's diseases
Authors: Williams Stephanie M. , Schulz Philip , Sierks Michael R. 
Published: September 2015

AbstractOligomeric forms of α‐synuclein and β‐amyloid are toxic protein variants that are thought to contribute to the onset and progression of Parkinson's disease (PD) and Alzheimer's disease (AD), respectively. The detection of toxic variants in human cerebrospinal fluid (CSF) and blood has great promise for facilitating early and accurate diagnoses of these devastating diseases. Two hurdles that have impeded the use of these protein variants as biomarkers are the availability of reagents that can bind the different variants and a sensitive assay to detect their very low concentrations. We previously isolated antibody‐based reagents that selectively bind two different oligomeric variants of α‐synuclein and two of β‐amyloid, and developed a phage‐based capture enzyme‐linked immunosorbent assay (ELISA) with subfemtomolar sensitivity to quantify their presence. Here, we used these reagents to show that these oligomeric α‐synuclein variants are preferentially present in PD brain tissue, CSF and serum, and that the oligomeric β‐amyloid variants are preferentially present in AD brain tissue, CSF, and serum. Some AD samples also had α‐synuclein pathology and some PD samples also had β‐amyloid pathology, and, very intriguingly, these PD cases also had a history of dementia. Detection of different oligomeric α‐synuclein and β‐amyloid species is an effective method for identifying tissue, CSF and sera from PD and AD samples, respectively, and samples that also contained early stages of other protein pathologies, indicating their potential value as blood‐based biomarkers for neurodegenerative diseases.
Lack of motor recovery after prolonged denervation of the neuromuscular junction is not due to regenerative failure
Authors: Sakuma Miyuki , Gorski Grzegorz , Sheu Shu‐Hsien , Lee Stella , Barrett Lee B. , Singh Bhagat , Omura Takao , Latremoliere Alban , Woolf Clifford J. 
Published: September 2015

AbstractMotor axons in peripheral nerves have the capacity to regenerate after injury. However, full functional motor recovery rarely occurs clinically, and this depends on the nature and location of the injury. Recent preclinical findings suggest that there may be a time after nerve injury where, while regrowth to the muscle successfully occurs, there is nevertheless a failure to re‐establish motor function, suggesting a possible critical period for synapse reformation. We have now examined the temporal and anatomical determinants for the re‐establishment of motor function after prolonged neuromuscular junction (NMJ) denervation in rats and mice. Using both sciatic transection–resuture and multiple nerve crush models in rats and mice to produce prolonged delays in reinnervation, we show that regenerating fibres reach motor endplates and anatomically fully reform the NMJ even after extended periods of denervation. However, in spite of this remarkably successful anatomical regeneration, after 1 month of denervation there is a consistent failure to re‐establish functional recovery, as assessed by behavioural and electrophysiological assays. We conclude that this represents a failure in re‐establishment of synaptic function, and the possible mechanisms responsible are discussed, as are their clinical implications.
Factors associated with recurrent stroke and recanalization in patients presenting with isolated symptomatic carotid occlusion
Authors: Damania D. , Kung N. T.‐M. , Jain M. , Jain A. R. , Liew J. A. , Mangla R. , Koch G. E. , Sahin B. , Miranpuri A. S. , Holmquist T. M. , Replogle R. E. , Benesch C. G. , Kelly A. G. , Jahromi B. S. 
Published: September 2015

Background and purposePatients with symptomatic internal carotid artery (ICA) occlusion constitute a small proportion of stroke/transient ischaemic attack patients who are at increased risk of early stroke recurrence and poor outcome. The optimal medical treatment for patients with symptomatic ICA occlusion who are ineligible for thrombolysis or thrombectomy is unknown.MethodsConsecutive patients presenting at a single center with newly diagnosed symptomatic ICA occlusion (not involving the circle of Willis) were retrospectively reviewed. Those treated with intravenous thrombolysis or intra‐arterial thrombolysis/thrombectomy were excluded. Patients were divided into two groups based on whether they experienced recurrent in‐hospital stroke.ResultsThe selected study population (n = 33) represented a small (20.4%) proportion of all newly symptomatic carotid occlusions, who nevertheless had an elevated risk of recurrent stroke during admission (24.2%). Of the variables examined (age, gender, admission National Institutes of Health Stroke Scale score, vascular risk factors, atrial fibrillation, prior stroke/transient ischaemic attack and anticoagulation within 48 h of presentation), only anticoagulation was significantly associated with a lower risk of in‐hospital recurrent stroke. Anticoagulated patients showed a decreased incidence of stroke recurrence within the first week (6.7% vs. 38.9%, P = 0.032) and fewer strokes or deaths at 1 month (13.3% vs. 47.1%, P = 0.040). Hemorrhagic transformation was not observed in any patient. On follow‐up imaging, ICA recanalization was significantly more frequent in anticoagulated patients (46.2% vs. 9.1%, P = 0.047).ConclusionPatients with newly diagnosed symptomatic ICA occlusion (not involving the circle of Willis) represent a small but high risk subgroup of patients with carotid occlusion. Early anticoagulation was associated with fewer recurrent strokes and increased ICA recanalization. Larger scale prospective studies may be justified.
Family‐based genome‐wide association study in Patagonia confirms the association of the DMD locus and cleft lip and palate
Authors: Fonseca Renata F. , de Carvalho Flávia M. , Poletta Fernando A. , Montaner David , Dopazo Joaquin , Mereb Juan C. , Moreira Miguel A. M. , Seuanez Hector N. , Vieira Alexandre R. , Castilla Eduardo E. , Orioli Iêda M. 
Published: September 2015

The etiology of cleft lip with or without cleft palate (CL±P) is complex and heterogeneous, and multiple genetic and environmental factors are involved. Some candidate genes reported to be associated with oral clefts are located on the X chromosome. At least three genes causing X‐linked syndromes [midline 1 (MID1), oral‐facial‐digital syndrome 1 (OFD1), and dystrophin (DMD)] were previously found to be associated with isolated CL±P. We attempted to confirm the role of X‐linked genes in the etiology of isolated CL±P in a South American population through a family‐based genome‐wide scan. We studied 27 affected children and their mothers, from 26 families, in a Patagonian population with a high prevalence of CL±P. We conducted an exploratory analysis of the X chromosome to identify candidate regions associated with CL±P. Four genomic segments were identified, two of which showed a statistically significant association with CL±P. One is an 11‐kb region of Xp21.1 containing the DMD gene, and the other is an intergenic region (8.7 kb; Xp11.4). Our results are consistent with recent data on the involvement of the DMD gene in the etiology of CL±P. The MID1 and OFD1 genes were not included in the four potential CL±P‐associated X‐chromosome genomic segments.
Ecology and evolution of pathogens in natural populations of Lepidoptera
Authors: Myers Judith H. , Cory Jenny S. 
Published: September 2015

AbstractPathogens are ubiquitous in insect populations and yet few studies examine their dynamics and impacts on host populations. We discuss four lepidopteran systems and explore their contributions to disease ecology and evolution. More specifically, we elucidate the role of pathogens in insect population dynamics. For three species, western tent caterpillars, African armyworm and introduced populations of gypsy moth, infection by nucleopolyhedrovirus (NPV) clearly regulates host populations or reduces their outbreaks. Transmission of NPV is largely horizontal although low levels of vertical transmission occur, and high levels of covert infection in some cases suggest that the virus can persist in a nonsymptomatic form. The prevalence of a mostly vertically transmitted protozoan parasite, Ophryocystis elektroscirrha, in monarch butterflies is intimately related to their migratory behaviour that culls highly infected individuals. Virulence and transmission are positively related among genotypes of this parasite. These systems clearly demonstrate that the interactions between insects and pathogens are highly context dependent. Not only is the outcome a consequence of changes in density and genetic diversity: environmental factors, particularly diet, can have strong impacts on virulence, transmission and host resistance or tolerance. What maintains the high level of host and pathogen diversity in these systems, however, remains a question.
Equine ophthalmic examination: Routine diagnostic techniques
Authors: Seruca C. , Lowe R. 
Published: September 2015

SummaryA complete, thorough ophthalmic examination is essential in the clinical approach to equine ocular diseases. In the majority of cases and more than in most systems, an ophthalmic diagnosis can be achieved at the time of examination because most ocular structures can be visualised either directly or indirectly. This article describes examination protocol and the techniques, instruments and diagnostic procedures currently available to equine general practitioners.