bluuebunny/crossref_metadata_2025 huggingface dataset:
Mold and dampness exposure and allergic outcomes from birth to adolescence: data from the BAMSE cohort
Authors: Thacher J. D. , Gruzieva O. , Pershagen G. , Melén E. , Lorentzen J. C. , Kull I. , Bergström A.
Published: December 2016

Background

Exposure to moldy or damp indoor environments is associated with allergic disease in young children, but it is unclear whether the effects persist to adolescence. Our objective was to assess whether exposure to mold or dampness during infancy increases the risk of asthma, rhinitis, or IgE sensitization in children followed from birth to 16 years of age.

Methods

We collected questionnaire derived reports of mold or dampness indicators and allergic outcomes from 3798 children in a Swedish birth cohort (BAMSE). Sensitization was assessed from blood samples in 3293 children. Longitudinal associations between prevalent asthma, rhinitis, and IgE sensitization and mold or dampness indicators were assessed using generalized estimating equations.

Results

Exposure to any mold or dampness indicator was associated with asthma up to 16 years of age (OR 1.31; 95% CI 1.08–1.59), while exposure to mold odor (OR 1.29; 95% CI 1.03–1.62) and visible mold (OR 1.28; 95% CI 1.04–1.58) were associated with rhinitis. Increased risks were observed for nonallergic asthma (OR 1.80; 95% CI 1.27–2.55) and rhinitis (OR 1.41; 95% CI 1.03–1.93). No association was observed between mold or dampness indicators and IgE sensitization. Exposure to any mold or dampness indicator was associated with persistent asthma (OR 1.73; 95% CI 1.20–2.50), but not with early‐transient or late‐onset asthma.

Conclusion

Exposure to mold or dampness during infancy increased the risk of asthma and rhinitis up to 16 years of age, particularly for nonallergic disease. Early exposure to mold or dampness appeared particularly associated with persistent asthma through adolescence.
A comparison of vaginal ultrasound and digital examination in predicting preterm delivery in women with threatened preterm labor: a cohort study
Authors: Pinton Anne , Severac François , Meyer Nicolas , Akladios Cherif Y. , Gaudineau Adrien , Favre Romain , Langer Bruno , Sananes Nicolas
Published: December 2016

Introduction

The aim of this study is to evaluate the utility of digital examination in addition to ultrasonic measurement of cervical length for predicting spontaneous preterm delivery in women with threatened preterm labor.

Material and methods

This was a prospective cohort study in Strasbourg University Hospital, France, between January 2013 and January 2015. All women with a singleton pregnancy hospitalized with threatened preterm labor between 23 and 34 weeks of gestation were included. Cases of iatrogenic preterm delivery were excluded. A multivariable logistic regression model to estimate the significant predictive parameters of spontaneous preterm delivery was performed. The primary endpoint of our study was a preterm birth before 34 weeks of gestation.

Results

A total of 395 women were included in our study. The rate of preterm delivery before 34 weeks was 13%. In univariate analysis every single cervical parameter assessed by the digital examination and all the ultrasound parameters were significantly associated with preterm delivery. The final model included five variables predicting preterm birth: visualization of the membranes at the speculum examination (OR 15.8, 95% CI 2.43–146), ultrasound cervical length (OR 0.82, 95% CI 0.75–0.89), signs of inflammation (OR 6.23, 95% CI 2.07–22.9), gestational age on admission (OR 0.84, 95% CI 0.71–1.0), and presence of vaginal infection (OR 4.28, 95% CI 1.52–12.7). None of the cervical parameters assessed by the digital examination provided additional predictive value of preterm delivery.

Conclusion

Our study suggests that digital examination does not add to the information given by vaginal ultrasound evaluation in predicting preterm labor.
New guidelines for screening, diagnosing, and treating gestational diabetes – evaluation of maternal and neonatal outcomes in Finland from 2006 to 2012
Authors: Ellenberg Anni , Sarvilinna Nanna , Gissler Mika , Ulander Veli‐Matti
Published: December 2016

Introduction

In this study, we have assessed the changes in pregnancy outcomes following the implementation of national guidelines for gestational diabetes mellitus (GDM). These national guidelines changed the screening policy from risk‐based to comprehensive screening.

Material and methods

We designed a retrospective register‐based cohort study based on the data from the Finnish Medical Birth Register and Hospital Discharge Register including 34 794 singleton births in 2006–2008 and 36 488 in 2010–2012. Maternal characteristics and pregnancy outcomes were analyzed.

Results

Overall, 29.6% of mothers underwent an oral glucose tolerance test in 2006–2008 compared with 59.7% in 2010–2012. The prevalence of GDM increased from 7.2 to 11.3% and was highest among obese women (body mass index ≥30 kg/m2) (from 30.0 to 34.7%; p < 0.001). The proportion of insulin‐treated women remained unchanged (12.5/12.3%; p = 0.70). The main pregnancy outcomes for the women with GDM were the increased usage of oxytocin (19.5/40.0%, p < 0.001), increased number of inductions (27.2/33.0%; p < 0.001) and reduced birthweight (mean ± SD: 3647 ± 575 g/3567 ± 575 g). Healthy and unscreened women displayed similar results. Children of both women with GDM and healthy screened women had fewer admissions to the neonatal intensive care unit (16.3%/12.1%; p < 0.001) and less asphyxia (11.3%/6.3%; p < 0.001). However, the rates of cesarean delivery (26.5%/25.4%, p = 0.31), resuscitation (2.6%/2.0%; p = 0.12), and perinatal mortality (1.2‰/3.1‰, p = 0.11) among women with GDM did not change, whereas the number of hypoglycemia cases increased (2.3%/5.2%; p < 0.001).

Conclusions

In conclusion, glucose tolerance tests were performed twice as often as a result of the implementation of the national GDM guidelines, but this comprehensive screening practice did not improve pregnancy and neonatal outcomes.
Preclinical Study of Anticoagulation Regimens in Sheep After Implantation of CH‐VAD Blood Pump
Authors: Xu Chuangye , Wu Guanghui , Liu Xiujian , He Yuna , Hou Xiaotong , Li Haiyang , Chen Chen , Yang Peng , Lin Changyan
Published: December 2016

Effective anticoagulation regimens are needed to reduce risks of thrombosis and bleeding in animal models of ventricular assist device to verify its hemocompatibility, biologic safety and reliability. This study is to develop a validated anticoagulation procedure for a sheep model to test the newly developed CH‐VAD. CH‐VAD models were established in six healthy sheep by constructing blood bypass of left ventricle → ventricular assist device → descending aorta. Heparin infusion was used during operation and in the prior 4 days to maintain activated clotting time 1.5–2.0 times the baseline. From the third day, proper dosage of warfarin was used orally to maintain international normalized ratio values within the range of 1.2–2.0. After termination, we examined whether there was thrombosis in the blood pump, grafts, and anastomotic stoma. Macroscopic and histopathologic examinations were performed in major organs to check for congestion and infarction. Bleeding complications were not found in any animals throughout the experiments. Activated clotting time values were 326 ± 33 s intraoperatively and 157 ± 28 s in the prior 4 days postoperatively. Activated partial thromboplastin time values increased slowly and reached the lower limit of the target range on the fourth day. Only in one of six cases was thrombus or fibrosis tissue found in the blood flow channel of the pump. Pathologic analysis showed no thrombosis, necrosis and microembolus in end‐stage organs. Under the anticoagulation regimens, coagulation system could be well controlled to avoid thrombosis and bleeding complications in sheep models for CH‐VAD.
A Mock Circulatory System Incorporating a Compliant 3D‐Printed Anatomical Model to Investigate Pulmonary Hemodynamics
Authors: Knoops Paul G.M. , Biglino Giovanni , Hughes Alun D. , Parker Kim H. , Xu Linzhang , Schievano Silvia , Torii Ryo
Published: December 2016

A realistic mock circulatory system (MCS) could be a valuable in vitro testbed to study human circulatory hemodynamics. The objective of this study was to design a MCS replicating the pulmonary arterial circulation, incorporating an anatomically representative arterial model suitable for testing clinically relevant scenarios. A second objective of the study was to ensure the system's compatibility with magnetic resonance imaging (MRI) for additional measurements. A latex pulmonary arterial model with two generations of bifurcations was manufactured starting from a 3D‐printed mold reconstructed from patient data. The model was incorporated into a MCS for in vitro hydrodynamic measurements. The setup was tested under physiological pulsatile flow conditions and results were evaluated using wave intensity analysis (WIA) to investigate waves traveling in the arterial system. Increased pulmonary vascular resistance (IPVR) was simulated as an example of one pathological scenario. Flow split between right and left pulmonary artery was found to be realistic (54 and 46%, respectively). No substantial difference in pressure waveform was observed throughout the various generations of bifurcations. Based on WIA, three main waves were identified in the main pulmonary artery (MPA), that is, forward compression wave, backward compression wave, and forward expansion wave. For IPVR, a rise in mean pressure was recorded in the MPA, within the clinical range of pulmonary arterial hypertension. The feasibility of using the MCS in the MRI scanner was demonstrated with the MCS running 2 h consecutively while acquiring preliminary MRI data. This study shows the development and verification of a pulmonary MCS, including an anatomically correct, compliant latex phantom. The setup can be useful to explore a wide range of hemodynamic questions, including the development of patient‐ and pathology‐specific models, considering the ease and low cost of producing rapid prototyping molds, and the versatility of the setup for invasive and noninvasive (i.e., MRI) measurements.
Red Blood Cell Mechanical Fragility Test for Clinical Research Applications
Authors: Ziegler Luke A. , Olia Salim E. , Kameneva Marina V.
Published: December 2016

Red blood cell (RBC) susceptibility to mechanically induced hemolysis, or RBC mechanical fragility (MF), is an important parameter in the characterization of erythrocyte membrane health. The rocker bead test (RBT) and associated calculated mechanical fragility index (MFI) is a simple method for the assessment of RBC MF. Requiring a minimum of 15.5 mL of blood and necessitating adjustment of hematocrit (Ht) to a “standard” value (40%), the current RBT is not suitable for use in most studies involving human subjects. To address these limitations, we propose a 6.5 mL reduced volume RBT and corresponding modified MFI (MMFI) that does not require prior Ht adjustment. This new method was assessed for i) correlation to the existing text, ii) to quantify the effect of Ht on MFI, and iii) validation by reexamining the protective effect of plasma proteins on RBC MF. The reduced volume RBT strongly correlated (r = 0.941) with the established large volume RBT at matched Hts, and an equation was developed to calculate MMFI: a numerical estimation (R2 = 0.923) of MFI if performed with the reduced volume RBT at “standard” (40%) Ht. An inversely proportional relationship was found between plasma protein concentration and RBC MF using the MMFI‐reduced volume method, supporting previous literature findings. The new reduced volume RBT and modified MFI will allow for the measurement of RBC MF in clinical and preclinical studies involving humans or small animals.
Ambiguity in the Presentation of Decellularized Tissue Composition: The Need for Standardized Approaches
Authors: Bruyneel Arne A.N. , Carr Carolyn A.
Published: December 2016

Decellularization offers great potential to the field of tissue engineering, as this method gives rise to scaffold material with the native organ architecture by removing all cellular material and leaving much of the extracellular matrix (ECM) intact. However, many parameters may affect decellularization efficacy and ECM retention and, therefore, decellularization protocols need to be optimized for specific needs. This requires robust methods for comparison of decellularized tissue composition. Various representation methods are used in literature to express tissue composition (DNA, glycosaminoglycans, collagen, other ECM proteins, and growth factors). Here, we present and compare the various methods used and demonstrate that normalization to either dry or wet decellularized weight might be misleading and may overestimate true component retention. Moreover, the magnitude of the confounding effect is likely to be decellularization treatment dependent. As a result, we propose alternative comparison strategies: normalization to whole organ or to a unit of whole initial organ weight. We believe proper assessment of decellularized tissue composition is paramount for the successful comparison of different decellularization protocols and clinical translation.
Parents' perceptions are that their child's health‐related quality of life is more impaired when they have a wheat rather than a grass allergy
Authors: Borres Nora , Nilsson Nora , Drake Isabel , Sjölander Sigrid , Nilsson Caroline , Hedlin Gunilla , Nordlund Björn
Published: December 2016

Aim

It is unknown whether food allergies have greater impact on quality of life than respiratory allergies. This study compared health‐related quality of life (HRQoL) in children allergic to wheat or grass.

Methods

We surveyed 63 children with wheat allergies (median age of five) and 72 with grass allergies (median age 12), with their parents. The Child Health Questionnaires for parents (CHQ‐PF28) and children (CHQ‐CF87) were applied.

Results

The parents of children in the wheat group recorded significantly lower CHQ‐PF28 scores for the impact of their child's allergy on general behaviour, general health perceptions, parental impact of emotions and time and family activities, than the parents of children with grass allergies (p values ≤0.001). However, parents in the grass group recorded lower scores for the change in health item than the parents of children with wheat allergies (p = 0.020). In the grass group, children and parents reported similar scores for the different questions, but there was poorer correlation between parents and children in the wheat allergy group.

Conclusion

HRQoL was lower in children with wheat than grass allergies according to parental reports, with more consistent perceptions of HRQoL among parents and children in the grass allergy than wheat allergy group.
Comparison on accuracy of different nonlinear models in predicting growth of Podolica bulls
Authors: Selvaggi Maria , Laudadio Vito , D'Alessandro Angela Gabriella , Dario Cataldo , Tufarelli Vincenzo
Published: December 2016

Animal growth does not follow a linear pattern, being explained mathematically by functions that have parameters with biological meaning. These parameters are used to estimate the expected weight of animals at specific ages. Several nonlinear models have been used to describe growth. This study was carried out to estimate the parameters of logistic, Gompertz, Richards and von Bertalanffy growth curve models in a sample of Podolica young bulls to determine the goodness of fit. Animals were weighed every 3 months from birth to 810 days of age. The results indicate that all the growth models used were easily fitted to the observed data with Gompertz and logistic functions presenting less computational difficulty in terms of number of iterations to achieve convergence. Moreover, logistic and Richards equations provided the best overall fit being useful to describe the growth of Podolica bulls. Considering that the literature lacks information on growth curves in Podolica breed, the study of a mathematical model for growth describing the developmental pattern of a specific population within a peculiar environment is a useful tool to improve Podolica breed production.
Oral administration ofSaccharomyces boulardiialters duodenal morphology, enzymatic activity and cytokine production response in broiler chickens
Authors: Sun Yajing , Rajput Imran Rashid , Arain Muhammad Asif , Li Yanfei , Baloch Dost Muhammad
Published: December 2016

The present study evaluated the effects ofSaccharomyces boulardiion duodenal digestive enzymes, morphology and cytokine induction response in broiler chicken. A total of 200 birds were allotted into two groups (n = 100) and each group divided into five replications (n = 20). The control group was fed basal diet in addition to antibiotic (virginiamycin 20 mg/kg), and treatment group received (1 × 108 colony‐forming units/kg feed)S. boulardiiin addition to basal diet lasting for 72 days. The results compared to control group revealed that adenosine triphosphatase, gamma glutamyl transpeptidase, lipase and trypsin activities were higher, while, no significant improvement was observed in amylase activities in the duodenum of the treatment group. Moreover, morphological findings showed that villus height, width and number of goblet cells markedly increased. Additionally, transmission electron microscopy visualized that villus height, width and structural condensation significantly increased in the treatment group. The immunohistological observations showed increased numbers of immunoglobulin A (IgA)‐positive cells in the duodenum of the treatment group. Meanwhile, cytokine production levels of tumor necrosis factor‐α, interleukin (IL)‐10, transforming growth factor‐β and secretory IgA markedly increased, and IL‐6 statistically remained unchanged as compared to the control group. These findings illustrated that initial contact ofS. boulardiito the duodenum has significant impact in improving enzymatic activity, intestinal morphology and cytokine response in broiler chicken.
Potential blood biomarkers in chronic spontaneous urticaria
Authors: Kolkhir P. , André F. , Church M. K. , Maurer M. , Metz M.
Published: December 2016

Chronic spontaneous urticaria (CSU) is a mast cell‐driven disease that is defined as the recurrence of weals, angioedema or both for > 6 weeks due to known or unknown causes. As of yet, disease diagnosis is purely clinical. Objective tools are needed to monitor the activity of CSU and the efficacy of treatment. Recently, several reports have suggested that blood parameters may be considered as potential disease‐related biomarkers. Here, we reviewed available literature on blood biomarkers for CSU diagnosis, activity monitoring, duration, patient subgroup allocation or response to treatment. We performed a PubMed, Google Scholar and Web of Science search and identified and analysed 151 reports published prior to January 2016. We found strong evidence for significant differences between patients with CSU and healthy controls in blood levels or values of D‐dimer, C‐reactive protein (CRP), matrix metalloproteinase‐9 (MMP‐9), mean platelet volume (MPV), factor VIIa, prothrombin fragment 1 + 2 (F1 + 2), tumour necrosis factor, dehydroepiandrosterone sulphate and vitamin D. Also, there is strong evidence for a significant association between CSU activity and blood levels or values of D‐dimer, F1 + 2, CRP, IL‐6 and MPV. Strong evidence for reduced basophil count and high levels of IgG anti‐FcεRI in the subgroup of CSU patients with positive autologous serum skin test was shown. In contrast, the evidence for all reported blood biomarkers for differentiating CSU from other diseases, or a role in prognosis, is weak, inconsistent or non‐existent. Taken together, we identified 10 biomarkers that are supported by strong evidence for distinguishing patients with CSU from healthy controls, or for measuring CSU activity. There is a need for further research to identify biomarkers that predict outcome or treatment response in CSU.
Prognostic significance of hepatic arterial collaterals in liver transplant recipients with biliary strictures
Authors: Viveiros André , Rehwald Rafael , Vettori Erich , Finkenstedt Armin , Effenberger Maria , Schaefer Benedikt , Dorn Livia , Tilg Herbert , Schneeberger Stefan , Glodny Bernhard , Zoller Heinz , Freund Martin C.
Published: December 2016

Background

The aim of this study was to determine the prevalence of hepatic artery stenosis (HAS) and the prognostic implications of hepatic arterial collaterals in liver transplant (LT) recipients with biliary strictures.

Methods

The 105 LT recipients transplanted between 2004 and 2015 at our center had documented biliary strictures. HAS and collaterals were assessed in high‐quality imaging of the hepatic artery available from 66 recipients. Clinical, demographic, and biochemical recipient and donor data were retrospectively analyzed and tested for their association with biliary or arterial complications after LT.

Results

The prevalence of HAS was 68% (45 of 66) in LT recipients with biliary strictures. Seventy‐six percent (37 of 49) of patients with nonanastomotic biliary strictures had HAS. This was significantly higher than in patients with anastomotic stricture, where 47% (8 of 17) of patients had a pathological hepatic arteriogram (P=.039). The location of bile duct strictures was not predictive for outcome. In contrast, arterial collaterals were associated with significantly better patient and graft survival.

Conclusion

Impaired hepatic arterial perfusion is frequently associated with nonanastomotic strictures, but less closely correlated with anastomotic strictures. On survival analysis, hepatic arterial collaterals have a protective effect.
Effect of early intervention in infants at very high risk of cerebral palsy: a systematic review
Authors: Hadders‐Algra Mijna , Boxum Anke G , Hielkema Tjitske , Hamer Elisa G
Published: December 2016

Aim

First, to systematically review the evidence on the effect of intervention applied during the first postnatal year in infants with or at very high risk of cerebral palsy (CP) on child and family outcome. Second, to assess whether type and dosing of intervention modify the effect of intervention.

Method

Relevant literature was identified by searching the PubMed, Embase, and CINAHL databases. Selection criteria included infants younger than 12 months corrected age with or at very high risk of CP. Methodological quality including risk of bias was scrutinized.

Results

Thirteen papers met the inclusion criteria. Seven studies with moderate to high methodological quality were analysed in detail; they evaluated neurodevelopmental treatment only (n=2), multisensory stimulation (n=1), developmental stimulation (n=2), and multifaceted interventions consisting of a mix of developmental stimulation, support of parent–infant interaction, and neurodevelopmental treatment (n=2). The heterogeneity precluded conclusions. Yet, two suggestions emerged: (1) dosing may be critical for effectiveness; (2) multifaceted intervention may offer best opportunities for child and family.

Interpretation

The literature on early intervention in very high‐risk infants with sufficient methodological quality is limited, heterogeneous, and provides weak evidence on the effect. More studies are urgently needed. Suggestions for future research are provided.
Reflections on the encouragement of altruism in dental education
Authors: Holden A. C. L.
Published: December 2016

Dental ethics and professionalism are often relegated to being taught on the coat‐tails of other disciplines, if they are taught at all. The assumption that students develop professionalism as a by‐product of other learned competencies in dentistry is well documented to be false, and yet, little has been done in many institutions to deal with this. This article seeks to propose that altruism should be championed in dental education and that traditional learning through the preaching of professional codes is not the appropriate way to achieve this. The environment of dental schools needs to be challenged and reformed so that altruism is promoted. If we fail to address declines in altruism in the dental profession, then damage to the professional status of dentistry is inevitable and the ability to fulfil the profession's social contract with society will be inhibited.
Transcriptomic characterization of candidate genes responsive to salt tolerance of Miscanthus energy crops
Authors: Song Zhihong , Xu Qin , Lin Cong , Tao Chengcheng , Zhu Caiyun , Xing Shilai , Fan Yangyang , Liu Wei , Yan Juan , Li Jianqiang , Sang Tao
Published: December 2016

Given the growing need for biofuel production but the lack of suitable land for producing biomass feedstock, development of stress‐tolerant energy crops will be increasingly important. We used comparative transcriptomics to reveal differential responses to long‐term salt stress among five populations of Miscanthus lutarioriparius grown in the natural habitats and salinity experimental site. A total of 59 genes were found to be potentially responsive to the high‐salinity conditions shared by the five populations, including those involved in detoxification, plant defense, photosynthesis, and signal transduction. Of these genes, about 70% were related to abiotic stress response. Among five populations, the most contrasting performance between relatively high survival rates and the relatively weak growing traits was in accordance with the down‐regulation of genes involved in growth and up‐regulation of genes related to plant stress tolerance in one of the populations. These results might reveal a potential tolerance‐productivity trade‐off, where resources were allocated from growth to stress resistance. The comparative transcriptomics of different populations among different environments will provide a basis for breeding and domestication of energy crops.
Parental cooperation in a changing climate: fluctuating environments predict shifts in care division
Authors: Vincze Orsolya , Kosztolányi András , Barta Zoltán , Küpper Clemens , Alrashidi Monif , Amat Juan A. , Argüelles Ticó Araceli , Burns Fiona , Cavitt John , Conway Warren C. , Cruz‐López Medardo , Desucre‐Medrano Atahualpa Eduardo , dos Remedios Natalie , Figuerola Jordi , Galindo‐Espinosa Daniel , García‐Peña Gabriel E. , Gómez Del Angel Salvador , Gratto‐Trevor Cheri , Jönsson Paul , Lloyd Penn , Montalvo Tomás , Parra Jorge Enrique , Pruner Raya , Que Pinjia , Liu Yang , Saalfeld Sarah T. , Schulz Rainer , Serra Lorenzo , St Clair James J. H. , Stenzel Lynne E. , Weston Michael A. , Yasué Maï , Zefania Sama , Székely Tamás
Published: December 2016

Aim

Parental care improves the survival of offspring and therefore has a major impact on reproductive success. It is increasingly recognized that coordinated biparental care is necessary to ensure the survival of offspring in hostile environments, but little is known about the influence of environmental fluctuations on parental cooperation. Assessing the impacts of environmental stochasticity, however, is essential for understanding how populations will respond to climate change and the associated increasing frequencies of extreme weather events. Here we investigate the influence of environmental stochasticity on biparental incubation in a cosmopolitan ground‐nesting avian genus.

Location

Global.

Methods

We assembled data on biparental care in 36 plover populations (Charadrius spp.) from six continents, collected between 1981 and 2012. Using a space‐for‐time approach we investigate how average temperature, temperature stochasticity (i.e. year‐to‐year variation) and seasonal temperature variation during the breeding season influence parental cooperation during incubation.

Results

We show that both average ambient temperature and its fluctuations influence parental cooperation during incubation. Male care relative to female care increases with both mean ambient temperature and temperature stochasticity. Local climatic conditions explain within‐species population differences in parental cooperation, probably reflecting phenotypic plasticity of behaviour.

Main conclusions

The degree of flexibility in parental cooperation is likely to mediate the impacts of climate change on the demography and reproductive behaviour of wild animal populations.
How many research nurses for how many clinical trials in an oncology setting? Definition of the Nursing Time Required by Clinical Trial—Assessment Tool (NTRCT‐AT)
Authors: Milani Alessandra , Mazzocco Ketti , Stucchi Sara , Magon Giorgio , Pravettoni Gabriella , Passoni Claudia , Ciccarelli Chiara , Tonali Alessandra , Profeta Teresa , Saiani Luisa
Published: December 2016

Few resources are available to quantify clinical trial–associated workload, needed to guide staffing and budgetary planning. The aim of the study is to describe a tool to measure clinical trials nurses' workload expressed in time spent to complete core activities. Clinical trials nurses drew up a list of nursing core activities, integrating results from literature searches with personal experience. The final 30 core activities were timed for each research nurse by an outside observer during daily practice in May and June 2014. Average times spent by nurses for each activity were calculated. The “Nursing Time Required by Clinical Trial—Assessment Tool” was created as an electronic sheet that combines the average times per specified activities and mathematic functions to return the total estimated time required by a research nurse for each specific trial. The tool was tested retrospectively on 141 clinical trials. The increasing complexity of clinical research requires structured approaches to determine workforce requirements. This study provides a tool to describe the activities of a clinical trials nurse and to estimate the associated time required to deliver individual trials. The application of the proposed tool in clinical research practice could provide a consistent structure for clinical trials nursing workload estimation internationally.
Feasibility and short‐term impact of the “case study in‐house group training program for family nursing” at medical facilities
Authors: Yamazaki Akemi , Tsumura Akemi , Mine Hiroko , Kimura Chisato , Soeda Akemi , Odatsu Kazumi , Kiwado Wataru
Published: December 2016

The aim of this study was to evaluate the feasibility and short‐term impact of case study training in family nursing care targeting midlevel nursing professionals. The intervention group participated in four 90‐minute case study training sessions over 6 months, while the control group participated in two 90‐minute lectures. Using primary outcome variables as evaluation indexes, we measured the participants' total scores on the Family Importance in Nursing Care Scale and 4 subitems 3 times (before, immediately after and 1 month after training) from May 2014 to March 2015 and then conducted 2‐way repeated‐measure analysis of variance. We asked the participants and training planners/managers to provide feedback on their evaluation and then performed content analysis on their responses. Although the primary impact due to the different measurement times was significant, no significant difference was observed in the interaction between measurement time and training differences. Of the 4 subitems, significant interactions because of measurement time and training differences were observed only in Fam‐B. Feedback data showed all participants felt that their understanding of the importance of family nursing care was strengthened, and participants in the intervention group specifically described how they were utilizing what they had learned from training in practice.
Depletion of CD52‐positive cells inhibits the development of central nervous system autoimmune disease, but deletes an immune‐tolerance promoting CD8 T‐cell population. Implications for secondary autoimmunity of alemtuzumab in multiple sclerosis
Authors: von Kutzleben Stephanie , Pryce Gareth , Giovannoni Gavin , Baker David
Published: December 2016

The objective was to determine whether CD52 lymphocyte depletion can act to promote immunological tolerance induction by way of intravenous antigen administration such that it could be used to either improve efficiency of multiple sclerosis (MS) inhibition or inhibit secondary autoimmunities that may occur following alemtuzumab use in MS. Relapsing experimental autoimmune encephalomyelitis was induced in ABH mice and immune cell depletion was therapeutically applied using mouse CD52 or CD4 (in conjunction with CD8 or CD20) depleting monoclonal antibodies. Immunological unresponsiveness was then subsequently induced using intravenous central nervous system antigens and responses were assessed clinically. A dose–response of CD4 monoclonal antibody depletion indicated that the 60–70% functional CD4 T‐cell depletion achieved in perceived failed trials in MS was perhaps too low to even stop disease in animals. However, more marked (~75–90%) physical depletion of CD4 T cells by CD4 and CD52 depleting antibodies inhibited relapsing disease. Surprisingly, in contrast to CD4 depletion, CD52 depletion blocked robust immunological unresponsiveness through a mechanism involving CD8 T cells. Although efficacy was related to the level of CD4 T‐cell depletion, the observations that CD52 depletion of CD19 B cells was less marked in lymphoid organs than in the blood provides a rationale for the rapid B‐cell hyper‐repopulation that occurs following alemtuzumab administration in MS. That B cells repopulate in the relative absence of T‐cell regulatory mechanisms that promote immune tolerance may account for the secondary B‐cell autoimmunities, which occur following alemtuzumab treatment of MS.
Adapalene 0.1%/benzoyl peroxide 2.5% gel reduces the risk of atrophic scar formation in moderate inflammatory acne: a split‐face randomized controlled trial
Authors: Dreno B. , Tan J. , Rivier M. , Martel P. , Bissonnette R.
Published: December 2016

Background

The efficacy of current topical acne treatments in mitigating the potential for acne scarring is not known.

Objective

To evaluate the effect of adapalene 0.1%/benzoyl peroxide 2.5% (A/BPO) gel compared to vehicle in reducing the risk of acne scarring.

Methods

Multicentre, randomized, investigator‐blinded, vehicle‐controlled, split‐face study conducted over 6 months. Subjects were adults with active moderate facial acne vulgaris and at least 10 atrophic acne scars at baseline. Efficacy evaluations included counts of atrophic acne scars and primary acne lesions as well as a Scar Global Assessment (SGA; 5‐point scale).

Results

After 6 months treatment, scar counts remained stable with A/BPO while increasing by approximately 25% with vehicle (mean scar count 11.58 vs. 13.55, respectively, at Month 6; P = 0.036). The percentage of subjects with a SGA of ‘almost clear’ (hardly visible scars) increased from 9.7% to 45.2% with A/BPO, whereas it did not change with vehicle (P = 0.0032). Total acne lesion counts decreased by 65% with A/BPO and 36% with vehicle (mean lesion count 8.5 vs. 16.1, respectively, at Month 6; P < 0.001).

Limitations

Relatively small study group (31 subjects).

Conclusion

Topical long‐term treatment with A/BPO is effective in reducing the risk of atrophic scars and improving the global severity of scarring.
Microcomputed Tomography Evaluation of Volumetric Shrinkage of Bulk‐Fill Composites in Class II Cavities
Authors: Algamaiah Hamad , Sampaio Camila S. , Rigo Lindiane C. , Janal Malvin N. , Giannini Marcelo , Bonfante Estevam A. , Coelho Paulo G. , Reis Andre F. , Hirata Ronaldo
Published: December 2016

Purpose

This study aimed to quantify polymerization shrinkage of one conventional and three bulk‐fill composites, under bonded and unbonded conditions, in Class II preparations using 3D microcomputed tomography (μCT) and report its location.

Materials and Methods

Preparations (2.5 mm occlusal depth × 4 mm wide × 4 mm mesial box and 1 mm beyond the CEJ distal box depth) were made in 48 human extracted molars (n = 6). Four composites were tested, one regular (Vitalescence/VIT) and three bulk‐fill: SureFil SDR Flow (SDR), Tetric EvoCeram Bulk Fill (TET), and Filtek flowable Bulk Fill (FIL). Teeth were divided into four groups according to restorative material used and subdivided into two subgroups, according to the presence of an adhesive system (XP Bond) application (bonded [‐B]) or its absence (unbonded [‐U]). Each tooth was scanned three times: (1) after cavity preparation, (2) before and (3) after composite light‐curing. Acquired μCT images were imported into 2D and 3D software for analysis.

Results

Significantly different volumetric shrinkage between bonded and unbonded conditions was observed only for TET group (p < 0.05), unbonded presenting significantly higher volumetric shrinkage. Among the bonded groups, TET‐B presented significantly lower shrinkage than both SDR‐B and FIL‐B but not significantly different from VIT‐B. Generally, shrinkage occurred at occlusal and distal surfaces.

Conclusions

When applied to bonded Class II cavities, TET exhibited significantly lower volumetric shrinkage compared to the other bulk‐fill composites. However, it also exhibited the highest difference of volumetric shrinkage values between unbonded and bonded cavities.

Clinical Significance

Volumetric polymerization shrinkage occurred with all composites tested, regardless of material type (conventional or bulk‐fill) or presence or absence of bonding. However, volumetric shrinkage has been reduced or at least maintained when bulk‐fill composites were used compared to a conventional composite resin, which makes them a potential time saving alternative for clinicians. (J Esthet Restor Dent 29:118–127, 2017)
Arabidopsis SUMO protease ASP1 positively regulates flowering time partially through regulating FLC stability
Authors: Kong Xiangxiong , Luo Xi , Qu Gao‐Ping , Liu Peng , Jin Jing Bo
Published: December 2016

The initiation of flowering is tightly regulated by the endogenous and environment signals, which is crucial for the reproductive success of flowering plants. It is well known that autonomous and vernalization pathways repress transcription of FLOWERING LOCUS C (FLC), a focal floral repressor, but how its protein stability is regulated remains largely unknown. Here, we found that mutations in a novel Arabidopsis SUMO protease 1 (ASP1) resulted in a strong late‐flowering phenotype under long‐days, but to a lesser extent under short‐days. ASP1 localizes in the nucleus and exhibited a SUMO protease activity in vitro and in vivo. The conserved Cys‐577 in ASP1 is critical for its enzymatic activity, as well as its physiological function in the regulation of flowering time. Genetic and gene expression analyses demonstrated that ASP1 promotes transcription of positive regulators of flowering, such as FT, SOC1 and FD, and may function in both CO‐dependent photoperiod pathway and FLC‐dependent pathways. Although the transcription level of FLC was not affected in the loss‐of‐function asp1 mutant, the protein stability of FLC was increased in the asp1 mutant. Taken together, this study identified a novel bona fide SUMO protease, ASP1, which positively regulates transition to flowering at least partly by repressing FLC protein stability.
Geology and tectono‐metamorphic evolution of the Himalayan metamorphic core: insights from the Mugu Karnali transect, Western Nepal (Central Himalaya)
Authors: Iaccarino S. , Montomoli C. , Carosi R. , Massonne H.‐J. , Visonà D.
Published: December 2016

New structural and tectono‐metamorphic data are presented from a geological transect along the Mugu Karnali valley, in Western Nepal (Central Himalaya), where an almost continuous cross‐section from the Lesser Himalaya Sequence to the Everest Series through the medium‐high‐grade Greater Himalayan Sequence (GHS) is exposed. Detailed meso‐ and micro‐structural analyses were carried out along the transect. Pressure (P)–temperature (T) conditions and P–T–deformation paths for samples from different structural units were derived by calculating pseudosections in the MnNKCFMASHT system. Systematic increase of P–T conditions, from ~0.75 GPa to 560 °C up to ≥1.0 GPa–750 °C, has been detected starting from the garnet zone up to the K‐feldspar + aluminosilicate zone. Our investigation reveals how these units are characterized by different P–T evolutions and well‐developed tectonic boundaries. Integrating our meso‐ and micro‐structural data with those of metamorphism and geochronology, a diachronism in deformation and metamorphism can be highlighted along the transect, where different crustal slices were underthrust, metamorphosed and exhumed at different times. The GHS is not a single tectonic unit, but it is composed of (at least) three different crustal slices, in agreement with a model of in‐sequence shearing by accretion of material from the Indian plate, where coeval activity of basal thrusting at the bottom with normal shearing at the top of the GHS is not strictly required for its exhumation.
Involvement of chemokine CXCL11 in the development of morphine tolerance in rats with cancer‐induced bone pain
Authors: Guo Genhua , Peng Yawen , Xiong Bingrui , Liu Daiqiang , Bu Huilian , Tian Xuebi , Yang Hui , Wu Zhen , Cao Fei , Gao Feng
Published: December 2016

Morphine is viewed as one of the classical treatments for intractable pain, but its role is limited by side effects, including analgesic tolerance. A few chemokines have been reported to be engaged in the mechanisms of morphine tolerance. However, the exact roles of CXC chemokine 11 (CXCL11) in chronic morphine tolerance remain unknown. In this study, Walker 256 mammary gland carcinoma cells were inoculated into the tibia of rats to provoke cancer‐induced bone pain. Then, morphine was intrathecally administered twice daily for seven consecutive days to induce drug tolerance. We found that the level of CXCL11 in lumbar spinal cord was increased during the development of morphine tolerance in cancer‐induced bone pain rats. Meanwhile, CXCL11 was co‐localized with markers of astrocytes and neurons in the spinal cord. Inhibition of CXCL11 by neutralizing antibodies could remarkably attenuate the degree of morphine tolerance and decrease the activation of astrocytes. Moreover, blocking astrocyte activation by d, l‐Fluorocitric acid could distinctly alleviate morphine tolerance and reduce the expression of CXCL11. Finally, morphine stimulation could induce the release of CXCL11 by cultured astrocytes and neurons in vitro. In summary, our results provide evidence that spinal CXCL11 plays a powerful modulatory role in the development of morphine tolerance through cross‐talking between astrocytes and neurons.

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Impact of Calcified Target Lesions on the Outcome of Percutaneous Coronary Intervention for Acute Coronary Syndrome: Insights From the BASE ACS Trial
Authors: Karjalainen Pasi P. , Nammas Wail , Kervinen Kari , de Belder Adam , Rivero‐Crespo Fernando , Ylitalo Antti , Airaksinen Juhani K. E.
Published: December 2016

Objectives

We performed a post hoc analysis of outcome in patients with, versus those without, calcified target lesions from the BASE ACS trial.

Background

The outcome of contemporary stent implantation in patients with calcified lesions presenting with acute coronary syndrome is unknown.

Methods

The BASE ACS trial randomized 827 patients (1:1) presenting with acute coronary syndrome to receive either titanium‐nitride‐oxide‐coated stents or everolimus‐eluting stents. Calcified lesions were defined as moderate or severe calcification in the vessel wall by coronary angiography. The primary endpoint was major adverse cardiac events (MACE): a composite of cardiac death, non‐fatal myocardial infarction or ischemia‐driven target lesion revascularization. Follow‐up was planned at 12 months, and yearly thereafter for up to 7 years.

Results

Of 827 patients enrolled in the trial, 352 (42.6%) had calcified target lesions. Median follow‐up was 5.0 years. The incidence of MACE was higher in patients with, versus those without, calcified target lesions (19.6% vs. 12.2%, respectively, P = 0.004). This was driven by more frequent cardiac death and non‐fatal myocardial infarction events (P < 0.05, both). The rates of ischemia‐driven target lesion revascularization were comparable (P > 0.05). MACE and the other endpoints were comparable between the 2 propensity‐score matched subgroups (P > 0.05 for all). Hypertension and smaller vessel size independently predicted MACE in patients treated for calcified lesions.

Conclusions

Patients presenting with acute coronary syndrome who were treated for calcified lesions had worse long‐term clinical outcome, compared with those treated for non‐calcified lesions, mainly due to more frequent safety events. In the propensity score‐matched analysis, the outcome was comparable.
Glycaemic control and excess risk of ischaemic and haemorrhagic stroke in patients with type 1 diabetes: a cohort study of 33 453 patients
Authors: Ståhl C. Hedén , Lind M. , Svensson A.‐M. , Gudbjörnsdottir S. , Mårtensson A. , Rosengren A.
Published: December 2016

Objective

To estimate the excess risk of stroke in relation to glycaemic control in patients with type 1 diabetes.

Methods

In this prospective, matched cohort study, we identified patients with type 1 diabetes, aged ≥18 years, who were registered in the Swedish National Diabetes Register from 1998–2011 and five control subjects for each case from the general population, matched for age, sex and county of residence. The risks of all strokes, ischaemic stroke and haemorrhagic stroke were estimated using Cox hazard regression.

Results

Of 33 453 type 1 diabetes patients [mean age, 35.5 (SD 14.4) years; mean follow‐up, 7.9 (SD 4.3) years; and mean diabetes duration, 20.2 years (SD 14.6)], 762 (2.3%) were diagnosed with stroke compared with 1122 (0.7%) of 159 924 control subjects [mean follow‐up, 8.2 (SD 4.3) years]. The overall multiple‐adjusted hazard ratios (HRs) for type 1 diabetes patients versus control subjects were 3.29 (95% CI: 2.96–3.66) and 2.49 (95% CI: 1.96–3.16) for ischaemic and haemorrhagic stroke, respectively. The risk of ischaemic and haemorrhagic stroke incrementally increased with increasing HbA1c; the risk of ischaemic stroke was significantly increased with HbA1c within target [≤6.9% (≤52 mmol mol‐1)] [multiple‐adjusted HR 1.89 (95% CI: 1.44–2.47)]. For HbA1c ≥9.7% (≥83 mmol mol‐1), there was a markedly increased risk of both ischaemic and haemorrhagic stroke, with multiple‐adjusted HRs of 7.94 (95% CI: 6.29–10.03) and 8.17 (95% CI 5.00–13.35), respectively.

Conclusions

Individuals with type 1 diabetes have an increased risk of ischaemic and haemorrhagic stroke, increasing markedly with poor glycaemic control.