bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of food on the pharmacokinetics of TAS‐102 and its efficacy and safety in patients with advanced solid tumors
Authors: Yoshino Takayuki , Kojima Takashi , Bando Hideaki , Yamazaki Tomoko , Naito Yoichi , Mukai Hirofumi , Fuse Nozomu , Goto Koichi , Ito Yuko , Doi Toshihiko , Ohtsu Atsushi
Published: February 2016

TAS‐102, a novel oral antitumor agent, consists of trifluridine and tipiracil hydrochloride (molar ratio, 1:0.5). We investigated the effects of food on trifluridine and tipiracil hydrochloride. The efficacy and safety of TAS‐102 were evaluated in patients with advanced solid tumors. We analyzed drug pharmacokinetics using a randomized, single‐dose, two‐treatment (fed versus fasting), two‐period, two‐sequence cross‐over design, followed by repeated administration. Patients were given single doses of TAS‐102 (35 mg/m2) in the pharmacokinetic phase and received twice‐daily doses of TAS‐102 in 28‐day cycles in the repeated administration phase for evaluating efficacy and safety. Food showed no effect on the area under the curve from 0 to 12 h or 0 h–infinity values of trifluridine following administration of TAS‐102 under fasting and fed conditions, whereas those of tipiracil hydrochloride decreased by approximately 40%. Maximum concentrations of both drugs decreased by approximately 40%, indicating that food influenced the absorption and bioavailability of trifluridine and tipiracil hydrochloride, respectively. During the repeated administration, stable disease was observed in nine patients with rectal, small‐cell lung, breast, thymic, duodenal, and prostate cancers. Major adverse events were neutropenia, leukopenia, anemia, and nausea. Postprandial administration was optimal for TAS‐102 because trifluridine's area under the curve was not changed by food, indicating that its clinical efficacy would not be affected. Additionally, postprandial administration was reasonable because the maximum concentration of trifluridine decreased in neutrophils, which correlated with previous studies. These results suggest that TAS‐102 would be an effective treatment for small‐cell lung, thymic, and colorectal cancers. This trial is registered with the Japan Pharmaceutical Information Center (no. JapicCTI‐111482).
Selective activator protein‐1 inhibitor T‐5224 prevents lymph node metastasis in an oral cancer model
Authors: Kamide Daisuke , Yamashita Taku , Araki Koji , Tomifuji Masayuki , Tanaka Yuya , Tanaka Shingo , Shiozawa Shunichi , Shiotani Akihiro
Published: February 2016

Activator protein‐1 (AP‐1) is a transcriptional factor that regulates the expression of various genes associated with tumor invasion and migration. The purpose of our study was to assess the therapeutic effects of a novel selective AP‐1 inhibitor, T‐5224, in preventing lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) in an orthotopic mouse model. We assessed the effect of T‐5224 on HNSCC cell invasion, migration, proliferation, and MMP activity by carrying out an in vitro study using an invasion assay, scratch assay, WST‐8 assay, and gelatin zymography. We also observed morphological changes in HNSCC cells by time‐lapse microscopy. Furthermore, cervical lymph node metastasis was assessed using an orthotopic tumor model of human oral squamous cell carcinoma cells (HSC‐3‐M3) injected in the tongue of a BALB/c nude mouse. T‐5224 (150 mg/kg) or vehicle was given orally every day for 4 weeks. Animals were killed and assessed for lymph node metastasis by H&E staining of resected lymph nodes. T‐5224 significantly inhibited the invasion, migration, and MMP activity of HNSCC cells in a dose‐dependent manner; there was no significant influence on cell proliferation. The antimetastatic effect of T‐5224 was also confirmed in our animal study. The rate of cervical lymph node metastasis in the model was 40.0% in the T‐5224‐treated group (n = 30) versus 74.1% in the vehicle‐treated group (n = 27; P < 0.05). In conclusion, T‐5224 inhibited the invasion and migration of HNSCC cells in vitro, and prevented lymph node metastasis in head and neck cancer in an animal model.
Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system
Authors: Klemann C , Wagner L , Stephan M , von Hörsten S
Published: February 2016

CD26/DPP4 (dipeptidyl peptidase 4/DP4/DPPIV) is a surface T cell activation antigen and has been shown to have DPP4 enzymatic activity, cleaving-off amino-terminal dipeptides with either L-proline or L-alanine at the penultimate position. It plays a major role in glucose metabolism by N-terminal truncation and inactivation of the incretins glucagon-like peptide-1 (GLP) and gastric inhibitory protein (GIP). In 2006, DPP4 inhibitors have been introduced to clinics and have been demonstrated to efficiently enhance the endogenous insulin secretion via prolongation of the half-life of GLP-1 and GIP in patients. However, a large number of studies demonstrate clearly that CD26/DPP4 also plays an integral role in the immune system, particularly in T cell activation. Therefore, inhibition of DPP4 might represent a double-edged sword. Apart from the metabolic benefit, the associated immunological effects of long term DPP4 inhibition on regulatory processes such as T cell homeostasis, maturation and activation are not understood fully at this stage. The current data point to an important role for CD26/DPP4 in maintaining lymphocyte composition and function, T cell activation and co-stimulation, memory T cell generation and thymic emigration patterns during immune-senescence. In rodents, critical immune changes occur at baseline levels as well as after in-vitro and in-vivo challenge. In patients receiving DPP4 inhibitors, evidence of immunological side effects also became apparent. The scope of this review is to recapitulate the role of CD26/DPP4 in the immune system regarding its pharmacological inhibition and T cell-dependent immune regulation.
Unaccompanied minors in the Netherlands and the care facility in which they flourish best
Authors: Kalverboer Margrite , Zijlstra Elianne , van Os Carla , Zevulun Daniëlle , ten Brummelaar Mijntje , Beltman Daan
Published: February 2016

This study compares the views of unaccompanied minors living in four different types of care facilities in the Netherlands: namely in foster care, small living units, children's living groups and campuses on their wellbeing, living circumstances and place in Dutch society. Interviews with 132 minors were both qualitatively and quantitatively analysed. Based on the transcripts from the interviews the researchers completed a questionnaire (BIC‐Q) to judge the quality of the child rearing environment in the different types of care facilities.

Minors in foster care fare best and are most positive about their place in Dutch society. Minors in small living units and small living groups often miss affectionate bonds, care, support and stability in their lives. Minors in campuses most often expressed feeling lonely and sad and being excluded from the Dutch society. They experience a lack of care and support from adults. The quality of the child rearing environment in campuses was judged by the researchers as being so low that these facilities appear to be unfit for unaccompanied minors.
Systemic and maxillofacial characteristics of 11 Japanese children with Russell–Silver syndrome
Authors: Sato Chiemi , Ogawa Takuya , Tsuge Risa , Shiga Momotoshi , Tsuji Michiko , Baba Yoshiyuki , Kosaki Kenjiro , Moriyama Keiji
Published: February 2016

Russell–Silver syndrome (RSS) is a congenital anomaly characterized by intrauterine and postnatal growth retardation, typical facial features, fifth‐finger clinodactyly, and skeletal asymmetry. Although data on intrauterine and postnatal growth retardation have been reported, there are few reports concerning the typical maxillofacial morphology in individuals with RSS. The aim of this study was to describe the details of this systemic condition and to characterize maxillofacial morphology based on cephalograms in 11 Japanese patients (age range, 3.9–12.0 years) with RSS. All 11 individuals had intrauterine and postnatal growth retardation. In addition, most showed mandibular retrognathia and relative macrocephaly. Lateral cephalogram measurements showed that mandibular retrognathia resulted from short mandibular body length, whereas the depth of the cranial base was close to normal. Although asymmetry of hand, foot, and limb length were present in most individuals, obvious facial asymmetry was not common. Differences between left and right skeletal and dental age were not observed, indicating that children with RSS might show asymmetry because of quantitative differences in skeletal growth rather than delayed growth rate. Our findings not only provide important information about the maxillofacial characteristics of RSS, but also help to clarify the association between these characteristics and genetics, which will add to the body of information on clinical symptoms.
Diverse prognostic value of the GTn promoter polymorphism in squamous cell and adeno carcinoma of the oesophagus
Authors: Ghadban T. , Miro J.T. , Trump F. , Tsui T.Y. , Uzunoglu F.G. , Reeh M. , Gebauer F. , Bachmann K. , Wellner U. , Kalinin V. , Pantel K. , Izbicki J.R. , Vashist Y.K.
Published: February 2016

The basal transcription of heme oxygenase‐1 (HO‐1) regulation is dependent upon a GT repeat germ line polymorphism (GTn) in the promoter of the HO‐1 gene. We determined the prognostic value of HO‐1 promoter polymorphism on the natural postoperative course of complete resected oesophageal cancer. Genomic DNA from 297 patients was amplified by polymerase chain reaction and sequenced. The results were correlated with clinicopathological parameters, disseminated tumour cells in bone marrow (DTC) and clinical outcome. Depending on short allele with <25 and long allele with ≥25, GTn repeats three genotypes (SS, SL and LL) were defined. A diverse role of GTn was evident in squamous cell carcinoma (SCC) and adenocarcinoma (AC). In SCC, the SS genotype presented less advanced tumours with lower rate DTC in bone marrow and relapse compared with L‐allele carriers. In contrast, AC patients with the SS genotype displayed a complete opposing tumour characteristic. The disease‐free (DFS) and overall survival (OS) in SCC patients was markedly reduced in LL genotypes (p < 0.001). In AC contrarily the SS genotype patients displayed the worst DFS and OS (p < 0.001). GTn is a strong prognostic factor with diverse prognostic value for recurrence and survival in AC and SCC.
Influence of rapid‐ and slow‐rate resorption collagen membrane in maxillary sinus augmentation
Authors: Bresaola Marco Dapievi , Matsumoto Mariza Akemi , Zahoui Abbas , Biguetti Claudia Cristina , Nary‐Filho Hugo
Published: February 2016

Objective

To evaluate the effects of low‐ and rapid‐resorption‐rate bioabsorbable collagen membranes in maxillary sinus augmentation procedure in rabbits considering Schneiderian membrane (SM) reaction and bone tissue formation.

Materials and methods

Eighteen male adult rabbits underwent bilateral maxillary sinus augmentation with particulate bovine hydroxyapatite to be divided into three groups, as follows: Group C – control, no membrane; Group RR – rapid resorbable collagen membrane; and Group SR – slow‐resorbable collagen membrane. The animals were euthanized after 30 and 120 days for specimen's removal to be prepared and analyzed under light microscopy, histomorphometry, and immunohistochemistry for Runx2 and VEGF labeling.

Results

Histopathology evaluation presented similar healing pattern among the groups with a satisfactory response of SM, both at day 30 and day 120. Bone histomorphometry did not reveal significant differences among the groups, as well as immunohistochemistry analysis, which presented intense immunolabeling for both proteins in all groups.

Conclusions

The presence of both membranes did not negatively interfere in bone formation and remodeling, and the focal mild inflammatory reaction caused by their degrading process did not impair the reconstructive procedure.
Cost‐effectiveness of conservation payment schemes for species with different range sizes
Authors: Drechsler Martin , Smith Henrik G. , Sturm Astrid , Wätzold Frank
Published: February 2016

Payments to compensate landowners for carrying out costly land‐use measures that benefit endangered biodiversity have become an important policy instrument. When designing such payments, it is important to take into account that spatially connected habitats are more valuable for many species than isolated ones. One way to incentivize provision of connected habitats is to offer landowners an agglomeration bonus, that is, a bonus on top of payments they are receiving to conserve land if the land is spatially connected. Researchers have compared the cost‐effectiveness of the agglomeration bonus with 2 alternatives: an all‐or‐nothing, agglomeration payment, where landowners receive a payment only if the conserved land parcels have a certain level of spatial connectivity, and a spatially homogeneous payment, where landowners receive a payment for conserved land parcels irrespective of their location. Their results show the agglomeration bonus is rarely the most cost‐effective option, and when it is, it is only slightly better than one of the alternatives. This suggests that the agglomeration bonus should not be given priority as a policy design option. However, this finding is based on consideration of only 1 species. We examined whether the same applied to 2 species, one for which the homogeneous payment is best and the other for which the agglomeration payment is most cost‐effective. We modified a published conceptual model so that we were able to assess the cost‐effectiveness of payment schemes for 2 species and applied it to a grassland bird and a grassland butterfly in Germany that require the same habitat but have different spatial‐connectivity needs. When conserving both species, the agglomeration bonus was more cost‐effective than the agglomeration and the homogeneous payment; thus, we showed that as a policy the agglomeration bonus is a useful conservation‐payment option.
Associations between bouted and non‐bouted physical activity on multimorbidity
Authors: Loprinzi Paul D.
Published: February 2016

Background

The association between objectively measured bouted (at least 10 min in duration) and non‐bouted (<10 min in duration) physical activity with multimorbidity is unknown, which was the purpose of this study.

Methods

Data from the 2003–2006 National Health and Nutrition Examination Survey (NHANES) were employed (n = 4 584 adults). Bouted physical activity and non‐bouted physical activity were assessed via accelerometry, with multimorbidity assessed via physician diagnosis and laboratory data.

Results

For the ordinal regression model, and after adjustment, both non‐bouted moderate‐to‐vigorous physical activity (MVPA; βadjusted = −0·63; 95% CI: −0·79 to −0·48; P<0·001) and bouted MVPA (βadjusted = −0·43; 95% CI: −0·63 to −0·23; P<0·001) were independently associated with multimorbidity. In a multivariable logistic regression, both non‐bouted MVPA (ORadjusted = 0·59; 95% CI: 0·48–0·72; P<0·001) and bouted MVPA (ORadjusted = 0·66; 95% CI: 0·52–0·84; P = 0·001) were associated with a reduced odds of being multimorbid.

Conclusion

Both bouted MVPA and non‐bouted MVPA were associated with reduced odds of multimorbidity, underscoring the importance of promoting both types of physical activity.
Effect of prior hepatitis B virus exposure on long‐term risk of liver‐related events after liver transplantation
Authors: Chen Po‐Hung , Limketkai Berkeley N. , Trilianos Panagiotis , Pirtini‐Cetingul Muge , Woreta Tinsay A. , Kim Brian , Gulsen Murat T. , Segev Dorry L. , Cameron Andrew M. , Gurakar Ahmet
Published: February 2016

Objective

To characterize the risk of liver‐related events and death in hepatitis B virus (HBV)‐exposed liver transplantation (LT) recipients.

Methods

Retrospective review was performed in all adults who underwent LT between January 1995 through December 2010 at the Johns Hopkins Hospital. Recipients with graft failure or death within 14 d of LT or missing HBV status were excluded, leaving 575 individuals for analysis. Patients were classified according to HBV exposure status: Unexposed, Resolved HBV, Chronic HBV, or hepatitis B core antibody (anti‐HBc) seropositive liver donor.

Results

Compared with HBV‐unexposed patients, the relative hazard of combined liver‐related events (rejection, cirrhosis, re‐transplantation) and death after LT was not increased in patients with a baseline history of resolved HBV infection or chronic hepatitis B. Using anti‐HBc seropositive donors also did not increase the risk of liver‐related events, death, or composite events (all p ≥ 0.05). However, hepatitis C was associated with liver‐related events [adjusted hazard ratio (aHR), 1.59; 95% confidence interval (CI), 1.00–2.52], and blacks had a higher risk of death (aHR, 1.50; 95% CI, 1.01–2.22).

Conclusion

LT of patients with prior HBV exposure or use of anti‐HBc seropositive donors is not associated with increased risk of liver‐related events or death.
Cost comparison of heart transplant vs. left ventricular assist device therapy at one year
Authors: Marasco Silvana F. , Summerhayes Robyn , Quayle Margaret , McGiffin David , Luthe Marco
Published: February 2016

With the worldwide shortage of donor organs, use of ventricular assist device (VAD) therapy is rapidly increasing in both the bridge to transplant and destination therapy settings. However, the high cost of VADs and VAD care is a cause for concern for policy makers who have relied on the limited supply of donor hearts to naturally cap health expenditure on heart transplantation (HTx). We sought to compare costs of the first 12 months of care of VADs vs. HTx. Single center retrospective study utilizing real generated costs over a three yr span from 2010–2012. Only patients with 12 months of costing data were included. Costs of 28 HTx patients and 24 VAD patients were analyzed. Index admission costs were more than double in the VAD group compared to the HTx group and this was driven by the procurement costs and length of stay which increased almost all aspects of in hospital care costs. Subsequent costs were six times higher in the HTx group and this was driven largely by pharmaceuticals. VAD therapy remains a very expensive treatment option for end stage heart failure patients. Device prices need to reduce substantially to make this a more widely applicable and cost effective treatment option.
Audit of cytology of upper urinary tract
Authors: Malta F. , Lenos M. , Leotsakos I. , Katafigiotis I. , Gakiopoulou H. , Constantinides C. , Mikou P.
Published: February 2016

Objective

Cytology is an essential tool for the investigation of urinary tract malignancy. In this audit, we aimed to assess our laboratory performance in the diagnosis of upper urinary tract malignancy and to use the information provided to improve our service.

Methods

We retrieved cytology reports of upper urinary tract specimens from two periods, re‐evaluated the cases, compared the reports with histology data and estimated the sensitivity, specificity and positive predictive value (PPV). In the time interval between the two periods, we adopted new terminology, established better communication with clinicians and gained experience in the field. Finally, the data from the two periods were compared.

Results

In phase A, we estimated a sensitivity of 73%, specificity of 86% and PPV of 84.6%. As a result of the cytological re‐evaluation, correlation with histology and clinical follow‐up, plus communication with the clinicians during the audit, we established new terminology and a new request form. A three tiered grading system of atypia (mild, moderate and severe) was replaced by a two tiered grading system. The first category “atypia probably benign” corresponded to “mild atypia” while the second category “atypia, not otherwise specified” corresponded to “moderate atypia”. The cases diagnosed as “severe atypia” were reclassified as “suspicious for malignancy”. In phase B, the sensitivity, specificity and PPV were 75%, 89% and 90%, respectively.

Conclusions

Our laboratory performance is in concordance with reported data and has been improved through this study. The audit process is extremely valuable for the identification of problems, for taking action and, finally, for the improvement of the clinical cytology service in the field of upper urinary tract malignancy.
Low levels of short‐ and medium‐chain acylcarnitines in HIV‐infected patients
Authors: Waagsbø Bjørn , Svardal Asbjørn , Ueland Thor , Landrø Linn , Øktedalen Olav , Berge Rolf K. , Flo Trude H. , Aukrust Pål , Damås Jan K.
Published: February 2016

Background

Carnitine plays an essential role in fatty acid metabolism, exerts substantial antioxidant action and regulates immune functions. We hypothesized that a disturbed carnitine metabolism could be involved in progression of HIV infection.

Materials and methods

Plasma levels of L‐carnitine, its precursors, and short‐, medium‐ and long‐chain acylcarnitines were analysed with HPLC/mass spectrometry in HIV‐infected patients with various disease severities including patients who acquired Mycobacterium avium complex (MAC) infection. In vitro, we examined the MAC‐purified protein derivate (PPD)‐induced release of TNF‐α and IFN‐γ in peripheral blood mononuclear cells (PBMCs) from patients with either high or low plasma levels of acylcarnitines.

Results

Plasma levels of the short‐chain (e.g. propionyl‐carnitine) and medium‐chain (e.g. octanoyl‐carnitine) acylcarnitines were reduced in patients with advanced HIV infection. These acylcarnitines gradually decreased in rapid progressors, while minimal changes were observed in the nonprogressors. Plasma levels of propionyl‐carnitine and octanoyl‐carnitine significantly increased during antiretroviral therapy (ART). However, ART did not restore levels to those observed in healthy controls. Depletion of propionyl‐carnitine and octanoyl‐carnitine was observed prior to MAC infection, and the release of TNF‐α and IFN‐γ from PBMC was decreased after stimulation with MAC‐PPD in samples from HIV‐infected patients with low levels of propionyl‐carnitine or octanoyl‐carnitine.

Conclusions

Our findings suggest an association between disturbed acylcarnitine metabolism, immune dysregulation and disease progression in HIV‐infected patients. Low levels of propionyl‐carnitine and octanoyl‐carnitine were associated with increased susceptibility to MAC infection in HIV patients with advanced disease.
Relative longevity of adult Nezara viridula in field cages of cotton, peanut, and soybean
Authors: Olson D.M. , Ruberson J.R. , Andow D.A.
Published: February 2016

Producers in the southeastern USA face significant crop losses from the stink bugs Nezara viridula (L.), Euschistus servus (Say), and Chinavia hilaris (Say) (all Hemiptera: Pentatomidae). Cotton, peanut, and soybean are major agronomic crops and host plants of stink bugs in the region. We conducted a field plot study to measure the relative longevity of adult, unmated N. viridula males and females caged on peanut, cotton, and soybean to test three hypotheses: (1) differences in mortality are associated with differences in host plant food suitability, (2) mortality rates increase with age, and (3) males have higher mortality than females. Using survival analysis, we found that the sex of the individual did not affect survival rates on any of the three host plants. Survival was significantly higher in cotton and soybean than in peanut. Mortality rates increased with age in peanut, but not in soybean or cotton. The frequency of canopy temperatures above 35 °C was higher in peanut than in soybean. Peanut appears to be a less than ideal habitat in terms of canopy temperature and/or food quality for N. viridula adults. Both, cotton and soybean were equally suitable food resources for N. viridula adults prior to maturation of the plants.
Neuronal central nervous system syndromes probably mediated by autoantibodies
Authors: Chefdeville Aude , Honnorat Jérôme , Hampe Christiane S. , Desestret Virginie
Published: February 2016

In the last few years, a rapidly growing number of autoantibodies targeting neuronal cell‐surface antigens have been identified in patients presenting with neurological symptoms. Targeted antigens include ionotropic receptors such as N‐methyl‐d‐aspartate receptor or the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor, metabotropic receptors such as mGluR1 and mGluR5, and other synaptic proteins, some of them belonging to the voltage‐gated potassium channel complex. Importantly, the cell‐surface location of these antigens makes them vulnerable to direct antibody‐mediated modulation. Some of these autoantibodies, generally targeting ionotropic channels or their partner proteins, define clinical syndromes resembling models of pharmacological or genetic disruption of the corresponding antigen, suggesting a direct pathogenic role of the associated autoantibodies. Moreover, the associated neurological symptoms are usually immunotherapy‐responsive, further arguing for a pathogenic effect of the antibodies. Some studies have shown that some patients’ antibodies may have structural and functional in vitro effects on the targeted antigens. Definite proof of the pathogenicity of these autoantibodies has been obtained for just a few through passive transfer experiments in animal models. In this review we present existing and converging evidence suggesting a pathogenic role of some autoantibodies directed against neuronal cell‐surface antigens observed in patients with central nervous system disorders. We describe the main clinical symptoms characterizing the patients and discuss conflicting arguments regarding the pathogenicity of these antibodies.
Biodiversity and ecosystem stability across scales in metacommunities
Authors: Wang Shaopeng , Loreau Michel
Published: February 2016

Although diversity–stability relationships have been extensively studied in local ecosystems, the global biodiversity crisis calls for an improved understanding of these relationships in a spatial context. Here, we use a dynamical model of competitive metacommunities to study the relationships between species diversity and ecosystem variability across scales. We derive analytic relationships under a limiting case; these results are extended to more general cases with numerical simulations. Our model shows that, while alpha diversity decreases local ecosystem variability, beta diversity generally contributes to increasing spatial asynchrony among local ecosystems. Consequently, both alpha and beta diversity provide stabilising effects for regional ecosystems, through local and spatial insurance effects respectively. We further show that at the regional scale, the stabilising effect of biodiversity increases as spatial environmental correlation increases. Our findings have important implications for understanding the interactive effects of global environmental changes (e.g. environmental homogenisation) and biodiversity loss on ecosystem sustainability at large scales.
The CHESS score: a simple tool for early prediction of shunt dependency after aneurysmal subarachnoid hemorrhage
Authors: Jabbarli R. , Bohrer A.‐M. , Pierscianek D. , Müller D. , Wrede K. H. , Dammann P. , El Hindy N. , Özkan N. , Sure U. , Müller O.
Published: February 2016

Background and Purpose

Acute hydrocephalus is an early and common complication of aneurysmal subarachnoid hemorrhage (SAH). However, considerably fewer patients develop chronic hydrocephalus requiring shunt placement. Our aim was to develop a risk score for early identification of patients with shunt dependency after SAH.

Methods

Two hundred and forty‐two SAH individuals who were treated in our institution between January 2008 and December 2013 and survived the initial impact were retrospectively analyzed. Clinical parameters within 72 h after the ictus were correlated with shunt dependency. Independent predictors were summarized into a new risk score which was validated in a subsequent SAH cohort treated between January and December 2014.

Results

Seventy‐five patients (31%) underwent shunt placement. Of 23 evaluated variables, only the following five showed independent associations with shunt dependency and were subsequently used to establish the Chronic Hydrocephalus Ensuing from SAH Score (CHESS, 0–8 points): Hunt and Hess grade ≥IV (1 point), location of the ruptured aneurysm in the posterior circulation (1 point), acute hydrocephalus (4 points), the presence of intraventricular hemorrhage (1 point) and early cerebral infarction on follow‐up computed tomography scan (1 point). The CHESS showed strong correlation with shunt dependency (P = 0.0007) and could be successfully validated in both internal SAH cohorts tested. Patients scoring ≥6 CHESS points had significantly higher risk of shunt dependency (P < 0.0001) than other patients.

Conclusion

The CHESS may become a valuable diagnostic tool for early estimation of shunt dependency after SAH. Further evaluation and external validation will be required in prospective studies.
Vascular risk factors aggravate cognitive impairment in first‐ever young ischaemic stroke patients
Authors: Lu D. , Ren S. , Zhang J. , Sun D.
Published: February 2016

Background and purpose

Young ischaemic stroke patients often suffer from cognitive impairment after stroke. However, the risk factors of cognitive impairment are still unclear. This study examined the impact of vascular risk factors (VRFs) on cognitive impairment in first‐ever young ischaemic stroke patients.

Methods

Subjects were divided into low (0–1 VRF, n = 27), medium (2–3 VRFs, n = 45) and high‐risk (≥4 VRFs, n = 12) groups according to their number of VRFs. The following VRFs were collected: hypertension, diabetes mellitus, dyslipidaemia, atrial fibrillation, obesity, smoking, excess alcohol consumption, coronary heart disease and hyperhomocysteinaemia. A battery of cognitive assessments was executed 2 weeks after stroke. Differences of cognitive performances between groups were compared. The correlation between VRFs and cognitive function was investigated with an emphasis on discovering the main VRFs.

Results

Eighty‐four patients were enrolled in this study eventually. Compared with the low‐risk group, the high‐risk group had significantly worse performance in most of the cognitive domains. VRFs had a correlation with general cognition, executive function, attention and verbal fluency. After adjusting the covariates, VRFs showed a linear correlation with global cognitive function (R = 0.640, P = 0.000), verbal fluency (R = 0.372, P = 0.000), delayed memory (R = 0.327, P = 0.002), visual attention (R = 0.290, P = 0.007) and executive function (R = 0.266, P = 0.015). Amongst all the VRFs, hypertension, hyperlipidaemia, smoking and hyperhomocysteinaemia were the main influencing VRFs.

Conclusion

Vascular risk factors aggravate cognitive impairment after young ischaemic stroke. Effective management of VRFs in young adults is urgent and this may reduce the cognitive impairment.
Substantia nigra hyperechogenicity is related to decline in verbal memory in healthy elderly adults
Authors: Yilmaz R. , Behnke S. , Liepelt‐Scarfone I. , Roeben B. , Pausch C. , Runkel A. , Heinzel S. , Niebler R. , Suenkel U. , Eschweiler G. W. , Maetzler W. , Berg D.
Published: February 2016

Background and purpose

Deficits in cognition have been reported in Parkinson's disease (PD) already in the early and even in the pre‐motor stages. Whilst substantia nigra hyperechogenicity measured by transcranial B‐mode sonography (TCS) represents a strong PD marker and is associated with an increased risk for PD in still healthy individuals, its association with cognitive performance in prodromal PD stages is not well established.

Methods

Two different cohorts of healthy elderly individuals were assessed by TCS and two different neuropsychological test batteries covering executive functions, verbal memory, language, visuo‐constructional function and attention. Cognitive performance was compared between individuals with hyperechogenicity (SN+) and without hyperechogenicity (SN−).

Results

In both cohorts, SN+ individuals performed significantly worse than the SN− group in tests assessing verbal memory (word list delayed recall P = 0.05, logical memory II P < 0.017). Significant differences in Mini‐Mental State Examination score (cohort 1, P = 0.02) and executive function tests (cohort 2, Stroop Color−Word Reading, P = 0.004) could only be shown in one of the two cohorts. No between‐group effects were found in other cognitive tests and domains.

Conclusions

These results indicate that individuals with the PD risk marker SN+ perform worse in verbal memory compared to SN− independent of the assessment battery. Memory performance should be assessed in detail in individuals at risk for PD.
Lingual vs. labial fixed orthodontic appliances: systematic review and meta‐analysis of treatment effects
Authors: Papageorgiou Spyridon N. , Gölz Lina , Jäger Andreas , Eliades Theodore , Bourauel Christoph
Published: February 2016

The aim of this systematic review was to compare the therapeutic and adverse effects of lingual and labial orthodontic fixed appliances from clinical trials on human patients in an evidence‐based manner. Randomized and prospective non‐randomized clinical trials comparing lingual and labial appliances were included. Risk of bias within and across studies was assessed using the Cochrane tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Random‐effects meta‐analyses were conducted, followed by subgroup and sensitivity analyses. Six electronic databases were searched from inception to July 2015, without limitations. A total of 13 papers pertaining to 11 clinical trials were included with a total of 407 (34% male/66% female) patients. Compared with labial appliances, lingual appliances were associated with increased overall oral discomfort, increased speech impediment (measured using auditory analysis), worse speech performance assessed by laypersons, increased eating difficulty, and decreased intermolar width. On the other hand, lingual appliances were associated with increased intercanine width and significantly decreased anchorage loss of the maxillary first molar during space closure. Based on existing trials, there is insufficient evidence to make robust recommendations for lingual fixed orthodontic appliances regarding their therapeutic or adverse effects, as the quality of evidence was low.
Influence of different pre‐etching times on fatigue strength of self‐etch adhesives to dentin
Authors: Takamizawa Toshiki , Barkmeier Wayne W. , Tsujimoto Akimasa , Suzuki Takayuki , Scheidel Donal D. , Erickson Robert L. , Latta Mark A. , Miyazaki Masashi
Published: February 2016

The purpose of this study was to use shear bond strength (SBS) and shear fatigue strength (SFS) testing to determine the influence on dentin bonding of phosphoric acid pre‐etching times before the application of self‐etch adhesives. Two single‐step self‐etch universal adhesives [Prime & Bond Elect (EL) and Scotchbond Universal (SU)], a conventional single‐step self‐etch adhesive [G‐ænial Bond (GB)], and a two‐step self‐etch adhesive [OptiBond XTR (OX)] were used. The SBS and SFS values were obtained with phosphoric acid pre‐etching times of 3, 10, or 15 s before application of the adhesives, and for a control without pre‐etching. For groups with 3 s of pre‐etching, SU and EL showed higher SBS values than control groups. No significant difference was observed for GB among the 3 s, 10 s, and control groups, but the 15 s pre‐etching group showed significantly lower SBS and SFS values than the control group. No significant difference was found for OX among the pre‐etching groups. Reducing phosphoric acid pre‐etching time can minimize the adverse effect on dentin bonding durability for the conventional self‐etch adhesives. Furthermore, a short phosphoric acid pre‐etching time enhances the dentin bonding performance of universal adhesives.
The crucial role of IL‐22 and its receptor in thymus and activation regulated chemokine production and T‐cell migration by house dust mite extract
Authors: Jang Mirim , Kim Hyemin , Kim Yejin , Choi Jiyea , Jeon Jane , Hwang Youngil , Kang Jae Seung , Lee Wang Jae
Published: February 2016

House dust mite (HDM) is known as one of the factors that causes atopic dermatitis (AD). Interleukin (IL)‐22 and thymus and activation regulated chemokine (TARC) are related to skin inflammatory disease and highly expressed in AD lesions. However, the effects of HDM on IL‐22 production in T cells and on TARC production and IL‐22Rα receptor expression in keratinocytes are unknown. To identify the role of HDM in keratinocytes and T cells, we investigated IL‐22Rα expression and TARC production in the human keratinocyte cell line HaCaT and IL‐22 production in T cells treated with HDM extract as well as their roles in HDM‐induced skin inflammation. HDM extract not only increased IL‐22Rα expression and TARC production in HaCaT but also enhanced IL‐22, tumor necrosis factor (TNF)‐α and interferon (IFN)‐γ production in T cells. The HDM extract‐induced IL‐22 from T cells significantly increased the production of IL‐1α, IL‐6 and TARC in HaCaT cells. In addition, we found that TARC produced in HDM extract‐treated HaCaT induced T‐cell recruitment. These results suggest that there is a direct involvement of HDM extract‐induced IL‐22 in TARC production and T‐cell migration. Taken together, TARC production in HaCaT through the interaction between IL‐22 and IL‐22Rα facilitates T‐cell migration. These data show one of the reasons for inflammation in the skin lesions of AD patients.
Interleukin‐15 inhibits the expression of differentiation markers induced by Ca2+ in keratinocytes
Authors: Luo Xin , Jin Rui , Wang Fang , Jia Bo , Luan Kang , Cheng Feng‐Wei , Li Lei , Sun Liang‐Dan , Yang Sen , Zhang Sheng‐Quan , Zhang Xue‐Jun
Published: February 2016

Interleukin (IL)‐15 is an important proinflammatory cytokine that can protect epidermal keratinocytes (KCs) from ultraviolet‐induced apoptosis and plays a role in the pathogenesis of psoriasis. However, the impact of IL‐15 on KC differentiation remains unknown. In this study, isolated human primary epidermal KCs were treated with various concentrations of IL‐15 for different times, and the expression of differentiation markers (keratin 1, involucrin and loricrin) and p53 as well as the activation of ERK, AKT and Notch induced by IL‐15 in the absence or presence of Ca2+ was detected by real‐time PCR and Western blot. The results showed that stimulation with Ca2+ alone increased the expression of KC differentiation markers and p53 and promoted the activation of Notch1. Pretreatment with IL‐15 resulted in a decrease in the Ca2+‐induced expression of KC differentiation markers and p53. Additionally, Ca2+ continually inhibited the phosphorylation of ERK1/2 and activated AKT, and IL‐15 reduced the effect of Ca2+ on ERK1/2 and AKT. FR180204, a specific inhibitor of ERK1/2 phosphorylation, slightly attenuated the effect of Ca2+ on the expression of differentiation markers and p53 and the activation of Notch1. In contrast, MK‐2206, an inhibitor of pAKT, strongly blocked the expression of the differentiation markers and p53 and the activation of Notch1. An anti‐IL‐15 antibody neutralized the effect of IL‐15 on KC differentiation. These results indicate that IL‐15 inhibits the Ca2+‐induced differentiation of KCs, mainly via the attenuation of Ca2+‐stimulated PI3K‐AKT signalling.
Fair trade fish: consumer support for broader seafood sustainability
Authors: McClenachan Loren , Dissanayake Sahan T M , Chen Xiaojie
Published: February 2016

Sustainable seafood initiatives began with efforts to promote and certify seafood sourced from well‐managed stocks caught with a reduced impact on the marine environment. More recently, social equity in fisheries has been the subject of increased concern with suggestions that seafood cannot be certified as sustainable if its production results in social harm, such as unfair wages or the use of forced or child labour. Together with local seafood, which has been promoted as an eco‐friendly and socially conscious alternative to globally sourced seafood, these initiatives signal a growing interest in fisheries as a social–ecological system. However, this increasingly complex landscape of environmental sustainability and social justice may be difficult for the public and seafood consumers to navigate. Here, we investigate consumer understanding of and responsiveness to a range of seafood sustainability initiatives by testing preferences and willingness to pay (WTP) for seafood across the three types of sustainability: ecological sustainability, local origin and social sustainability. More than half of respondents demonstrated good understandings of both ecological sustainability and social sustainability with respect to seafood, and respondents were willing to pay more for all three types of sustainability. However, WTP for social sustainability benefits was the lowest, and consumers perceived a high degree of overlap of these benefits with those from locally sourced seafood. These results indicate that seafood certification taking a system‐wide approach has potential to succeed, but that it will need to emerge in concert with the increased public education about social problems associated with globalized fisheries.
Multimodel approaches in shark and ray growth studies: strengths, weaknesses and the future
Authors: Smart Jonathan J , Chin Andrew , Tobin Andrew J , Simpfendorfer Colin A
Published: February 2016

Multimodel frameworks are common in contemporary elasmobranch growth literature. These techniques offer a proposed improvement over individual growth functions by incorporating additional candidate models with alternative characteristics. Sigmoid functions (e.g. Gompertz and logistic) are a popular alternative to the commonly used von Bertalanffy growth function (VBGF) as they are hypothesized to better suit certain taxa based on body shape (such as batoids) or reproductive mode (such as egg‐layers). However, this hypothesis has never been tested. This study examined 74 elasmobranch multimodel growth studies by comparing the growth curves of their respective candidate models. Hypotheses regarding model performances were rejected as the VBGF was equally likely to fit best for all taxa and reproductive modes. Subsequently, no individual model was suited to be used a priori. Differences between candidate model fits were greatest at age zero with Gompertz and logistic functions providing estimates that were 15% and 23% larger on average than the VBGF, respectively. However, length‐at‐age estimates of the different models became negligible at older ages. Differences between candidate models were mostly small (≤5%), and the multimodel framework only marginally affected length‐at‐age estimates. However, there were cases where some candidate models provided inappropriate fits that contrasted considerably to the best fitting model. In some of these instances, a single‐model framework could have yielded biologically unrealistic growth estimates. Therefore, no study could pre‐empt whether or not it required a multimodel framework. A framework was subsequently recommended to maximize the accuracy of model fits for elasmobranch length‐at‐age estimates using multimodel approaches.
Numerical methods of multiaxial fatigue life prediction for elastomers under variable amplitude loadings
Authors: Chung J. , Kim N. H.
Published: February 2016

In this paper, numerical methods of fatigue life prediction for elastomers subjected to multidirectional, variable amplitude loadings are presented. Because experiments and numerical methods use different stress measures in large deformation, transformation between nominal stress and the second Piola–Kirchhoff stress is performed before fatigue life calculation. In order to incorporate the Mullins effect, the material properties of elastomers are calculated after an initial transition period. An efficient interpolation scheme using load stress/strain curves under unidirectional loading is proposed based on the fatigue characteristic of elastomers. A rainflow counting method with multi‐stress components is developed for variable amplitude loadings, and the critical plane method is applied to find the plane with the maximum damage parameter. Fatigue life predictions using the proposed numerical method are validated against experimental results. As a practical example, the fatigue life of a rubber engine mount is predicted using the proposed numerical method.
Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway
Authors: Troutwine B. R. , Ghezzi A. , Pietrzykowski A. Z. , Atkinson N. S.
Published: February 2016

A growing body of evidence has shown that alcohol alters the activity of the innate immune system and that changes in innate immune system activity can influence alcohol‐related behaviors. Here, we show that the Toll innate immune signaling pathway modulates the level of alcohol resistance in Drosophila. In humans, a low level of response to alcohol is correlated with increased risk of developing an alcohol use disorder. The Toll signaling pathway was originally discovered in, and has been extensively studied in Drosophila. The Toll pathway is a major regulator of innate immunity in Drosophila, and mammalian Toll‐like receptor signaling has been implicated in alcohol responses. Here, we use Drosophila‐specific genetic tools to test eight genes in the Toll signaling pathway for effects on the level of response to ethanol. We show that increasing the activity of the pathway increases ethanol resistance whereas decreasing the pathway activity reduces ethanol resistance. Furthermore, we show that gene products known to be outputs of innate immune signaling are rapidly induced following ethanol exposure. The interaction between the Toll signaling pathway and ethanol is rooted in the natural history of Drosophila melanogaster.
Experimental whole‐lake increase of dissolved organic carbon concentration produces unexpected increase in crustacean zooplankton density
Authors: Kelly Patrick T. , Craig Nicola , Solomon Christopher T. , Weidel Brian C. , Zwart Jacob A. , Jones Stuart E.
Published: February 2016

The observed pattern of lake browning, or increased terrestrial dissolved organic carbon (DOC) concentration, across the northern hemisphere has amplified the importance of understanding how consumer productivity varies with DOC concentration. Results from comparative studies suggest these increased DOC concentrations may reduce crustacean zooplankton productivity due to reductions in resource quality and volume of suitable habitat. Although these spatial comparisons provide an expectation for the response of zooplankton productivity as DOC concentration increases, we still have an incomplete understanding of how zooplankton respond to temporal increases in DOC concentration within a single system. As such, we used a whole‐lake manipulation, in which DOC concentration was increased from 8 to 11 mg L−1 in one basin of a manipulated lake, to test the hypothesis that crustacean zooplankton production should subsequently decrease. In contrast to the spatially derived expectation of sharp DOC‐mediated decline, we observed a small increase in zooplankton densities in response to our experimental increase in DOC concentration of the treatment basin. This was due to significant increases in gross primary production and resource quality (lower seston carbon‐to‐phosphorus ratio; C:P). These results demonstrate that temporal changes in lake characteristics due to increased DOC may impact zooplankton in ways that differ from those observed in spatial surveys. We also identified significant interannual variability across our study region, which highlights potential difficulty in detecting temporal responses of organism abundances to gradual environmental change (e.g., browning).