bluuebunny/crossref_metadata_2025 huggingface dataset:
Secukinumab efficacy and safety in Japanese patients with moderate‐to‐severe plaque psoriasis: Subanalysis from ERASURE, a randomized, placebo‐controlled, phase 3 study
Authors: Ohtsuki Mamitaro , Morita Akimichi , Abe Masatoshi , Takahashi Hidetoshi , Seko Noriko , Karpov Alexander , Shima Tomohiro , Papavassilis Charis , Nakagawa Hidemi ,   the ERASURE Study Japanese subgroup
Published: October 2014

Secukinumab, a fully human anti‐IL‐17A monoclonal antibody, neutralizes IL‐17A, a key cytokine in the pathogenesis of psoriasis. Efficacy and safety of secukinumab was evaluated in Japanese patients with moderate‐to‐severe plaque psoriasis as part of a large Phase 3 global study (ERASURE). In this 52‐week, double‐blind study (ClinicalTrials.gov Identifier: NCT01365455, JapicCTI‐111529), 87 patients from Japan (11.8% of 738 patients randomized in the overall study population) were equally randomized to receive secukinumab 300 mg or 150 mg, or placebo once weekly at baseline and at Weeks 1, 2, 3 and 4, then every 4 weeks. Co‐primary endpoints (Week 12) were ≥75% improvement in psoriasis area‐and‐severity index (PASI 75) from baseline and a score of 0 (clear) or 1 (almost clear) on a 5‐point Investigator's Global Assessment scale (IGA mod 2011 0/1) versus placebo. PASI 75 and IGA mod 2011 0/1 responses at Week 12 were superior with secukinumab 300 mg (82.8% and 55.2%, respectively) or 150 mg (86.2% and 55.2%, respectively) versus placebo (6.9% and 3.4%, respectively; P < 0.0001 for all). Greater than 90% improvement in PASI (PASI 90) was also superior with secukinumab 300 mg (62.1%) or 150 mg (55.2%) versus placebo (0.0%) at Week 12 (P < 0.0001 for both). Clinical responses were sustained up to Week 52 in the majority of patients. During a 12‐week induction period, adverse event incidences were 48.3% with secukinumab 300 mg, 55.2% with 150 mg, and 41.4% with placebo. Secukinumab showed robust and sustainable efficacy in symptom reduction for moderate‐to‐severe plaque psoriasis in the Japanese patients.
Congenital “self‐healing” Langerhans cell histiocytosis (Hashimoto‐Pritzker disease): A report of two cases with the same cutaneous manifestations but different clinical course
Authors: Mandel Victor Desmond , Ferrari Chiara , Cesinaro Anna Maria , Pellacani Giovanni , Del Forno Corrado
Published: October 2014

Congenital self‐healing Langerhans cell histiocytosis or Hashimoto‐Pritzker disease is a rare condition present at birth or in the neonatal period characterized by small reddish‐brown crusted papulonodular lesions. In most cases these lesions are not accompanied by systemic findings and tend to involute spontaneously within weeks or months, but in other cases there may be extracutaneous involvement and/or recurrence of the disease. This emphasizes that the clinical course is variable and a long‐term follow‐up is mandatory in order to reveal possible systemic involvement. We describe two cases of congenital self‐healing Langerhans cell histiocytosis with widespread and very similar cutaneous manifestations but different clinical course. The first patient had multisystemic disease (with lymph nodes, bones, liver and lungs affected) that required systemic therapy. The second patient had cutaneous and bony lesions that resolved spontaneously. We think that the adjective “self‐healing” is misleading and should be abandoned. We stress the importance of a complete systemic evaluation and the necessity of a long‐term follow‐up.
Valsartan Blocked Alcohol‐Induced, Toll‐Like Receptor 2 Signaling‐Mediated Inflammation in Human Vascular Endothelial Cells
Authors: Wang Yushu , Li Yi , Shen Qingyu , Li Xiangpen , Lu Juan , Li Xiangping , Yin Deling , Peng Ying
Published: October 2014

Background

Alcohol consumption induces inflammatory damage in vessels, and the underlying mechanism is unclear. Valsartan, as one of the angiotensin receptor blockers (ARBs), plays a role in the inhibition of inflammatory reactions in vascular dysfunction. This study is to investigate the role of Toll‐like receptor 2 (TLR2) in alcohol‐induced inflammatory damage in vascular endothelial cells in vitro and to explore the protective effect of valsartan on alcohol‐induced and TLR2‐mediated inflammatory damage.

Methods

The human umbilical vein cell line (EA.hy926) were exposed to alcohol at 0 to 80 mM for 0 to 48 hours with or without valsartan pretreatment. The expression of TLR2 signaling, including TLR2, tumor necrosis factor receptor associated factor 6 (TRAF‐6) and nuclear factor kappa B (NF‐κB) p65 were detected by Western blot. The levels of proinflammatory cytokines, tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6), were determined by ELISA. To confirm the role of TLR2, we functionally up‐regulated or down‐regulated TLR2 by using TLR2 agonist or TLR2 small interfering RNA (siRNA), respectively. To further investigate the mechanism of alcohol on renin‐angiotensin system, we detected the expression of angiotensin II receptor type 1 (AGTR1) in protein levels.

Results

The expression of TLR2, TRAF‐6, NF‐κB p65, and the proinflammatory cytokines, TNF‐α and IL‐6, were significantly increased after alcohol exposure in EA.hy926 endothelial cells. This was enhanced by TLR2 agonist, and was inhibited by TLR2 siRNA transfection. The pretreatment of valsartan resulted in an inhibition of TLR2 signaling and proinflammatory cytokines. The expression of AGTR1 was up‐regulated after alcohol exposure, and was blocked by valsartan pretreatment.

Conclusions

TLR2 signaling‐mediated alcohol induced inflammatory response in human vascular epithelial cells in vitro, which was inhibited by valsartan.
Impacts of Small‐scale Clearings due to Selective logging on Dung Beetle Communities
Authors: Hosaka Tetsuro , Niino Masahiro , Kon Masahiro , Ochi Teruo , Yamada Toshihiro , Fletcher Christine D. , Okuda Toshinori
Published: October 2014

Conservation of biodiversity in production forests is crucial for mitigating biodiversity loss in the tropics. The major ecological impacts of selective logging are often the result of small clearings for skid trails, logging roads, log yards, and logging camps; however, their impacts on forest biodiversity have rarely been examined. The purpose of this study was to assess the impacts of these clearings on a forest‐dependent faunal group, dung beetles, and to identify the environmental factors responsible. Abundance and species richness of dung beetles decreased drastically in clearings, but directly increased in forests with the distance from roads/trails; abundance and species richness at 10 m from roads/trails were almost comparable with those detected in further interior forests. Similarly, species composition was significantly different between forests and clearings (except skid trails) but recovered within a short distance from roads/trails. Canopy openness was the most important environmental factor affecting the abundance, and species richness and composition of dung beetles; most dung beetle species were concentrated under closed forest canopy with less than 10 percent of canopy openness, whereas canopy openness ranged from 16 to 53 percent in clearings. Our study demonstrates that even small‐scale, unpaved clearings affect dung beetle communities through increased canopy openness. Although the effective distance was not very large, a considerable portion of logged areas can be affected when road networks are dense therefore minimizing the density of road networks and enhancing canopy recovery after logging are important for retaining biodiversity in tropical production forests.
Key Structures and Interactions for Binding of Mycobacterium tuberculosis Protein Kinase B Inhibitors from Molecular Dynamics Simulation
Authors: Punkvang Auradee , Kamsri Pharit , Saparpakorn Patchreenart , Hannongbua Supa , Wolschann Peter , Irle Stephan , Pungpo Pornpan
Published: October 2014

Substituted aminopyrimidine inhibitors have recently been introduced as antituberculosis agents. These inhibitors show impressive activity against protein kinase B, a Ser/Thr protein kinase that is essential for cell growth of M. tuberculosis. However, up to now, X‐ray structures of the protein kinase B enzyme complexes with the substituted aminopyrimidine inhibitors are currently unavailable. Consequently, structural details of their binding modes are questionable, prohibiting the structural‐based design of more potent protein kinase B inhibitors in the future. Here, molecular dynamics simulations, in conjunction with molecular mechanics/Poisson–Boltzmann surface area binding free‐energy analysis, were employed to gain insight into the complex structures of the protein kinase B inhibitors and their binding energetics. The complex structures obtained by the molecular dynamics simulations show binding free energies in good agreement with experiment. The detailed analysis of molecular dynamics results shows that Glu93, Val95, and Leu17 are key residues responsible to the binding of the protein kinase B inhibitors. The aminopyrazole group and the pyrimidine core are the crucial moieties of substituted aminopyrimidine inhibitors for interaction with the key residues. Our results provide a structural concept that can be used as a guide for the future design of protein kinase B inhibitors with highly increased antagonistic activity.
What role do bacteria play in persisting fistula formation in idiopathic and Crohn's anal fistula?
Authors: Tozer P. J. , Rayment N. , Hart A. L. , Daulatzai N. , Murugananthan A. U. , Whelan K. , Phillips R. K. S.
Published: October 2014

Aim

The aetiology of Crohn's disease‐related anal fistula remains obscure. Microbiological, genetic and immunological factors are thought to play a role but are not well understood. The microbiota within anal fistula tracts has never been examined using molecular techniques. The present study aimed to characterize the microbiota in the tracts of patients with Crohn's and idiopathic anal fistula.

Method

Samples from the fistula tract and rectum of patients with Crohn's and idiopathic anal fistula were analysed using fluorescent in situ hybridization, Gram staining and scanning electron microscopy were performed to identify and quantify the bacteria present.

Results

Fifty‐one patients, including 20 with Crohn's anal fistula, 18 with idiopathic anal fistula and 13 with luminal Crohn's disease and no anal fistula, were recruited. Bacteria were not found in close association with the luminal surface of any of the anal fistula tracts.

Conclusion

Anal fistula tracts generally do not harbour high levels of mucosa‐associated microbiota. Crohn's anal fistulas do not seem to harbour specific bacteria. Alternative explanations for the persistence of anal fistula are needed.
Pulmonary pyoderma gangrenosum without cutaneous manifestations
Authors: Sakata Kenneth Kazuto , Penupolu Sudheer , Colby Thomas Vail , Gotway Michael Bruce , Wesselius Lewis Jon
Published: October 2014

Pyoderma gangrenosum is a chronic sterile skin disorder that is frequently seen in association with systemic disorders such as inflammatory bowel disease. Extracutaneous pyoderma gangrenosum is rare and most commonly occurs in the lungs. It is particularly unusual for extracutaneous pyoderma gangrenosum to manifest prior to skin findings and without an associated systemic disorder. A 19‐year‐old white man presented with shortness of breath and a productive cough. His skin exam was normal. Unenhanced chest computed tomography showed peripheral consolidations, areas of cavitation, nodules and bilateral pleural effusions. A bronchoalveolar lavage and an autoimmune panel were unremarkable. Right lung wedge biopsies via thoracostomy was performed and showed pulmonary pyoderma gangrenosum. He was treated with corticosteroids and has returned back to his baseline. This is the first case of pulmonary pyoderma gangrenosum without any associated underlying systemic disorder and without any cutaneous manifestations to date. Serial follow‐ups are necessary to assess for the development of an associated systemic disorder or skin lesions.
Adapting streams for climate change using riparian broadleaf trees and its consequences for stream salmonids
Authors: Thomas Stephen M. , Griffiths Siân W. , Ormerod Steve J.
Published: October 2014

The societal value, ecological importance and thermal sensitivity of stream‐dwelling salmonids have prompted interest in adaptive management strategies to limit the effects of climate change on their habitats. Additionally, in northern temperate regions, the management and restoration of riparian broadleaf forest is advocated increasingly to dampen variations in stream water temperature and discharge, but might have collateral effects on salmonids by changing allochthonous subsidies.

Here, in a cross‐sectional analysis of 18 temperate headwaters with different riparian and catchment land use, we use classical fisheries data alongside stable isotope ratios in salmonids and their macroinvertebrate prey to examine whether increasing catchment cover of broadleaf trees could (i) increase the density, biomass and size of salmonids, (ii) increase brown trout (Salmo trutta) dietary reliance on production of terrestrial origin and (iii) mediate allochthonous energy flux between aquatic macroinvertebrates and brown trout.

Contrary to expectation, catchment broadleaf cover had no systematic effect on salmonid density or individual size, although salmonid biomass was lowest in streams draining non‐native conifers. Moreover, there was no major effect of land use on the dependence of S. trutta on terrestrial production: averaged across all sites, trout used more production from in‐stream (62 ± 3%: mean ± 1 SE) than terrestrial (38 ± 3%) sources. Dependence on terrestrial production varied more substantially among individual streams than with riparian land use, mirroring site‐specific patterns observed in macroinvertebrates.

Although increased broadleaf cover could benefit salmonids by offsetting the impacts of warming related to climate change, these results imply that broadleaf restoration along temperate, upland headwaters is neutral with respect to salmonid biomass, density and terrestrial subsidies. In contrast, the use of non‐native conifers for stream shading could have negative effects on salmonid production. Knowledge of the ecological implications of climate change adaptation remains rudimentary, and we advocate further evaluations like ours not only for fresh waters, but for ecosystems more generally.
Bridging nursing practice and education through a strategic global partnership
Authors: Stringer Marilyn , Rajeswaran Lakshmi , Dithole Kefalotse , Hoke Linda , Mampane Patricia , Sebopelo Sheila , Molefe Margret , Muecke Marjorie A , Rich Victoria L , Polomano Rosemary C
Published: October 2014

To forge strong relationships among nurse scholars from the University of Pennsylvania School of Nursing, Philadelphia, PA (USA); University of Botswana School of Nursing, Gaborone, Botswana; the Hospital of the University of Pennsylvania, Philadelphia; Princess Marina Hospital (PMH), Gaborone; and the Ministry of Health of Botswana, a strategic global partnership was created to bridge nursing practice and education. This partnership focused on changing practice at PMH through the translation of new knowledge and evidence‐based practice. Guided by the National Institutes of Health team science field guide, the conceptual implementation of this highly successful practice change initiative is described in detail, highlighting our strategies, challenges and continued collaboration for nurses to be leaders in improving health in Botswana.
A System‐Wide Analysis Using a Senior‐Friendly Hospital Framework Identifies Current Practices and Opportunities for Improvement in the Care of Hospitalized Older Adults
Authors: Wong Ken S. , Ryan David P. , Liu Barbara A.
Published: October 2014

Older adults are vulnerable to hospital‐associated complications such as falls, pressure ulcers, functional decline, and delirium, which can contribute to prolonged hospital stay, readmission, and nursing home placement. These vulnerabilities are exacerbated when the hospital's practices, services, and physical environment are not sufficiently mindful of the complex, multidimensional needs of frail individuals. Several frameworks have emerged to help hospitals examine how organization‐wide processes can be customized to avoid these complications. This article describes the application of one such framework—the Senior‐Friendly Hospital (SFH) framework adopted in Ontario, Canada—which comprises five interrelated domains: organizational support, processes of care, emotional and behavioral environment, ethics in clinical care and research, and physical environment. This framework provided the blueprint for a self‐assessment of all 155 adult hospitals across the province of Ontario. The system‐wide analysis identified practice gaps and promising practices within each domain of the SFH framework. Taken together, these results informed 12 recommendations to support hospitals at all stages of development in becoming friendly to older adults. Priorities for system‐wide action were identified, encouraging hospitals to implement or further develop their processes to better address hospital‐acquired delirium and functional decline. These recommendations led to collaborative action across the province, including the development of an online toolkit and the identification of accountability indicators to support hospitals in quality improvement focusing on senior‐friendly care.
Force‐controlled biting alters postural control in bipedal and unipedal stance
Authors: Ringhof S. , Stein T. , Potthast W. , Schindler H.‐J. , Hellmann D.
Published: October 2014

Human posture is characterised by inherent body sway which forces the sensory and motor systems to counter the destabilising oscillations. Although the potential of biting to increase postural stability has recently been reported, the mechanisms by which the craniomandibular system (CMS) and the motor systems for human postural control are functionally coupled are not yet fully understood. The purpose of our study was, therefore, to investigate the effect of submaximum biting on postural stability and on the kinematics of the trunk and head. Twelve healthy young adults performed force‐controlled biting (FB) and non‐biting (NB) during bipedal narrow stance and single‐leg stance. Postural stability was quantified on the basis of centre of pressure (COP) displacements, detected by use of a force platform. Trunk and head kinematics were investigated by biomechanical motion analysis, and bite forces were measured using a hydrostatic system. The results revealed that FB significantly improved postural control in terms of reduced COP displacements, providing additional evidence for the functional coupling of the CMS and human posture. Our study also showed, for the first time, that reductions in the sway of the COP were accompanied by reduced trunk and head oscillations, which might be attributable to enhanced trunk stiffness during FB. This physiological response to isometric activation of the masticatory muscles raises questions about the potential of oral motor activity as a strategy to reduce the risk of falls among the elderly or among patients with compromised postural control.
Scalp hair and blood cadmium levels in association with chewing gutkha, mainpuri, and snuff, among patients with oral cancer in Pakistan
Authors: Arain Sadaf Sadia , Kazi Tasneem Gul , Afridi Hassan Imran , Talpur Farah Naz , Kazi Atif Gul , Brahman Kapil Dev , Panhwar Abdul Haleem , Arain Mariam Shahzadi
Published: October 2014

Background

It has been reported that smokeless tobacco (SLT) chewing can lead to caners of oral cavity. In this study, the relationship between cadmium exposure via consumption of different SLT products by patients with oral cancer with related to referents belongs to different cities of Pakistan are investigated.

Methods

The cadmium in different types of SLT products (gutkha, mainpuri and snuff) consumed by studied population and biological samples (scalp hair and blood) of cancerous and healthy subjects were analyzed. Both referents and patients with cancer have same age group (ranged 30–60 years), socioeconomic status, localities, and dietary habits. The concentrations of cadmium in SLT products and biological samples were measured by electrothermal atomic absorption spectrophotometer after microwave‐assisted acid digestion. The validity and accuracy of the methodology were checked by certified reference materials.

Results

It was estimated that 10 g intake of different types of gutkha, mainpuri, and snuff could contribute, 18–40%, 15.7–33.6%, and 14–68% of the provisional maximum tolerable daily intake of cadmium, respectively for adults (60 kg). The results of present study showed that the mean value of cadmium was significantly higher in scalp hair and blood samples of patients with oral cancer as compared to those results obtained for referents (P < 0.001).

Conclusions

The high exposure of cadmium due to consuming different SLT products may have synergistic effects with other risk factors associated for oral cancer.
Evaluation of facial expression in acute pain in cats
Authors: Holden E. , Calvo G. , Collins M. , Bell A. , Reid J. , Scott E. M. , Nolan A. M.
Published: October 2014

OBJECTIVES

To describe the development of a facial expression tool differentiating pain‐free cats from those in acute pain.

METHODS

Observers shown facial images from painful and pain‐free cats were asked to identify if they were in pain or not. From facial images, anatomical landmarks were identified and distances between these were mapped. Selected distances underwent statistical analysis to identify features discriminating pain‐free and painful cats. Additionally, thumbnail photographs were reviewed by two experts to identify discriminating facial features between the groups.

RESULTS

Observers (n = 68) had difficulty in identifying pain‐free from painful cats, with only 13% of observers being able to discriminate more than 80% of painful cats. Analysis of 78 facial landmarks and 80 distances identified six significant factors differentiating pain‐free and painful faces including ear position and areas around the mouth/muzzle. Standardised mouth and ear distances when combined showed excellent discrimination properties, correctly differentiating pain‐free and painful cats in 98% of cases. Expert review supported these findings and a cartoon‐type picture scale was developed from thumbnail images.

CLINICAL SIGNIFICANCE

Initial investigation into facial features of painful and pain‐free cats suggests potentially good discrimination properties of facial images. Further testing is required for development of a clinical tool.
Impact of a Multidisciplinary Vulvodynia Program on Sexual Functioning and Dyspareunia
Authors: Brotto Lori A. , Yong Paul , Smith Kelly B. , Sadownik Leslie A.
Published: October 2014

Introduction

For many years, multidisciplinary approaches, which integrate psychological, physical, and medical treatments, have been shown to be effective for the treatment of chronic pain. To date, there has been anecdotal support, but little empirical data, to justify the application of this multidisciplinary approach toward the treatment of chronic sexual pain secondary to provoked vestibulodynia (PVD).

Aim

This study aimed to evaluate a 10-week hospital-based treatment (multidisciplinary vulvodynia program [MVP]) integrating psychological skills training, pelvic floor physiotherapy, and medical management on the primary outcomes of dyspareunia and sexual functioning, including distress.

Method

A total of 132 women with a diagnosis of PVD provided baseline data and agreed to participate in the MVP. Of this group, n = 116 (mean age 28.4 years, standard deviation 7.1) provided complete data at the post-MVP assessment, and 84 women had complete data through to the 3- to 4-month follow-up period.

Results

There were high levels of avoidance of intimacy (38.1%) and activities that elicited sexual arousal (40.7%), with many women (50.4%) choosing to focus on their partner’s sexual arousal and satisfaction at baseline. With treatment, over half the sample (53.8%) reported significant improvements in dyspareunia. Following the MVP, there were strong significant effects for the reduction in dyspareunia (P = 0.001) and sex-related distress (P < 0.001), and improvements in sexual arousal (P < 0.001) and overall sexual functioning (P = 0.001). More modest but still statistically significant were improvements in sexual desire, lubrication, orgasmic function, and sexual satisfaction. All improvements were retained at 2- to 3-month follow-up.

Conclusion

This study provides strong support for the efficacy of a multidisciplinary approach (psychological, pelvic floor physiotherapy, and medical management) for improving dyspareunia and all domains of sexual functioning among women with PVD. The study also highlights the benefits of incorporating sexual health education into general pain management strategies for this population.
Associations of Maternal Atopic Diseases with Adverse Pregnancy Outcomes: a National Cohort Study
Authors: Trønnes Håvard , Wilcox Allen J. , Markestad Trond , Tollånes Mette Christophersen , Lie Rolv Terje , Moster Dag
Published: October 2014

Background

Maternal asthma has been associated with adverse pregnancy outcomes. Little is known about the influence of other atopic diseases on pregnancy outcomes. We assessed how various maternal atopic diseases might affect preterm birth, stillbirth, and neonatal death.

Methods

By linking Norwegian national registries, we acquired information on maternal health, socio‐demographic factors, pregnancy, birth, and neonatal outcome on all births in Norway from 1967 to 2003.

Results

A total of 1 974 226 births were included. Of these, 1.8% had a record of maternal asthma, 3.4% of maternal atopic dermatitis, and 0.4% of maternal allergic rhinoconjunctivitis. Overall rates of preterm birth, stillbirth, and neonatal death were 6.0%, 0.6%, and 0.5%, respectively. After adjustments for possible confounders, maternal asthma was associated with increased risk of preterm birth (relative risk (RR), 1.15, [95% confidence interval (CI) 1.10, 1.21]). In contrast, maternal atopic dermatitis was associated with decreased risk of preterm birth (RR 0.90, [95% CI 0.86, 0.93]), stillbirth (RR 0.70, [95% CI 0.62, 0.79]), and neonatal death (RR 0.76, [95% CI 0.65, 0.90]). Similarly, maternal allergic rhinoconjunctivitis was associated with decreased risk of preterm birth (RR 0.84, [95% CI 0.76, 0.94]) and stillbirth (RR 0.40, [95% CI 0.25, 0.66]).

Conclusions

We confirmed the previously reported association of maternal asthma with increased risk for preterm birth. Unexpectedly, maternal atopic dermatitis and allergic rhinoconjunctivitis were associated with decreased risk of preterm birth and stillbirth. Mechanisms for these protective associations are unclear, and our findings require confirmation in further studies.
Antigen Conjugated to Anti‐CD23 Antibodies is Rapidly Transported to Splenic Follicles by Recirculating B Cells
Authors: Xu H. , van Mechelen L. , Henningsson F. , Heyman B.
Published: October 2014

IgE–antigen complexes, administered intravenously to mice, induce a several 100‐fold higher specific antibody response than antigen alone. Additionally, in vivo activation and proliferation of specific CD4+ T cells is enhanced. The mechanism behind these effects is thought to be that peripheral B cells capture IgE–antigen complexes via their low‐affinity receptor for IgE, CD23, and rapidly transport them to splenic B cell follicles where an immune response is initiated. Here, we demonstrate that ovalbumin, covalently coupled to anti‐CD23 antibodies and administered intravenously to mice, is also transported to splenic follicles and induces an enhanced primary antibody response. These effects are absent in CD23‐deficient mice. No enhanced induction of immunological memory was observed. These findings extend previous observations regarding the in vivo role of CD23 and emphasize that recirculating B cells play an important role in antigen transport to the spleen.
Neuropsychological test norms controlled for physical health: Does it matter?
Authors: Bergman Ingvar , Almkvist Ove
Published: October 2014

The objective of the present study was to investigate the effects of physical health on neuropsychological test norms. Medical and neuropsychological data from 118 healthy volunteer controls, aged 26–91 years, were collected during five recruitment occasions. The examinations included a clinical investigation, brain neuroimaging, and a comprehensive neuropsychological test battery. Test‐specific statistical regression‐weights for age, education and gender were calculated to establish preliminary test norms. Hierarchical regression analyses demonstrated that control in addition for physical health moved best performance from age 60 to 65 for abstraction; replaced a plateau above age 70 for verbal fluency, with a continued rise in performance; eliminated significant negative influences of age on auditory learning, spatial reasoning and complex copying; reduced them on wordlist recall, psychomotor speed, visual scanning and mental shifting; and slightly reduced negative influences of low education on most verbal tests, several memory tests, and psychomotor speed, indicating rises in normative scores of up to 0.8 SD at age 80 and 0.4 SD at age 60. No differences were found at age 40. Although the sample size is not adequate to be used for normative data, the findings indicate that norms uncontrolled for health overestimate the negative influence of advanced age and low education, implying a risk of drawing false diagnostic conclusions.
Tests for Coefficients in High‐dimensional Additive Hazard Models
Authors: Zhong Ping‐Shou , Hu Tao , Li Jun
Published: October 2014

We consider hypothesis testing problems for low‐dimensional coefficients in a high dimensional additive hazard model. A variance reduced partial profiling estimator (VRPPE) is proposed and its asymptotic normality is established, which enables us to test the significance of each single coefficient when the data dimension is much larger than the sample size. Based on the p‐values obtained from the proposed test statistics, we then apply a multiple testing procedure to identify significant coefficients and show that the false discovery rate can be controlled at the desired level. The proposed method is also extended to testing a low‐dimensional sub‐vector of coefficients. The finite sample performance of the proposed testing procedure is evaluated by simulation studies. We also apply it to two real data sets, with one focusing on testing low‐dimensional coefficients and the other focusing on identifying significant coefficients through the proposed multiple testing procedure.
Changes in the clinical and epidemiological features of group A streptococcal bacteraemia in Australia's Northern Territory
Authors: Gear R. J. , Carter J. C. , Carapetis J. R. , Baird R. , Davis J. S.
Published: October 2014

Objective

Invasive group A streptococcus (iGAS) disease is an important cause of mortality globally. The incidence of iGAS in Australia's tropical Northern Territory (NT) has been previously reported as 32.2/100 000 in Indigenous people for the period 1991–1996. We aimed to measure the incidence and severity of iGAS disease in the NT since this time.

Methods

We collected demographic data for all GAS blood culture isolates over a 12‐year period (1998–2009) from the three hospital laboratories serving the tropical NT. We then collected detailed clinical information from hospital records and databases for the subset of these patients who were admitted to Royal Darwin Hospital during 2005–2009.

Results

There were 295 confirmed cases of GAS bacteraemia over the study period, with a mean (SD) age of 42.1 (22.0) years, and 163 (55.0%) were male. The annual age‐adjusted incidence was 15.2 (95% CI 13.4–16.9)/100 000 overall and 59.4 (95% CI 51.2–67.6) in Indigenous Australians. For 2005–2009, there were 123 cases with the most common focus of infection being skin/soft tissue [44 (35.6%)]; 29 patients (23.6%) required intensive care unit admission and 20 (16.3%) had streptococcal toxic shock syndrome. Antecedent sore throat or use of non‐steroidal anti‐inflammatory drugs was rare, but current or recent scabies, pyoderma and trauma were common.

Conclusion

The incidence and severity of iGAS are high and increasing in tropical northern Australia, and urgent attention is needed to improve surveillance and the social determinants of health in this population. This study adds to emerging data suggesting increasing importance of iGAS in low‐ and middle‐income settings globally.
Transport of Phosphatidylserine from the Endoplasmic Reticulum to the Site of Phosphatidylserine Decarboxylase2 in Yeast
Authors: Kannan Muthukumar , Riekhof Wayne R. , Voelker Dennis R.
Published: October 2014

Over the past two decades, most of the genes specifying lipid synthesis and metabolism in yeast have been identified and characterized. Several of these biosynthetic genes and their encoded enzymes have provided valuable tools for the genetic and biochemical dissection of interorganelle lipid transport processes in yeast. One such pathway involves the synthesis of phosphatidylserine (PtdSer) in the endoplasmic reticulum (ER), and its non‐vesicular transport to the site of phosphatidylserine decarboxylase2 (Psd2p) in membranes of the Golgi and endosomal sorting system. In this review, we summarize the identification and characterization of the yeast phosphatidylserine decarboxylases, and examine their role in studies of the transport‐dependent pathways of de novo synthesis of phosphatidylethanolamine (PtdEtn). The emerging picture of the Psd2p‐specific transport pathway is one in which the enzyme and its non‐catalytic N‐terminal domains act as a hub to nucleate the assembly of a multiprotein complex, which facilitates PtdSer transport at membrane contact sites between the ER and Golgi/endosome membranes. After transport to the catalytic site of Psd2p, PtdSer is decarboxylated to form PtdEtn, which is disseminated throughout the cell to support the structural and functional needs of multiple membranes.
Dermoscopic evaluation of skin in healthy cats
Authors: Zanna Giordana , Auriemma Edoardo , Arrighi Silvana , Attanasi Anna , Zini Eric , Scarampella Fabia
Published: October 2014

Background

Dermoscopy is a diagnostic tool that can reveal morphological structures not visible upon clinical examination.

Hypothesis/Objectives

To assess the usefulness and applicability of dermoscopy for the examination of healthy cat skin.

Animals

Twenty‐one domestic short‐haired cats from a feline rescue association.

Methods

Four regions (head, dorsal neck, sacral and abdominal regions) were examined with both a contact hand‐held nonpolarized light dermoscope at 10‐fold magnification and a videodermoscope at 70‐fold magnification. Findings were assessed using histological analysis of skin samples cut both longitudinally and transversely, set as the gold standard.

Results

With a hand‐held dermoscope at 10‐fold magnification, thick, straight primary hairs surrounded by multiple secondary hairs were observed. With a videodermoscope at 70‐fold magnification, hair shaft thickness was measured and the follicular openings and arrangement of vessels were clearly observed. Correspondence was observed between dermoscopic and histological results.

Conclusions and clinical importance

Dermoscopy represents a valid noninvasive and reproducible technique that could be helpful in clinical examination.
Physical Activity and Sedentary Behavior Among Adults 60 Years and Older: New York City Residents Compared With a National Sample
Authors: Evenson Kelly R. , Morland Kimberly B. , Wen Fang , Scanlin Kathleen
Published: October 2014

This study describes moderate to vigorous physical activity (MVPA) and sedentary behavior among New York City (NYC) residents 60 years and older and compared with national United States’ estimates. Adults aged 60 or older living in NYC (n = 760) were compared with similar aged adults from the National Health and Nutrition Examination Survey (NHANES; n = 2,451 adults). Both groups wore an ActiGraph accelerometer for one week. The NYC sample recorded 13.2, 23.8, and 37.8 mean min/day of MVPA and the NHANES sample recorded 10.6, 21.1, and 39.3, depending on the definition. Sedentary behavior averaged 9.6 hr/day for the NYC sample and 9.3 hr/day for the NHANES sample. The NYC sample spent a longer proportion of time in sedentary behavior and light activities, but more time in MVPA than the NHANES sample. Urbanicity may explain some of the differences between the two samples.
Relationships of Individual, Social, and Physical Environmental Factors With Older Adults’ Television Viewing Time
Authors: Van Cauwenberg Jelle , De Donder Liesbeth , Clarys Peter , De Bourdeaudhuij Ilse , Owen Neville , Dury Sarah , De Witte Nico , Buffel Tine , Verté Dominique , Deforche Benedicte
Published: October 2014

Sedentary behaviors (involving prolonged sitting) can be associated detrimentally with health outcomes. Older adults, the most sedentary age group, are especially at risk due to their high levels of television viewing time. This study examined individual, social, and physical environmental correlates of older adults’ television viewing. Data on daily television viewing time, plus individual, social, and physical environmental factors were collected from 50,986 noninstitutionalized older adults (≥ 65 years) in Flanders (Belgium). The results showed significant relationships between television viewing time and individual, social, and physical environmental factors. Subgroups at risk for high levels of television viewing were those who were functionally limited, less educated, widowed, and (semi)urban-dwelling older adults. Our findings illustrate a cross-sectional link between older adults’ television viewing time and social composition of their neighborhood, formal participation, access to alternative activities, and safety from crime.
Telephone-Based Motivational Interviewing to Promote Physical Activity and Stage of Change Progression in Older Adults
Authors: Lilienthal Kaitlin R. , Pignol Anna Evans , Holm Jeffrey E. , Vogeltanz-Holm Nancy
Published: October 2014

This study examined the efficacy of motivational interviewing (MI) for increasing physical activity in aging adults. Eighty-six participants aged 55 years and older were randomly assigned to receive either four weekly sessions of telephone-based MI for increasing physical activity, or a healthy activity living guide (information only control). Changes from baseline weekly caloric expenditure from physical activity, self-efficacy for physical activity, and stage of change for physical activity were compared across groups at posttreatment and six months follow-up. Results indicated that MI participants had higher weekly caloric expenditures from physical activity at posttreatment, but not at six months follow-up; higher self-efficacy for physical activity at six months follow-up; and demonstrated greater stage of change progression across assessments. These findings support the use of telephone-based MI for increasing physical activity in older adults in the short-term. Future studies will need to determine if follow-up booster sessions increase long-term efficacy.
The Association Between Objectively Measured Physical Activity and Academic Achievement in Dutch Adolescents: Findings From the GOALS Study
Authors: Van Dijk Martin L. , De Groot Renate H.M. , Savelberg Hans H.C.M. , Van Acker Frederik , Kirschner Paul A.
Published: October 2014

The main goal of this study was to investigate the association between objectively measured physical activity and academic achievement in adolescents. Students in Grades 7 and 9 (N = 255) were included. Overall, we found no significant dose–response association between physical activity and academic achievement. However, in Grade 7 total physical activity volume (Total PA) was negatively associated with academic achievement, while moderate-to-vigorous physical activity (MVPA) was negatively associated with both academic achievement and mathematics performance. In contrast, in Grade 9 both Total PA and MVPA were positively associated with mathematics performance. In addition, the overall association between MVPA and academic achievement followed an inverted U-shaped curve. Finally, Total PA was positively associated with executive functioning, while executive functioning in turn mediated the associations between Total PA and both academic achievement and mathematics performance. These results indicate that the association between physical activity and academic achievement in adolescents is complex and might be affected by academic year, physical activity volume and intensity, and school grade.
Moving and Academic Learning Are Not Antagonists: Acute Effects on Executive Function and Enjoyment
Authors: Vazou Spyridoula , Smiley-Oyen Ann
Published: October 2014

Classroom-based physical activity is a new approach aiming to improve both physical activity levels and academic achievement. This study investigated the acute effect of a 10-min bout of aerobic physical activity integrated with math practice, compared with a seated math practice, on executive function and enjoyment among normal-weight (n = 24) and overweight children (n = 11). Thirty-five typically developing prepubescent children (10.55 ± 0.74 years) completed a session of physical activity integrated with math practice and a seated math practice session in counterbalanced order. Results showed that following integrated physical activity, the response time in the Standard Flanker improved more than after seated practice. Among the overweight children, physical activity benefitted performance in the Standard Flanker by preventing the decline associated with seated practice. Children enjoyed the physical activity practice more than the seated practice. These findings suggest that integrating physical activity with academic instruction may be a realistic strategy for promoting physical activity because it may facilitate, not antagonize, executive function.
Facilitation of Hoffmann Reflexes of Ankle Muscles in Prone but Not Standing Positions by Focal Ankle-Joint Cooling
Authors: Kim Kyung-Min , Ingersoll Christopher D. , Hertel Jay
Published: October 2014

Context:

Focal ankle-joint cooling (FAJC) has been shown to increase Hoffmann (H) reflex amplitudes of select leg muscles while subjects lie prone, but it is unknown whether the neurophysiological cooling effects persist in standing.

Objective:

To assess the effects of FAJC on H-reflexes of the soleus and fibularis longus during 3 body positions (prone, bipedal, and unipedal stances) in individuals with and without chronic ankle instability (CAI).

Design:

Crossover.

Setting:

Laboratory.

Participants:

15 young adults with CAI (9 male, 6 female) and 15 healthy controls.

Intervention:

All subjects received both FAJC and sham treatments on separate days in a randomized order. FAJC was accomplished by applying a 1.5-L plastic bag filled with crushed ice to the ankle for 20 min. Sham treatment involved room-temperature candy corn.

Main Outcome Measures:

Maximum amplitudes of H-reflexes and motor (M) waves were recorded while subjects lay prone and then stood in quiet bipedal and unipedal stances before and immediately after each treatment. Primary outcome measures were Hmax:Mmax ratios for the soleus and fibularis longus. Three-factor (group × treatment condition × time) repeated-measures ANOVAs and Fisher LSD tests were performed for statistical analyses.

Results:

Significant interactions of treatment condition by time for prone Hmax:Mmax ratios were found in the soleus (P = .001) and fibularis longus (P = .003). In both muscles, prone Hmax:Mmax ratios moderately increased after FAJC but not after sham treatment. The CAI and healthy groups responded similarly to FAJC. In contrast, there were no significant interactions or main effects in the bipedal and unipedal stances in either muscle (P > .05).

Conclusions:

FAJC moderately increased H-reflex amplitudes of the soleus and fibularis longus while subjects were prone but not during bipedal or unipedal standing. These results were not different between groups with and without CAI.
Seeking out Majorana under the microscope
Authors: Lee Patrick A.
Published: October 2014

A chain of iron atoms on lead may reveal a signature of the elusive Majorana particle

[Also see Research Article by

Nadj-Perge
et al.

]
Phase I/II Randomized Double-Blind Study of the Safety and Immunogenicity of a Nonadjuvanted Vero Cell Culture-Derived Whole-Virus H9N2 Influenza Vaccine in Healthy Adults
Authors: Aichinger Gerald , Grohmann-Izay Barbara , van der Velden Maikel V. W. , Fritsch Sandor , Koska Manuela , Portsmouth Daniel , Hart Mary Kate , El-Amin Wael , Kistner Otfried , Barrett P. Noel
Published: October 2014

Studies on candidate pandemic vaccines against avian influenza viruses have focused on H5N1, but viruses of other subtypes, such as A/H9N2, are also considered to have pandemic potential. We investigated the safety and immunogenicity of two immunizations with one of five different antigen doses (ranging from 3.75 to 45 μg of hemagglutinin antigen) of a nonadjuvanted whole-virus G9 lineage H9N2 influenza virus vaccine in healthy adults aged 18 to 49 years. The antibody responses were measured by hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays. To investigate a hypothesis that previous exposure to H2N2 viruses in subjects born in or before 1968 might prime for more robust antibody responses to H9N2 vaccination than that in subjects born after 1968, apost hocage-stratified analysis of antibody responses was done. Both vaccinations in all dose groups were safe and well tolerated. No vaccine-related serious adverse events were reported, and the majority of the adverse reactions were rated as mild. The rates of injection site reactions were lower in the 3.75-μg- and 7.5-μg-dose groups than those in the higher-dose groups; the rates of systemic reactions were similar across all dose groups. The seroprotection rates among the different dose groups 21 days after the second immunization ranged from 52.8% to 88.9% as measured by HI assay, from 88.7% to 98.1% or 82.7% to 96.2% as measured by MN assay (MN titer cutoffs, 1:40 and 1:80, respectively), and from 94.2% to 100% as measured by SRH assay. Higher antibody responses were not induced in subjects born in or before 1968. These data indicate that a nonadjuvanted whole-virus H9N2 vaccine is well tolerated and immunogenic in healthy adults. (This study has been registered atClinicalTrials.govunder registration no. NCT01320696.)