bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractAimThe 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.MethodSamples 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.ResultsFifty‐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.ConclusionAnal 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

AbstractPyoderma 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

Summary

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.
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

SummaryHuman 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

BackgroundIt 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.MethodsThe 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.ResultsIt 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).ConclusionsThe 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

OBJECTIVESTo describe the development of a facial expression tool differentiating pain‐free cats from those in acute pain.METHODSObservers 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.RESULTSObservers (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 SIGNIFICANCEInitial 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

ABSTRACT

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 &lt; 0.001), and improvements in sexual arousal (P &lt; 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

AbstractBackgroundMaternal 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.MethodsBy 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.ResultsA 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]).ConclusionsWe 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

AbstractIgE–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

AbstractWe 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

AbstractObjectiveInvasive 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.MethodsWe 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.ResultsThere 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.ConclusionThe 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.
Dermoscopic evaluation of skin in healthy cats
Authors: Zanna Giordana , Auriemma Edoardo , Arrighi Silvana , Attanasi Anna , Zini Eric , Scarampella Fabia 
Published: October 2014

BackgroundDermoscopy is a diagnostic tool that can reveal morphological structures not visible upon clinical examination.Hypothesis/ObjectivesTo assess the usefulness and applicability of dermoscopy for the examination of healthy cat skin.AnimalsTwenty‐one domestic short‐haired cats from a feline rescue association.MethodsFour 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.ResultsWith 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 importanceDermoscopy represents a valid noninvasive and reproducible technique that could be helpful in clinical examination.