bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcompartmental reversal of single fibre hyperexcitability in juxtaparanodal Kv1.1‐deficient vagus nerve axons by activation of nodal KCNQ channels
Authors: Glasscock Edward , Qian Jing , Kole Matthew J. , Noebels Jeffrey L. 
Published: May 2012

Key points
Voltage‐gated Kv1.1 potassium channels cluster at juxtaparanodes of myelinated axons in the vagus nerve, which provides parasympathetic innervation to the heart.
Kcna1 knockout mice lacking Kv1.1 channels exhibit frequent atrioventricular cardiac conduction blocks that are abolished by atropine, suggestive of a vagal mechanism.
Electrophysiological analysis of single myelinated axons from wild‐type and Kv1.1‐deficient mouse vagus nerves revealed that the absence of Kv1.1 channels rendered large myelinated vagal axons far more susceptible to spontaneous ectopic firing in the presence of 4‐aminopyridine.
KCNQ2 potassium channels are present within vagal nodes of Ranvier and their activation with flupirtine rescued single axon hyperexcitability mediated by juxtaparanodal Kv1.1‐deficiency.
These results demonstrate a functional synergy between nodal and extranodal K+ channels and implicate KCNQ channels as potential targets for Kv1‐related peripheral nerve hyperexcitability.
Abstract  Kv1.1 channels cluster at juxtaparanodes of myelinated axons in the vagus nerve, the primary conduit for parasympathetic innervation of the heart. Kcna1‐null mice lacking these channels exhibit neurocardiac dysfunction manifested by atropine‐sensitive atrioventricular conduction blocks and bradycardia that may culminate in sudden death. To evaluate whether loss of Kv1.1 channels alters electrogenic properties within the nerve, we compared the intrinsic excitability of single myelinated A‐ and Aδ‐axons from excised cervical vagus nerves of young adult Kcna1‐null mice and age‐matched, wild‐type littermate controls. Although action potential shapes and relative refractory periods varied little between genotypes, Kv1.1‐deficient large myelinated A‐axons showed a fivefold increase in susceptibility to 4‐aminopyridine (4‐AP)‐induced spontaneous ectopic firing. Since the repolarizing currents of juxtaparanodal Kv1 channels and nodal KCNQ potassium channels both act to dampen repetitive activity, we examined whether augmenting nodal KCNQ activation could compensate for Kv1.1 loss and reverse the spontaneous hyperexcitability in Kv1.1‐deficient A‐axons. Application of the selective KCNQ opener flupirtine raised A‐axon firing threshold while profoundly suppressing 4‐AP‐induced spontaneous firing, demonstrating a functional synergy between the two compartments. We conclude that juxtaparanodal Kv1.1‐deficiency causes intrinsic hyperexcitability in large myelinated axons in vagus nerve which could contribute to autonomic dysfunction in Kcna1‐null mice, and that KCNQ openers reveal a transcompartmental synergy between Kv1 and KCNQ channels in regulating axonal excitability.
Comparison of topogram‐based body size indices for CT dose consideration and scan protocol optimization
Authors: Li Baojun , Behrman Richard H. , Norbash Alexander M. 
Published: May 2012

Purpose:To retrospectively compare different topogram‐based patient body size indices and to determine the optimal topogram‐based body size index as a basis for body computed tomography (CT) dose consideration and scan protocol optimization.Methods:Forty‐three routine thorax and abdomen CT scans are studied retrospectively, with patient ages ranging from 18 to 67 yr. The individual patient's water‐equivalent diameter (Dw) of the scanned body region is computed from CT DICOM images as the “gold standard,” after first converting from Hounsfield units values to μa values, where μ is the normalized tissue attenuation coefficient and a is the area per pixel. Four topogram‐based body size indices [average diameter , girth (G), topogram projection area (Etopo), and improved topogram projection area ] are computed and correlated with Dw using linear regression analysis. Specifically, is calculated by averaging the coronal and sagittal diameters; G is computed by modeling the patient's cross‐section as an ellipse; Etopo is the product of the mean topogram pixel value and the width of the scanned body region; and incorporates Etopo with correction of patient miscentering and water attenuation coefficient. The accuracy of these four approaches for estimation of Dw is assessed using linear regression models. Results are given in terms of 95% confidence intervals (CIs).Results:Regression analysis results in four different linear models. The standard error (95% CI) for estimation ofDw from and G was ±2.8 and ±3.1 cm, respectively (p = 0.297). The standard error for estimation of Dw from Etopo was significantly less than that from (±2.1 cm, p < 0.01). The standard error for estimation of Dw from was ±1.3 cm, significantly less than that from Etopo (p < 0.01).Conclusions:Among the four topogram‐based patient body indices, is the most accurate for estimation of individual x‐ray attenuation of the scanned body region. Thus, is an optimal topogram‐based patient body size index that is relevant for determining the proper CT dose level for individual patients.
Socio-demographic and other patient characteristics associated with time between colonoscopy and surgery, and choice of treatment centre for colorectal cancer: a retrospective cohort study
Authors: Goldsbury David , Harris Mark Fort , Pascoe Shane , Olver Ian , Barton Michael , Spigelman Allan , O'Connell Dianne 
Published: May 2012

ObjectivesTo investigate key patient clinical and demographic characteristics associated with time between colonoscopy and surgery, and choice of treatment centre for colorectal cancer (CRC) patients. This will add to the little published research examining the pathway following CRC diagnosis and prior to surgery.DesignRetrospective cohort analysis of linked data.SettingA population-based sample of people diagnosed August 2004 to December 2007 in New South Wales, Australia.Participants569 CRC patients, of whom 407 (72%, 95% CI 68% to 75%) had colonoscopy followed by surgery.Primary outcome measuresTime between colonoscopy and surgery, and whether the surgery took place in a specialist cancer centre.ResultsAmong the 407 eligible patients analysed, the median time from colonoscopy to surgery was 19 days (IQR 12–29 days). After adjusting for key demographic and clinical characteristics such as age and disease stage, the time was longer for rectal cancer patients and those reporting fair/poor health, although differences in medians were <5 days. 24% (95% CI 20% to 28%) had surgery in a specialist cancer centre, which was more common among people resident in metropolitan areas (37% vs 14% for others, adjusted p=0.001) and those without private health insurance (30% vs 21% for others, adjusted p=0.03).ConclusionsThere do not appear to be systemic issues affecting time from colonoscopy to surgery related to patients' socio-demographic characteristics. However, patients with private insurance and those living in rural areas may be less likely to receive optimal specialist treatment. A more systematic approach might be needed to ensure cancer patients are treated in specialist cancer centres, particularly patients requiring more specialised treatment.
A qualitative approach using the integrative model of behaviour change to identify intervention strategies to increase optimal child restraint practices among culturally and linguistically diverse families in New South Wales
Authors: Brown Julie , Burton Danielle , Nikolin Stevan , Crooks Philippa Jane , Hatfield Julie , Bilston Lynne E 
Published: May 2012

ObjectivesTo qualitatively explore barriers to optimal child restraint use using the integrative behaviour change model in culturally and linguistically diverse (CALD) communities in New South Wales (NSW), Australia.MethodsA semi-structured discussion was used to conduct 11 language specific focus groups in Arabic, Assyrian, Cantonese, Mandarin, Vietnamese and Turkish. Translated transcriptions were analysed using the major concepts of the integrative behaviour change model.ResultsRestraint use intent among CALD community carers is related to perceived safety of their children and complying with the law. While most participants appreciated the safety benefits of correct and appropriate use, a minority did not. Child restraint legislation may positively influence social norms, and enforcement appears to increase parental self-efficacy. However, concerns over child comfort may negatively influence both norms and self-efficacy. There are clear deficits in knowledge that may act as barriers as well as confusion over best practice in safely transporting children. Large family size, vehicle size and cost appear to be real environmental constraints in CALD communities.ConclusionDeterminants of intent and deficits in knowledge in this diverse range of CALD communities in NSW Australia are similar to those reported in other qualitative studies regardless of the population studied. This indicates that key messages should be the same regardless of the target population. However, for CALD communities there is a specific need to ensure access to detailed information through appropriate delivery strategies and languages. Furthermore, practical constraints such as cost of restraints and family size may be particularly important in CALD communities.
Differences in incidence of injury between rural and urban children in Canada and the USA: a systematic review
Authors: Kim Kyungsu , Ozegovic Dejan , Voaklander Donald C 
Published: May 2012

ObjectiveThe goal of the study was to systematically review available evidence regarding differences in injury incidence between rural and urban paediatric populations in Canada and the USA.Data sourceEight electronic databases, institutional websites and reference lists of relevant studies including published and unpublished reports.Selection criteriaPopulation-based observational studies or surveys published from 1970 to February 2011 that compared injury incidence or injury-related healthcare outcomes between rural and urban children (<18) living in Canada or the USA.Data collection and analysisTwo reviewers independently applied selection criteria and assessed methodological quality of studies. Data were extracted by one author and independently verified by the second author. Injury rate ratios for rural and urban children were extracted or calculated. Data were synthesised descriptively due to substantial heterogeneity among studies.ResultsA total of 41 studies were included for this review (seven surveys and 34 studies using administrative health databases). Internal validity of included studies was moderate. Rural children were at higher risk of overall injury, motor vehicle crash injury and suicide, whereas urban children in the USA experienced higher rates of firearm-related homicides. Greater rural–urban injury disparities were likely to be found between more extreme rural and urban areas. In particular, children in remote rural areas are at increased risk of severe injuries than urban counterparts. Overall, healthcare costs per child for injury were higher for rural children.ConclusionThese findings indicate the need of developing geographic area-specific injury-prevention strategies. Future research is required to investigate rural–urban disparity for less-studied injuries and related health outcomes (eg, disability).Systematic review registration numberCRD42011001244 (PROSPERO 2011).
The Development of Empathy and Group Analysis
Authors: Yogev Herzel 
Published: May 2012

Empathy is the ability to understand and share the feelings of another. Kohut (1984) defined empathy as the capacity to think and feel the other’s internal world. Empathy serves two clinical objectives: (1) Comprehension, by which the analyst perceives what the patient is experiencing at a particular moment and communicates in a verbal or non-verbal manner that the patient’s experience is understood, and (2) Explication, in which the analyst uses this comprehension, accumulated over time, to explain the meaning of the patient’s experience, connecting it with past experiences. In the current article, a continuum theory of empathy is offered, whereby empathy may be viewed as composed of three continuums: the resonance continuum, the comprehension continuum and the identification of needs continuum. These elements are not linear but in interaction with each other and will be detailed below. It is further proposed that empathy exists in two dimensions: a non-verbal/facial dimension that is timeless, existing only in the here and now, and a verbal dimension that is necessarily in time and involves communication.
Home Versus Hospital Mortality From Cancer in México (1999-2009)
Authors: Castillo-Guzmán Sandra , Palacios-Ríos Dionicio , Nava-Obregón Teresa Adriana , Torres-Pérez Juan Francisco , González-Santiago Omar 
Published: May 2012

Objective: To analyze the place of death from cancer in México from 1999 to 2009 and find the associated factors. Methods: We collected data on mortality by cancer from the national database including age, gender, area of residence, level of education, place of death, and type of cancer. Results: The proportion of deaths at home and hospital was 55.67% and 39%, respectively. Factors associated with home deaths were old age, female gender, rural area of residence, and lack of formal education. There was a short but significant decrease in home deaths for cervical cancer and leukemia. Conclusions: In México, mortality in home is greater than in hospital for patients with cancer. Our results have important implications for palliative care professionals and health services of México.
Elastic modulus and Poisson’s ratio determination of micro-lattice cellular structures by analytical, numerical and homogenisation methods
Authors: Ptochos Evangelos , Labeas George 
Published: May 2012

The mechanical properties of micro-lattice structures made of interconnected metallic struts are calculated analytically, in order to derive their elastic modulus and Poisson’s ratio in the three Cartesian directions. The geometry of the investigated unit cell is a body centered cuboid, which is a more generic case of the well-known body centered cubic geometry. The Bernoulli–Euler and Timoshenko beam theories are used for the analytical solution of the unit cell response under complex loading. The derived elastic constants are compared to the relative numerical ones. The influence of geometrical parameters on the stiffness coefficients of the cellular structure is parametrically determined. The derived elasticity matrices are introduced in a homogenised numerical model of the core and its results are compared to a numerical model with explicit representation of the core geometry indicating an excellent accuracy, while the solution time is considerably reduced.
Anatomically versus biologically unifocal prostate cancer: a pathological evaluation in the context of focal therapy
Authors: Karavitakis Markos , Ahmed Hashim U. , Abel Paul D. , Hazell Steven , Winkler Mathias H. 
Published: May 2012

Objectives: Since tumor focality in prostate cancer continues to be considered a major limitation for focal prostate therapy, in this study we attempted to compare the pathological features and the proportion of patients with anatomically unifocal versus biologically unifocal tumors (i.e. multifocal prostate cancer in which the secondary nonindex elements are small, low grade and clinically insignificant) who were suitable for focal therapy. Methods: Ninety-five consecutive whole mount laparoscopic radical prostatectomy samples underwent pathological assessment (from January 2007 to November 2009). Tumor focality, laterality, Gleason score and volume of individual foci, total tumor volume, pathological stage and surgical margin status were assessed. The index lesion was defined as the largest by volume. Patients suitable for focal ablation were defined as having tumors that were unifocal, organ confined, with a Gleason score (GS) up to 7 prostate cancer, or multifocal, organ confined, GS up to 7 prostate cancer, with one large index lesion and the remaining foci demonstrating features of clinically insignificant disease (total tumor volume of all secondary foci ≤0.5 cm3 with GS ≤ 6). Results: Patients with biologically unifocal cancer had significantly lower total tumor volume (3.26 versus 7.28 cm3; p < 0.001), index lesion volume (2.9 versus 7.16 cm3; p < 0.001), rates of seminal vesicle invasion (4% versus 34%; p < 0.001), rates of positive surgical margins (22.4% versus 52.1%; p < 0.001) and rates of 4+3 GS tumors (10.2% versus 29.1%; p = 0.018). The proportion of patients suitable for focal therapy was higher in the biologically unifocal versus anatomically unifocal cancer group, although without reaching statistical significance (65.3% versus 45.8%; p = 0.11). Conclusions: Patients with biologically unifocal tumors have better pathological outcome than those with anatomically unifocal disease. At present the assumption that multifocality should a priori exclude patients from any organ-preserving prostate cancer treatment is only theoretical and needs to be validated by future clinical trials since there are a large proportion of patients with multifocal disease apparently suitable for focal prostate therapy.
Identification of binding pockets in protein structures using a knowledge-based potential derived from local structural similarities
Authors: Bianchi Valerio , Gherardini Pier Federico , Helmer-Citterich Manuela , Ausiello Gabriele 
Published: May 2012

Abstract

Background
The identification of ligand binding sites is a key task in the annotation of proteins with known structure but uncharacterized function. Here we describe a knowledge-based method exploiting the observation that unrelated binding sites share small structural motifs that bind the same chemical fragments irrespective of the nature of the ligand as a whole.

Results
PDBinder compares a query protein against a library of binding and non-binding protein surface regions derived from the PDB. The results of the comparison are used to derive a propensity value for each residue which is correlated with the likelihood that the residue is part of a ligand binding site. The method was applied to two different problems: i) the prediction of ligand binding residues and ii) the identification of which surface cleft harbours the binding site. In both cases PDBinder performed consistently better than existing methods.
PDBinder has been trained on a non-redundant set of 1356 high-quality protein-ligand complexes and tested on a set of 239 holo and apo complex pairs. We obtained an MCC of 0.313 on the holo set with a PPV of 0.413 while on the apo set we achieved an MCC of 0.271 and a PPV of 0.372.

Conclusions
We show that PDBinder performs better than existing methods. The good performance on the unbound proteins is extremely important for real-world applications where the location of the binding site is unknown. Moreover, since our approach is orthogonal to those used in other programs, the PDBinder propensity value can be integrated in other algorithms further increasing the final performance.
Sex and Genes, Part 1: Sexuality and Down, Prader–Willi, and Williams Syndromes
Authors: Watson Shelley Lynn , Richards Deborah A. , Miodrag Nancy , Fedoroff J. Paul 
Published: May 2012

AbstractSpecific genetic syndromes affect individuals' sexual development, experiences, and fertility. Individuals with specific syndromes can also display inappropriate sexual behavior resulting from vulnerabilities presented by their genetic makeup. Using clinical case studies, we discuss the specific impact that Down, Prader–Willi, and Williams syndromes can have on sexual development and behavior. Applying a biopsychosocial approach, we present the primary sexual effects, such as delayed sexual development and infertility. These genetic syndromes are also associated with challenges that are not specifically sexual in nature but that affect sexual expression, such as self-injury, mental health issues, or epilepsy. Medication side effects are also discussed. We conclude with treatment recommendations for individuals with sexual challenges, considering the unique effects of these three syndromes on sexuality.
Cervical and Breast Cancer–screening Knowledge of Women with Developmental Disabilities
Authors: Parish Susan L. , Swaine Jamie G. , Luken Karen , Rose Roderick A. , Dababnah Sarah 
Published: May 2012

AbstractWomen with developmental disabilities are significantly less likely than women without disabilities to receive cervical and breast cancer screening according to clinical guidelines. The reasons for this gap are not understood. The present study examined the extent of women's knowledge about cervical and breast cancer screening, with the intention of informing the development and testing of interventions to increase cervical and breast cancer screening rates for these women. In a sample of 202 community-dwelling women with developmental disabilities, most women had little knowledge of cervical and breast cancer screening. Women who were living at home with family caregivers had the most limited understanding of cervical and breast cancer screening. Policy and practice implications are discussed.
Survival and neonatal outcome after fetoscopic guided laser occlusion (FLOC) of twin-to-twin transfusion syndrome (TTTS) in Sweden
Authors: Halvorsen Cecilia Pegelow , Ek Sverker , Dellgren Annika , Grunewald Charlotta , Kublickas Marius , Westgren Magnus , Norman Mikael 
Published: May 2012

Abstract

Aim: To determine infant survival and neonatal outcome after fetoscopic laser treatment of twin-to-twin transfusion syndrome (TTTS).

Results: In 53/71(75%) laser-treated TTTS cases, at least one twin was liveborn and in 42/71(59%) cases at least one twin survived infancy. Fetal survival did not differ between donors [41/71(58%)] and recipients [46/71(65%), P=0.36]. Among liveborns, infant survival was 29/41(71%) in donors and 36/46(78%) in recipients (P=0.12). Infant survival did not correlate to maternal characteristics (age, BMI, smoking or parity), gestational age at treatment or severity of TTTS (Quintero stage). No TTTS infant born before 25 weeks of gestation survived the first week. Among the 87 infant survivors, 26 (30%) had an Apgar score <7 at 5 min, 47 (54%) developed respiratory distress syndrome, 10 (11%) showed signs of severe brain damage, nine (10%) renal failure, eight (9%) bronchopulmonary dysplasia, and five (6%) infants developed retinopathy of prematurity ≥stage 3. There was no significant difference in neonatal morbidity between recipients and donors.

Conclusions: Fetal survival after laser treatment was comparable to that reported by other international centers. There was no significant difference in survival or neonatal morbidity between donors and recipients. Major neonatal morbidity was common, and combined with extremely preterm delivery the prognosis of TTTS is poor.