Photosensitized Hydrogen Evolution on a Floating Electrocatalyst Coupled to Electrochemical Recycling.
Photoexcited protonated tetrathiafulvalene (HTTF+) was found to act as a photosensitizer, injecting electrons into Pt microparticles (floating electrocatalysts) to produce H2 and TTF•+ in acidic acetonitrile. In addition, TTF•+ was electrochemically reduced back to TTF on a carbon electrode, to be further protonated to continuously produce H2 photochemically. The onset potential for the electrochemical recycling of TTF•+ on carbon was set at a potential 500 mV more positive than the potential required for the direct reduction of protons. HTTF+ showed no signs of decomposition after 51 h of continuous recycling and photoinduced production of H2, proving stability and reversibility.


Telephone-Based Progressive Tinnitus Management for Persons With and Without Traumatic Brain Injury: A Randomized Controlled Trial.
This randomized controlled trial evaluated the efficacy of delivering coping skills education from Progressive Tinnitus Management (PTM) by telephone (Tele-PTM). The trial followed a previous pilot study that showed positive results for Tele-PTM. Participants included individuals with bothersome tinnitus (N = 205) located anywhere within the United States. A special emphasis was given to including individuals who had experienced one or more traumatic brain injuries (TBIs). Participants were randomized to either Tele-PTM intervention or 6-month wait-list control (WLC). The Tele-PTM intervention involved five telephone appointments-two led by an audiologist (teaching how to use therapeutic sound) and three by a psychologist (teaching coping skills derived from cognitive-behavioral therapy). It was hypothesized that Tele-PTM would be more effective than WLC in reducing functional effects of tinnitus as measured with the Tinnitus Functional Index. Additional outcome measures included the Self-Efficacy for Managing Reactions to Tinnitus questionnaire and the Hospital Anxiety and Depression Scale. The effect of Tele-PTM on outcomes was estimated using linear mixed models. Overall results showed convincingly that the Tele-PTM group had significantly better outcomes than the WLC group. These results were consistent across all outcome measures, indicating not only a reduction of tinnitus functional distress but also increased self-efficacy. Improvements in measures of anxiety and depression were also observed. Tele-PTM participants in all TBI categories showed significant improvement. Results provide strong support for use of Tele-PTM methodology for persons with bothersome tinnitus, regardless of whether the person also has TBI symptoms. The effect size for Tele-PTM was high for the primary outcome measure, the Tinnitus Functional Index, and all other outcome measures showed significant improvement. Combined with our previous pilot study, the Tele-PTM method is validated for potential nationwide provision of tinnitus services.


Venous impulse foot pumps: should graduated compression stockings be used?
It is not known whether the effect of Foot Pumps (Novamedix, Andover, UK) is enhanced by simultaneous use of graduated compression stockings (by controlling calf compliance) or hindered (by restricting preload). To address this question, we studied 20 healthy volunteers with duplex ultrasound. The peak velocity in the popliteal vein was measured at rest with the legs flat, foot-up, and foot-down, then it was measured when the AV Impulse Foot Pump was activated. These measurements each were performed with and without graduated compression stockings. In each leg position, the use of simultaneous graduated compression stockings reduced the peak velocity. On physiologic grounds, graduated stockings should not be used simultaneously with Foot Pumps.


A trial of complement inhibition in a patient with cryoglobulin-induced glomerulonephritis.
Cryoglobulinemia induces an immune complex-mediated glomerulonephritis that is characterized by the presence of large immune deposits, including complement C3 and C5b-9, marked macrophage influx and mesangial cell proliferation. The precise role of complement in cryoglobulin-induced glomerulonephritis in humans remains unclear, whereas in mice there has been evidence that complement activation might be a central factor favoring glomerular inflammation, particularly by the recruitment of neutrophils. We report on an exceptional case of cryoglobulin-induced glomerulonephritis in a patient with mixed essential cryoglobulinemia type II. The clinical features included relapsing proteinuria and renal function impairment that were controlled by plasmapheresis. Complement was low in plasma and two renal biopsies at 1-year interval showed prominent immunoglobulin and complement deposits, with unusual high numbers of neutrophils. In a 1-patient clinical trial, we tested whether the monoclonal anti-C5 antibody eculizumab would be sufficient to control renal function at the time of a relapse. Although during the initial weeks renal function was stabilized, slow increase in creatinine could not be controlled by this treatment, so that plasmapheresis was reinstituted. This result suggests that despite evidence for a role of complement in enhancing renal damage in this patient, other inflammatory processes dominated.


A learning-based similarity fusion and filtering approach for biomedical image retrieval using SVM classification and relevance feedback.
This paper presents a classification-driven biomedical image retrieval framework based on image filtering and similarity fusion by employing supervised learning techniques. In this framework, the probabilistic outputs of a multiclass support vector machine (SVM) classifier as category prediction of query and database images are exploited at first to filter out irrelevant images, thereby reducing the search space for similarity matching. Images are classified at a global level according to their modalities based on different low-level, concept, and keypoint-based features. It is difficult to find a unique feature to compare images effectively for all types of queries. Hence, a query-specific adaptive linear combination of similarity matching approach is proposed by relying on the image classification and feedback information from users. Based on the prediction of a query image category, individual precomputed weights of different features are adjusted online. The prediction of the classifier may be inaccurate in some cases and a user might have a different semantic interpretation about retrieved images. Hence, the weights are finally determined by considering both precision and rank order information of each individual feature representation by considering top retrieved relevant images as judged by the users. As a result, the system can adapt itself to individual searches to produce query-specific results. Experiment is performed in a diverse collection of 5 000 biomedical images of different modalities, body parts, and orientations. It demonstrates the efficiency (about half computation time compared to search on entire collection) and effectiveness (about 10%-15% improvement in precision at each recall level) of the retrieval approach.


Optical estimation of absolute membrane potential using fluorescence lifetime imaging.
All cells maintain ionic gradients across their plasma membranes, producing transmembrane potentials (Vmem). Mounting evidence suggests a relationship between resting Vmem and the physiology of non-excitable cells with implications in diverse areas, including cancer, cellular differentiation, and body patterning. A lack of non-invasive methods to record absolute Vmem limits our understanding of this fundamental signal. To address this need, we developed a fluorescence lifetime-based approach (VF-FLIM) to visualize and optically quantify Vmem with single-cell resolution in mammalian cell culture. Using VF-FLIM, we report Vmem distributions over thousands of cells, a 100-fold improvement relative to electrophysiological approaches. In human carcinoma cells, we visualize the voltage response to growth factor stimulation, stably recording a 10-15 mV hyperpolarization over minutes. Using pharmacological inhibitors, we identify the source of the hyperpolarization as the Ca2+-activated K+ channel KCa3.1. The ability to optically quantify absolute Vmem with cellular resolution will allow a re-examination of its signaling roles.


Detection of Babesia Sp. EU1 and members of spotted fever group rickettsiae in ticks collected from migratory birds at Curonian Spit, North-Western Russia.
To reveal the prevalence of spotted fever group (SFG) rickettsiae and Babesia sp. in Ixodes ricinus (L.) ticks from migratory birds, 236 specimens represented 8 species of Passeriformes and were collected at Curonian Spit in Kaliningrad enclave of North-Western Russia. The ticks (total 126) being detached from four bird species, Turdus philomelos, Fringilla coelebs, Parus major, and Sturnus vulgaris, were investigated by PCR using the primers Rp CS.877p/Rp CS.1258n for the detection of Rickettsia and BJ1/BN2 for Babesia spp. Babesia spp. were detected in 2 of 126 (1.6%) ticks. The partial sequence of 18S rDNA had 100% similarity to human pathogenic Babesia sp. EU1. The SFG rickettsiae were detected in 19 of 126 (15.1%) ticks collected from the above-mentioned bird species. BLAST analysis of SFG rickettsia gltA assigned sequences to human pathogenic Rickettsia helvetica (10.3%), Rickettsia monacensis (3.9%), and Rickettsia japonica (0.8%) with 98%-100% sequence similarity. The SFG rickettsiae and Babesia sp. EU1 in ticks collected from the passerines in Russia were detected for the first time. The survey indicates that migratory birds may become a reservoir for Babesia spp. and SFG rickettsiae. Future investigations need to characterize the role of birds in the epidemiology of these human pathogens in the region.


Survival after abdominal aortic aneurysm repair is affected by socioeconomic status.
The association between socioeconomic status (SES) and outcome after abdominal aortic aneurysm (AAA) repair is largely unknown. This study aimed to determine the influence of SES on postoperative survival after AAA repair. Patients undergoing surgical treatment of AAA at a tertiary referral center between January 1993 and July 2013 were retrospectively collected. Thirty-day postoperative mortality and long-term mortality were documented through medical record review and the Michigan Social Security Death Index. SES was quantified using the neighborhood deprivation index (NDI), which is a standardized and reproducible index used in research that summarizes eight domains of socioeconomic deprivation and is based on census tracts derived from patients' individual addresses. The association between SES and survival was studied by univariable and multivariable Cox regression analysis. A total of 767 patients were included. The mean age was 73 years; 80% were male, 77% were white, and 20% were African American. There was no difference in SES of patients who underwent open vs endovascular repair of AAA (P = .489). The average NDI was -0.18 (minimum, -1.47; maximum, 2.35). After adjusting for the variables that were significant on univariable analysis (age, medical comorbidities, length of stay, and year of surgery), the association between NDI and long-term mortality was significant (P = .021; hazard ratio, 1.21 [1.05-1.37]). Long-term mortality after AAA repair is associated with SES. Further studies are required to assess which risk factors (behavioral, psychosocial) are responsible for this decreased long-term survival in low SES patients after AAA repair.


Model for an incoherent optical neuron that subtracts.
An incoherent optical neuron is proposed that subtracts inhibitory inputs from excitatory inputs optically by utilizing two separate device responses. Functionally it accommodates positive and negative weights, excitatory and inhibitory inputs, and nonnegative neuron outputs, and it can be used in a variety of neural network models. An extension is given to include bipolar neuron outputs in the case of fully connected networks.


The smartphone brain scanner: a portable real-time neuroimaging system.
Combining low-cost wireless EEG sensors with smartphones offers novel opportunities for mobile brain imaging in an everyday context. Here we present the technical details and validation of a framework for building multi-platform, portable EEG applications with real-time 3D source reconstruction. The system--Smartphone Brain Scanner--combines an off-the-shelf neuroheadset or EEG cap with a smartphone or tablet, and as such represents the first fully portable system for real-time 3D EEG imaging. We discuss the benefits and challenges, including technical limitations as well as details of real-time reconstruction of 3D images of brain activity. We present examples of brain activity captured in a simple experiment involving imagined finger tapping, which shows that the acquired signal in a relevant brain region is similar to that obtained with standard EEG lab equipment. Although the quality of the signal in a mobile solution using an off-the-shelf consumer neuroheadset is lower than the signal obtained using high-density standard EEG equipment, we propose mobile application development may offset the disadvantages and provide completely new opportunities for neuroimaging in natural settings.


Shortening velocity and myosin heavy- and light-chain isoform mRNA in rabbit arterial smooth muscle cells.
In smooth muscle cells (SMCs) isolated from rabbit carotid, femoral, and saphenous arteries, relative myosin isoform mRNA levels were measured in RT-PCR to test for correlations between myosin isoform expression and unloaded shortening velocity. Unloaded shortening velocity and percent smooth muscle myosin heavy chain 2 (SM2) and myosin light chain 17b (MLC(17b)) mRNA levels were not significantly different in single SMCs isolated from the luminal and adluminal regions of the carotid media. Saphenous artery SMCs shortened significantly faster (P < 0.05) than femoral SMCs and had more SM2 mRNA (P < 0.05) than carotid SMCs and less MLC(17b) mRNA (P < 0.001) and higher tissue levels of SMB mRNA (P < 0.05) than carotid and femoral SMCs. No correlations were found between percent SM2 and percent MLC(17b) mRNA levels and unloaded shortening velocity in SMCs from these arteries. We have previously shown that myosin heavy chain (MHC) SM1/SM2 and SMA/SMB and MLC(17a)/MLC(17b) isoform mRNA levels correlate with protein expression for these isoforms in rabbit smooth muscle tissues. Thus we interpret these results to suggest that 1) SMC myosin isoform expression and unloaded shortening velocity do not vary with distance from the lumen of the carotid artery but do vary in arteries located longitudinally within the arterial tree, 2) MHC SM1/SM2 and/or MLC(17a)/MLC(17b) isoform expression does not correlate with unloaded shortening velocity, and 3) intracellular expression of the MHC SM1/SM2 and MLC(17a)/MLC(17b) isoforms is not coregulated.


The human microbiome.
Until recently, human microbiology was based on the identification of single microbes, such as bacteria, fungi and viruses, frequently isolated from patients with acute or chronic infections. Novel culture-independent molecular biochemical analyses (genomics, transcriptomics, proteomics, metabolomics) allow today to detect and classify the diverse microorganisms in a given ecosystem (microbiota), such as the gastrointestinal tract, the skin, the airway system, the urogenital tract and others, and to assess all genomes in these ecosystems (microbiome) as well as their gene products. These analyses revealed that each individual has its own microbiota that plays a role in health and disease. In addition, they greatly contributed to the recent advances in the understanding of the pathogenesis of a wide range of human diseases. It is to be expected that these new insights will translate into diagnostic, therapeutic and preventive measures in the context of personalized/precision medicine.


Acupuncture for the treatment of chronic painful peripheral diabetic neuropathy: a long-term study.
Forty-six diabetic patients with chronic painful peripheral neuropathy were treated with acupuncture analgesia to determine its efficacy and long-term effectiveness. Twenty-nine (63%) patients were already on standard medical treatment for painful neuropathy. Patients initially received up to six courses of classical acupuncture analgesia over a period of 10 weeks, using traditional Chinese Medicine acupuncture points. Forty-four patients completed the study with 34 (77%) showing significant improvement in their primary and/or secondary symptoms (P < 0.01). These patients were followed up for a period of 18-52 weeks with 67% were able to stop or reduce their medications significantly. During the follow-up period only eight (24%) patients required further acupuncture treatment. Although 34 (77%) patients noted significant improvement in their symptoms, only seven (21%) noted that their symptoms cleared completely. All the patients but one finished the full course of acupuncture treatment without reported or observed side effects. There were no significant changes either in the peripheral neurological examination scores, VPT or in HbA1c during the course of treatment. These data suggest that acupuncture is a safe and effective therapy for the long-term management of painful diabetic neuropathy, although its mechanism of action remains speculative.


Relationship of depression screening in cardiometabolic disease with vascular events and mortality: findings from a large primary care cohort with 4 years follow-up.
Benefits of routine depression screening for cardiometabolic disease patients remain unclear. We examined the association between depression screening and all-cause mortality and vascular events in cardiometabolic disease patients. 125 143 patients with cardiometabolic diseases (coronary heart disease, diabetes or previous stroke) in the UK participated in primary care chronic disease management in 2008/09, which included depression screening using the Hospital Anxiety and Depression Score. 10 670 receiving depression treatment exempted, 35 537 screened, while 78 936 not screened. We studied all-cause mortality and vascular events at 4 years, by electronic data linkage of 124 414 patients (99.4%) on primary care registers to hospital discharge and mortality records and used Cox proportional hazards on matched data using propensity score. Mean age for the screened and not screened population was 69 years (standard deviation-SD 11.9) and 67 years (SD 14.3), respectively; 58% (20 658) of the screened population were men and 65.3% (22 726) were socioeconomically deprived, compared with 54.2% (42 727) and 67.4% (51 686), respectively, in the not screened population. The screened population had lower all-cause mortality (Hazard Ratio-HR 0.89) and vascular events (HR 0.85) in the matched data of N = 21 893 patients each in the screened and the unscreened groups. Depression screening was associated with a reduction in all-cause mortality and vascular events in patients with cardiometabolic diseases. The uptake of screening was poor for unknown reasons. Reverse causality and confounding by disease severity and quality of care are important possible limitations. Further research to determine reproducibility and explore underlying mechanisms is merited.


The impact of p53 and p73 on aneuploidy and cancer.
Initiation, progression and evasion are sequential steps in cancer formation, with autonomous cell proliferation as a final outcome. Genetic or epigenetic alterations of key regulatory genes of the cell cycle are frequently associated with these phenomena. Recently, chromosomal instability, a long-supposed driving force of tumorigenesis, was associated with dysregulation of mitotic genes, providing advantages to tumor cells. Numerous molecules thus provide a key link in the chain of relationships between chromosomal instability and cancer. Here, we discuss emerging evidence revealing that two p53 family members, p53 and p73, might be key regulatory genes at the heart of the relationship between chromosomal instability and cancer. We argue that the role of members of the p53 family as tumor suppressor proteins, their impact on the control of cellular ploidy, and their newly emerging connection with mitotic checkpoint regulatory genes support the suggestion that p73 and p53 could be two of the missing links among chromosomal instability, the mitotic checkpoint and cancer.


Sensor technology to support Aging in Place.
Older adults want to age in place at home. Sensor technology has the potential to help by monitoring individuals' health status, detecting emergency situations, and notifying health care providers. Researchers at the University of Missouri are investigating the impact of registered nurse care coordination and technology on the ability of older adults to age in place. Technology coupled with care coordination has improved clinical outcomes. This article presents an overview of the Aging in Place research, TigerPlace as a Missouri-sponsored Aging in Place facility, and the sensor technology developed to support Aging in Place.


Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema.
Hereditary angioedema due to C1 inhibitor deficiency is characterized by recurrent acute attacks of swelling that can be painful and sometimes life-threatening. We conducted two randomized trials to evaluate nanofiltered C1 inhibitor concentrate in the management of hereditary angioedema. The first study compared nanofiltered C1 inhibitor concentrate with placebo for treatment of an acute attack of angioedema. A total of 68 subjects (35 in the C1 inhibitor group and 33 in the placebo group) were given one or two intravenous injections of the study drug (1000 units each). The primary end point was the time to the onset of unequivocal relief. The second study was a crossover trial involving 22 subjects with hereditary angioedema that compared prophylactic twice-weekly injections of nanofiltered C1 inhibitor concentrate (1000 units) with placebo during two 12-week periods. The primary end point was the number of attacks of angioedema per period, with each subject acting as his or her own control. In the first study, the median time to the onset of unequivocal relief from an attack was 2 hours in the subjects treated with C1 inhibitor concentrate but longer than 4 hours in those given placebo (P=0.02). In the second study, the number of attacks per 12-week period was 6.26 with C1 inhibitor concentrate given as prophylaxis, as compared with 12.73 with placebo (P<0.001); the subjects who received the C1 inhibitor concentrate also had significant reductions in both the severity and the duration of attacks, in the need for open-label rescue therapy, and in the total number of days with swelling. In subjects with hereditary angioedema, nanofiltered C1 inhibitor concentrate shortened the duration of acute attacks. When used for prophylaxis, nanofiltered C1 inhibitor concentrate reduced the frequency of acute attacks. (Funded by Lev Pharmaceuticals; ClinicalTrials.gov numbers, NCT00289211, NCT01005888, NCT00438815, and NCT00462709.)


Is fasting leptin associated with insulin resistance among nondiabetic individuals? The Miami Community Health Study.
Whether serum leptin levels are associated with insulin resistance independent of the effects of hyperinsulinemia and adiposity is an important unanswered question. We examined the relationship between the rate of insulin-mediated glucose uptake and serum leptin concentrations among nondiabetic men and women. A cross-sectional analysis was performed among 49 young to middle-aged men and women who participated in the Miami Community Health Study. All participants had measures of insulin resistance (euglycemic-hyperinsulinemic clamp), postchallenge insulin levels, fasting serum leptin levels, and several measures of adiposity. The rate of insulin-mediated glucose uptake (M in milligrams per kilogram per minute) was significantly associated with leptin concentrations in both men (r = -0.83; P < 0.001) and women (r = -0.59; P < 0.001). M was also inversely related to percent body fat and to the 2-h insulin area under the curve (AUC). After covariate adjustment for sex, percent body fat, and AUC, leptin remained a significant correlate of M (P = 0.04). Cross-sectionally, leptin was significantly associated with insulin resistance in this nondiabetic sample of men and women. There may be a different physiological mechanism to explain the leptin/insulin resistance association apart from the insulin/adiposity link. Confirmatory evidence awaits the results of clinical trials.


Costs of medicines and health care: a concern for Australian women across the ages.
Evidence from Australia and other countries suggests that some individuals struggle to meet the costs of their health care, including medicines, despite the presence of Government subsidies for low-income earners. The aim of our study was to elucidate women's experiences with the day to day expenses that relate to medicines and their health care. The Australian Longitudinal Study on Women's Health (ALSWH) conducts regular surveys of women in three age cohorts (born 1973-78, 1946-51, and 1921-26). Our data were obtained from free text comments included in surveys 1 to 5 for each cohort. All comments were scanned for mentions of attitudes, beliefs and behaviours around the costs of medicines and health care. Relevant comments were coded by category and themes identified. Over 150,000 responses were received to the surveys, and 42,305 (27%) of these responses included free-text comments; 379 were relevant to medicines and health care costs (from 319 individuals). Three broad themes were identified: costs of medicines (33% of relevant comments), doctor visits (49%), and complementary medicines (13%). Age-specific issues with medicine costs included contraceptive medicines (1973-78 cohort), hormone replacement therapy (1946-51 cohort) and osteoporosis medications (1921-26 cohort). Concerns about doctor visits mostly related to reduced (or no) access to bulk-billed medical services, where there are no out-of-pocket costs to the patient, and costs of specialist services. Some women in the 1973-78 and 1946-51 cohorts reported 'too much income' to qualify for government health benefits, but not enough to pay for visits to the doctor. In some cases, care and medicines were avoided because of the costs. Personal feelings of embarrassment over financial positions and judgments about bulk-billing practices ('good ones don't bulk-bill') were barriers to service use, as were travel expenses for rural women. For some individuals, difficulty in accessing bulk-billing services and increasing out-of-pocket costs in Australia limit affordability of health services, including medications. At greatest risk may be those falling below thresholds for subsidised care such as self-funded retirees and those on low-middle incomes, in addition to those on very low incomes, who may find even small co-payments difficult to manage.


[Evaluating post-abortion care in 13 Colombian hospitals].
This work describes Post-abortion Care strategy (PAC) experience in 13 Colombian hospitals regarding three components (counselling, suitable treatment and family planning). The study had quantitative (cross-sectional study) and qualitative components. Colombian hospitals receiving PAC training between 1999 and 2002 and fulfilling inclusion and exclusion criteria. Sequential convenience sampling was used; 127 patients, 13 managers and 39 health-care providers were interviewed. 26,199 women were treated for incomplete abortion during the study period. 40 % were treated using Manual Vacuum Aspiration (MVA) and 60 % using sharp curettage (SC). Family planning counselling was provided for 99,8 % of MVA cases; however, only 57,3 % of SC cases received it. There were 9 uterine perforations using SC and none in MVA cases (Chi square: 2.16; p=0.14). There were 2 vagal reactions using MVA. Uterine evacuation was needed in 13 SC cases but in only one MVA case (Chi square: 6,25 p=0.01). Patient satisfaction levels with hospital treatment were evaluated: 90 % of those receiving MVA treatment reported being satisfied or very satisfied, compared to just 60 % of those treated with SC. All health-care providers and 12 out of 13 managers reported satisfaction with the PAC strategy and with 12 out of 13 managers as well. MVA treatment was associated with less treatment-related morbidity and higher levels of satisfaction amongst patients. Most managers and all health-care providers stated their satisfaction with the PAC strategy.


Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods.
Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) study, a federally funded, randomized trial comparing two pharmacologic strategies against a control condition to manage SGA-related weight gain. The design and methodology considerations of the IMPACT trial are described and embedded in a description of health risks associated with antipsychotic-related weight gain and the limitations of currently available research. The IMPACT study is a 4-site, six month, randomized, open-label, clinical trial of overweight/obese youth ages 8-19 years with pediatric schizophrenia-spectrum and bipolar-spectrum disorders, psychotic or non-psychotic major depressive disorder, or irritability associated with autistic disorder. Youth who have experienced clinically significant weight gain during antipsychotic treatment in the past 3 years are randomized to either (1) switch antipsychotic plus healthy lifestyle education (HLE); (2) add metformin plus HLE; or (3) HLE with no medication change. The primary aim is to compare weight change (body mass index z-scores) for each pharmacologic intervention with the control condition. Key secondary assessments include percentage body fat, insulin resistance, lipid profile, psychiatric symptom stability (monitored independently by the pharmacotherapist and a blinded evaluator), and all-cause and specific cause discontinuation. This study is ongoing, and the targeted sample size is 132 youth. Antipsychotic-related weight gain is an important public health issue for youth requiring ongoing antipsychotic treatment to maintain psychiatric stability. The IMPACT study provides a model for pediatric research on adverse event management using state-of-the art methods. The results of this study will provide needed data on risks and benefits of two pharmacologic interventions that are already being used in pediatric clinical settings but that have not yet been compared directly in randomized trials. Clinical Trials.gov NCT00806234.


Inhibition of transfer of collagen-induced arthritis into SCID mice by ex vivo infection of spleen cells with retroviruses expressing soluble tumor necrosis factor receptor.
Collagen-induced arthritis can be transferred into severe combined immunodeficiency (SCID) mice by spleen cells from diseased DBA/1 mice. The development of arthritis in SCID animals can be prevented by infection ex vivo of DBA/1 spleen cells with retroviruses expressing the monomeric soluble human p75 tumor necrosis factor (TNF) receptor (TNF-R). In addition, a vector engineered to express a polycystronic mRNA with TNF-R and the herpes simplex virus thymidine kinase (HSVtk) gene, while producing low levels of TNF-R, had a limited effect which could be blocked by treating the animals with ganciclovir. A retroviral vector expressing the HSVtk gene alone had no effect on this arthritis transfer model with or without ganciclovir. Serum levels of TNF-R did not correlate with clinical signs, however, lower anti-collagen antibody levels corresponded with lack of clinical symptoms. These results indicate that local production of cytokine inhibitor is essential for therapeutic purposes while systemic levels may not be required.


Isolation and partial characterization of catechol 1,2-dioxygenase of phenol degrading yeast Candida tropicalis.
Candida tropicalis yeast is a microorganism that possesses high tolerance for phenol and shows strong phenol degrading activity. This yeast is capable of utilizing phenol as the sole carbon and energy source. While the enzyme participating on the first step of phenol biodegradation, NADPH-dependent phenol hydroxylase, has already been characterized, information on the enzyme participating in the second step of its degradation, catechol 1,2-dioxygenase, is scarce. The development of the procedure suitable for catechol 1,2-dioxygenase isolation and partial characterization of this enzyme are the aims of this study. Combination of chromatography on DEAE-Sepharose and gel-permeation chromatography on Sephadex G-100 was used for isolation of cytosolic catechol 1,2-dioxygenase from C. tropicalis yeast. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and gel chromatography on Sephadex G-100 were used to evaluate the molecular mass of the enzyme. The enzyme activity was followed by HPLC (catechol consumption and/or cis,cis-muconic acid formation). Using the isolation procedure consisting of chromatography and re-chromatography on a column of DEAE-Sepharose and gel filtration on Sephadex G-100, catechol 1,2-dioxygenase was purified from C. tropicalis cytosol to homogeneity. Catechol 1,2-dioxygenase was found to be a homodimer with a subunit molecular mass of 30000 +/- 5000. The enzyme oxidized catechol producing cis,cis-muconic acid. The optimal temperature and pH were 30 degrees C and 7.7, respectively. The data are the first report showing the isolation of eukaryotic catechol 1,2-dioxygenase from C. tropicalis to homogeneity and its partial characterization.


Can radiologist training and testing ensure high performance in CT colonography? Lessons From the National CT Colonography Trial.
The objective of this article is to describe the experience of the National CT Colonography Trial with radiologist training and qualification testing at CT colonography (CTC) and to correlate this experience with subsequent performance in a prospective screening study. Ten inexperienced radiologists participated in a 1-day educational course, during which partial CTC examinations of 27 cases with neoplasia and full CTC examinations of 15 cases were reviewed using primary 2D and 3D search. Subsequently 15 radiologists took a qualification examination composed of 20 CTC cases. Radiologists who did not pass the first qualification examination attended a second day of focused retraining of 30 cases, which was followed by a second qualification examination. The results of the initial and subsequent qualification tests were compared with reader performance in a large prospective screening trial. All radiologists took and passed the qualification examinations. Seven radiologists passed the qualification examination the first time it was offered, and eight radiologists passed after focused retraining. Significantly better sensitivities were obtained on the second versus the first examination for the retrained radiologists (difference = 16%, p < 0.001). There was no significant difference in sensitivities between the groups who passed the qualification examination the first time versus those who passed the second time in the prospective study (88% vs 92%, respectively; p = 0.612). In the prospective study, the odds of correctly identifying diseased cases increased by 1.5 fold for every 50-case increase in reader experience or formal training (p < 0.025). A significant difference in performance was observed among radiologists before formalized training, but testing and focused retraining improved radiologist performance, resulting in an overall high sensitivity across radiologists in a subsequent, prospective screening study.


Neuroanatomy of melanocortin-4 receptor pathway in the lateral hypothalamic area.
The central melanocortin system regulates body energy homeostasis including the melanocortin-4 receptor (MC4R). The lateral hypothalamic area (LHA) receives dense melanocortinergic inputs from the arcuate nucleus of the hypothalamus and regulates multiple processes including food intake, reward behaviors, and autonomic function. By using a mouse line in which green fluorescent protein (GFP) is expressed under control of the MC4R gene promoter, we systemically investigated MC4R signaling in the LHA by combining double immunohistochemistry, electrophysiology, and retrograde tracing techniques. We found that LHA MC4R-GFP neurons coexpress neurotensin as well as the leptin receptor but do not coexpress other peptide neurotransmitters found in the LHA including orexin, melanin-concentrating hormone, and nesfatin-1. Furthermore, electrophysiological recording demonstrated that leptin, but not the MC4R agonist melanotan II, hyperpolarizes the majority of LHA MC4R-GFP neurons in an ATP- sensitive potassium channel-dependent manner. Retrograde tracing revealed that LHA MC4R-GFP neurons do not project to the ventral tegmental area, dorsal raphe nucleus, nucleus accumbens, and spinal cord, and only limited number of neurons project to the nucleus of the solitary tract and parabrachial nucleus. Our findings provide new insights into MC4R signaling in the LHA and its potential implications in homeostatic regulation of body energy balance.


Design and Outcomes of a Community Trial to Increase Pap Testing in Pacific Islander Women.
Pap tests remain an essential cervical cancer detection method in the United States, yet they are underutilized among Pacific Islanders (PI) who experience elevated cervical cancer incidence and mortality. This study describes the design, methods, participants, and outcomes of a multiyear (2010-2016), community-based randomized intervention trial in southern California. Based upon strong collectivistic norms, the trial tested the efficacy of a unique social support intervention targeting Chamorro, Samoan, and Tongan women and their male husbands/partners. A single-session educational intervention was designed and tailored for ethnic- and gender-specific groups to increase men's social support for their female wives/partners to receive a Pap test, and for women to receive a Pap test. The comparison group received preexisting brochures on Pap testing (for women) or general men's health (for men). Pretest and 6-month follow-up data were analyzed. Intervention and comparison groups were mostly equivalent on pretest demographics and outcome variables. Intervention women who were not compliant with Pap screening recommendations at pretest were significantly more likely to have scheduled and received a Pap test at 6-month follow-up. However, 6-month follow-up results indicated no intervention effect on changes in women's Pap testing knowledge, fatalistic attitudes, or perceived social support from their male partner. Ethnic- and gender-tailored community interventions can successfully increase Pap test behaviors for PI women, although more research is needed on the specific pathways leading to behavior change. Collaborative community-based interventions lead to increases in women's cancer prevention and early detection for Pacific Islander and other collectivistic communities.


A chromosomal region promoting outcrossing in a conifer.
Prefertilization mechanisms influencing selfing rates are thought to be absent in conifers. Outcrossing in conifers is promoted via an embryo-lethal system, but the genetic mechanism is poorly understood. This study is the first experimental profile of the genetic mechanism promoting outcrossing in conifers. Molecular dissection of a Pinus taeda L. selfed pedigree detected a chromosomal region identified as PtTX3020-RPtest9. Within this region, a semilethal factor was tightly linked (r = 0.0076) to a polymorphic expressed sequence tag (EST). The linkage group flanking the lethal factor showed strong heterozygote advantage. Using genotypic frequencies for the linkage group, three hypotheses about the semilethal factor could be tested: (1) the presence of a balanced lethal system, i.e., a lethal factor present in each of the two marker intervals; (2) gametic selection operative prior to fertilization; and (3) a stage-specific lethal factor. Selection acted via the embryo-lethal system. No support for a genetic mechanism operating prior to fertilization was found. The semilethal factor exerted no effect after embryo maturity. The genetic mechanism promoting outcrossing in P. taeda L. appears to have a balancing selection system due to either pseudo-overdominance or true overdominance.


Acute occupational injury among adolescent farmworkers from South Texas.
This combined cross-sectional/cohort study addressed research gaps by estimating the rate of non-fatal occupational injury and identifying potential determinants among a population of adolescent farmworkers who are largely Hispanic and migrant. The cohort included 410 farmworkers (aged 13-19 years) attending high school in South Texas along the border with Mexico. Data collection involved a self-administered, Web-based survey that solicited information on demographics, farm work variables including person-time at risk, occupational injury, health status and health risk behaviours. Cox regression was used to identify potential risk factors for non-fatal injury events experienced during a 9-month recall period. Depending on the definition of injury, the rate of non-fatal injury ranged from 27.0-73.6/100 full time equivalents. Variables with an increased and statistically significant HR in an adjusted Cox model included: age groups <15 years-old (5.82) and 16 years-old (4.47), usually sleeping <8 h during the week (2.10), feeling tense, stressed or anxious sometimes/often (2.25), not watching TV (2.65), working around ditches (2.01) and detasseling (2.70). The high observed rates of non-fatal injury combined with the potential negative consequences and cost of these injuries signifies a compelling need for injury prevention efforts targeting adolescent, Hispanic, farmworkers.


Mouse Sin3A interacts with and can functionally substitute for the amino-terminal repression of the Myc antagonist Mxi1.
Mxi1 is a basic region helix-loop-helix leucine zipper (bHLH/LZ) protein that, in association with Max, antagonizes Myc oncogenic activities. A possible mechanistic basis for Mxi1-mediated repression was provided by the recent demonstration that the repressive potential of Mxi1 correlates with its ability to physically associate with mSin3B, one of two mammalian homologues of the yeast transcriptional repressor SIN3. Here, we sought to characterize more fully the physical properties of the second homologue, mSin3A and to determine whether the recruitment of mSin3A by Mxi1 is indeed required for anti-Myc activity. Transient transfection of mammalian cells showed that the mSin3A protein can associate with the strong repressive isoform of Mxi1 (Mxi1-SR) and that, like other Myc superfamily members, both mSin3A and Mxi1-SR localize to the nucleus. From a developmental standpoint, a comparative analysis of Myc, Mxi1-SR and Sin3A expression during postnatal mouse development and in differentiating mouse erythroleukemia (MEL) cells revealed that dramatic and reciprocal changes in Myc and Mxi1-SR mRNA levels are accompanied by minimal stage-specific changes in mSin3A gene expression. This constant expression profile, coupled with the observation that over-expression of mSin3A does not augment the anti-Myc activity of Mxi1-SR in the rat embryo fibroblast (REF) transformation assay, suggests that mSin3A is not a limiting factor in the regulation of Myc superfamily function. Finally, a mSin3A-Mxi1 fusion protein, in which the amino terminal mSin3-interacting domain of Mxi1-SR was replaced with the full-length mSin3A, exhibited a level of repression activity equivalent to, or greater than, the level of repression obtained with Mxi1-SR. Taken together, these observations directly demonstrate that the amino-terminal repression domain of Mxi1-SR functions solely to recruit mSin3A and possibly other proteins like mSin3A and this association is necessary for the anti-Myc activity of Mxi1-SR.


Models of neocortical layer 5b pyramidal cells capturing a wide range of dendritic and perisomatic active properties.
The thick-tufted layer 5b pyramidal cell extends its dendritic tree to all six layers of the mammalian neocortex and serves as a major building block for the cortical column. L5b pyramidal cells have been the subject of extensive experimental and modeling studies, yet conductance-based models of these cells that faithfully reproduce both their perisomatic Na(+)-spiking behavior as well as key dendritic active properties, including Ca(2+) spikes and back-propagating action potentials, are still lacking. Based on a large body of experimental recordings from both the soma and dendrites of L5b pyramidal cells in adult rats, we characterized key features of the somatic and dendritic firing and quantified their statistics. We used these features to constrain the density of a set of ion channels over the soma and dendritic surface via multi-objective optimization with an evolutionary algorithm, thus generating a set of detailed conductance-based models that faithfully replicate the back-propagating action potential activated Ca(2+) spike firing and the perisomatic firing response to current steps, as well as the experimental variability of the properties. Furthermore, we show a useful way to analyze model parameters with our sets of models, which enabled us to identify some of the mechanisms responsible for the dynamic properties of L5b pyramidal cells as well as mechanisms that are sensitive to morphological changes. This automated framework can be used to develop a database of faithful models for other neuron types. The models we present provide several experimentally-testable predictions and can serve as a powerful tool for theoretical investigations of the contribution of single-cell dynamics to network activity and its computational capabilities.


Abdominal obesity in adolescents: prevalence and association with physical activity and eating habits.
Abdominal obesity in adolescents is associated with cardiovascular and metabolic diseases, but its prevalence and the factors associated with its occurrence are unknown. To determine the prevalence of abdominal obesity in adolescents, and to evaluate whether the indicators of physical activity and dietary habits are associated with the occurrence of abdominal obesity in adolescents. The sample included 4138 high school students (14-19 years), selected by cluster sampling in two stages. We obtained data using the Global School-based Health Survey, and anthropometric measurements were taken for determination of overweight and abdominal obesity. Logistic regression was used for analysis of behavioral factors associated with the occurrence of abdominal obesity. The identification of cases of abdominal obesity was performed by waist circumference analysis, using age- and gender-related cutoff points as reference. The mean age was 16.8 years (s = 1.4), and 59.8% of subjects were female. The prevalence of abdominal obesity was 6% (95%CI: 5.3-6.7), and it was significantly higher among girls (6.7%, 95%CI: 5.8-7.8) than among boys (4.9%, 95%CI: 3, 9-6, 0). In the crude analysis, gender and overweight were associated with the occurrence of abdominal obesity. The analysis adjustment by logisic regression allowed us to observe that physical activity was significantly associated with the occurrence of obesity in this group (OR = 0.7; 95% CI: 0.49-0.99), regardless of the presence of overweight. The prevalence of abdominal obesity was low compared to that observed in international studies, and physical activity was a factor associated with the occurrence of this event in adolescents.


Management of alcoholic liver disease.
Understanding alcohol addiction and abstinence is key to treating alcoholic liver disease, since abstinence leads to improvement in all forms of alcoholic liver damage. Although pharmacotherapy for alcoholism, using agents such as naltrexone, acamprosate, topiramate, and baclofen, is an exciting field, few studies have included patients with liver disease or cirrhosis. To treat alcoholic liver injury, corticosteroids have become the standard of care in patients with severe alcoholic hepatitis. In contrast, the role of pharmacotherapy to treat alcoholic fibrosis is unclear, with failure to observe a benefit in randomized, placebo-controlled clinical trials of colchicine, S-adenosylmethionine (SAMe), or phosphatidylcholine. Liver transplantation remains an option in selected patients with life-threatening alcoholic liver disease.


Fracture incidence and secular trends between 1989 and 2013 in a population based cohort: The Rotterdam Study.
Fracture incidence needs to be evaluated over time to assess the impact of the enlarging population burden of fractures (due to increase in lifespan) and the efficacy of fracture prevention strategies. Therefore, we aimed to evaluate the association of femoral neck bone mineral density (FN-BMD) measured using dual-energy X-ray absorptiometry (DXA) at baseline with fracture risk over a long follow-up time period. Incident non-vertebral fractures were assessed in 14,613 individuals participating in the Rotterdam Study with up to 20 years of follow-up. During a mean follow-up of 10.7 ± 6.2 years, 2971 (20.3%) participants had at least one incident non-vertebral fracture. The risk for any non-vertebral fracture was 1.37 (95% Confidence Interval (CI): 1.25-1.49) and 1.42 (95%CI: 1.35-1.50) for men and women, respectively. The majority (79% in men and 75% in women) of all fractures occurred among participants a normal or osteopenic T-score. The incidence rates per 1000 person-years for the most common fractures were 5.3 [95%CI: 5.0-5.7] for hip, 4.9 [95%CI: 4.6-5.3] for wrist and 2.3 [95%CI: 2.0-2.5] for humerus. To examine the predictive ability of BMD through follow-up time we determined fracture hazard ratios (HR) per standard deviation decrease in femoral neck BMD across five year bins. No differences were observed, with a HR of 2.5 (95%CI: 2.0-3.1) after the first 5 years, and of 1.9 (95%CI: 1.1-3.3) after 20 years. To assess secular trends in fracture incidence at all skeletal sites we compared participants at an age of 70-80 years across two time periods: 1989-2001 (n = 2481, 60% women) and 2001-2013 (n = 2936, 58% women) and found no statistically significant difference (p < 0.05) between fracture incidence rates (i.e., incidence of non-vertebral fractures of 26.4 per 1000 PY [95%CI: 24.4-28.5]) between 1989 and 2001, and of 25.4 per 1000 PY [95%CI: 23.0-28.0] between 2001 and 2013. In conclusion, BMD is still predictive of future fracture over a long period of time. While no secular changes in fractures rates seem to be observed after a decade, the majority of fractures still occur above the osteoporosis threshold, emphasizing the need to improve the screening of osteopenic patients.


Role of marijuana components on the regenerative ability of stem cells.
Stem cell therapy promotes tissue regeneration and wound healing. Efforts have been made to prime stem cells to enhance their regenerative abilities. Certain marijuana components, namely the non-psychoactive cannabidiol (CBD) and psychoactive tetrahydrocannabinol (THC), are defined as immunomodulators.9 We test whether two sources of stem cells, primed with CBD or THC, would demonstrate improved regenerative abilities. Human adipose-derived stem cells (ASCs) and bone marrow-derived stem cells (BMDSCs), not obtained from the same individual, were treated with low (300 nM) or high (3 μM) concentration CBD. Porcine ASCs and BMDSCs were isolated from a single pig, and treated with either low or high concentrations of CBD or THC. Transwell migration and MTT proliferation assays were performed on the human ASCs and BMDSCs. Also, transwell migration assay was performed on the porcine ASCs and BMDSCs. Finally, a wound healing scratch assay in porcine primary fibroblasts (PFs) was performed, co-cultured with the cannabinoid-treated ASCs. CBD priming at low concentration induces migration by 180% (P < .01) in porcine ASCs, and by only 93% (P < .02) in porcine BMDSCs. In porcine stem cells, THC priming at low concentration induces migration by 91.6% (P < .01) in ASCs but by only 44.3% (P < .03) in BMDSCs. Compared to PFs co-cultured with untreated ASCs, PFs co-cultured with low CBD-primed ASCs had 75% faster wound closure at 18 hours (P < .01). CBD and THC priming of ASCs and BMDSCs, particularly at lower doses, enhances a number of regenerative parameters, suggesting that these major marijuana components may improve stem cell-based therapies. SIGNIFICANCE OF THE STUDY: Our study demonstrates that cannabinoids can enhance the regenerative capacity of two major sources of stem cells, adipose- and bone marrow-derived, from human and porcine donors. Stem cell isolation and expansion is invasive, costly and time consuming. Stem cells with improved regenerative properties may be effective in the treatment of acute or chronic wounds. This is the first study to compare the priming potential of two sources of stem cells from the same animal, with the same genetic and epigenetic profile, as well as the first to prime with THC.


Lipid bilayer coated Al(2)O(3) nanopore sensors: towards a hybrid biological solid-state nanopore.
Solid-state nanopore sensors are highly versatile platforms for the rapid, label-free electrical detection and analysis of single molecules, applicable to next generation DNA sequencing. The versatility of this technology allows for both large scale device integration and interfacing with biological systems. Here we report on the development of a hybrid biological solid-state nanopore platform that incorporates a highly mobile lipid bilayer on a single solid-state Al(2)O(3) nanopore sensor, for the potential reconstitution of ion channels and biological nanopores. Such a system seeks to combine the superior electrical, thermal, and mechanical stability of Al(2)O(3) solid-state nanopores with the chemical specificity of biological nanopores. Bilayers on Al(2)O(3) exhibit higher diffusivity than those formed on TiO(2) and SiO(2) substrates, attributed to the presence of a thick hydration layer on Al(2)O(3), a key requirement to preserving the biological functionality of reconstituted membrane proteins. Molecular dynamics simulations demonstrate that the electrostatic repulsion between the dipole of the DOPC headgroup and the positively charged Al(2)O(3) surface may be responsible for the enhanced thickness of this hydration layer. Lipid bilayer coated Al(2)O(3) nanopore sensors exhibit excellent electrical properties and enhanced mechanical stability (GΩ seals for over 50 h), making this technology ideal for use in ion channel electrophysiology, the screening of ion channel active drugs and future integration with biological nanopores such as α-hemolysin and MspA for rapid single molecule DNA sequencing. This technology can find broad application in bio-nanotechnology.


Minimally-Invasive Neural Interface for Distributed Wireless Electrocorticogram Recording Systems.
This paper presents a minimally-invasive neural interface for distributed wireless electrocorticogram (ECoG) recording systems. The proposed interface equips all necessary components for ECoG recording, such as the high performance front-end integrated circuits, a fabricated flexible microelectrode array, and wireless communication inside a miniaturized custom-made platform. The multiple units of the interface systems can be deployed to cover a broad range of the target brain region and transmit signals via a built-in intra-skin communication (ISCOM) module. The core integrated circuit (IC) consists of 16-channel, low-power push-pull double-gated preamplifiers, in-channel successive approximation register analog-to-digital converters (SAR ADC) with a single-clocked bootstrapping switch and a time-delayed control unit, an ISCOM module for wireless data transfer through the skin instead of a power-hungry RF wireless transmitter, and a monolithic voltage/current reference generator to support the aforementioned analog and mixed-signal circuit blocks. The IC was fabricated using 250 nm CMOS processes in an area of 3.2 × 0.9 mm² and achieved the low-power operation of 2.5 µW per channel. Input-referred noise was measured as 5.62 µVrms for 10 Hz to 10 kHz and ENOB of 7.21 at 31.25 kS/s. The implemented system successfully recorded multi-channel neural activities in vivo from a primate and demonstrated modular expandability using the ISCOM with power consumption of 160 µW.


Allorecognition in the Tasmanian devil (Sarcophilus harrisii), an endangered marsupial species with limited genetic diversity.
Tasmanian devils (Sarcophilus harrisii) are on the verge of extinction due to a transmissible cancer, devil facial tumour disease (DFTD). This tumour is an allograft that is transmitted between individuals without immune recognition of the tumour cells. The mechanism to explain this lack of immune recognition and acceptance is not well understood. It has been hypothesized that lack of genetic diversity at the Major Histocompatibility Complex (MHC) allowed the tumour cells to grow in genetically similar hosts without evoking an immune response to alloantigens. We conducted mixed lymphocyte reactions and skin grafts to measure functional MHC diversity in the Tasmanian devil population. The limited MHC diversity was sufficient to produce measurable mixed lymphocyte reactions. There was a wide range of responses, from low or no reaction to relatively strong responses. The highest responses occurred when lymphocytes from devils from the east of Tasmania were mixed with lymphocytes from devils from the west of Tasmania. All of the five successful skin allografts were rejected within 14 days after surgery, even though little or no MHC I and II mismatches were found. Extensive T-cell infiltration characterised the immune rejection. We conclude that Tasmanian devils are capable of allogeneic rejection. Consequently, a lack of functional allorecognition mechanisms in the devil population does not explain the transmission of a contagious cancer.


Association between Periodontal disease and Prostate cancer: Results of a 12-year Longitudinal Cohort Study in South Korea.
The incidence of prostate cancer (PC) accompanying periodontal disease (PD) is anticipated to increase due to population aging. The aim of this study was to determine the association between PD and PC using data in the National Health Insurance Service-Health Examinee Cohort (NHIS-HEC). A random stratified sample of 187,934 South Koreans was collected from the NHIS database from 2002 to 2013. We assessed the relationship between PD and PC while adjusting for potential confounding factors (sex, age, household income, insurance status, residence area, hypertension, diabetes mellitus, cerebral infarction, angina pectoris, myocardial infarction, smoking status, alcohol intake, and regular exercise). The overall incidence of PC with PD among those aged 40 years and older was 0.28% (n = 531). In the multivariate Cox proportional-hazard regression analysis with adjustment for confounding factors, PD was associated with a 14% higher risk of PC (HR = 1.14, 95% CI = 1.01-1.31, P = 0.042). The findings of this study suggest that PD is significantly and positively associated with PC. Further studies are required to identify the mechanisms underlying the links between PD and PC.


[Postmenopausal osteoporosis. Role of vitamin K in the prevention of osteoporosis].
Low vitamin K1 intake and low plasma vitamin K1 levels are associated with low bone mineral density (BMD) and increased osteoporotic fracture risk in postmenopausal women. Despite the lack of a significant change or the occurrence of only a modest increase in bone mineral density, high-dose vitamin K(1) supplementation improved indices of bone strength in the femoral neck and reduced the incidence of clinical fractures.


Errors in the administration of intravenous medications in hospital and the role of correct procedures and nurse experience.
Intravenous medication administrations have a high incidence of error but there is limited evidence of associated factors or error severity. To measure the frequency, type and severity of intravenous administration errors in hospitals and the associations between errors, procedural failures and nurse experience. Prospective observational study of 107 nurses preparing and administering 568 intravenous medications on six wards across two teaching hospitals. Procedural failures (eg, checking patient identification) and clinical intravenous errors (eg, wrong intravenous administration rate) were identified and categorised by severity. Of 568 intravenous administrations, 69.7% (n = 396; 95% CI 65.9 to 73.5) had at least one clinical error and 25.5% (95% CI 21.2 to 29.8) of these were serious. Four error types (wrong intravenous rate, mixture, volume, and drug incompatibility) accounted for 91.7% of errors. Wrong rate was the most frequent and accounted for 95 of 101 serious errors. Error rates and severity decreased with clinical experience. Each year of experience, up to 6 years, reduced the risk of error by 10.9% and serious error by 18.5%. Administration by bolus was associated with a 312% increased risk of error. Patient identification was only checked in 47.9% of administrations but was associated with a 56% reduction in intravenous error risk. Intravenous administrations have a higher risk and severity of error than other medication administrations. A significant proportion of errors suggest skill and knowledge deficiencies, with errors and severity reducing as clinical experience increases. A proportion of errors are also associated with routine violations which are likely to be learnt workplace behaviours. Both areas suggest specific targets for intervention.


Switchgrass (Panicum virgatum L) flag leaf transcriptomes reveal molecular signatures of leaf development, senescence, and mineral dynamics.
Switchgrass flag leaves can be expected to be a source of carbon to the plant, and its senescence is likely to impact the remobilization of nutrients from the shoots to the rhizomes. However, many genes have not been assigned a function in specific stages of leaf development. Here, we characterized gene expression in flag leaves over their development. By merging changes in leaf chlorophyll and the expression of genes for chlorophyll biosynthesis and degradation, a four-phase molecular roadmap for switchgrass flag leaf ontogeny was developed. Genes associated with early leaf development were up-regulated in phase 1. Phase 2 leaves had increased expression of genes for chlorophyll biosynthesis and those needed for full leaf function. Phase 3 coincided with the most active phase for leaf C and N assimilation. Phase 4 was associated with the onset of senescence, as observed by declining leaf chlorophyll content, a significant up-regulation in transcripts coding for enzymes involved with chlorophyll degradation, and in a large number of senescence-associated genes. Of considerable interest were switchgrass NAC transcription factors with significantly higher expression in senescing flag leaves. Two of these transcription factors were closely related to a wheat NAC gene that impacts mineral remobilization. The third switchgrass NAC factor was orthologous to an Arabidopsis gene with a known role in leaf senescence. Other genes coding for nitrogen and mineral utilization, including ureide, ammonium, nitrate, and molybdenum transporters, shared expression profiles that were significantly co-regulated with the expression profiles of the three NAC transcription factors. These data provide a good starting point to link shoot senescence to the onset of dormancy in field-grown switchgrass.


MRI of blood flow of the human retina.
This study reports a high-resolution MRI approach to image basal blood flow and hypercapnia-induced blood-flow changes in the unanesthetized human retina on a 3-T MRI scanner. Pseudocontinuous arterial spin labeling technique with static tissue suppression was implemented to minimize movement artifacts and improve blood-flow sensitivity. Turbo spin-echo acquisition was used to achieve high spatial resolution free of susceptibility artifacts. The size, shape, and position of a custom-made receive radiofrequency coil were optimized for sensitivity in the posterior retina. Synchronized eye blink and respiration to the end of each data readout minimized eye movement and physiological fluctuation. Robust high-contrast blood-flow MRI of the unanesthetized human retina was obtained at 500 × 800 μm(2) in-plane resolution. Blood flow in the posterior retina was 93 ± 31 mL/(100 mL min) (mean ± standard deviation, N = 5). Hypercapnic inhalation (5% CO(2)) increased blood flow by 12 ± 4% relative to air (P < 0.01, N = 5). This study demonstrates the feasibility of blood-flow MRI of the retina of unanesthetized human. Because blood flow is tightly coupled to metabolic function under normal conditions and it is often perturbed in diseases, this approach could provide unique insights into retinal physiology and serve as an objective imaging biomarker for disease staging and testing of novel therapeutic strategies. This approach could open up new avenue of retinal research.


Research needs in allergy: an EAACI position paper, in collaboration with EFA.
In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.


Environmental-dependent acceleration of a developmental switch: the floral transition.
The transition from vegetative growth to reproductive growth in plants in which flowers are produced requires the activation of specific genes. Simpson and Dean discuss two recent reports that characterize the FLOWERING LOCUS T (FT) gene in Arabidopsis, which is part of the floral transition pathway. Unlike many of the known genes that initiate flower production, the FT gene appears to encode a membrane-associated protein that could function in signaling from the cell surface.


Spatial organization based reciprocal switching of enzyme-free nucleic acid circuits.
We report a new nucleic acid sensing strategy through an intelligent design of spatial organization based reciprocal switching of catalytic hairpin assembly (CHA). The so-called SORS-CHA not only turns a well-designed CHA circuit into a relatively universal detector for any targeting sequence, but also guarantees a much enhanced signal resolution and a believability to minimize the misreading induced by unexpected signal drifts. With more trustworthy results, but a simpler sequence design, nucleic acid circuits could become competitive in real-world applications.


Three sudden cardiac deaths associated with Lyme carditis - United States, November 2012-July 2013.
Lyme disease is a multisystem illness caused by Borrelia burgdorferi, a spirochete transmitted by certain species of Ixodes ticks. Approximately 30,000 confirmed and probable cases of Lyme disease were reported in the United States in 2012, primarily from high-incidence states in the Northeast (Connecticut, Delaware, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont) and upper Midwest (Minnesota and Wisconsin). Common manifestations include cutaneous, neurologic, and rheumatologic signs and symptoms. Symptomatic infection of the heart is rare in recognized Lyme disease cases and usually resolves promptly with appropriate antibiotic therapy. Nonetheless, cardiac involvement occasionally can cause life-threatening cardiac conduction abnormalities. During November 2012-July 2013, one woman and two men (ranging in age from 26 to 38 years) from high-incidence Lyme disease states experienced sudden cardiac death and, on postmortem examination, were found to have evidence of Lyme carditis. The three deaths were investigated by the Connecticut Department of Public Health, Massachusetts Department of Public Health, New Hampshire Department of Public Health, New York State Department of Health, and CDC. Donated corneas from two decedents had been transplanted to three recipients before the diagnosis of Lyme disease was established, but no evidence of disease transmission was found. Although death from Lyme carditis is rare, it should be considered in cases of sudden cardiac death in patients from high-incidence Lyme disease regions. Reducing exposure to ticks is the best method for preventing Lyme disease and other tickborne infections.


The first described joint-associated intraneural ganglion cyst.
This article describes the identification of the first known specimen in which an articular origin for an intraneural cyst was recognized. Prompted by early citations in the 20th century of a valuable 1904 tibial intraneural ganglion housed at St. Bartholomew's Hospital in London, we traveled there to research it. We fortuitously discovered a citation to an earlier joint-related specimen, one that had not previously been referenced correctly in subsequent publications on intraneural cysts for more than a century. The original anatomic description dating to 1884, summarized in 3 lines in a museum catalog, was attributed to T. Swinford Edwards. This cadaveric specimen affected the deep branch of the ulnar nerve and arose from a carpal joint. Additional information was provided in a Transactions in 1884. An original drawing of the specimen was published in a textbook written in 1889 by Anthony Bowlby, a former curator, both of which credited F. (Frederick) Swinford Edwards, a demonstrator in anatomy and surgery at St. Bartholomew's. Unfortunately, the specimen could not be located and is presumed lost. To establish this specimen as the first known example of a joint-related intraneural cyst, we completed a review of >400 other cases and confirmed this statement. The first observation of an articular origin for an intraneural cyst, made by 2 eminent surgeons, has not been properly acknowledged. Considered with a modern perspective, this historical case solidifies the articular (synovial) origin for these unusual intraneural cysts, a finding that has important treatment implications.


Diagnostic accuracy of conventional and digital radiography for detecting misfit between the tooth and restoration in metal-restored teeth.
Although the postprocessing of digital images with enhancement filters could lead to the presence of artifacts and result in false-positive diagnoses, no study has analyzed whether the use of digital radiographs and/or postprocessing of digital images interferes with the diagnosis of marginal adaptation in metal-restored teeth. The purpose of this study was to compare the diagnostic accuracy of conventional and digital radiographic images with and without filters for detecting a misfit between the tooth and restoration in metal-restored teeth. Forty teeth with mesial-occlusal-distal inlays and 40 with complete crowns (each with a perfect fit, 20 with a 0.2-mm gap and 20 with a 0.4-mm gap) were imaged with conventional film and digital phosphor plate systems. Digital radiographs were exported as original images and with edge enhancement (high and low), inversion, and pseudo-3-dimensional filters. Four examiners assessed the presence of gaps by using a categorical scale (fit, misfit, cannot decide). Sensitivity, specificity, and overall accuracy were calculated for each variable. In addition, time spent scoring the images was recorded. A multivariate logistic regression was performed with accuracy as the dependent variable. Of the images, 6.2% received the score "cannot decide," most of them with a high edge enhancement filter and in the crown group. A tendency for higher sensitivity (range 0.67-0.83), specificity (range 0.81-0.92), and accuracy (range 0.73-0.86) values was found in conventional and digital original images. Results of a logistic regression found that restoration type, gap size, and high enhancement and inversion filters had a statistically significant impact on accuracy (P<.05). Original nonfiltered images should be used to assess teeth with metal restorations. High enhancement filters and image inversion should be avoided, especially when metal crowns are present.


Insufficient evidence to deny antibiotic treatment to chronic Lyme disease patients.
The severity, length of illness, and cost of chronic Lyme disease (CLD) have been well described. A number of oral, intravenous, and intramuscular antibiotics have been prescribed for CLD. Surprisingly few antibiotic schedules prescribed for the treatment of CLD have been evaluated in randomized double-blind placebo-controlled clinical trials (RCTs). Physicians have increasingly turned to clinical treatment guideline (CPG) panels to judge the mixed results of the evidence. Two CPG panels have looked at the evidence only to reach opposite conclusions: (1) antibiotic therapy for CLD is not effective and (2) antibiotic therapy for CLD is effective. Physicians have been advised by guideline developers to use clinical discretion in diagnosing and treating CLD. Nevertheless, many health insurers - relying exclusively upon only one CPG - have a policy of automatically denying antibiotics to CLD patients regardless of the specifics of each case or the recommendations of the patient's physician. This paper examined the eight limitations of the evidence used to conclude that antibiotics therapy for CLD is not effective in forming the following hypothesis: insufficient evidence to deny antibiotic treatment to CLD patients. There are eight limitations that support the hypothesis: (1) the power of the evidence is inadequate to draw definite conclusions, (2) the evidence is too heterogeneous to make strong recommendations, (3) the risk to an individual of facing a long-term debilitating illness has not been considered, (4) the risk to society of a growing chronically ill population has not been considered, (5) treatment delay has not been considered as a confounder, (6) co-infections have not been considered as a confounder, (7) the design of RCTs did not address the range of treatment options in an actual practice, and (8) the findings cannot be generalized to actual practice. This hypothesis suggests that physicians should consider the limitations of the evidence before denying antibiotic treatment for CLD. Physicians who deny antibiotic treatment to CLD patients might inform their patients that there are some clinicians who disagree with that position, and then offer to refer them for a second opinion to a doctor who could potentially present a different point of view. The hypothesis also suggests that health care insurers should consider the limitations of the evidence before adopting policies that routinely deny antibiotic treatment for CLD patients and should expand coverage of CLD to include clinical discretion for specific clinical situations.


[Comparison of decoding performance between spike and local field potential signals during goal-directed decision-making task of pigeons].
Both spike and local field potential (LFP) signals are two of the most important candidate signals for neural decoding. At present there are numerous studies on their decoding performance in mammals, but the decoding performance in birds is still not clear. We analyzed the decoding performance of both signals recorded from nidopallium caudolaterale area in six pigeons during the goal-directed decision-making task using the decoding algorithm combining leave-one-out and k-nearest neighbor (LOO- kNN). And the influence of the parameters, include the number of channels, the position and size of decoding window, and the nearest neighbor k value, on the decoding performance was also studied. The results in this study have shown that the two signals can effectively decode the movement intention of pigeons during the this task, but in contrast, the decoding performance of LFP signal is higher than that of spike signal and it is less affected by the number of channels. The best decoding window is in the second half of the goal-directed decision-making process, and the optimal decoding window size of LFP signal (0.3 s) is shorter than that of spike signal (1 s). For the LOO- kNN algorithm, the accuracy is inversely proportional to the k value. The smaller the k value is, the larger the accuracy of decoding is. The results in this study will help to parse the neural information processing mechanism of brain and also have reference value for brain-computer interface.


Urine Bacteria-Derived Extracellular Vesicles and Allergic Airway Diseases in Children.
Microbiota and human allergic airway diseases have been proven to be interrelated. Bacteria-derived extracellular vesicle (EV)s are known to play important roles in interbacterial and human-bacteria communications, but their relationship with allergies has not been examined yet. Urine EVs were investigated to determine whether they could be used as biomarkers for monitoring allergic airway diseases in children. Subjects were 4 groups of chronic rhinitis (CR), allergic rhinitis (AR), atopic asthma (AS) and healthy controls. Single voided urine samples were collected. Urine EVs were isolated and their DNA was extracted for 16S-rDNA pyrosequencing. A total of 118 children participated in this study; 27, 39, 19, and 33 were in the CR, AR, AS, and control group, respectively. The AR had a significantly high Chao-1 index than that of controls. Principal component analysis revealed dysbiosis in the CR, AR, and AS compared to the controls. One phylum and 19 families and genera were significantly enriched or depleted in the disease groups compared to the controls; the Actinobacteria phylum and the Sphingomonadaceae family were more abundant in the AS and CR, the Comamonadaceae family, the Propionibacteraceae family, Propionibacterium and Enhydrobacter were more enriched in the CR, and the Methylobacteriaceae family and Methylobacterium were more abundant in each disease group, while the Enterobacteriaceae family was depleted in each disease group. CR, AR, and AS had a distinct composition of urine EVs. Urine EVs could be an indicator for assessing allergic airway diseases in children.


Multicenter study of retrograde open mesenteric artery stenting through laparotomy for treatment of acute and chronic mesenteric ischemia.
Retrograde open mesenteric stenting (ROMS) through laparotomy was introduced as an alternative to surgical bypass in patients with acute mesenteric ischemia (AMI). The purpose of this study was to evaluate the indications and outcomes of ROMS for treatment of AMI and chronic mesenteric ischemia. We reviewed the clinical data and outcomes of all consecutive patients treated by ROMS in seven academic centers from 2001 to 2013. ROMS was performed through laparotomy with retrograde access into the target mesenteric artery and stent placement using a retrograde or antegrade approach. End points were early (<30 days) and late mortality, morbidity, patency rates, and freedom from symptom recurrence and reintervention. There were 54 patients, 13 male and 41 female, with a mean age of 72 ± 11 years. Indications for ROMS were AMI in 44 patients (81%) and subacute-on-chronic mesenteric ischemia with flush mesenteric occlusion in 10 patients (19%). A total of 56 target mesenteric vessels were stented, including 52 superior mesenteric arteries and 4 celiac axis lesions, with a mean treatment length of 42 ± 26 mm. Retrograde mesenteric access was used in all patients, but 16 patients also required a simultaneous antegrade brachial approach. The retrograde puncture was closed primarily in 34 patients and with patch angioplasty in 17 patients; 1 patient had manual compression. Bowel resection was needed in 29 patients (66%) with AMI because of perforation or gangrene. Technical success was achieved in all (98%) except one patient for whom ROMS failed, who was treated by bypass. Early mortality was 45% (20/44) for AMI and 10% (1/10) for subacute-on-chronic mesenteric ischemia (P = .04). Early morbidity was 73% for AMI and 50% for subacute-on-chronic mesenteric ischemia (P = .27). Patient survival for the entire cohort was 43% ± 9% at 2 years. Primary patency and secondary patency at 2 years were 76% ± 8% and 90% ± 8%, respectively. Freedom from symptom recurrence and freedom from reinterventions were 72% ± 8% and 74% ± 8% at the same interval. ROMS offers an alternative to bypass or percutaneous stenting in patients with AMI who require abdominal exploration and in those who have flush mesenteric occlusions and have failed to respond to or are considered unsuitable for stenting by a percutaneous approach. Despite high technical success, mortality remains elevated in patients with AMI. Patency rates and freedom from symptom recurrence and reinterventions are comparable to the results achieved with stenting using percutaneous technique.


Phenomenological predictions of cohesive energy and structural transition of nanoparticles.
In this paper, it is shown that a liquid-drop model (LDM) can predict the size-dependent cohesive energy (SDCE) of large nanoparticles and clusters (particles with few atoms) quantitatively. The cohesive energy decreases linearly with the inverse of the particle size both for large nanoparticles and clusters though the slopes are different. This indicates that there are three different regions (I-III) of SDCE in the complete size range. Regions I and II represent the SDCE of large nanoparticles and clusters, respectively, while region II represents the intermediate region where the cohesive energy is almost size-independent. Different regions of SDCE correspond to different structures of nanoparticles, and structural transition associated with the particle size can easily be predicted from the SDCE. Analyzing the cohesive energy data on the basis of LDM, it is shown that the surface tension decreases with decreasing size for very small nanoparticles. The Tolman equation can account for the variation of surface tension by predicting the size dependency of the Tolman length.


Assessment of alcohol problems using AUDIT in a prison setting: more than an 'aye or no' question.
Alcohol problems are a major UK and international public health issue. The prevalence of alcohol problems is markedly higher among prisoners than the general population. However, studies suggest alcohol problems among prisoners are under-detected, under-recorded and under-treated. Identifying offenders with alcohol problems is fundamental to providing high quality healthcare. This paper reports use of the AUDIT screening tool to assess alcohol problems among prisoners. Universal screening was undertaken over ten weeks with all entrants to one male Scottish prison using the AUDIT standardised screening tool and supplementary contextual questions. The questionnaire was administered by trained prison officers during routine admission procedures. Overall 259 anonymised completed questionnaires were analysed. AUDIT scores showed a high prevalence of alcohol problems with 73% of prisoner scores indicating an alcohol use disorder (8+), including 36% having scores indicating 'possible dependence' (20-40). AUDIT scores indicating 'possible dependence' were most apparent among 18-24 and 40-64 year-olds (40% and 56% respectively). However, individual questions showed important differences, with younger drinkers less likely to demonstrate habitual and addictive behaviours than the older age group. Disparity between high levels of harmful/hazardous/dependent drinking and low levels of 'treatment' emerged (only 27% of prisoners with scores indicating 'possible dependence' reported being 'in treatment'). Self-reported associations between drinking alcohol and the index crime were identified among two-fifths of respondents, rising to half of those reporting violent crimes. To our knowledge, this is the first study to identify differing behaviours and needs among prisoners with high AUDIT score ranges, through additional analysis of individual questions. The study has identified high prevalence of alcohol use, varied problem behaviours, and links across drinking, crime and recidivism, supporting the argument for more extensive provision of alcohol-focused interventions in prisons. These should be carefully targeted based on initial screening and assessment, responsive, and include care pathways linking prisoners to community services. Finally, findings confirm the value and feasibility of routine use of the AUDIT screening tool in prison settings, to considerably enhance practice in the detection and understanding of alcohol problems, improving on current more limited questioning (e.g. 'yes or no' questions).


Combining nerve fiber layer parameters to optimize glaucoma diagnosis with optical coherence tomography.
To identify the best combination of Stratus optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness parameters for the detection of glaucoma. Observational cross-sectional study. Eighty-nine age-matched normal and perimetric glaucoma participants enrolled in the Advanced Imaging for Glaucoma Study. The Zeiss Stratus OCT system was used to obtain the circumpapillary RNFL thickness in both eyes of each participant. Right and left eye clock-hour data are analyzed together, assuming mirror-image symmetry. The RNFL diagnostic parameters were combined using either or-logic or and-logic approaches. Area under the receiver operating characteristic curve (AROC), sensitivity, and specificity are used to evaluate diagnostic performance. Overall average RNFL thickness has the highest AROC value (0.89) of all single parameters evaluated, followed by the inferior and superior quadrants (0.88 and 0.86, respectively). The clock hours with the best AROC values are in the inferior and superior quadrants. The highest AROC (0.92) was achieved by the or-logic combination of overall, inferior, and superior quadrant RNFL thicknesses. The 3-parameter combination was significantly better than the overall average alone (P = 0.01). The addition of more quadrants or clock hours to the combination reduced diagnostic performance. The best stand-alone diagnostic strategy for Stratus OCT RNFL data is to classify an eye as glaucomatous if the overall, inferior quadrant, or superior quadrant RNFL thickness average is below normal.


Factors underlying scalp-EEG interictal epileptiform discharges in intractable frontal lobe epilepsy.
Scalp-EEG interictal epileptiform discharges (IEDs) may be less predictive of the outcome of frontal lobe epilepsy surgery than of temporal lobe epilepsy surgery. We identified factors associated with the location of scalp-EEG IEDs in intractable frontal lobe epilepsy. Ten factors were assessed in a retrospective review of 53 patients with either concordant (frontal lobe seizure focus) or discordant (generalized or outside frontal seizure focus) IED or both, who had excellent surgical outcomes. The Fisher exact test and the Wilcoxon rank sum test determined statistically significant associations. Thirty-six patients (68%) had concordant IED, 24 (45%) discordant IED, and 17 (32%) both. Younger age at onset was significantly associated with discordant IED (mean, 7.5 years versus 17 years for patients without discordant IED; P < 0.01), whereas duration of epilepsy was not. Seizure foci at the frontal convexity were associated with concordant IED. About 72% of patients with a convexity seizure focus had concordant IED, compared with only 33% of patients with mesial frontal foci having concordant IED (P = 0.06). Early seizure onset in intractable frontal lobe epilepsy is associated with IEDs discordant with seizure focus. Frontal convexity seizure foci are more likely than mesial frontal seizure foci to be associated with concordant discharges.


FRAMA: from RNA-seq data to annotated mRNA assemblies.
Advances in second-generation sequencing of RNA made a near-complete characterization of transcriptomes affordable. However, the reconstruction of full-length mRNAs via de novo RNA-seq assembly is still difficult due to the complexity of eukaryote transcriptomes with highly similar paralogs and multiple alternative splice variants. Here, we present FRAMA, a genome-independent annotation tool for de novo mRNA assemblies that addresses several post-assembly tasks, such as reduction of contig redundancy, ortholog assignment, correction of misassembled transcripts, scaffolding of fragmented transcripts and coding sequence identification. We applied FRAMA to assemble and annotate the transcriptome of the naked mole-rat and assess the quality of the obtained compilation of transcripts with the aid of publicy available naked mole-rat gene annotations. Based on a de novo transcriptome assembly (Trinity), FRAMA annotated 21,984 naked mole-rat mRNAs (12,100 full-length CDSs), corresponding to 16,887 genes. The scaffolding of 3488 genes increased the median sequence information 1.27-fold. In total, FRAMA detected and corrected 4774 misassembled genes, which were predominantly caused by fusion of genes. A comparison with three different sources of naked mole-rat transcripts reveals that FRAMA's gene models are better supported by RNA-seq data than any other transcript set. Further, our results demonstrate the competitiveness of FRAMA to state of the art genome-based transcript reconstruction approaches. FRAMA realizes the de novo construction of a low-redundant transcript catalog for eukaryotes, including the extension and refinement of transcripts. Thereby, results delivered by FRAMA provide the basis for comprehensive downstream analyses like gene expression studies or comparative transcriptomics. FRAMA is available at https://github.com/gengit/FRAMA .


Breast cancer screening behavior in Turkish women: Relationships with health beliefs and self-esteem, body perception and hopelessness.
The purpose was to examine breast cancer screening behavior in Turkish women, the reasons for not doing screening and the relationship between health beliefs and levels of self-esteem, body perception, and hopelessness. This research was conducted as a descriptive, correlational study in an area covered by three neighborhood primary health care clinics in Bornova, Izmir. The data were collected between April and November 2006 from 382 women over 40 years of age who were selected using a stratified random sampling method and a descriptive information form, Champion's Health Belief Model Scale (CHBMS), the Rosenberg Self-Esteem Scale (RSES), the Body Cathexis Scale (BCS) and the Beck Hopelessness Scale (BHS). The breast cancer screening methods used by women participating in the research were, respectively, mammography (34%), clinical breast examination (14.1%), breast self-examination (BSE) (59.4%). The reasons why women did not do breast cancer screening methods were determined to be: not having any symptoms, neglect, not sensing the need, and not knowing how BSE is done. In the examination of the women's CHBMS subscale score means and RSES, BCS and BHS score mean a statistically significant relationships were determined between Benefits-BSE, Barriers-BSE, Confidence, Health motivation, Benefits-mammography and barriers-mammography subscale score means and RSES, BCS and BHS mean scores (p<0.01). It was found out that women with high level of self-esteem, high level of hope for the future and with a positive body perception have more positive health beliefs on breast cancer screening.


Exploring the sustainability of quality improvement interventions in healthcare organisations: a multiple methods study of the 10-year impact of the 'Productive Ward: Releasing Time to Care' programme in English acute hospitals.
The 'Productive Ward: Releasing Time to Care' programme is a quality improvement (QI) intervention introduced in English acute hospitals a decade ago to: (1) Increase time nurses spend in direct patient care. (2) Improve safety and reliability of care. (3) Improve experience for staff and patients. (4) Make changes to physical environments to improve efficiency. To explore how timing of adoption, local implementation strategies and processes of assimilation into day-to-day practice relate to one another and shape any sustained impact and wider legacies of a large-scale QI intervention. Multiple methods within six hospitals including 88 interviews (with Productive Ward leads, ward staff, Patient and Public Involvement representatives and senior managers), 10 ward manager questionnaires and structured observations on 12 randomly selected wards. Resource constraints and a managerial desire for standardisation meant that, over time, there was a shift away from the original vision of empowering ward staff to take ownership of Productive Ward towards a range of implementation 'short cuts'. Nonetheless, material legacies (eg, displaying metrics data; storage systems) have remained in place for up to a decade after initial implementation as have some specific practices (eg, protected mealtimes). Variations in timing of adoption, local implementation strategies and contextual changes influenced assimilation into routine practice and subsequent legacies. Productive Ward has informed wider organisational QI strategies that remain in place today and developed lasting QI capabilities among those meaningfully involved in its implementation. As an ongoing QI approach Productive Ward has not been sustained but has informed contemporary organisational QI practices and strategies. Judgements about the long-term sustainability of QI interventions should consider the evolutionary and adaptive nature of change processes.


Development and evaluation of the Korean Health Literacy Instrument.
The purpose of this study is to develop and validate the Korean Health Literacy Instrument, which measures the capacity to understand and use health-related information and make informed health decisions in Korean adults. In Phase 1, 33 initial items were generated to measure functional, interactive, and critical health literacy with prose, document, and numeracy tasks. These items included content from health promotion, disease management, and health navigation contexts. Content validity assessment was conducted by an expert panel, and 11 items were excluded. In Phase 2, the 22 remaining items were administered to a convenience sample of 292 adults from community and clinical settings. Exploratory factor and item difficulty and discrimination analyses were conducted and four items with low discrimination were deleted. In Phase 3, the remaining 18 items were administered to a convenience sample of 315 adults 40-64 years of age from community and clinical settings. A confirmatory factor analysis was performed to test the construct validity of the instrument. The Korean Health Literacy Instrument has a range of 0 to 18. The mean score in our validation study was 11.98. The instrument exhibited an internal consistency reliability coefficient of 0.82, and a test-retest reliability of 0.89. The instrument is suitable for screening individuals who have limited health literacy skills. Future studies are needed to further define the psychometric properties and predictive validity of the Korean Health Literacy Instrument.