From data repositories to submission portals: rethinking the role of domain-specific databases in CollecTF.
Domain-specific databases are essential resources for the biomedical community, leveraging expert knowledge to curate published literature and provide access to referenced data and knowledge. The limited scope of these databases, however, poses important challenges on their infrastructure, visibility, funding and usefulness to the broader scientific community. CollecTF is a community-oriented database documenting experimentally validated transcription factor (TF)-binding sites in the Bacteria domain. In its quest to become a community resource for the annotation of transcriptional regulatory elements in bacterial genomes, CollecTF aims to move away from the conventional data-repository paradigm of domain-specific databases. Through the adoption of well-established ontologies, identifiers and collaborations, CollecTF has progressively become also a portal for the annotation and submission of information on transcriptional regulatory elements to major biological sequence resources (RefSeq, UniProtKB and the Gene Ontology Consortium). This fundamental change in database conception capitalizes on the domain-specific knowledge of contributing communities to provide high-quality annotations, while leveraging the availability of stable information hubs to promote long-term access and provide high-visibility to the data. As a submission portal, CollecTF generates TF-binding site information through direct annotation of RefSeq genome records, definition of TF-based regulatory networks in UniProtKB entries and submission of functional annotations to the Gene Ontology. As a database, CollecTF provides enhanced search and browsing, targeted data exports, binding motif analysis tools and integration with motif discovery and search platforms. This innovative approach will allow CollecTF to focus its limited resources on the generation of high-quality information and the provision of specialized access to the data.Database URL: http://www.collectf.org/.


Elevated protein tyrosine phosphatase activity and increased membrane viscosity are associated with impaired activation of the insulin receptor kinase in old rats.
Insulin resistance is very common in the elderly, and may be associated with glucose intolerance or frank diabetes. In previous studies we demonstrated that insulin resistance in old Wistar rats is associated with decreased autophosphorylation and activation of the hepatic insulin receptor kinase (IRK) in vivo. We now show that this defect can be reproduced in vitro, where the extent of insulin-induced activation of IRK in liver membranes of old rats was decreased by approximately 50% compared with young controls. The defect could be largely abolished after solubilization of the membranes with Triton X-100. We also show that: (a) the viscosity of membranes from the old rats was significantly (P < 0.001, n = 4) higher (by 15%) compared with young controls; (b) incubation of plasma membranes from old animals with lecithin liposomes, which lowered their cholesterol levels, partially abolished the defect in IRK activation; and (c) Triton extracts of liver membranes prepared from old rats did not interfere with the activation of IRK derived from young controls. Additionally, non-membrane components did contribute to the development of this defect. We observed a significant (approximately 30%) (P < 0.001, n = 18) elevation of cytosolic protein tyrosine phosphatase (PTP) activity directed against the beta subunit of the insulin receptor in livers of old rats. No such elevation of PTP activity could be demonstrated with synthetic substrates. Our findings are consistent with a model in which increased membrane viscosity as well as enhancement of a cytosolic PTP activity both markedly inhibit the activation in vivo of the hepatic IRK in old animals.


Strain and Satisfaction in Caregivers of Veterans With Type 2 Diabetes.
Purpose The purpose of this study was to identify predictors of informal caregiver strain and satisfaction associated with caring for veterans with type 2 diabetes (T2DM). Methods This study is a secondary analysis of data from 2 prior studies of caregiving in the Veterans Health Administration. The original studies used a telephone survey to examine veteran and caregiver (CG) characteristics associated with caregivers' responses to caregiving. The data reported here include 202 veterans with T2DM and 202 caregivers. Linear regression models were generated alternatively using forward and backward selection of veteran and caregiver characteristics. Results Higher caregiver strain was associated with the CG providing activities of daily living assistance, CG receiving less help from friends and relatives and use of unpaid help, CG use of coping strategies, and CG depression scores. Predictors of CG satisfaction included better relationship quality with the veteran and receipt of social support. Conclusions The important role of family and friends in supporting patients with T2DM is widely accepted. Clinicians may engage the caregiver when there is inadequate self-care by the patient. However, less attention has been focused on the effect of caregiving on the caregiver. Greater attention needs to be focused on in-depth exploration of family needs to design and test effective interventions to meet these needs.


Bichat guidelines for the clinical management of Q fever and bioterrorism-related Q fever.
Q fever is a zoonotic disease caused by Coxiella burnetii. Its interest as a potential biological weapon stems from the fact that an aerosol of very few organisms could infect humans. Another route of transmission of C. burnetii could be through adding it to the food supply. Nevertheless, C. burnetii is considered to be one of the less suitable candidate agents for use in a bioterrorist attack; the incubation is long, many infections are inapparent and the mortality is low. In the case of an intentional release of C. burnetii by a terrorist, clinical presentation would be similar to naturally occurring disease. It may be asymptomatic, acute, normally accompanied by pneumonia or hepatitis, or chronic, usually manifested as endocarditis. Most cases of acute Q fever are asymptomatic and resolve spontaneously without specific treatment. Nevertheless, treatment can shorten the duration of illness and decrease the risk of complications such as endocarditis. Post-exposure prophylaxis is recommended after the exposure in the case of a bioterrorist attack.


An update in treatment options for multiple myeloma in nontransplant eligible patients.
Despite the fact that multiple myeloma (MM) is still an incurable disease, the outcome of patients who are eligible and ineligible for high-dose therapy has dramatically improved with the introduction of novel agents, that is proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). However, this improvement is often not seen in elderly patients (above 75 years). This review will focus on the impact of known prognostic factors in elderly MM patients, and risk factors to identify frail elderly patients. Furthermore, data on known and novel PIs and IMiDs, as well as data on other promising novel treatment strategies, chosen based on current practice and anticipated timely approval, will be discussed. Novel treatment strategies include the use of monoclonal antibodies, such as elotuzumab, daratumumab, SAR650984 and more targeted therapies, such as histone deacetylase inhibitors, kinesin spindle protein inhibitors, and selective inhibitors of nuclear export. Besides efficacy of treatment, toxicity and quality of life play an important role in treatment choice. Treatment and treatment dosing for the frail elderly as well as risk factors to identify the frail elderly require further consideration, as these patients frequently do not benefit from these novel agents due to early discontinuation of treatment due to toxicity.


Neural network for control of rearrangeable Clos networks.
Rapid evolution in the field of communication networks requires high speed switching technologies. This involves a high degree of parallelism in switching control and routing performed at the hardware level. The multistage crossbar networks have always been attractive to switch designers. In this paper a neural network approach to controlling a three-stage Clos network in real time is proposed. This controller provides optimal routing of communication traffic requests on a call-by-call basis by rearranging existing connections, with a minimum length of rearrangement sequence so that a new blocked call request can be accommodated. The proposed neural network controller uses Paull's rearrangement algorithm, along with the special (least used) switch selection rule in order to minimize the length of rearrangement sequences. The functional behavior of our model is verified by simulations and it is shown that the convergence time required for finding an optimal solution is constant, regardless of the switching network size. The performance is evaluated for random traffic with various traffic loads. Simulation results show that applying the least used switch selection rule increases the efficiency in switch rearrangements, reducing the network convergence time. The implementation aspects are also discussed to show the feasibility of the proposed approach.


Influenza infection leads to increased susceptibility to subsequent bacterial superinfection by impairing NK cell responses in the lung.
Influenza viral infection is well-known to predispose to subsequent bacterial superinfection in the lung but the mechanisms have remained poorly defined. We have established a murine model of heterologous infections by an H1N1 influenza virus and Staphylococcus aureus. We found that indeed prior influenza infection markedly increased the susceptibility of mice to secondary S. aureus superinfection. Severe sickness and heightened bacterial infection in flu and S. aureus dual-infected animals were associated with severe immunopathology in the lung. We further found that flu-experienced lungs had an impaired NK cell response in the airway to subsequent S. aureus bacterial infection. Thus, adoptive transfer of naive NK cells to the airway of prior flu-infected mice restored flu-impaired antibacterial host defense. We identified that TNF-alpha production of NK cells played an important role in NK cell-mediated antibacterial host defense as NK cells in flu-experienced lungs had reduced TNF-alpha expression and adoptive transfer of TNF-alpha-deficient NK cells to the airway of flu-infected mice failed to restore flu-impaired antibacterial host defense. Defected NK cell function was found to be an upstream mechanism of depressed antibacterial activities by alveolar macrophages as contrast to naive wild-type NK cells, the NK cells from flu-infected or TNF-alpha-deficient mice failed to enhance S. aureus phagocytosis by alveolar macrophages. Together, our study identifies the weakened NK cell response in the lung to be a novel critical mechanism for flu-mediated susceptibility to bacterial superinfection.


Automated cardiovascular magnetic resonance image analysis with fully convolutional networks.
Cardiovascular resonance (CMR) imaging is a standard imaging modality for assessing cardiovascular diseases (CVDs), the leading cause of death globally. CMR enables accurate quantification of the cardiac chamber volume, ejection fraction and myocardial mass, providing information for diagnosis and monitoring of CVDs. However, for years, clinicians have been relying on manual approaches for CMR image analysis, which is time consuming and prone to subjective errors. It is a major clinical challenge to automatically derive quantitative and clinically relevant information from CMR images. Deep neural networks have shown a great potential in image pattern recognition and segmentation for a variety of tasks. Here we demonstrate an automated analysis method for CMR images, which is based on a fully convolutional network (FCN). The network is trained and evaluated on a large-scale dataset from the UK Biobank, consisting of 4,875 subjects with 93,500 pixelwise annotated images. The performance of the method has been evaluated using a number of technical metrics, including the Dice metric, mean contour distance and Hausdorff distance, as well as clinically relevant measures, including left ventricle (LV) end-diastolic volume (LVEDV) and end-systolic volume (LVESV), LV mass (LVM); right ventricle (RV) end-diastolic volume (RVEDV) and end-systolic volume (RVESV). By combining FCN with a large-scale annotated dataset, the proposed automated method achieves a high performance in segmenting the LV and RV on short-axis CMR images and the left atrium (LA) and right atrium (RA) on long-axis CMR images. On a short-axis image test set of 600 subjects, it achieves an average Dice metric of 0.94 for the LV cavity, 0.88 for the LV myocardium and 0.90 for the RV cavity. The mean absolute difference between automated measurement and manual measurement is 6.1 mL for LVEDV, 5.3 mL for LVESV, 6.9 gram for LVM, 8.5 mL for RVEDV and 7.2 mL for RVESV. On long-axis image test sets, the average Dice metric is 0.93 for the LA cavity (2-chamber view), 0.95 for the LA cavity (4-chamber view) and 0.96 for the RA cavity (4-chamber view). The performance is comparable to human inter-observer variability. We show that an automated method achieves a performance on par with human experts in analysing CMR images and deriving clinically relevant measures.


High quantum-efficiency photon-number-resolving detector for photonic on-chip information processing.
The integrated optical circuit is a promising architecture for the realization of complex quantum optical states and information networks. One element that is required for many of these applications is a high-efficiency photon detector capable of photon-number discrimination. We present an integrated photonic system in the telecom band at 1550 nm based on UV-written silica-on-silicon waveguides and modified transition-edge sensors capable of number resolution and over 40 % efficiency. Exploiting the mode transmission failure of these devices, we multiplex three detectors in series to demonstrate a combined 79 % ± 2 % detection efficiency with a single pass, and 88 % ± 3 % at the operating wavelength of an on-chip terminal reflection grating. Furthermore, our optical measurements clearly demonstrate no significant unexplained loss in this system due to scattering or reflections. This waveguide and detector design therefore allows the placement of number-resolving single-photon detectors of predictable efficiency at arbitrary locations within a photonic circuit - a capability that offers great potential for many quantum optical applications.


Use of the orthogonal projection approach (OPA) to monitor batch processes.
The orthogonal projection approach (OPA) and multivariate curve resolution (MCR) are presented as a way to monitor batch processes using spectroscopic data. Curve resolution allows one to look within a batch and predict on-line real concentration profiles of the different species appearing during reactions. Taking into account the variations of the process by using an augmented matrix of complete batches, the procedure explained here calculates some prediction coefficients that can afterwards be applied for a new batch.


Habitat fragmentation, species loss, and biological control.
Fragmentation of habitats in the agricultural landscape is a major threat to biological diversity, which is greatly determined by insects. Isolation of habitat fragments resulted in decreased numbers of species as well as reduced effects of natural enemies. Manually established islands of red clover were colonized by most available herbivore species but few parasitoid species. Thus, herbivores were greatly released from parasitism, experiencing only 19 to 60 percent of the parasitism of nonisolated populations. Species failing to successfully colonize isolated islands were characterized by small and highly variable populations. Accordingly, lack of habitat connectivity released insects from predator control.


On-column ion-exchange preconcentration of inorganic anions in open tubular capillary electrochromatography with elution using transient-isotachophoretic gradients. 3. Implementation and method development.
A solid-phase extraction method based on an ion-exchange retention mechanism has been used for in-line preconcentration of inorganic anions prior to their separation by capillary electrophoresis (CE). A single capillary containing a preconcentration and a separation zone has been used in a commercial CE instrument without instrumental modification. Analyte anions were retained on a preconcentration zone comprising an adsorbed layer of cationic latex particles, while separation was achieved in a separation zone comprising fused silica modified by adsorption of a cationic polymer. Elution of the adsorbed analytes was achieved using an eluotropic gradient formed by a transient isotachophoretic boundary between a fluoride electrolyte and a naphthalenedisulfonate electrolyte. Optimization of the electrolyte concentrations, sample injection times, and back-flushing times allowed the successful separation of sub-ppb levels of inorganic anions using a 100-min injection at 2 bar pressure, introducing over 40 capillary volumes of sample. A method based on a 10-min injection allowed a 100-fold increase in sensitivity over conventional hydrodynamic injection for Br-, I-, NO3-, CrO4(2-), and MoO4(2-) with a total analysis time of 25 min. Detection limits were dependent on the injection time but were in the range 2.2-11.6 ppb for a 10-min injection time. This approach was used to determine NO3- in Antarctic ice cores where the analysis could be performed using a sample volume 100 times less than that used for ion chromatography.


The effect of equal daily dose achieved by different power densities of low-level laser therapy at 635 and 670 nm on wound tensile strength in rats: a short report.
The aim of our study was to compare the effects of different power densities of LLLT at 635 and 670 nm achieving a daily dose of 5 J/cm(2) on wound tensile strength (TS) in rats. Optimal parameters of low-level laser therapy (LLLT) are still unknown. Under general anesthesia, one full-thickness skin incision was performed on the back of each rat (n = 40) and immediately closed using an intradermal running suture. Rats were separated into five groups depending on treatment parameters: (1) sham irradiated control group (SIC); (2) 635 nm laser-treated group at 4 mW/cm(2) (L-635/4); (3) 635 nm laser-treated group at 15 mW/cm(2) (L-635/15); (4) 670 nm laser-treated group at 4 mW/cm(2) (L-670/4); and (5) 670 nm laser-treated group at 15 mW/cm(2) (L-670/15). The total daily dose was 5 J/cm(2). Seven days after surgery each wound was removed for wound TS measurement. The lowest wound TS results were measured in the SIC rats (10.5 +/- 2.8 g/mm(2)). Higher wound TS results were measured in group L-670/15 (11.5 +/- 2.5 g/mm(2)) and group L-635/4 (11.7 +/- 4.3 g/mm(2)) rats, while significantly higher results were found in group L-670/4 (15.8 +/- 4.4 g/mm(2)) and group L-635/15 (15.9 +/- 4.8 g/mm(2)). The differences were significant between certain groups (p < 0.01: SIC vs. L-635/15, SIC vs. L-670/4; p < 0.05: L-635/4 vs. L-635/15, L-635/4 vs. L-670/4, L-635/15 vs. L-670/15, L-670/4 vs. L-670/15). Both red lasers significantly increased wound TS at selected parameters. Whereas the 635 nm laser significantly improved wound healing by using the higher power density, the 670 nm laser improved healing using a lower power density.


Whole-Grain Intake, Reflected by Dietary Records and Biomarkers, Is Inversely Associated with Circulating Insulin and Other Cardiometabolic Markers in 8- to 11-Year-Old Children.
Background: Whole-grain consumption seems to be cardioprotective in adults, but evidence in children is limited.Objective: We investigated whether intakes of total whole grain and dietary fiber as well as specific whole grains were associated with fat mass and cardiometabolic risk profile in children.Methods: We collected cross-sectional data on parental education, puberty, diet by 7-d records, and physical activity by accelerometry and measured anthropometry, fat mass index by dual-energy X-ray absorptiometry, and blood pressure in 713 Danish children aged 8-11 y. Fasting blood samples were obtained and analyzed for alkylresorcinols, biomarkers of whole-grain wheat and rye intake, HDL and LDL cholesterol, triacylglycerols, insulin, and glucose. Linear mixed models included puberty, parental education, physical activity, and intakes of energy, fruit and vegetables, saturated fat, and n-3 (ω-3) polyunsaturated fatty acids.Results: Median (IQR) whole-grain and dietary fiber intakes were 52 g/d (35-72 g/d) and 17 g/d (14-22 g/d), respectively. Fourteen percent of children were overweight or obese and most had low-risk cardiometabolic profiles. Dietary whole-grain and fiber intakes were not associated with fat mass index but were inversely associated with serum insulin [both P < 0.01; e.g., with 0.68 pmol/L (95% CI: 0.26, 1.10 pmol/L) lower insulin · g whole grain-1 · MJ-1]. Whole-grain oat intake was inversely associated with fat mass index, systolic blood pressure, and LDL cholesterol (all P < 0.05) as well as insulin (P = 0.003), which also tended to be inversely associated with whole-grain rye intake (P = 0.11). Adjustment for fat mass index did not change the associations. The C17-to-C21 alkylresorcinol ratio, reflecting whole-grain rye to wheat intake, was inversely associated with insulin (P < 0.001).Conclusions: Higher whole-grain intake was associated with lower serum insulin independently of fat mass in 8- to 11-y-old Danish children. Whole-grain oat intake was linked to an overall protective cardiometabolic profile, and whole-grain rye intake was marginally associated with lower serum insulin. This supports whole grains as healthy dietary components in childhood. This trial was registered at clinicaltrials.gov as NCT01577277.


Upscaling behavioural studies to the field using acoustic telemetry.
Laboratory-based behavioural assays are often used in ecotoxicological studies to assess the environmental risk of aquatic contaminants. While results from such laboratory-based risk assessments may be difficult to extrapolate to natural environments, technological advancements over the past decade now make it possible to perform risk assessments through detailed studies of exposed individuals in natural settings. Acoustic telemetry is a technology to monitor movement and behaviour of aquatic organism in oceans, lakes, and rivers. The technology allows for tracking of multiple individuals simultaneously with very high temporal and spatial resolution, with the option to incorporate sensors to measure various physiological and environmental parameters. Although frequently used in fisheries research, aquatic ecotoxicology has been slow to adopt acoustic telemetry as a tool in field-based studies. This mini-review intends to introduce acoustic telemetry to aquatic ecotoxicologists, focusing on the potential of the technology to bridge the gap between laboratory assays and natural behaviours when making toxicological risk assessments.


Trait urgency and gambling problems in young people by age: the mediating role of decision-making processes.
Although the personality trait of urgency has been linked to problem gambling, less is known about psychological mechanisms that mediate the relationship between urgency and problem gambling. One individual variable of potential relevance to impulsivity and addictive disorders is age. The aims of this study were to examine: (i) a theoretical model associating urgency and gambling problems, (ii) the mediating effects of decision-making processes (operationalized as preference for small/immediate rewards and lower levels of deliberative decision-making); and (iii) age differences in these relationships. Participants comprised 986 students (64% male; mean age=19.51 years; SD=2.30) divided into three groups: 16-17 years, 18-21 years, and 22-25 years. All participants completed measures of urgency, problem gambling, and a delay-discounting questionnaire involving choices between a smaller amount of money received immediately and a larger amount of money received later. Participants were also asked to reflect on their decision-making process. Compared to those aged 16-17 years and 22-25 years, participants aged 18-21 years had a higher level of gambling problems and decreased scores on lower levels of deliberative decision-making. Higher levels of urgency were associated with higher levels of gambling problems. The association was mediated by a lower level of deliberative decision-making and preference for an immediate/small reward. A distinct pathway was observed for lower levels of deliberative decision-making. Young people who tend to act rashly in response to extreme moods, had lower levels of deliberative decision-making, that in turn were positively related to gambling problems. This study highlights unique decision-making pathways through which urgency trait may operate, suggesting that those developing prevention and/or treatment strategies may want to consider the model's variables, including urgency, delay discounting, and deliberative decision-making.


Intertrial priming of popout search on visual prior entry.
When the features of a visual target and of nontargets are repeated between successive search displays, responding to a subsequent target is faster than when the features of the target and the nontargets switch between trials. This intertrial priming effect can influence perceptual processes, postperceptual processes (e.g., episodic retrieval), or both. Previous studies have shown that repeating irrelevant visual features that do not define the target or the response can influence postperceptual processes. The present study examined whether intertrial priming by irrelevant features also influences perceptual processes. Subjects completed a temporal order judgment task that appeared within a popout visual search display containing a color singleton among nonsingletons, all of which served as placeholders for two probes. Intertrial priming by the placeholder colors shifted the psychometric function. Specifically, the probes appearing at the color singleton in the switch condition needed to appear earlier than the probes at the color singleton in the repeat condition to be perceived simultaneous with the probes on a nonsingleton. This suggests there was an influence of intertrial priming by the irrelevant colors on visual prior entry; hence, repeating irrelevant features between trials can influence perpetual processes.


Hydrogen-bonding cavities about metal ions: synthesis, structure, and physical properties for a series of monomeric M-OH complexes derived from water.
The tripodal ligand N[CH2CH2NHC(O)NHC(CH3)3]3 ([H61]) was used to synthesize a series of monomeric complexes with terminal hydroxo ligands. The complexes [Co(II/III)H31(OH)](2-/1-), [Fe(II/III)H31(OH)](2-/1-), and [Zn(II)H31(OH)](2-) have been isolated and characterized. The source of the hydroxo ligand in these complexes is water, which was confirmed with an isotopic labeling study for [Co(III)H31(OH)](1-). The synthesis of [M(II)H31(OH)](2-) complexes was accomplished by two routes. Method A used 3 equiv of base prior to metalation and water binding, affording yields of < or = 40% for [Co(II)H31(OH)](2-). When 4 equiv of base was used (method B), yields ranged from 50% to 70% for all of the M(II)H31(OH)](2-) complexes. This improvement is attributed to the presence of an intramolecular basic site within the cavity, which scavenges protons produced during formation of the M(II)-OH complexes. The molecular structures of [Zn(II)H31(OH)](2-), [Fe(II)H31(OH)](2-), [Co(II)H31(OH)](2-), and [Co(III)H31(OH)](1-) were examined by X-ray diffraction methods. The complexes have trigonal bipyramidal coordination geometry with the hydroxo oxygen trans to the apical nitrogen. The three M(II)-OH complexes crystallized with nearly identical lattice parameters, and each contains two independent anions in the asymmetric unit. The complexes have intramolecular H-bonds from the urea cavity of [H31](3-) to the coordinated hydroxo oxygen. All the complexes have long M-O(H) bond lengths (>2.00 A) compared to those of the few previously characterized synthetic examples. The longer bond distances in [M(II)H31(OH)](2-) reflect the intramolecular H-bonds in the complexes. The five-coordinate [Zn(II)H31(OH)](2-) has an average Zn-O(H) distance of 2.024(2) A, which is similar to that found for the zinc site in carbonic anhydrase II (2.05(2) A). The enzyme active site also has an extensive network of intramolecular H-bonds to the hydroxo oxygen. [Co(II)H31(OH)](2-) and [Fe(II)H31(OH)](2-) have one-electron redox processes at -0.74 and -1.40 V vs SCE. Both complexes can be chemically oxidized to yield their corresponding M(III)-OH complexes. [Co(III)H31(OH)](1-), with an S = 1 ground state, is a rare example of a paramagnetic Co(III) complex.


Optimizing college health promotion in the digital age: Comparing perceived well-being, and health behaviors, health education needs and preferences between college students enrolled in fully online versus campus-based programss.
Background: There is little published about non-traditional and online college students' health and well-being. College health services must evolve to address the needs of this growing population. The purpose of this study was to explore risk factors, perceived well-being, health behaviors, and health education preferences of US college students enrolled in a fully online academic programs compared to a national sample of college students enrolled in campus based programs. Methods: This cross-sectional study included a volunteer sample of 961 college students enrolled in two large, U.S. accredited online universities. Participants completed an online survey that included questions and sub scales from the National College Health Assessment (NCHA, IIb). Responses on survey items from student learning online were compared to an equal sample of college students enrolled in non-online programs, randomly drawn from the NCHA IIb national data set (n = 961). Frequencies on survey items were calculated and mean scores of subset measures for online students were compared against those from the NCHA data set using two tailed z-test scores and independent sample t-tests with alpha at 0.05. Results: Online students reported significantly (P ≤ 0.05) higher percentages of chronic illnesses, psychiatric conditions, mobility disabilities, deafness/hearing loss, speech/language disorders,cigarette use, obesity, sedentary activity, and depression than the NCHA national sample. Implication for Practice: Health professionals and leaders who work in higher education must consider the shifting landscape and demographics in higher education in order to develop more tailored, innovative digital health promotion approaches that effectively reach the growing population of online, commuter, and older learners.


Human umbilical vein-derived dopaminergic-like cell transplantation with nerve growth factor ameliorates motor dysfunction in a rat model of Parkinson's disease.
Mesenchymal stem cells are capable of differentiating into dopaminergic-like cells, but currently no report has been available to describe the induction of human umbilical vein mesenchymal stem cells (HUVMSCs) into dopaminergic-like cells. In this study, we induced HUVMSCs in vitro into neurospheres constituted by neural stem-like cells, and further into cells bearing strong morphological, phenotypic and functional resemblances with dopaminergic-like cells. These HUVMSC-derived dopaminergic-like cells, after grafting into the brain of a rat model of Parkinson's disease (PD), showed a partial therapeutic effect in terms of the behavioral improvement. Nerve growth factor was reported to improve the local microenvironment of the grafted cells, and we therefore further tested the effect of dopaminergic-like cell grafting combined with nerve growth factor (NGF) administration at the site of cell transplantation. The results showed that NGF administration significantly promoted the survival of the grafted cells in the host brain and enhanced the content of dopaminergic in the local brain tissue. Behavioral test demonstrated a significant improvement of the motor function of the PD rats after dopaminergic-like cell grafting with NGF administration as compared with that of rats receiving the cell grafting only. These results suggest that transplantation of the dopaminergic-like cells combined with NGF administration may represent a new strategy of stem cell therapy for PD.


Field evaluation and treatment of short-term psycho-medical trauma after sexual assault in the Democratic Republic of Congo.
During the horrific war in the Democratic Republic of Congo during the years 1996-2007 the number of casualties is estimated to be 5.4 million. In addition, 1.8 million women, children and men were raped, many as a social weapon of war. Many of these women still suffer from post-traumatic stress disorder (PTSD) and mutilated genitals. To assess a short-term interventional team for the evaluation and treatment of sexual trauma victims. The intervention program comprised four components: training the local staff, medical evaluation and treatment of patients, psychological evaluation and treatmentof trauma victims, and evacuation and transport of patients with mutilated genitals. A diagnostic tool for posttraumatic stress disorder (PTSD)--the Impact Event Scale (IES)--was used. The psychological treatment was based on EMDR (eye movement desensitization and reprocessing) principles. Using questionnaires, the information was obtained from patients, medical staff and medical records. Three primary care clinics were chosen for intervention. Of the 441 women who attended the clinics over a period of 20 days, 52 women were diagnosed with severe PTSD. Psychological intervention was offered to only 23 women because of transport limitations. The most common medical problems were pelvic inflammatory disease and secondary infertility. Nine patients suffered genital mutilation and were transferred for surgical correction. The 32 local nurses and 2 physicians who participated in the theoretical and practical training course showed improved knowledge as evaluated by a written test. With the short-term interventional team model for sexual assault victims the combined cost of medical and psychological services is low. The emphasis is on training local staff to enhance awareness and providing them with tools to diagnose and treat sexual assault and mutilation.


External Iliac Arterial Obstruction Caused by Satinsky Atrauma Forceps in Renal Transplantation.
External iliac arterial obstruction is relatively rare in renal transplantation, and may cause surgical failure and ipsilateral leg ischaemia. Prompt diagnosis and management of this kind of complication is essential to rescue the patient and allograft. Four patients with external iliac arterial obstruction caused by Satinsky atrauma forceps in renal transplantation were analysed and summarized. In case one, the obstruction of the external iliac artery distal to the renal allograft caused ipsilateral leg ischaemia. After surgical fixation of the endarterium, the patient recovered from the lower limb ischaemia. In case two, the obstruction of the external iliac artery was located proximal to the renal allograft. Since the endarterial rupture was not found and fixed in time, the renal allograft was lost. The third case was similar to the second. Based on the previous experience, we fixed the endarterium promptly and transplanted the kidney back successfully. In case four, there was endarterial rupture with atherosclerosis located around the anastomosis stoma. After taking out the atherosclerotic plaque and fixing the endarterium, the blood supply of kidney and lower limb was good. External iliac arterial rupture and obstruction caused by Satinsky atrauma forceps in renal transplantation is rare, but may cause severe and depressing outcome. The critical step is to find and fix the impaired endarterium as early as possible.


Headteachers' prior beliefs on child health and their engagement in school based health interventions: a qualitative study.
Schools play an important role in promoting the health of children. However, little consideration is often given to the influence that headteachers' and school staff's prior beliefs have on the implementation of public health interventions. This study examined primary school headteachers' and school health co-ordinators' views regarding child health in order to provide greater insights on the school's perspective for those designing future school-based health interventions. A qualitative study was conducted using 19 semi-structured interviews with headteachers, deputy headteachers and school health co-ordinators in the primary school setting. All transcripts were analysed using thematic analysis. Whilst many participants in this study believed good health was vital for learning, wide variance was evident regarding the perceived health of school pupils and the magnitude of responsibility schools should take in addressing child health behaviours. Although staff in this study acknowledged the importance of their role, many believed the responsibility placed upon schools for health promotion was becoming too much; suggesting health interventions need to better integrate school, parental and societal components. With mental health highlighted as an increasing priority in many schools, incorporating wellbeing outcomes into future school based health interventions is advocated to ensure a more holistic understanding of child health is gained. Understanding the health beliefs of school staff when designing interventions is crucial as there appears to be a greater likelihood of interventions being successfully adopted if staff perceive a health issue as important among their pupils. An increased dependability on schools for addressing health was expressed by headteachers in this study, highlighting a need for better understanding of parental, child and key stakeholder perspectives on responsibility for child health. Without this understanding, there is potential for certain child health issues to be ignored.


Characteristics of optical guided modes in lossy waveguides.
A number of analysis techniques aimed at determining the characteristics of optical guided waves propagating in lossy structures are examined. The exact theory is used as a guide to assess the validity of several approximate methods based on two basic approaches: (a) geometrical optics and (b) perturbation calculations. The limitations of the conventional perturbation techniques are specified. We present a generalized procedure that permits an accurate description of metal boundaries at optical frequencies. In this case, TM modes differ from their TE counterparts by a field buildup near conducting walls and by the existence of an additional surface plasma mode. The dependence of attenuation coefficients on film thickness and mode order are discussed. The use of low-index dielectric buffers to reduce ohmic losses is considered. It is found that, with increasing buffer thickness, TM(N) modes undergo a continuous transformation to become TM(N+1).


Definition of the minimal MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. The European Consortium on Men1, (GENEM 1; Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1).
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with a high penetrance characterized by tumors of the parathyroid glands, the endocrine pancreas, and the anterior pituitary. The MEN1 gene, a putative tumor suppressor gene, has been mapped to a 3- to 8-cM region in chromosome 11q13 but it remains elusive as yet. We have combined the efforts and resources from four laboratories to form the European Consortium on MEN1 with the aims of establishing the genetic and the physical maps of 11q13 and of further narrowing the MEN1 region. A 5-Mb integrated map of the region was established by fluorescence in situ hybridization on both metaphase chromosomes and DNA fibers, by hybridization to DNA from somatic cell hybrids containing various parts of human chromosome 11, by long-range restriction mapping, and by characterization of YACs and cosmids. Polymorphic markers were positioned and ordered by physical mapping and genetic linkage in 86 MEN1 families with 452 affected individuals. Two critical recombinants identified in two affected cases placed the MEN1 gene in an approximately 2-Mb region around PYGM, flanked by D11S1883 and D11S449.


Serum levels of lipids, calcium and magnesium in women with hypothyroidism and cardiovascular diseases.
Lipid abnormalities in hypothyroidism contribute to the disproportionate increase in cardiovascular risk. A possible relationship between serum level of magnesium (Mg) and calcium (Ca) and cardiovascular disease was recorded. In this work, the possible correlation between lipid profile components and serum cations Ca and Mg was investigated. Matched healthy women were evaluated in a cross-sectional study. All parameters were measured spectrophotometrically. The results showed a significant decrease (P < 0.05) in high-density lipoprotein-cholesterol (HDL-C), total and ionized Mg in hypothyroid patients in comparing with control group. There was a significant increase (P <0.05) in serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and (LDL-C)/(HDL-C) ratio in hypothyroid patients as compared with control group. However, no correlation was found between the cation levels and lipid profile of the studied groups. It can be concluded that patients with hypothyroidism exhibited elevated atherogenic parameters (TC and LDL-C) and high risk of cardiovascular diseases.


Fighting Doping in Elite Sports: Blood for All Tests!
In the fight against doping, detection of doping substances in biological matrices is paramount. Analytical possibilities have evolved and sanctioning a doping scenario by detecting forbidden bioactive compounds circulating unmodified in blood is nowadays very attractive. In addition, the World Anti-Doping Agency (WADA) introduced the Athlete Biological Passport (ABP) a decade ago as a new paradigm inferring the use of prohibited substances or methods through longitudinal profiling, or serial analyses of indirect biomarkers of doping, to be both scientifically and legally robust. After the introduction in 2008 of an hematological module (i.e., based on variations of blood variables) aiming to identify enhancement of oxygen transport and any form of blood transfusion or manipulation, a urinary steroidal module was additionally introduced in 2014 composed of concentrations and ratios of various endogenously produced steroidal hormones. Some evidence tends to discredit steroid profiles obtained from urine analyses to detect the use of endogenous androgenic anabolic steroids (EAAS), when administered exogenously, due to high rates of false negatives with short half-life and topical formulations rendering profile alteration only minimal or equivocal. On the other hand, steroid hormones quantification in blood showed a promising ability to detect testosterone doping and interesting complementarities to the ABP thanks to the most recent analytical techniques (UHPLC-HRMS or/and MS/MS). This perspective article explores the opportunities of blood samples to monitor not only hematological but also steroid profiles in elite athletes.


Complex movement disorders at disease onset in childhood narcolepsy with cataplexy.
Narcolepsy with cataplexy is characterized by daytime sleepiness, cataplexy (sudden loss of bilateral muscle tone triggered by emotions), sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. Narcolepsy with cataplexy is most often associated with human leucocyte antigen-DQB1*0602 and is caused by the loss of hypocretin-producing neurons in the hypothalamus of likely autoimmune aetiology. Noting that children with narcolepsy often display complex abnormal motor behaviours close to disease onset that do not meet the classical definition of cataplexy, we systematically analysed motor features in 39 children with narcolepsy with cataplexy in comparison with 25 age- and sex-matched healthy controls. We found that patients with narcolepsy with cataplexy displayed a complex array of 'negative' (hypotonia) and 'active' (ranging from perioral movements to dyskinetic-dystonic movements or stereotypies) motor disturbances. 'Active' and 'negative' motor scores correlated positively with the presence of hypotonic features at neurological examination and negatively with disease duration, whereas 'negative' motor scores also correlated negatively with age at disease onset. These observations suggest that paediatric narcolepsy with cataplexy often co-occurs with a complex movement disorder at disease onset, a phenomenon that may vanish later in the course of the disease. Further studies are warranted to assess clinical course and whether the associated movement disorder is also caused by hypocretin deficiency or by additional neurochemical abnormalities.


Vascular endothelial growth factor suppresses TNFSF15 production in endothelial cells by stimulating miR-31 and miR-20a expression via activation of Akt and Erk signals.
Tumor necrosis factor superfamily-15 (TNFSF15; VEGI; TL1A) is a negative modulator of angiogenesis for blood vessel homeostasis and is produced by endothelial cells in a mature vasculature. It is known to be downregulated by vascular endothelial growth factor (VEGF), a major regulator of neovascularization but the mechanism of this interaction is unclear. Here we report that VEGF is able to stimulate the production of two microRNAs, miR-20a and miR-31, which directly target the 3'-UTR of TNFSF15. Additionally, we show that two VEGF-stimulated cell growth signals, Erk and Akt, are responsible for promoting the expression of miR-20a and miR-31. Treatment of human umbilical vein endothelial cells (HUVECs) with Akt inhibitor LY294002 results in diminished miR-20a and miR-31 production, while Erk inhibitor U0126 prevented VEGF-stimulated expression of miR-20a but not that of miR-31. Furthermore, inactivation of either Erk or Akt signals restores TNFSF15 gene expression. In an angiogenesis assay, elevated miR-20a or miR-31 levels in HUVECs leads to enhancement of capillary-like tubule formation in vitro, whereas lowered miR-20a and miR-31 levels results in an inhibition. These findings are consistent with the view that miR-20a and miR-31 mediate VEGF-induced downregulation of TNFSF15. Targeting these microRNA molecules may therefore provide an effective approach to inhibit angiogenesis.


Suicidality, internalizing problems and externalizing problems among adolescent bullies, victims and bully-victims.
The aim of this study is to compare suicidality, internalizing problems and externalizing problems among adolescent victims, bullies and bully-victims. This study examined bullying involvement among a subset of the baseline sample of the Climate and Preventure study, a trial of a comprehensive substance use prevention intervention for adolescents in 2012. The sample included 1588 Year 7-9 students in New South Wales and Victoria, Australia. Victims, bullies and bully-victims had more problems than uninvolved students. Students with internalizing problems were more likely to be a victim than a bully. Some externalizing problems (alcohol and tobacco use) were associated with increased odds of being a bully, but not others (cannabis use and conduct/hyperactivity symptoms). Suicidal ideation, internalizing problems and some externalizing problems increased the odds of being a bully-victim compared to being a bully or a victim. Early intervention for adolescents frequently involved in bullying may reduce the onset of substance use and other mental disorders. It would be advisable for bullying interventions to include a focus on substance use and mental health problems. A reduction in these chronic and detrimental problems among adolescents could potentially lead to a concomitant reduction in bullying involvement.


Polymorphisms of methylene-tetrahydrofolate reductase and risk of lung cancer: a case-control study.
Previous studies have suggested that low folate intake is associated with increased risk of lung cancer. Methylene-tetrahydrofolate reductase (MTHFR) is one of the enzymes involved in folate metabolism and is thought to influence DNA methylation and nucleotide synthesis. MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. Therefore, we hypothesized that these variant genotypes may play a role in the etiology of lung cancer. To test this hypothesis, we investigated the association between two common MTHFR polymorphisms (C677T and A1298C) and risk of lung cancer in a non-population-based case-control study of 550 histologically confirmed lung cancer cases and 554 healthy controls. The subjects were non-Hispanic whites, and the controls were frequency-matched to the cases by age (+ or -5 years), sex, and smoking status (ever or never). Folate intake and alcohol consumption were estimated from a self-administered food-frequency questionnaire. The cases consumed significantly less folate (162 microg/day/1000 kcal) than the controls did (172 microg/day/1000 kcal; P = 0.033). However, we found no evidence for an association between the MTHFR C677T and A1298C polymorphisms and risk of lung cancer in either all of the subjects or the low folate intake subgroup; nor did we find evidence for an interaction between these two MTHFR polymorphisms and dietary folate intake or alcohol use. In multivariate logistic regression analysis, the adjusted odds ratios and 95% confidence intervals for MTHFR C677T were 1.1 (0.8-1.4) for 677CT versus 677CC wild type and 1.1 (0.7-1.7) for 677TT versus 677CC, and for MTHFR A1298C, they were 1.0 (0.8-1.3) for 1298AC versus 1298AA wild type and 1.1 (0.7-1.8) for 1298CC versus 1298AA. These results suggest that the MTHFR C677T and A1298C polymorphisms by themselves do not play an important role in the etiology of lung cancer.


Comprehensive gene expression analysis of peroxisome proliferator-treated immortalized hepatocytes: identification of peroxisome proliferator-activated receptor alpha-dependent growth regulatory genes.
Chemicals known as peroxisome proliferators (PPs) are the subject of intense study because of their ability to cause hepatocellular carcinoma in laboratory rodents. These chemicals act through a family of proteins termed the peroxisome proliferator-activated receptors (PPARs), in particular PPARalpha. It has become increasingly apparent that the role of the PPs in the development of cancer encompasses many different aspects of cell growth regulation. Immortalized hepatocytes from wild-type (PPARalpha(+/+)) and PPARalpha(-/-) mice were generated using a temperature-sensitive SV40 virus. Characterization of the murine SV40 hepatocytes (MuSH) generated from both genotypes (MuSHalpha(+/+), MuSHalpha(-/-)) show markers of differentiation such as albumin expression, but is devoid of Kupffer cell contamination. Hallmark PPARalpha-mediated responses such as induction of acyl-CoA oxidase mRNA by PPs are present in the MuSHalpha(+/+) but are absent in MuSHalpha(-/-) cells. In contrast to most cell culture systems, the wild-type MuSH hepatocytes retain the mitogenic activity of PPs, whereas the MuSHalpha(-/-) does not respond in this manner, thus making this cell culture system an ideal tool to examine growth regulatory gene expression affected by PPs. Microarray experiments performed on both cell types identified many genes in which regulation is dependent on the presence of PPARalpha, and these changes were verified with reverse transcriptase-PCR. Genes involved in carcinogenesis and control of the cell cycle that are regulated by PPs in a PPARalpha-dependent manner include ubiquitin COOH-terminal hydrolase 37 (also known as UCT-L5) and cyclin T1. These results show that MuSH cells reflect the biological properties of both the wild-type and PPARalpha-null animals and can be used to identify novel PPARalpha-regulated genes that could be involved in regulation of the cell cycle and carcinogenesis.


Mitochondria in living cells: an analysis of movements.
Time-lapse cinephotomicrography of mouse embryonic fibroblasts before and shortly after perfusion of tissue cultures reveals that the elongation of mitochondria caused by coenzyme A results from the terminal association of many shorter rods into a smaller number of long filaments. These are not permanent associations, but they reflect an exaggeration of the cohesive tendency of mitochondria, which in untreated cells is counterbalanced by frequent disjoinings and breakings of the anastomotic network. Our own observations and a survey of the literature suggest that elongate mitochondria with rapid movement and high metabolic activity tend to accompany proliferation in tissue cultures, and that mitotic inhibition of cultured cells may go together with short, slow mitochondria of low metabolic activity. The movement of mitochondria may be both active, reflecting metabolic exchanges with the cytoplasm, and passive, the result of hyaloplasmic currents.


Corticospinal circuit plasticity in motor rehabilitation from spinal cord injury.
Restoring corticospinal function after spinal cord injury is a significant challenge as the corticospinal tract elicits no substantive, spontaneous regeneration, and its interruption leaves a permanent deficit. The corticospinal circuit serves multiple motor and sensory functions within the mammalian nervous system as the direct link between isocortex and spinal cord. Maturation of the corticospinal circuit involves the refinement of projections within the spinal cord and a subsequent refinement of motor maps within the cortex. The plasticity of these cortical motor maps mirrors the acquisition of skilled motor learning, and both the maps and motor skills are disrupted following injury to the corticospinal tract. The motor cortex exhibits the capacity to incorporate changes in corticospinal projections induced by both spontaneous and therapeutic-mediated plasticity of corticospinal axons through appropriate rehabilitation. An understanding of the mechanisms of corticospinal plasticity in motor learning will undoubtedly help inform strategies to improve motor rehabilitation after spinal cord injury.


Work attendance among healthcare workers: prevalence, incentives, and long-term consequences for health and performance.
This paper is a report of a cohort study of healthcare workers' work attendance, and its long-term consequences' on health, burnout, work ability and performance. Concepts and measures of work attendance have varied in the scientific literature. Attending work in spite of being sick can have serious consequences on health. There is little knowledge on which individual and work-related conditions that increase work attendance and the long-term impact on health and performance. Prospective analyses of three measures of work attendance i.e. sickness attendance, uninterrupted long-term attendance and balanced attendance (≤7 days of sick leave per year and no sickness attendance) were done using questionnaire data from a 2-year cohort study (2004-2006) of randomly selected healthcare workers (n = 2624). Incentives (e.g. effort-reward balance, social support, meaningfulness) and requirements (e.g. time-pressure, dutifulness, high responsibility) to attend work as well as general health, burnout, sick leave, work ability and performance were assessed. There was a positive relation between balanced work attendance and incentives, whereas high sickness attendance was associated with requirements. Follow up after 2 years showed that balanced attendance was associated with sustained health and performance while sickness attendance was associated with poor health, burnout, sick-leave and decreased performance. It is important to distinguish between measures of work attendance as they differ in relation to incentives, and health- and performance-related consequences. Sickness attendance seems to be an important risk indicator. A balanced work attendance should be promoted for sustained health and performance in healthcare organisations.


On statistical methods for clustering: a case study on infant mortality, Northern Sweden, 1831-1890.
This article considers the interfamily clustering of infant mortality (defined as mortality during the first year of life). We developed and evaluated statistical tools to detect clustering and a measure to quantify excess clustering for nineteenth-century data from Skellefteå, Sweden. The detection was performed using the standard methods of generalized linear models and logistic regression. The index of clustering was constructed by comparing the observed numbers of families with specific numbers of deaths to the corresponding observed numbers, after correcting for explanatory variables. To the best of our knowledge, no clustering index of this kind has ever been created.


Identification and characterization of a cDNA encoding mouse CAP: a homolog of the yeast adenylyl cyclase associated protein.
CAP, an adenylyl cyclase associated protein, is present in Saccharomyces cerevisiae and Schizosaccharomyces pombe. In both organisms, CAP is bifunctional: the N-terminal domain binds to adenylyl cyclase, thereby enabling adenylyl cyclase to respond appropriately to upstream regulatory signals, such as RAS in S. cerevisiae; the C-terminal domain is required for cellular morphogenesis. Here, we describe the isolation of a cDNA encoding a CAP homolog from a higher eukaryote. The mouse CAP cDNA contains an open reading frame capable of encoding a 474 amino acid protein. The protein encoded by the mouse CAP cDNA shows extensive homology to the yeast CAP proteins, particularly in the central poly-proline rich region and in the C-terminal domain. By northern analysis, the CAP message appears to be ubiquitous, but not uniform. By indirect immunofluorescence, ectopically expressed mouse CAP protein is found in the cytoplasm of fibroblasts and, in migrating cells, at the leading edge. Expression of the mouse CAP cDNA in S. cerevisiae complements defects associated with loss of the yeast CAP carboxy-terminal domain. Hence, the function of the CAP carboxy-terminal domain has been conserved from yeast to mouse.


Optimization of wireless Bluetooth sensor systems.
Within this study, three different Bluetooth sensor systems, replacing cables for transmission of biomedical sensor data, have been designed and evaluated. The three sensor architectures are built on 1-, 2- and 3-chip solutions and depending on the monitoring situation and signal character, different solutions are optimal. Essential parameters for all systems have been low physical weight and small size, resistance to interference and interoperability with other technologies as global- or local networks, PC's and mobile phones. Two different biomedical input signals, ECG and PPG (photoplethysmography), have been used to evaluate the three solutions. The study shows that it is possibly to continuously transmit an analogue signal. At low sampling rates and slowly varying parameters, as monitoring the heart rate with PPG, the 1-chip solution is the most suitable, offering low power consumption and thus a longer battery lifetime or a smaller battery, minimizing the weight of the sensor system. On the other hand, when a higher sampling rate is required, as an ECG, the 3-chip architecture, with a FPGA or micro-controller, offers the best solution and performance. Our conclusion is that Bluetooth might be useful in replacing cables of medical monitoring systems.


Relaxation and guided imagery do not reduce stress, pain and unpleasantness for 11- to 12-year-old girls during vaccinations.
Relaxation and guided imagery is a distraction technique known to reduce discomfort during paediatric medical procedures. We examined whether its use decreased the stress experienced by 11- to 12-year-old girls receiving the human papilloma virus vaccination, as well as the intensity and unpleasantness of any pain. A randomised crossover trial was conducted with 37 girls. During the first vaccination, each girl was randomised to receive either relaxation and guided imagery or standard care. They then received the other form of care during the second vaccination. Salivary cortisol was measured before each vaccination, and 30 minutes after it was administered. The girls reported pain intensity and pain unpleasantness before and directly after each vaccination and stress after each vaccination. On a group level, relaxation and guided imagery did not decrease cortisol levels, self-reported stress, pain intensity and pain unpleasantness. Salivary cortisol levels decreased significantly in both groups during the second vaccination. Relaxation and guided imagery did not prove beneficial during the vaccination of 11- to 12-year-old girls and is not recommended as a regular nursing intervention. However, further research is needed into effective techniques to help children who experience pain unpleasantness in connection with needle procedures.


Dietary interventions for induction and maintenance of remission in inflammatory bowel disease.
Inflammatory bowel disease (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic mucosal inflammation, frequent hospitalizations, adverse health economics, and compromised quality of life. Diet has been hypothesised to influence IBD activity. To evaluate the efficacy and safety of dietary interventions on IBD outcomes. We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, Embase, Web of Science, Clinicaltrials.gov and the WHO ICTRP from inception to 31 January 2019. We also scanned reference lists of included studies, relevant reviews and guidelines. We included randomized controlled trials (RCTs) that compared the effects of dietary manipulations to other diets in participants with IBD. Studies that exclusively focused on enteral nutrition, oral nutrient supplementation, medical foods, probiotics, and parenteral nutrition were excluded. Two review authors independently performed study selection, extracted data and assessed bias using the risk of bias tool. We conducted meta-analyses where possible using a random-effects model and calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. We assessed the certainty of evidence using GRADE. The review included 18 RCTs with 1878 participants. The studies assessed different dietary interventions for active CD (six studies), inactive CD (seven studies), active UC (one study) and inactive UC (four studies). Dietary interventions involved either the consumption of low amounts or complete exclusion of one or more food groups known to trigger IBD symptoms. There was limited scope for data pooling as the interventions and control diets were diverse. The studies were mostly inadequately powered. Fourteen studies were rated as high risk of bias. The other studies were rated as unclear risk of bias.The effect of high fiber, low refined carbohydrates, low microparticle diet, low calcium diet, symptoms-guided diet and highly restricted organic diet on clinical remission in active CD is uncertain. At 4 weeks, remission was induced in: 100% (4/4) of participants in the low refined carbohydrates diet group compared to 0% (0/3) of participants in the control group (RR 7.20, 95% CI 0.53 to 97.83; 7 participants; 1 study; very low certainty evidence). At 16 weeks, 44% (23/52) of participants in the low microparticle diet achieved clinical remission compared to 25% (13/51) of control-group participants (RR 3.13, 95% CI 0.22 to 43.84; 103 participants; 2 studies; I² = 73%; very low certainty evidence). Fifty per cent (16/32) of participants in the symptoms-guided diet group achieved clinical remission compared to 0% (0/19) of control group participants (RR 20.00, 95% CI 1.27 to 315.40; 51 participants ; 1 study; very low certainty evidence) (follow-up unclear). At 24 weeks, 50% (4/8) of participants in the highly restricted organic diet achieved clinical remission compared to 50% (5/10) of participants in the control group (RR 1.00, 95% CI 0.39 to 2.53; 18 participants; 1 study; very low certainty evidence). At 16 weeks, 37% (16/43) participants following a low calcium diet achieved clinical remission compared to 30% (12/40) in the control group (RR 1.24, 95% CI 0.67 to 2.29; 83 participants; 1 study; very low certainty evidence).The effect of low refined carbohydrate diets, symptoms-guided diets and low red processed meat diets on relapse in inactive CD is uncertain. At 12 to 24 months, 67% (176/264) of participants in low refined carbohydrate diet relapsed compared to 64% (193/303) in the control group (RR 1.04, 95% CI 0.87 to 1.25; 567 participants; 3 studies; I² = 35%; low certainty evidence). At 6 to 24 months, 48% (24/50) of participants in the symptoms-guided diet group relapsed compared to 83% (40/48) participants in the control diet (RR 0.53, 95% CI 0.28 to 1.01; 98 participants ; 2 studies; I² = 54%; low certainty evidence). At 48 weeks, 66% (63/96) of participants in the low red and processed meat diet group relapsed compared to 63% (75/118) of the control group (RR 1.03, 95% CI 0.85 to 1.26; 214 participants; 1 study; low certainty evidence). At 12 months, 0% (0/16) of participants on an exclusion diet comprised of low disaccharides / grains / saturated fats / red and processed meat experienced clinical relapse compared to 26% (10/38) of participants on a control group (RR 0.11, 95% CI 0.01 to 1.76; 54 participants; 1 study; very low certainty evidence).The effect of a symptoms-guided diet on clinical remission in active UC is uncertain. At six weeks, 36% (4/11) of symptoms-guided diet participants achieved remission compared to 0% (0/10) of usual diet participants (RR 8.25, 95% CI 0.50 to 136.33; 21 participants; 1 study; very low certainty evidence).The effect of the Alberta-based anti-inflammatory diet, the Carrageenan-free diet or milk-free diet on relapse rates in inactive UC is uncertain. At 6 months, 36% (5/14) of participants in the Alberta-based anti-inflammatory diet group relapsed compared to 29% (4/14) of participants in the control group (RR 1.25, 95% CI 0.42 to 3.70; 28 participants; 1 study; very low certainty evidence). Thirty per cent (3/10) of participants following the carrageenan-free diet for 12 months relapsed compared to 60% (3/5) of the participants in the control group (RR 0.50, 95% CI 0.15 to 1.64; 15 participants; 1 study; very low certainty evidence). At 12 months, 59% (23/39) of milk free diet participants relapsed compared to 68% (26/38) of control diet participants (RR 0.83, 95% CI 0.60 to 1.15; 77 participants; 2 studies; I² = 0%; low certainty evidence).None of the included studies reported on diet-related adverse events. The effects of dietary interventions on CD and UC are uncertain. Thus no firm conclusions regarding the benefits and harms of dietary interventions in CD and UC can be drawn. There is need for consensus on the composition of dietary interventions in IBD and more RCTs are required to evaluate these interventions. Currently, there are at least five ongoing studies (estimated enrollment of 498 participants). This review will be updated when the results of these studies are available.


Plasmodium vivax merozoite surface protein-3 (PvMSP3): expression of an 11 member multigene family in blood-stage parasites.
Three members of the Plasmodium vivax merozoite surface protein-3 (PvMSP3) family (PvMSP3-α, PvMSP3-β and PvMSP3-γ) were initially characterized and later shown to be part of a larger highly diverse family, encoded by a cluster of genes arranged head-to-tail in chromosome 10. PvMSP3-α and PvMSP3-β have become genetic markers in epidemiological studies, and are being evaluated as vaccine candidates. This research investigates the gene and protein expression of the entire family and pertinent implications. A 60 kb multigene locus from chromosome 10 in P. vivax (Salvador 1 strain) was studied to classify the number of pvmsp3 genes present, and compare their transcription, translation and protein localization patterns during blood-stage development. Eleven pvmsp3 paralogs encode an N-terminal NLRNG signature motif, a central domain containing repeated variable heptad sequences, and conserved hydrophilic C-terminal features. One additional ORF in the locus lacks these features and was excluded as a member of the family. Transcripts representing all eleven pvmsp3 genes were detected in trophozoite- and schizont-stage RNA. Quantitative immunoblots using schizont-stage extracts and antibodies specific for each PvMSP3 protein demonstrated that all but PvMSP3.11 could be detected. Homologs were also detected by immunoblot in the closely related simian species, P. cynomolgi and P. knowlesi. Immunofluorescence assays confirmed that eight of the PvMSP3s are present in mature schizonts. Uniquely, PvMSP3.7 was expressed exclusively at the apical end of merozoites. Specific proteins were detected representing the expression of 10 out of 11 genes confirmed as members of the pvmsp3 family. Eight PvMSP3s were visualized surrounding merozoites. In contrast, PvMSP3.7 was detected at the apical end of the merozoites. Pvmsp3.11 transcripts were present, though no corresponding protein was detected. PvMSP3 functions remain unknown. The ten expressed PvMSP3s are predicted to have unique and complementary functions in merozoite biology.


Pharmacokinetics of a Single Dose of Turmeric Curcuminoids Depends on Formulation: Results of a Human Crossover Study.
Curcuminoids from turmeric rhizome have significant health benefits but low bioavailability. To assess the pharmacokinetics of a novel natural turmeric dried colloidal suspension compared with 4 other turmeric formulations (including a standardized extract) at their respective recommended dosages. Thirty healthy men and women (18 to 45 y old) were enrolled in a randomized, open-labeled, crossover trial, and sequentially consumed single oral doses of standard turmeric extract (1500 mg), liquid micellar preparation (1000 mg), piperine-curcuminoid combination (1515 mg), phytosome formulation (1000 mg), or the dried colloidal suspension (300 mg). Eleven blood samples were obtained over 24 h, plasma was extracted with or without deconjugation with β-glucuronidase or sulfatase, and ultra-high-pressure liquid chromatography/tandem MS was used to quantify the 3 parent curcuminoids and 12 metabolites. Classical pharmacokinetics parameters were derived. The total AUC values of unconjugated curcuminoids were highly variable within participants, with no significant differences between formulations. However, the AUC values for total curcuminoids (including all metabolites) showed significant product effects. Indeed, the micellar preparation delivered higher levels of total curcuminoids than any other formulation (8540 ng·h/mL), reaching significance when compared with the dried colloidal suspension and standard extract (6520 and 5080 ng·h/mL, respectively). After dose normalization, both micellar and dried colloidal formulations showed significantly higher AUC levels than the standard extract (respectively 136 and 72.9, compared with 3.7 ng·h/mL/mg). Total curcuminoid absorption levels were also significantly higher for the dried colloidal suspension when compared with either piperine or phytosome formulations. Interestingly, no significant differences were observed between the piperine-curcuminoid combination and the standard extract. No serious adverse events were reported. The administration of a low dose of the novel natural dried colloidal suspension provided high unconjugated and conjugated curcuminoid absorption, with significant beneficial differences when compared with the high dose of standard extract.This trial was registered at clinicaltrials.gov as NCT03621865.


A complete Leishmania donovani reference genome identifies novel genetic variations associated with virulence.
Leishmania donovani is responsible for visceral leishmaniasis, a neglected and lethal parasitic disease with limited treatment options and no vaccine. The study of L. donovani has been hindered by the lack of a high-quality reference genome and this can impact experimental outcomes including the identification of virulence genes, drug targets and vaccine development. We therefore generated a complete genome assembly by deep sequencing using a combination of second generation (Illumina) and third generation (PacBio) sequencing technologies. Compared to the current L. donovani assembly, the genome assembly reported within resulted in the closure over 2,000 gaps, the extension of several chromosomes up to telomeric repeats and the re-annotation of close to 15% of protein coding genes and the annotation of hundreds of non-coding RNA genes. It was possible to correctly assemble the highly repetitive A2 and Amastin virulence gene clusters. A comparative sequence analysis using the improved reference genome confirmed 70 published and identified 15 novel genomic differences between closely related visceral and atypical cutaneous disease-causing L. donovani strains providing a more complete map of genes associated with virulence and visceral organ tropism. Bioinformatic tools including protein variation effect analyzer and basic local alignment search tool were used to prioritize a list of potential virulence genes based on mutation severity, gene conservation and function. This complete genome assembly and novel information on virulence factors will support the identification of new drug targets and the development of a vaccine for L. donovani.


Mechanosensitive hyaluronan secretion: stimulus-response curves and role of transcription-translation-translocation in rabbit joints.
Joint movement was recently shown to stimulate the secretion of the lubricant hyaluronan (HA); also, exercise therapy and intra-articular hyaluronan injections are used to treat moderate osteoarthritis. The present study quantifies the stimulus-response curves for HA secretion in vivo and reports a role of transcription-translation-translocation in the secretory response. After washing out endogenous HA from anaesthetized, cannulated rabbit knees, the joints were cycled passively at various frequencies and durations, with or without intra-articular inhibitors of protein synthesis and Golgi processing. Newly secreted HA was harvested for analysis after 5 h. Joints displayed graded, non-linear stimulus-response curves to both duration and frequency of movement; 1 min duration per 15 min or a frequency of 0.17 Hz raised HA secretion by 42-54%, while rapid (1.5 Hz) or prolonged cycling (9 min per 15 min) raised it by 110-130%. Movement-stimulated secretion and phorbol ester-stimulated secretion were partly inhibited by the translation inhibitor cycloheximide, by the transcription-translation inhibitors actinomycin D and puromycin and by the Golgi translocation inhibitor brefeldin A. There is thus a graded coupling between HA secretion and cyclic joint movement that depends partly on new protein synthesis. This is likely to be important for joint homeostasis, providing protection during repetitive cycling and potentially contributing to exercise therapy for osteoarthritis.


Intensity-modulated radiotherapy and volumetric-modulated arc therapy for malignant pleural mesothelioma after extrapleural pleuropneumonectomy.
Radiotherapy reduces the local relapse rate after pleuropneumonectomy of malignant pleural mesothelioma (MPM). The optimal treatment technique with photons remains undefined. Comparative planning for intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) was performed. Six MPM patients with significant postoperative intrathoracic air cavities were planned with IMRT and VMAT. A dose comparison for the targets and organ at risks (OAR) was performed. Robustness was assessed in respect to the variation of target dose with change in volume of air cavities. VMAT reduced the dose to the contralateral lung by reducing the volume covered by 13 Gy and 20 Gy by a factor 1.8 and 2.8, in respect to IMRT (p = 0.02). Dose distribution with VMAT was the most stable technique in regard to postsurgical air cavity variation. For IMRT, V90, V95, and the minimal target dose decreased by 40%, 64%, and 12% compared to 29%, 47%, and 7% with VMAT when air cavity decreased. Two arcs compared to one arc decreased the dose to all the organs at risk (OAR) while leaving PTV dose coverage unchanged. Increasing the number of arcs from two to three did not reduce the dose to the OAR further, but increased the beam-on time by 50%. Using partial arcs decreased the beam-on time by 43%. VMAT allows a lower lung dose and is less affected by the air cavity variation than IMRT. The best VMAT plans were obtained with two partial arcs. VMAT seems currently the most suitable technique for the treatment of MPM patients when air cavities are remaining and no adaptive radiotherapy is performed.


Current epidemiological understanding of citrus Huanglongbing .
Huanglongbing (HLB) is the most destructive citrus pathosystem worldwide. Previously known primarily from Asia and Africa, it was introduced into the Western Hemisphere in 2004. All infected commercial citrus industries continue to decline owing to inadequate current control methods. HLB increase and regional spatial spread, related to vector populations, are rapid compared with other arboreal pathosystems. Disease dynamics result from multiple simultaneous spatial processes, suggesting that psyllid vector transmission is a continuum from local area to very long distance. Evolutionarily, HLB appears to have originated as an insect endosymbiont that has moved into plants. Lack of exposure of citrus to the pathogen prior to approximately 100 years ago did not provide sufficient time for development of resistance. A prolonged incubation period and regional dispersal make eradication nonviable. Multiple asymptomatic infections per symptomatic tree, incomplete systemic distribution within trees, and prolonged incubation period make detection difficult and greatly complicate disease control.


Post-Marketing Regulation of Medicines Withdrawn from the Market Because of Drug-Attributed Deaths: An Analysis of Justification.
Several medicinal products have been withdrawn from the market because of drug-attributed deaths. However, there has been no investigation of whether such withdrawals were justified, and the extent to which confirmatory studies are used to investigate drug-adverse event relationships when deaths are reported is uncertain. We documented medicinal products withdrawn from the market because of drug-attributed deaths, identified confirmatory studies investigating the drug-adverse event relationships, examined whether withdrawals of medicinal products because of drug-attributed deaths after marketing were justified based on a mechanistic analysis, and examined the trends over time. We searched electronic and non-electronic sources to identify medicinal products that were withdrawn because of drug-attributed deaths. We used a previously published algorithm to examine whether the withdrawals of products were justified. We then searched PubMed and Google Scholar to identify studies investigating the drug-adverse event relationships, used the Oxford Centre for Evidence-Based Medicine criteria to document the levels of evidence, and assessed whether the evidence of an association was confirmed. We included 83 medicinal products. The reasons for withdrawal appeared to have been justified in 80 cases (96%). The median interval between the first reported adverse reaction that was related to the cause of death and the first reported death was 1 year (interquartile range = 1-3); products were withdrawn sooner when the interval between the first reported relevant adverse reaction and the first death was shorter. Confirmatory studies were conducted in 57 instances (69%), and there was evidence of an association in 52 cases (63%). Four products (5%) were re-introduced after initial withdrawal. Regulatory authorities have been justified in making withdrawal decisions when deaths have been attributed to medicinal products, using the precautionary principle when alternative decisions could have been made. Medicinal products are likely to be quickly withdrawn from the market when there is a short interval to the first reported deaths. The use of an algorithm such as we have used in this study could help to expedite the process of decision making.


"Dub"bing a tumor suppressor pathway.
The autosomal recessive disease Fanconi anemia (FA) causes bone marrow failure and a hugely increased propensity to develop cancer. Cells from FA patients are prone to chromosome breakage, indicating that FA gene products are required to ensure genomic integrity. Most of the identified FA proteins are components of a nuclear complex whose principal function is to activate FANCD2 by monoubiquitination. Monoubiquitinated FANCD2 accumulates at sites of genome damage, where it probably functions to facilitate DNA repair. A recent paper in Molecular Cell (Nijmanet al., 2005) reports the identification of an enzyme that is responsible for regulating the FA pathway by deactivating FANCD2.


Cross-Cultural Differences and Similarities in Human Value Instantiation.
Previous research found that the within-country variability of human values (e.g., equality and helpfulness) clearly outweighs between-country variability. Across three countries (Brazil, India, and the United Kingdom), the present research tested in student samples whether between-nation differences reside more in the behaviors used to concretely instantiate (i.e., exemplify or understand) values than in their importance as abstract ideals. In Study 1 (N = 630), we found several meaningful between-country differences in the behaviors that were used to concretely instantiate values, alongside high within-country variability. In Study 2 (N = 677), we found that participants were able to match instantiations back to the values from which they were derived, even if the behavior instantiations were spontaneously produced only by participants from another country or were created by us. Together, these results support the hypothesis that people in different nations can differ in the behaviors that are seen as typical as instantiations of values, while holding similar ideas about the abstract meaning of the values and their importance.


Identifying structural domains of proteins using clustering.
Protein structures are comprised of modular elements known as domains. These units are used and re-used over and over in nature, and usually serve some particular function in the structure. Thus it is useful to be able to break up a protein of interest into its component domains, prior to similarity searching for example. Numerous computational methods exist for doing so, but most operate only on a single protein chain and many are limited to making a series of cuts to the sequence, while domains can and do span multiple chains. This study presents a novel clustering-based approach to domain identification, which works equally well on individual chains or entire complexes. The method is simple and fast, taking only a few milliseconds to run, and works by clustering either vectors representing secondary structure elements, or buried alpha-carbon positions, using average-linkage clustering. Each resulting cluster corresponds to a domain of the structure. The method is competitive with others, achieving 70% agreement with SCOP on a large non-redundant data set, and 80% on a set more heavily weighted in multi-domain proteins on which both SCOP and CATH agree. It is encouraging that a basic method such as this performs nearly as well or better than some far more complex approaches. This suggests that protein domains are indeed for the most part simply compact regions of structure with a higher density of buried contacts within themselves than between each other. By representing the structure as a set of points or vectors in space, it allows us to break free of any artificial limitations that other approaches may depend upon.


Antimicrobial promotion of pig growth is associated with tissue-specific remodeling of bile acid signature and signaling.
The spread of bacterial resistance to antimicrobials (AMA) have intensified efforts to discontinue the non-therapeutic use of AMA in animal production. Finding alternatives to AMA, however, is currently encumbered by the obscure mechanism that underlies their growth-promoting action. In this report, we demonstrate that combinations of antibiotics and zinc oxide at doses commonly used for stimulating growth or preventing post-weaning enteritis in pigs converge in promoting microbial production of bile acids (BA) in the intestine. This leads to tissue-specific modifications in the proportion of BA, thereby amplifying BA signaling in intestine, liver, and white adipose tissue (WAT). Activation of BA-regulated pathways ultimately reinforces the intestinal protection against bacterial infection and pathological secretion of fluids and electrolytes, attenuates inflammation in colon and WAT, alters protein and lipid metabolism in liver, and increases the circulating levels of the hormone FGF19. Conceivably, these alterations could spare nutrients for growth and improve the metabolic efficiency of AMA-treated animals. This work provides evidence that BA act as signaling molecules that mediate host physiological, metabolic, and immune responses to the AMA-induced alterations in gut microbial metabolism, eventually permitting the growth-promoting action of AMA. Consequently, BA emerge as a promising target for developing efficacious alternatives to AMA.


Using anthropometric and performance characteristics to predict selection in junior UK Rugby League players.
Research examining the factors influencing selection within talented junior Rugby League players is limited. The aims of this study were firstly to determine whether differences existed for anthropometric and performance characteristics between regional and national selection in high performance UK junior Rugby League players, and secondly to identify variables that discriminated between these selection levels. Regional representative (n=1172) selected junior players (aged 13-16 years) undertook an anthropometric and fitness testing battery with players split according to selection level (i.e., national, regional). MANCOVA analyses, with age and maturation controlled, identified national players as having lower sum of 4 skinfolds scores compared to regional players, and also performed significantly better on all physical tests. Stepwise discriminant analysis identified that estimated maximum oxygen uptake (VO2max), chronological age, body mass, 20 m sprint, height, sum of 4 skinfolds and sitting height discriminated between selection levels, accounting for 28.7% of the variance. This discriminant analysis corresponded to an overall predictive accuracy of 63.3% for all players. These results indicate that performance characteristics differed between selection levels in junior Rugby League players. However, the small magnitude of difference between selection levels suggests that physical qualities only partially explain higher representative selection. The monitoring and evaluation of such variables, alongside game related performance characteristics, provides greater knowledge and understanding about the processes and consequences of selection, training and performance in youth sport.


Recent advances in three-dimensional electroanatomical mapping guidance for the ablation of complex atrial and ventricular arrhythmias.
To provide a brief overview of some relevant technological advances in the field of three-dimensional electroanatomical mapping (3D-EAM) that have recently entered the clinical arena and their role in guiding catheter ablation (CA) of complex atrial and ventricular arrhythmias. In this technical report, we describe the general features of three novel algorithms featured in the updated CARTO PRIME™ mapping module for CARTO®3 version 7 3D-EAM system (Biosense Webster Inc., Diamond Bar, CA, USA): local activation time (LAT) hybrid, coherent mapping and map replay modules. We also report three challenging arrhythmia cases in which CA was successfully guided by these softwares. The LAT hybrid module was used in a case of premature ventricular complex originating from the right coronary cusp. This algorithm facilitated safe positioning of the ablation catheter away from the right coronary ostium, avoiding potential harm to this vital structure. The coherent mapping module helped to identify the critical as well as a bystander isthmus of an atrial macro-re-entrant tachycardia in a grown-up patient with congenital heart disease. The map replay module allowed rapid retrospective activation mapping of two unstable ventricular tachycardias in a case of nonischemic cocaine-associated cardiomyopathy. 3D-EAM systems offer significant advantages in the management of challenging arrhythmias, and the introduction of novel algorithms underpins improvements in patients' outcomes. Given the increasing sophistication of these systems, however, a close collaboration among cardiac electrophysiologists, engineers and technicians is highly needed in order to get the best from the available technology.


The role of mutational analysis of KIT and PDGFRA in gastrointestinal stromal tumors in a clinical setting.
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Most GIST harbor a mutation affecting either the KIT or PDGFRA genes, whereas a small subgroup of tumors is wild type for mutations.Mutation of tyrosine kinase receptors is a mechanism of drug resistance that can occur either at the beginning of treatment (primary resistance) or during the course of therapy (secondary resistance). In addition, mutational status can predict the response to treatment with tyrosine kinase inhibitors, but the role of mutational status as a prognostic factor remains controversial.Evidence of a potential role of mutational status as a prognostic factor has emerged over the past decade. The presence of KIT exon 11 insertion/deletion involving either one or both Trp557-Lys558 amino acids correlates with a poorer clinical outcome if compared to patients with tumors wild type for KIT exon 11 mutations. A malignant clinical behavior has also been documented for KIT exon 13 and KIT exon 9 mutant GIST. Patients with GIST harboring a PDGFRA mutation seem to have a better prognosis than the others.The aim of this paper is to review the clinical significance of tyrosine kinase mutational status.


An electrophysiological analysis of extra-axonal sodium and potassium concentrations in the central nervous system of the cockroach (Periplaneta americana L.).
Simultaneous intracellular and sucrose-gap recordings showed, in contrast to previous findings, that the electrical parameters of giant axons were similar to intact and desheathed connectives bathed with the 'extracellular Ringer' of Yamasaki & Narahashi. This implies that the extra-axonal sodium concentration, in situ, is likely to be lower than had been previously supposed. Axonal responses showed that, despite the high blood concentration of 24-2 mM-K+ measured by flame photometry, the effective concentration in the blood was 10-15 mM-K+ which corresponds to the measurements made with potassium-selective electrodes. The activity of the blood potassium ions caused a marked reduction in the amplitude of the action potentials following surgical desheathing or disruption of the blood-brain barrier with hypertonic urea. It is suggested that a regulatory mechanism exists in the central nervous system which counteracts the effects of the high blood potassium level.


Detection of Alicyclobacillus species in fruit juice using a random genomic DNA microarray chip.
This study describes a method using a DNA microarray chip to rapidly and simultaneously detect Alicyclobacillus species in orange juice based on the hybridization of genomic DNA with random probes. Three food spoilage bacteria were used in this study: Alicyclobacillus acidocaldarius, Alicyclobacillus acidoterrestris, and Alicyclobacillus cycloheptanicus. The three Alicyclobacillus species were adjusted to 2 × 10(3) CFU/ml and inoculated into pasteurized 100% pure orange juice. Cy5-dCTP labeling was used for reference signals, and Cy3-dCTP was labeled for target genomic DNA. The molar ratio of 1:1 of Cy3-dCTP and Cy5-dCTP was used. DNA microarray chips were fabricated using randomly fragmented DNA of Alicyclobacillus spp. and were hybridized with genomic DNA extracted from Bacillus spp. Genomic DNA extracted from Alicyclobacillus spp. showed a significantly higher hybridization rate compared with DNA of Bacillus spp., thereby distinguishing Alicyclobacillus spp. from Bacillus spp. The results showed that the microarray DNA chip containing randomly fragmented genomic DNA was specific and clearly identified specific food spoilage bacteria. This microarray system is a good tool for rapid and specific detection of thermophilic spoilage bacteria, mainly Alicyclobacillus spp., and is useful and applicable to the fruit juice industry.


The influence of social comparison on cognitive bias modification and emotional vulnerability.
The Cognitive Bias Modification (CBM) paradigm was devised to test predictions that cognitive biases have a causal influence on emotional status. Increasingly, however, researchers are testing the potential clinical applications of CBM. Although generally successful in reducing emotional vulnerability in clinical populations, the impact of CBM interventions has been somewhat variable. The aim of the current experiment was to investigate whether social comparison processing might be an important moderator of CBM. Healthy participants were presented with 80 valenced scenarios devised to induce a positive or negative interpretative bias. Critically, participants answered a series of questions designed to establish whether they assimilated or contrasted themselves with the valenced descriptions. The induction of an interpretation bias that was congruent with the valence of the training scenarios was successful only for participants who tended to assimilate the valenced scenarios, and not for those participants who tended to evaluate themselves against the scenarios. Furthermore, the predicted influence of CBM on emotional outcomes occurred only for those who had an assimilative rather than evaluative orientation toward CBM training material. Of key importance, results indicated that "evaluators" showed increased emotional vulnerability following positive CBM training. This result has both theoretical and clinical implications in suggesting that the success of CBM is dependent upon the way in which participants socially compare themselves with CBM training material.


Multivariate ensemble classification for the prediction of symptoms in patients with Brugada syndrome.
Identification of asymptomatic patients at higher risk for suffering cardiac events remains controversial and challenging in Brugada syndrome (BS). In this work, we proposed an ECG-based classifier to predict BS-related symptoms, by merging the most predictive electrophysiological features derived from the ventricular depolarization and repolarization periods, along with autonomic-related markers. The initial feature space included local and dynamic ECG markers, assessed during a physical exercise test performed in 110 BS patients (25 symptomatic). Morphological, temporal and spatial properties quantifying the ECG dynamic response to exercise and recovery were considered. Our model was obtained by proposing a two-stage feature selection process that combined a resampled-based regularization approach with a wrapper model assessment for balancing, simplicity and performance. For the classification step, an ensemble was constructed by several logistic regression base classifiers, whose outputs were fused using a performance-based weighted average. The most relevant predictors corresponded to the repolarization interval, followed by two autonomic markers and two other makers of depolarization dynamics. Our classifier allowed for the identification of novel symptom-related markers from autonomic and dynamic ECG responses during exercise testing, suggesting the need for multifactorial risk stratification approaches in order to predict future cardiac events in asymptomatic BS patients. Graphical abstract Pipeline for feature selection and predictive modeling of symptoms in Brugada syndrome.