Objectively measured short sleep duration and later sleep midpoint in pregnancy are associated with a higher risk of gestational diabetes.
Experimental and epidemiologic data suggest that among nonpregnant adults, sleep duration may be an important risk factor for chronic disease. Although pregnant women commonly report poor sleep, few studies objectively evaluated the quality of sleep in pregnancy or explored the relationship between sleep disturbances and maternal and perinatal outcomes. Our objective was to examine the relationship between objectively assessed sleep duration, timing, and continuity (measured via wrist actigraphy) and maternal cardiovascular and metabolic morbidity specific to pregnancy. This was a prospective cohort study of nulliparous women. Women were recruited between 16 0/7 and 21 6/7 weeks' gestation. They were asked to wear a wrist actigraphy monitor and complete a daily sleep log for a period of 7 consecutive days. The primary sleep exposure variables were the averages of the following over the total valid nights (minimum 5, maximum 7 nights): short sleep duration during the primary sleep period (<7 h/night), late sleep midpoint (midpoint between sleep onset and sleep offset >5 am), and top quartile of minutes of wake time after sleep onset and sleep fragmentation index. The primary outcomes of interest were a composite of hypertensive disorders of pregnancy (mild, severe, or superimposed preeclampsia; eclampsia; or antepartum gestational hypertension) and gestational diabetes mellitus. We used χ2 tests to assess associations between sleep variables and categorical baseline characteristics. Crude odds ratios and 95% confidence intervals were estimated from univariate logistic regression models to characterize the magnitude of the relationship between sleep characteristics and hypertensive disorders of pregnancy and gestational diabetes. For associations significant in univariate analysis, multiple logistic regression was used to explore further the association of sleep characteristics with pregnancy outcomes. In all, 901 eligible women consented to participate; 782 submitted valid actigraphy studies. Short sleep duration and a later sleep midpoint were associated with an increased risk of gestational diabetes (odds ratio, 2.24; 95% confidence interval, 1.11-4.53; and odds ratio, 2.58; 95% confidence interval, 1.24-5.36, respectively) but not of hypertensive disorders. A model with both sleep duration and sleep midpoint as well as their interaction term revealed that while there was no significant interaction between these exposures, the main effects of both short sleep duration and later sleep midpoint with gestational diabetes remained significant (adjusted odds ratio, 2.06; 95% confidence interval, 1.01-4.19; and adjusted odds ratio, 2.37; 95% confidence interval, 1.13-4.97, respectively). Additionally, after adjusting separately for age, body mass index, and race/ethnicity, both short sleep duration and later sleep midpoint remained associated with gestational diabetes. No associations were demonstrated between the sleep quality measures (wake after sleep onset, sleep fragmentation) and hypertensive disorders or gestational diabetes. Our results demonstrate a relationship between short sleep duration and later sleep midpoint with gestational diabetes. Our data suggest independent contributions of these 2 sleep characteristics to the risk for gestational diabetes in nulliparous women.


Practice nurse involvement in primary care depression management: an observational cost-effectiveness analysis.
Most evidence on the effect of collaborative care for depression is derived in the selective environment of randomised controlled trials. In collaborative care, practice nurses may act as case managers. The Primary Care Services Improvement Project (PCSIP) aimed to assess the cost-effectiveness of alternative models of practice nurse involvement in a real world Australian setting. Previous analyses have demonstrated the value of high level practice nurse involvement in the management of diabetes and obesity. This paper reports on their value in the management of depression. General practices were assigned to a low or high model of care based on observed levels of practice nurse involvement in clinical-based activities for the management of depression (i.e. percentage of depression patients seen, percentage of consultation time spent on clinical-based activities). Linked, routinely collected data was used to determine patient level depression outcomes (proportion of depression-free days) and health service usage costs. Standardised depression assessment tools were not routinely used, therefore a classification framework to determine the patient's depressive state was developed using proxy measures (e.g. symptoms, medications, referrals, hospitalisations and suicide attempts). Regression analyses of costs and depression outcomes were conducted, using propensity weighting to control for potential confounders. Capacity to determine depressive state using the classification framework was dependent upon the level of detail provided in medical records. While antidepressant medication prescriptions were a strong indicator of depressive state, they could not be relied upon as the sole measure. Propensity score weighted analyses of total depression-related costs and depression outcomes, found that the high level model of care cost more (95% CI: -$314.76 to $584) and resulted in 5% less depression-free days (95% CI: -0.15 to 0.05), compared to the low level model. However, this result was highly uncertain, as shown by the confidence intervals. Classification of patients' depressive state was feasible, but time consuming, using the classification framework proposed. Further validation of the framework is required. Unlike the analyses of diabetes and obesity management, no significant differences in the proportion of depression-free days or health service costs were found between the alternative levels of practice nurse involvement.


Renin, a secretory glycoprotein, acquires phosphomannosyl residues.
Renin is an aspartyl protease which is highly homologous to the lysosomal aspartyl protease cathepsin D. During its biosynthesis, cathepsin D acquires phosphomannosyl residues that enable it to bind to the mannose 6-phosphate (Man-6-P) receptor and to be targeted to lysosomes. The phosphorylation of lysosomal enzymes by UDP-GlcNAc:lysosomal enzyme N-acetylglucosaminylphosphotransferase (phosphotransferase) occurs by recognition of a protein domain that is thought to be present only on lysosomal enzymes. In order to determine whether renin, being structurally similar to cathepsin D, also acquires phosphomannosyl residues, human renin was expressed from cloned DNA in Xenopus oocytes and a mouse L cell line and its biosynthesis and posttranslational modifications were characterized. In Xenopus oocytes, the majority of the renin remained intracellular and underwent a proteolytic cleavage which removed the propiece. Most of the renin synthesized by oocytes was able to bind to a Man-6-P receptor affinity column (53%, 57%, and 90%, in different experiments), indicating the presence of phosphomannosyl residues. In the L cells, the majority of the renin was secreted but 5-6% of the renin molecules contained phosphomannosyl residues as demonstrated by binding of [35S]methionine-labeled renin to the Man-6-P receptor as well as direct analysis of [2-3H]mannose-labeled oligosaccharides. Although the level of renin phosphorylation differed greatly between the two cell types examined, these results demonstrate that renin is recognized by the phosphotransferase and suggest that renin contains at least part of the lysosomal protein recognition domain.


Effect of HIV infection on the acute antibody response to malaria antigens in children: an observational study.
In sub-Saharan Africa, the distributions of malaria and HIV widely overlap. Among pregnant and non-pregnant adults, HIV affects susceptibility to malaria, its clinical course and impairs antibody responses to malaria antigens. However, the relationship between the two diseases in childhood, when most deaths from malaria occur, is less clear. It was previously reported that HIV is associated with admission to hospital in rural Kenya with severe malaria among children, except in infancy. HIV-infected children with severe malaria were older, had higher parasite density and increased mortality, raising a hypothesis that HIV interferes with naturally acquired immunity to malaria, hence with little effect at younger ages (a shorter history of exposure). To test this hypothesis, levels of anti-merozoite and schizont extract antibodies were compared between HIV-infected and uninfected children who participated in the original study. IgG responses to malaria antigens that are potential targets for immunity to malaria (AMA1, MSP2, MSP3 and schizont extract) were compared between 115 HIV-infected and 115 age-matched, HIV-uninfected children who presented with severe malaria. The children were classified as high and low responders for each antigen and assigned antibody-response breadth scores according to the number of antigens to which they were responsive. A predictive logistic regression model was used to test if HIV was an effect modifier on the age-related acquisition of antibody responses, with age as a continuous variable. Point estimates of the responses to all antigens were lower amongst HIV-infected children, but this was only statistically significant for AMA1 (P = 0.028). HIV-infected children were less likely to be high responders to AMA1 [OR 0.44 (95%CI, 0.2-0.90) P = 0.024]. HIV was associated with a reduced breadth of responses to individual merozoite antigens (P = 0.02). HIV strongly modified the acquisition of antibodies against schizont extract with increasing age (P < 0.0001), but did not modify the rate of age-related acquisition of responses to individual merozoite antigens. In children with severe malaria, HIV infection is associated with a lower magnitude and narrower breadth of IgG responses to merozoite antigens and stunting of age-related acquisition of the IgG antibody response to schizont extract.


Platelet-rich plasma in orthopaedic applications: evidence-based recommendations for treatment.
Autologous platelet-rich plasma (PRP) therapies have seen a dramatic increase in breadth and frequency of use for orthopaedic conditions in the past 5 years. Rich in many growth factors that have important implications in healing, PRP can potentially regenerate tissue via multiple mechanisms. Proposed clinical and surgical applications include spinal fusion, chondropathy, knee osteoarthritis, tendinopathy, acute and chronic soft-tissue injuries, enhancement of healing after ligament reconstruction, and muscle strains. However, for many conditions, there is limited reliable clinical evidence to guide the use of PRP. Furthermore, classification systems and identification of differences among products are needed to understand the implications of variability.


Development and internal validation of the male osteoporosis risk estimation score.
We wanted to develop and validate a clinical prediction rule to identify men at risk for osteoporosis and subsequent hip fracture who might benefit from dual-energy x-ray absorptiometry (DXA). We used risk factor data from the National Health and Nutrition Examination Survey III to develop a best fitting multivariable logistic regression model in men aged 50 years and older randomized to either the development (n = 1,497) or validation (n = 1,498) cohorts. The best fitting model was transformed into a simplified scoring algorithm, the Male Osteoporosis Risk Estimation Score (MORES). We validated the MORES, comparing sensitivity, specificity, and area under the receiver operating characteristics (ROC) curve in the 2 cohorts and assessed clinical utility with an analysis of the number needed-to-screen (NNS) to prevent 1 additional hip fracture. The MORES included 3 variables-age, weight, and history of chronic obstructive pulmonary disease-and showed excellent predictive validity in the validation cohort. A score of 6 or greater yielded an overall sensitivity of 0.93 (95% CI, 0.85-0.97), a specificity of 0.59 (95% CI, 0.56-0.62), and an area under the ROC curve of 0.832 (95% CI, 0.807-0.858). The overall NNS to prevent 1 additional hip fracture was 279 in a cohort of men representative of the US population. Osteoporosis is a major predictor of hip fractures. Experts believe bisphosphonate treatment in men should yield results similar to that in women and reduce hip fracture rates associated with osteoporosis. In men aged 60 years and older, the MORES is a simple approach to identify men at risk for osteoporosis and refer them for confirmatory DXA scans.


Development of normal gestational ranges for the right myocardial performance index in the Australian population with three alternative caliper placements.
To construct gestational age-adjusted reference ranges for the right fetal modified myocardial performance index (RMPI) in an Australian population and to assess the influence of valve click caliper position on constituent time intervals and the RMPI. A prospective cross-sectional study of RMPI from 235 normal fetuses at 17-38 weeks of gestation was performed. Two Doppler waveforms were obtained: tricuspid and pulmonary valves for 'a' and 'b' readings, respectively. The ultrasound machine settings were: Doppler sweep velocity 15 cm/s, angle of insonation <15°, minimal gain, and wall motion filter 300 Hz. The 'a' and 'b' intervals were measured at three different caliper positions in each fetus: at the beginning of the original valve clicks ('original'), at the beginning of the reflected tricuspid and pulmonary closure clicks ('reflected') and at the peak of valve clicks ('peak'). RMPI was calculated as (a - b)/b. The three readings were obtained and averaged per examination, with intraobserver repeatability assessed by intraclass correlation coefficient (ICC) and 95% CI. For 'original', 'reflected' and 'peak' RMPI, mean ± SD, ICC (95% CI) were: 0.53 ± 0.10, 0.86 (0.83-0.89); 0.48 ± 0.10, 0.84 (0.81-0.87) and 0.48 ± 0.10, 0.89 (0.87-0.91), respectively. The RMPI increased by approximately 15% as gestation increased and decreased slightly with increasing heart rate. This is the first publication of reference ranges for RMPI based on caliper position. All methods showed good ICC, including the 'peak' method which we have previously proposed for routine use based on its repeatability and ease of identification when measuring the myocardial performance index.


Zinc is a potential therapeutic for chemoresistant ovarian cancer.
Ovarian cancer is the leading cause of death from gynecological cancer. The high mortality rate reflets the lack of early diagnosis and limited treatment alternatives. We have observed a number of properties of zinc cytotoxicity that make it attractive from a therapeutic standpoint. Using SKOV3 and ES2 cells, ovarian cancer cell lines that demonstrate varied degrees of resistance to known therapeutics, we show that zinc killing is time and concentration dependent. Death is preceded by distinct changes in cell shape and size. The effects of zinc are additive with cisplatin or doxorubicin, whose morphological effects are distinct from those of zinc. Cytotoxicity of paclitaxel is minimal, making it difficult to determine additivity with zinc. Paclitaxel results in changes in cell shape and size similar to those of zinc but has different effects on cell cycle progression and cyclin expression. The data indicate that the means by which zinc kills ovarian cancer cells is distinct from currently used chemotherapeutics. Based on the properties reported here, zinc has the potential to be developed as either a primary treatment or as a second line of defense against cancers that have developed resistance to currently used chemotherapeutics.


Comparison of two outcome measures for infants with cerebral palsy and infants with motor delays.
The purpose of this study was to compare the Gross Motor Function Measure (GMFM) and the Peabody Developmental Gross Motor Scale (PDMS-GM) as measures of change in infants with cerebr-al palsy (CP) and infants with motor delays. We hypothesized that mean change scores would be greater for the GMFM than for the PDMS-GM. Subjects were 42 infants with a mean adjusted age of 13.9 months (SD=6.1, range=4.2-24.2). Twenty-four infants had CP, and 18 infants had motor delays. The GMFM and the PDMS-GM were administered to the infants 3 times over a 6-month period. Raw scores were standardized for data analysis. Data were analyzed using a 3-factor repeated-measures analysis of variance. For the 6-month period, mean PDMS-GM age-equivalent scores increased 3.8 months and mean scaled scores increased 35 points for infants with motor delays compared with increased scores of 1.8 months and 13 points for infants with CP. Mean GMFM scores increased by 12.2% for infants with rmotor delays and by 4.2% for infants with CP. The diagnosis X time interaction was significant. Infants with motor delays had a greater change in motor development compared with the infants with CP. The hypothesis that the GMFM is more responsive to change than the PDMS-GM was not supported. The findings suggest that the GMFM and the PDMS-GM are comparable in measuring change in infants with CP or motor delays. Implications for selection and use of either measure are discussed.


Development of a community-based model for respiratory care services.
Chronic respiratory diseases are a major cause of mortality and morbidity, and represent a high chronic disease burden, which is expected to rise between now and 2020. Care for chronic diseases is increasingly located in community settings for reasons of efficiency and patient preference, though what services should be offered and where is contested. Our aim was to identify the key characteristics of a community-based service for chronic respiratory disease to help inform NHS commissioning decisions. We used the Delphi method of consensus development. We derived components from Wagner's Chronic Care Model (CCM), an evidence-based, multi-dimensional framework for improving chronic illness care. We used the linked Assessment of Chronic Illness Care to derive standards for each component.We established a purposeful panel of experts to form the Delphi group. This was multidisciplinary and included national and international experts in the field, as well as local health professionals involved in the delivery of respiratory services. Consensus was defined in terms of medians and means. Participants were able to propose new components in round one. Twenty-one experts were invited to participate, and 18 agreed to take part (85.7% response). Sixteen responded to the first round (88.9%), 14 to the second round (77.8%) and 13 to the third round (72.2%). The panel rated twelve of the original fifteen components of the CCM to be a high priority for community-based respiratory care model, with varying levels of consensus. Where consensus was achieved, there was agreement that the component should be delivered to an advanced standard. Four additional components were identified, all of which would be categorised as part of delivery system design. This consensus development process confirmed the validity of the CCM as a basis for a community-based respiratory care service and identified a small number of additional components. Our approach has the potential to be applied to service redesign for other chronic conditions.


Is the 90th Percentile Adequate? The Optimal Waist Circumference Cutoff Points for Predicting Cardiovascular Risks in 124,643 15-Year-Old Taiwanese Adolescents.
Adolescent obesity has increased to alarming proportions globally. However, few studies have investigated the optimal waist circumference (WC) of Asian adolescents. This study sought to establish the optimal WC cutoff points that identify a cluster of cardiovascular risk factors (CVRFs) among 15-year-old ethnically Chinese adolescents. This study was a regional population-based study on the CVRFs among adolescents who enrolled in all the senior high schools in Taipei City, Taiwan, between 2011 and 2014. Four cross-sectional health examinations of first-year senior high school (grade 10) students were conducted from September to December of each year. A total of 124,643 adolescents aged 15 (boys: 63,654; girls: 60,989) were recruited. Participants who had at least three of five CVRFs were classified as the high-risk group. We used receiver-operating characteristic curves and the area under the curve (AUC) to determine the optimal WC cutoff points and the accuracy of WC in predicting high cardiovascular risk. WC was a good predictor for high cardiovascular risk for both boys (AUC: 0.845, 95% confidence interval [CI]: 0.833-0.857) and girls (AUC: 0.763, 95% CI: 0.731-0.795). The optimal WC cutoff points were ≥78.9 cm for boys (77th percentile) and ≥70.7 cm for girls (77th percentile). Adolescents with normal weight and an abnormal WC were more likely to be in the high cardiovascular risk group (odds ratio: 3.70, 95% CI: 2.65-5.17) compared to their peers with normal weight and normal WC. The optimal WC cutoff point of 15-year-old Taiwanese adolescents for identifying CVRFs should be the 77th percentile; the 90th percentile of the WC might be inadequate. The high WC criteria can help health professionals identify higher proportion of the adolescents with cardiovascular risks and refer them for further evaluations and interventions. Adolescents' height, weight and WC should be measured as a standard practice in routine health checkups.


A Case of Radiation Fibrosis Appearing as Mass-Like Consolidation after SBRT with Elevation of Serum CEA.
We report a case of radiation fibrosis appearing as mass-like consolidation, which was difficult to distinguish from local recurrence. A 72-year-old woman was diagnosed as having primary lung cancer (cT1N0M0 stage IA) in the right upper lobe and was treated with SBRT of 48 Gy in 4 fractions. After 12 months, mass-like consolidation appeared around the irradiated area, and after 13 months, it had increased in size. FDG-PET revealed high uptake (SUV max = 5.61) for the consolidation. CT-guided biopsy was performed, but we could not confirm the diagnosis. Considering her poor respiratory function and her age, short-interval follow-up was performed. After 15 months, the consolidation enlarged at the dorsal side, and carcinoembryonic antigen (CEA) became elevated (14.6 ng/mL). Serum KL-6 (436 U/mL) and SP-D (204 ng/mL) were also elevated. However, after 16 months, serum CEA slightly decreased. The consolidation gradually retracted on follow-up CT images. CEA, KL-6, and SP-D were also decreased by degrees. After 40 months, there is no evidence of local recurrence.


Meeting report - INDEPTH kick-off meeting.
The precise location of chromatin domains within the cell nucleus has seen growing recognition in the past decade as an additional mechanism of controlling gene expression in both plants and animals (Dekker et al., 2017). Consequently, international efforts are devoted to understanding the organising principle of this organelle in plants, and notably the nature and the role of functional compartments on gene expression (Graumann et al., 2013; Sotelo-Silveira et al., 2018). The European cooperation 'Impact of Nuclear Domains on Gene Expression and Plant Traits' (INDEPTH) brings together molecular cell biologists, plant physiologists, bioinformaticians, image analysts and computer scientists. They aim to address the question of how nuclear architecture, chromatin organisation and gene expression are connected in plants, particularly in relation to traits of interest such as biomass, reproduction and resistance to pathogens (https://www.brookes.ac.uk/indepth/). The kick-off meeting of the INDEPTH consortium took place in Clermont-Ferrand, France, on 12-14th March 2018, where more than 80 researchers set the agenda for the coming four years of research and collaboration.


Synchronizing nuclear import of ribosomal proteins with ribosome assembly.
Ribosomal proteins are synthesized in the cytoplasm, before nuclear import and assembly with ribosomal RNA (rRNA). Little is known about coordination of nucleocytoplasmic transport with ribosome assembly. Here, we identify a transport adaptor, symportin 1 (Syo1), that facilitates synchronized coimport of the two 5S-rRNA binding proteins Rpl5 and Rpl11. In vitro studies revealed that Syo1 concomitantly binds Rpl5-Rpl11 and furthermore recruits the import receptor Kap104. The Syo1-Rpl5-Rpl11 import complex is released from Kap104 by RanGTP and can be directly transferred onto the 5S rRNA. Syo1 can shuttle back to the cytoplasm by interaction with phenylalanine-glycine nucleoporins. X-ray crystallography uncovered how the α-solenoid symportin accommodates the Rpl5 amino terminus, normally bound to 5S rRNA, in an extended groove. Symportin-mediated coimport of Rpl5-Rpl11 could ensure coordinated and stoichiometric incorporation of these proteins into pre-60S ribosomes.


Percutaneous vertebroplasty in vertebral osteonecrosis (Kummell's spondylitis).
The authors report the clinical symptoms and response to therapy of a series of patients who presented with subacute or chronic back pain due to vertebral osteonecrosis (Kummell's spondylitis) and who underwent percutaneous vertebroplasty. The authors performed a retrospective chart review of a series of 95 patients in whom 149 painful, nonneoplastic compression fractures were demonstrated and who were treated with percutaneous transpediculate polymethylmethacrylate (PMMA) vertebroplasty. In six of these patients there was evidence of vertebral osteonecrosis, as evidenced by the presence of an intravertebral vacuum cleft on radiography or by intravertebral fluid on magnetic resonance (MR) imaging. Clinical and radiological findings on presentation were noted. Technical aspects of the vertebroplasty technique were compiled. Response to therapy, defined as qualitative change in pain severity and change in level of activity, was noted immediately following the procedure and at various periods on follow-up reviews. One man and five women, who ranged in age from 72 to 90 years (mean 81 years), were treated. Each patient had one compression fracture. The fractures were at T-11 (one patient), L-1 (two patients), L-3 (two patients), and L-4 (one patient). The pain pattern was described as severe and localized to the affected vertebra, and sometimes radiated along either flank. Pain duration ranged from 2 to 12 weeks, and the pain was refractory to conservative therapy that consisted of bedrest, analgesics, and external bracing. At the time of treatment, all patients were bedridden because of severe back pain. In all patients either plain radiographic or computerized tomography evidence of intravertebral vacuum cleft or MR imaging evidence of vertebral fluid collection consistent with avascular necrosis of the vertebral body was demonstrated. Four patients underwent bilateral transpediculate vertebroplasty, and two patients underwent unilateral transpediculate vertebroplasty. The fracture cavities were specifically targeted for PMMA injection. Additional fortification of the osteoporotic vertebral body trabeculae was also performed when feasible. "Cavitygrams" or intraosseous venograms with gentle contrast injection were obtained prior to application of cement mixture. In all patients subjective improvement in pain and increased mobility were demonstrated posttreatment. The follow-up period ranged from 4 to 24 hours after treatment. Two patients made additional office visits at 1 and 3 months, respectively. Patients presenting with vertebral osteonecrosis (Kummell's spondylitis) often suffer from local paraspinous or referred pain. When performing vertebroplasty on these patients, confirmation of entry into the fracture cavities with contrast-enhanced "cavitygrams" should be performed prior to injection of PMMA cement. The response to vertebroplasty with regard to amelioration of pain and improved mobility is encouraging.


Validation of a rule for termination of resuscitation in out-of-hospital cardiac arrest.
We prospectively evaluated a clinical prediction rule to be used by emergency medical technicians (EMTs) trained in the use of an automated external defibrillator for the termination of basic life support resuscitative efforts during out-of-hospital cardiac arrest. The rule recommends termination when there is no return of spontaneous circulation, no shocks are administered, and the arrest is not witnessed by emergency medical-services personnel. Otherwise, the rule recommends transportation to the hospital, in accordance with routine practice. The study included 24 emergency medical systems in Ontario, Canada. All patients 18 years of age or older who had an arrest of presumed cardiac cause and who were treated by EMTs trained in the use of an automated external defibrillator were included. The patients were treated according to standard guidelines. Characteristics of diagnostic tests for the prediction rule were calculated. These characteristics include sensitivity, specificity, and positive and negative predictive values. Follow-up data were obtained for all 1240 patients. Of 776 patients with cardiac arrest for whom the rule recommended termination, 4 survived (0.5 percent). The rule had a specificity of 90.2 percent for recommending transport of survivors to the emergency department and had a positive predictive value for death of 99.5 percent when termination was recommended. Implementation of this rule would result in a decrease in the rate of transportation from 100 percent of patients to 37.4 percent. The addition of other criteria (a response interval greater than eight minutes or a cardiac arrest not witnessed by a bystander) would further improve both the specificity and positive predictive value of the rule but would result in the transportation of a larger proportion of patients. The use of a clinical prediction rule for the termination of resuscitation may help clinicians decide whether to terminate basic life support resuscitative efforts in patients having an out-of-hospital cardiac arrest.


Factors affecting the interrelationship between cynical hostility and dental anxiety among dental patients.
The objectives of this study were to assess the relationship between dental anxiety and cynical hostility in a sample of dental patients and to study the possible role of socioeconomic status (SES) in this relationship. A total of 288 dental patients completed a self-administered questionnaire consisting of the cynical distrust scale (CDS) and the modified dental anxiety scale (MDAS). Data on sociodemographic characteristics were also collected. Dental anxiety as reflected by mean MDAS scores was significantly higher among the younger age group (P = 0.002), among females (P = 0.025), and the lower SES groups (P = 0.001). Cynical hostility was significantly higher among the older age group (P = 0.03), among males (P = 0.02), and among the lower SES groups, respectively, (P = 0.001). When the CDS scores for individuals with and without dental anxiety were compared within the context of the three socioeconomic strata, there was a statistically significant difference (P = 0.029) in scores between the two anxiety groups in the middle socioeconomic strata where the cynical distrust scores were lower among the anxiety group. Mediation analysis revealed that SES played an important role in the association between dental anxiety and cynical hostility. It also showed that the mediating effect is not uniform across socioeconomic strata and may be different in different societies with their own unique population structures and classes.


The Impact of Implementation Fidelity on Mortality Under a CD4-Stratified Timing Strategy for Antiretroviral Therapy in Patients With Tuberculosis.
Among patients with tuberculosis and human immunodeficiency virus type 1, CD4-stratified initiation of antiretroviral therapy (ART) is recommended, with earlier ART in those with low CD4 counts. However, the impact of implementation fidelity to this recommendation is unknown. We examined a prospective cohort study of 395 adult patients diagnosed with tuberculosis and human immunodeficiency virus between August 2007 and November 2009 in Kinshasa, Democratic Republic of the Congo. ART was to be initiated after 1 month of tuberculosis treatment at a CD4 count of <100 cells/mm(3) or World Health Organization stage 4 (other than extrapulmonary tuberculosis) and after 2 months of tuberculosis treatment at a CD4 count of 100-350 cells/mm(3). We used the parametric g-formula to estimate the impact of implementation fidelity on 6-month mortality. Observed implementation fidelity was low (46%); 54% of patients either experienced delays in ART initiation or did not initiate ART, which could be avoided under perfect implementation fidelity. The observed mortality risk was 12.0% (95% confidence interval (CI): 8.2, 15.7); under complete (counterfactual) implementation fidelity, the mortality risk was 7.8% (95% CI: 2.4, 12.3), corresponding to a risk reduction of 4.2% (95% CI: 0.3, 8.1) and a preventable fraction of 35.1% (95% CI: 2.9, 67.9). Strategies to achieve high implementation fidelity to CD4-stratified ART timing are needed to maximize survival benefit.


Updated international consensus report on the investigation and management of primary immune thrombocytopenia.
Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This article is an update of the International Consensus Report published in 2010. A critical review was performed to identify all relevant articles published between 2009 and 2018. An expert panel screened, reviewed, and graded the studies and formulated the updated consensus recommendations based on the new data. The final document provides consensus recommendations on the diagnosis and management of ITP in adults, during pregnancy, and in children, as well as quality-of-life considerations.


Emergency management of agitation in schizophrenia.
Schizophrenia is a common psychiatric condition, affecting approximately 1% of the population. Acute emergent presentations often include hallucinations, delusions, thought, and speech disorders. Agitation is common among emergency patients with schizophrenia. Decisional capacity should be assessed in all patients. Reversible causes of agitation should be ruled out, including infection, metabolic disorders, endocrine disorders, trauma, pain, noncompliance, toxicological disorders, and structural brain abnormalities. Agitation may be managed acutely using a combination of pharmacological agents and nonpharmacological interventions. Effective pharmacological agents include several classes of antipsychotic agents and benzodiazepines. Potential life-threatening complications of pharmacological therapy should be anticipated, which may include neuroleptic malignant syndrome (NMS), prolonged QT syndrome, and respiratory depression. Nonpharmacological interventions may include a quiet environment, physical restraints, and behavioral interventions. Disposition decisions should be made based on the etiology of agitation, effective management, decisional capacity, and presence of suicidal or homicidal intentions. Many patients who have required nonpharmacological or pharmacological management of agitation require inpatient psychiatric treatment, either voluntarily or involuntarily. Psychiatric consultation should be sought for patients with schizophrenia and uncertain disposition determinations, or those requiring other complex management decisions.


SARS-CoV-2 antigen lateral flow tests for detecting infectious people: linked data analysis.
To investigate the proportion of lateral flow tests (LFTs) that produce negative results in those with a high risk of infectiousness from SARS-CoV-2, to investigate the impact of the stage and severity of disease, and to compare predictions made by influential mathematical models with findings of empirical studies. Linked data analysis combining empirical evidence of the accuracy of the Innova LFT, the probability of positive viral culture or transmission to secondary cases, and the distribution of viral loads of SARS-CoV-2 in individuals in different settings. Testing of individuals with symptoms attending NHS Test-and-Trace centres across the UK, residents without symptoms attending municipal mass testing centres in Liverpool, and students without symptoms screened at the University of Birmingham. Evidence for the sensitivity of the Innova LFT, based on 70 individuals with SARS-CoV-2 and LFT results. Infectiousness was based on viral culture rates on 246 samples (176 people with SARS-CoV-2) and secondary cases among 2 474 066 contacts; distributions of cycle threshold (Ct) values from 231 497 index individuals attending NHS Test-and-Trace centres; 70 people with SARS-CoV-2 detected in Liverpool and 62 people with SARS-CoV-2 in Birmingham (54 imputed). The predicted proportions who were missed by LFT and viral culture positive and missed by LFT and sources of secondary cases, in each of the three settings. Predictions were compared with those made by mathematical models. The analysis predicted that of those with a viral culture positive result, Innova would miss 20% attending an NHS Test-and-Trace centre, 29% without symptoms attending municipal mass testing, and 81% attending university screen testing without symptoms, along with 38%, 47%, and 90% of sources of secondary cases. In comparison, two mathematical models underestimated the numbers of missed infectious individuals (8%, 10%, and 32% in the three settings for one model, whereas the assumptions from the second model made it impossible to miss an infectious individual). Owing to the paucity of usable data, the inputs to the analyses are from limited sources. The proportion of infectious people with SARS-CoV-2 missed by LFTs is substantial enough to be of clinical importance. The proportion missed varied between settings because of different viral load distributions and is likely to be highest in those without symptoms. Key models have substantially overestimated the sensitivity of LFTs compared with empirical data. An urgent need exists for additional robust well designed and reported empirical studies from intended use settings to inform evidence based policy.


Hot topic: Definition and implementation of a breeding value for feed efficiency in dairy cows.
A new breeding value that combines the amount of feed saved through improved metabolic efficiency with predicted maintenance requirements is described. The breeding value includes a genomic component for residual feed intake (RFI) combined with maintenance requirements calculated from either a genomic or pedigree estimated breeding value (EBV) for body weight (BW) predicted using conformation traits. Residual feed intake is only available for genotyped Holsteins; however, BW is available for all breeds. The RFI component of the "feed saved" EBV has 2 parts: Australian calf RFI and Australian lactating cow RFI. Genomic breeding values for RFI were estimated from a reference population of 2,036 individuals in a multi-trait analysis including Australian calf RFI (n=843), Australian lactating cow RFI (n=234), and UK and Dutch lactating cow RFI (n=958). In all cases, the RFI phenotypes were deviations from a mean of 0, calculated by correcting dry matter intake for BW, growth, and milk yield (in the case of lactating cows). Single nucleotide polymorphism effects were calculated from the output of genomic BLUP and used to predict breeding values of 4,106 Holstein sires that were genotyped but did not have RFI phenotypes themselves. These bulls already had BW breeding values calculated from type traits, from which maintenance requirements in kilograms of feed per year were inferred. Finally, RFI and the feed required for maintenance (through BW) were used to calculate a feed saved breeding value and expressed as the predicted amount of feed saved per year. Animals that were 1 standard deviation above the mean were predicted to eat 66 kg dry matter less per year at the same level of milk production. In a data set of genotyped Holstein sires, the mean reliability of the feed saved breeding value was 0.37. For Holsteins that are not genotyped and for breeds other than Holsteins, feed saved is calculated using BW only. From April 2015, feed saved has been included as part of the Australian national selection index, the Balanced Performance Index (BPI). Selection on the BPI is expected to lead to modest gains in feed efficiency.


An osmosensing signal transduction pathway in mammalian cells.
The osmotic balance between the cytoplasmic and extracellular compartments of cells is critical for the control of cell volume. A mammalian protein kinase, Jnk, which is a distant relative of the mitogen-activated protein kinase group, was activated by phosphorylation on threonine and tyrosine in osmotically shocked cells. The activation of Jnk may be relevant to the biological response to osmotic shock because the expression of human Jnk in the yeast Saccharomyces cerevisiae rescued a defect in growth on hyper-osmolar media. These data indicate that related protein kinases may mediate osmosensing signal transduction in yeast and mammalian cells.


Transcriptomic profiles of 33 opium poppy samples in different tissues, growth phases, and cultivars.
Opium poppy is one of the most important medicinal plants and remains the only commercial resource of morphinan-based painkillers. However, little is known about the regulatory mechanisms involved in benzylisoquinoline alkaloids (BIAs) biosynthesis in opium poppy. Herein, the full-length transcriptome dataset of opium poppy was constructed for the first time in accompanied with the 33 samples of Illumina transcriptome data from different tissues, growth phases and cultivars. The long-read sequencing produced 902,140 raw reads with 55,114 high-quality transcripts, and short-read sequencing produced 1,923,679,864 clean reads with an average Q30 rate of 93%. The high-quality transcripts were subsequently quantified using the short reads, and the expression of each unigene among different samples was calculated as reads per kilobase per million mapped reads (RPKM). These data provide a foundation for opium poppy transcriptomic analysis, which may aid in capturing splice variants and some non-coding RNAs involved in the regulation of BIAs biosynthesis. It can also be used for genome assembly and annotation which will favor in new transcript identification.


Effects of dietary n-3 polyunsaturated fatty acids from plant and marine origin on platelet aggregation in healthy elderly subjects.
In the present intervention study we compared the effects of alpha-linolenic acid with those of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on platelet aggregation in vitro and ex vivo in healthy non-institutionalized elderly subjects. We also compared the effects of alpha-linolenic acid on platelet aggregation in elderly subjects with those in younger volunteers. During a run-in period of 3 weeks all subjects (thirty-eight elderly (> 60 years) and twelve younger volunteers (< 35 years)) received a diet rich in oleic acid. For the next 6 weeks the elderly subjects received a diet rich in oleic acid (n 11), alpha-linolenic acid (n 14) (6.8 g/d) or EPA/DHA (n 13) (1.05 g EPA plus 0.55 g DHA). The younger subjects were given a diet rich in alpha-linolenic acid. The diets did not affect ADP- or collagen-induced platelet aggregation in vitro in either platelet-rich plasma or whole blood. The ex vivo platelet aggregation as measured with filtragometry was significantly decreased in the elderly group that received EPA/DHA compared with the alpha-linolenic acid (P = 0.006) and the oleic acid (P = 0.005) diet groups. Effects of alpha-linolenic acid were not age-dependent. Our results suggest that alpha-linolenic acid and EPA/DHA do not change in vitro platelet aggregation. Compared with oleic acid, EPA/DHA, but not alpha-linolenic acid, favourably affects ex vivo platelet aggregation in healthy elderly subjects.


Formal concept analysis of disease similarity.
Previous work shows that gene associations and network properties common between pairs of diseases can provide molecular evidence of comorbidity, but relationships among diseases may extend to larger groups. Formal concept analysis allows the study of multiple diseases based on a concept lattice whose structure indicates gene set commonality. We use the concept lattice for gene associations to evaluate the complexity of the relationships among diseases, and to identify concepts whose gene sets are candidates for further functional analysis. For this, we define a heuristic on the lattice structure that allows the identification of concepts whose gene sets indicate strong relationships among the included diseases, which are distinguished from other diseases in the family. Applying this approach to a family of renal diseases we demonstrate that this approach finds gene sets that may be promising for studying common (and differing) mechanism among a family of comorbid or phenotypically related diseases.


Resilience 2.0: social media use and (self-)care during the 2011 Norway attacks.
Departing from the understanding that resilience is a technique of self-organization during emergencies, this article provides a study on the way in which the use of social media influenced and engendered societal resilience practices during the 2011 Norway attacks. It builds on the concepts of governmentality and mediality to discuss how the interplay between social media and its users created new forms of self-initiated and mediated emergency governance. Empirically, it draws on material from 20 in-depth interviews with Norwegians who explained and reflected upon their social media use during the attacks. The article presents an overview of the different functions that social media assumed in the process of dealing with the attacks and discusses these vis-à-vis their related challenges. It draws conclusions about the way in which resilience practices and the resilient subject are influenced by the networked character of 2.0 technologies.


Disease-causing missense mutations affect enzymatic activity, stability and oligomerization of glutaryl-CoA dehydrogenase (GCDH).
Glutaric aciduria type 1 (GA1) is an autosomal recessive neurometabolic disorder caused by mutations in the glutaryl-CoA dehydrogenase gene (GCDH), leading to an accumulation and high excretion of glutaric acid and 3-hydroxyglutaric acid. Considerable variation in severity of the clinical phenotype is observed with no correlation to the genotype. We report here for the first time on expression studies of four missense mutations c.412A > G (p.Arg138Gly), c.787A > G (p.Met263Val), c.1204C > T (p.Arg402Trp) and c.1240G > A (p.Glu414Lys) identified in GA1 patients in mammalian cells. Biochemical analyses revealed that all mutants were enzymatically inactive with the exception of p.Met263Val which showed 10% activity of the expressed wild-type enzyme. Western blot and pulse-chase analyses demonstrated that the amount of expressed p.Arg402Trp protein was significantly reduced compared with cells expressing wild-type protein which was due to rapid intramitochondrial degradation. Upon cross-linkage the formation of homotetrameric GCDH was strongly impaired in p.Met263Val and p.Arg402Trp mutants. In addition, GCDH appears to interact with distinct heterologous polypeptides to form novel 97, 130 and 200 kDa GCDH complexes. Molecular modeling of mutant GCDH suggests that Met263 at the surface of the GCDH protein might be part of the contact interface to interacting proteins. These results indicate that reduced intramitochondrial stability as well as the impaired formation of homo- and heteromeric GCDH complexes can underlie GA1.


Nursing staff's understanding expressions of people with advanced dementia disease.
People with advanced dementia disease (ADD) are known to have communication difficulties and thus it presents a challenge in understanding the expressions of these people. Because successful communication presupposes cooperation at least between 2 individuals, both individual's actions must be acknowledged. The aim of this study is to describe nursing staff's ways of understanding the expressions of people with ADD when communicating with them. Interviews from 8 nursing staff were analyzed using qualitative content analysis. Two themes were constructed: "Being in communication" and "Doing communication." Being in communication means that nursing staff perceive people with ADD as being capable of communication. Doing communication means that nursing staff attempt different individualized strategies to understand what people with ADD communicate. Good care of people with ADD presupposes nursing staff that are willing and able to relate to other people and to maintain good care for people with ADD continuous education and supervision are needed.


A prospective study of total sleep duration and incident metabolic syndrome: the ARIRANG study.
Chronic sleep deprivation is increasingly common in industrialized societies. Recent data have revealed that chronic sleep deprivation is associated with negative health outcome. While prospective studies lack the predictive value of sleep duration to identify individuals at high risk of new-onset metabolic syndrome, total sleep duration may play a role in the development of metabolic abnormalities. This study investigates the association between total sleep duration and the incidence of metabolic syndrome in a population-based longitudinal study. At baseline, a prospective cohort study was conducted with 2579 adults without metabolic syndrome aged between 40 and 70 years. Based on a self-reported questionnaire, the participants in this study were investigated between 2005-2008 (baseline) and 2008-2011 (follow-up) and were categorized according to their total sleep duration (<6 h, 6-7.9 h, 8-9.9 h, ≥10 h). Metabolic syndrome was defined according to the recent harmonized definition. During an average of 2.6 years of follow-up, 558 (21.6%) subjects developed metabolic syndrome. In multivariable adjusted models, the odds ratio (95% confidence interval (CI)) for incident metabolic syndrome comparing the 6 to 7.9 h to the <6 h of total sleep duration was 1.41 (1.06-1.88). The corresponding odds ratios (95% CI) for high waist circumference, low high-density lipoprotein (HDL) cholesterol, high triglycerides, high blood pressure, and high blood glucose were 1.30 (0.98-1.69), 0.75 (0.56-0.97), 0.82 (0.60-1.11), 1.56 (1.19-2.03), and 1.31 (0.96-1.79), respectively. Short sleep duration is an independent risk factor for incident metabolic syndrome in a population-based longitudinal study.


Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine.
Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2',2'-difluorodeoxycytidine) into its inactive form, 2',2'-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bacterial enzyme cytidine deaminase (CDDL), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDDL expression, and abrogated by cotreatment with the antibiotic ciprofloxacin. Gemcitabine is commonly used to treat pancreatic ductal adenocarcinoma (PDAC), and we hypothesized that intratumor bacteria might contribute to drug resistance of these tumors. Consistent with this possibility, we found that of the 113 human PDACs that were tested, 86 (76%) were positive for bacteria, mainly Gammaproteobacteria.


A prospective study of the PUSH tool in diabetic foot ulcers.
The purpose of this study was to examine the predictive validity of Pressure Ulcer Scale for Healing (PUSH; v. 3.0) in monitoring healing of neuropathic foot ulcers in patients with diabetes mellitus. This is a 13-week descriptive, prospective study describing the trajectory of change over time and the time-to-heal associated with PUSH scores. The study monitored a convenience sample of 18 subjects with Wagner 2 or greater neuropathic, nonischemic ulcers on the plantar surface of the foot, which healed completely over a 13-week follow-up period. Every 2 weeks, the study ulcers were evaluated via PUSH. Healing was defined as complete reepithelialization. PUSH scores were modeled using a piecewise linear regression. PUSH values decreased significantly (P < .0001) at a rate of 0.6656 per week, until 2 weeks before healing, and then decreased significantly (P < .0001) at a rate of 2.2496 per week for the last 2 weeks of healing. Conversely, the time-to-heal (in weeks) increased significantly (P < .0001), at a rate of 0.6412 per each unit increase in PUSH for PUSH values of 4 or less, and then significantly (P < .0001) increased at a rate of 1.072 for PUSH values greater than 5. In predicting time-to-heal, the subitem of length × width alone (R = 0.81) is comparable to the total PUSH score (R = 0.76). Individually, exudate (R = 0.36) and tissue type (R = 0.42) are not nearly as useful as length × width. Our findings indicate that PUSH scores significantly decrease over time in healing neuropathic diabetic foot ulcers (DFUs) that have no arterial etiologic component. Findings also suggest that total PUSH scores predict time-to-heal for DFU. We showed that a DFU with a PUSH score of 10 would be expected to heal in 8.8 weeks (95% CI: 7.4-10.2) and a DFU with a PUSH score of 4 in 2.6 weeks (95% CI: 1.88-3.25). Finally, measurements of size alone predict healing time for neuropathic DFU. This finding could greatly simplify clinical assessments.


Anti-osteoporosis activity of naringin in the retinoic acid-induced osteoporosis model.
Isoflavonoids isolated from plants have been confirmed to fight osteoporosis and promote bone health. However, few studies have been conducted to describe the anti-osteoporosis activity of botanical flavonone. Based on the experimental outcomes, we demonstrated the ability of naringin to fight osteoporosis in vitro. We developed a retinoic acid-induced osteoporosis model of rats to assess whether naringin has similar bioactivity against osteoporosis in vitro. After a 14-day supplement of retinoic acid to induce osteoporosis, SD rats were administered naringin. A blood test showed that naringin-treated rats experienced significantly lower activity of serum alkaline phosphatase and had higher femur bone mineral density, compared to untreated rats. All three dosages of naringin improved the decrease in bone weight coefficient, the length and the diameter of the bone, the content of bone ash, calcium, and phosphorus content induced by retinoic acid. The data of histomorphological metrology of naringin groups showed no difference as compared to normal control rats. These outcomes suggest that naringin offer a potential in the management of osteoporosis in vitro.


A common polymorphism in the ABCB11 gene is associated with advanced fibrosis in hepatitis C but not in non-alcoholic fatty liver disease.
Chronic HCV (hepatitis C virus)-associated cirrhosis represents a major indication for liver transplantation. Bile acids contribute to hepatic stellate cell activation as a key event in fibrogenesis. The aim of the present study was to investigate the role of bile acids and polymorphisms in bile acid level-regulating genes on fibrosis progression. A total of 206 subjects with chronic HCV infection were included for ABCB11 (ATP-binding cassette, subfamily B, member II) 1331T>C and NR1H4 (nuclear receptor) -1G>T genotyping, 178 of which were analysed for fibrosis stage. Exclusion criteria were HBV (hepatitis B virus) or HIV coinfection, alcohol >40 g/day and morbid obesity. A total of 358 patients with NAFLD (non-alcoholic fatty liver disease) were genotyped for comparison with a non-viral liver disease. Caucasian individuals (n = 110), undergoing liver resection for focal hepatic metastasis, served as controls. The ABCB11 1331C allele was significantly overrepresented in HCV patients compared with controls {allelic frequency 62.9%; OR (odds ratio), 1.41 [95% CI (confidence interval), 1.012-1.965]}. Median plasma bile acid levels were not significantly increased in the CC compared with TT genotype [7.2 (1-110) μmol/l compared with 3.5 (1-61) μmol/l; values are medians (range). A significant association between the presence of cirrhosis and ABCB11 genotype (CC compared with CT or TT, P=0.047) was observed in the χ2 test and independent of other risk factors of age, gender, body mass index and disease duration in multivariate analysis (P = 0.010). No such association could be observed in fatty liver patients with regard to advanced fibrosis (F ≥ 2). The common ABCB11 1331CC genotype, which is present in 40% of HCV patients and renders the carrier susceptible to increased bile acid levels, is associated with cirrhosis.


Introgression of chromosomal segments conferring early heading date from wheat diploid progenitor, Aegilops tauschii Coss., into Japanese elite wheat cultivars.
The breeding of agriculturally useful genes from wild crop relatives must take into account recent and future climate change. In Japan, the development of early heading wheat cultivars without the use of any major gene controlling the heading date is desired to avoid overlap of the harvesting time before the rainy season. Here, we backcrossed two early heading lines of a synthetic hexaploid wheat, derived from a crossing between durum wheat and the wild wheat progenitor Aegilops tauschii, with four Japanese elite cultivars to develop early heading lines of bread wheat. In total, nine early heading lines that showed a heading date two to eight days earlier than their parental cultivars in field conditions were selected and established from the selfed progenies of the two- or three-times backcrossed populations. The whole appearance and spike shape of the selected early heading lines looked like their parental wheat cultivars. The mature grains of the selected lines had the parental cultivars' characteristics, although the grains exhibited longer and narrower shapes. RNA sequencing-based genotyping was performed to detect single nucleotide polymorphisms between the selected lines and their parental wheat cultivars, which revealed the chromosomal regions transmitted from the parental synthetic wheat to the selected lines. The introgression regions could shorten wheat heading date, and their chromosomal positions were dependent on the backcrossed wheat cultivars. Therefore, early heading synthetic hexaploid wheat is useful for fine-tuning of the heading date through introgression of Ae. tauschii chromosomal regions.


Self-supported nickel-cobalt nanowires as highly efficient and stable electrocatalysts for overall water splitting.
The development and design of highly active and stable electrocatalysts based on cheap and Earth-abundant materials is critically important to enable water splitting as a desirable renewable energy source. Herein, we fulfill the significant electrochemical water splitting enhancement in both electrocatalytic activity and durability by constructing self-supported nickel-cobalt nanowire catalysts with abundant oxygen vacancies. Specifically, the rich oxygen vacancies can largely promote the oxygen evolution reaction (OER) activity of optimal Ni1Co1O2 NWs with a relatively low overpotential of 248 mV to drive a current density of 10 mA cm-2. More significantly, after the phosphorization of Ni1Co1O2 NWs, the resultant Ni1Co1P NWs can also display excellent electrocatalytic hydrogen evolution reaction (HER) performances with an overpotential of only 101 mV to achieve a current density of 10 mA cm-2. Furthermore, benefiting from the unique 1D nanowire structure, the synergistic effect, and the optimal Gibbs free energy for hydrogen evolution evolved from the phosphorization, the Ni1Co1O2 NWs//Ni1Co1P NWs couple is thus highly active and stable for overall water electrolysis with a low voltage of 1.58 V at 10 mA cm-2, showing extraordinary promise for practical overall water splitting electrolysis.


Aesthetic facial surgery for the asian male.
Cosmetic surgery of the Asian face has become increasingly popular in the Far East and the West. The Asian male identity has undergone an evolution in Western media toward a more positive change. The standards of beauty have also changed, being defined by more multicultural models and styles of dress than before. To undertake cosmetic surgery of the Asian face, particularly of the Asian male, requires a different psychological understanding of the individual as well as an entirely different surgical technique in most cases. This brief article does not delve into the technical details of each procedure but concentrates on the salient differences in how to approach the Asian male patient for each of the different procedures, including Asian blepharoplasty, augmentation rhinoplasty, lip reduction, dimple fabrication, otoplasty, facial contouring and aging face procedures, and hair restoration.


Safety of probiotics and synbiotics in children under 18 years of age.
This study aimed to systematically evaluate safety of probiotics and synbiotics in children ageing 0-18 years. This study is the third and final part in a safety trilogy and an update is provided using the most recent available clinical data (2008-2013) by means of the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification. Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 74 clinical studies indicated that probiotic and/or synbiotic administration in children is safe with regard to the specific evaluated strains, dosages and duration. The population of children include healthy, immune compromised and obese subjects, as well as subjects with intestinal disorders, infections and inflammatory disorders. This study revealed no major safety concerns, as the adverse events (AEs) were unrelated, or not suspected to be related, to the probiotic or synbiotic product. In general the study products were well tolerated. Overall, AEs occurred more frequent in the control arm compared to children receiving probiotics and/or synbiotics. Furthermore, the results indicate inadequate reporting and classification of AEs in the majority of the studies. In addition, generalizability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes.


Facultative Viviparity in a Flesh Fly (Diptera: Sarcophagidae): Forensic Implications of High Variability in Rates of Oviparity in Blaesoxipha plinthopyga (Diptera: Sarcophagidae).
Flesh flies are major primary consumers of carrion and are commonly found on human remains. Due to this latter feeding habit, their development rates can be used to provide temporal information in forensic investigations. This is usually done by referencing published flesh fly development datasets. Flesh flies are typically assumed to be strictly viviparous and datasets reporting their development rates therefore start at the first larval instar. However, an increasing number of studies has identified oviposition by flesh flies, including the forensically relevant species Blaesoxipha plinthopyga Wiedemann. To assess the impact of egg-laying behavior on casework, oviparity rates and time before larval hatching were assessed under controlled laboratory conditions that reflect common casework conditions in Harris County, Texas. We demonstrated systematic deposition of viable eggs but at a very variable rate between samples. Similarly, the duration between oviposition and larval hatching was highly variable, with some eggs taking more than a day to hatch after deposition. These results highlight the need to account for embryonic development in forensic investigations including B. plinthopyga and advocates for the re-evaluation of the assumed strict viviparity of the Sarcophagidae.


Highly luminescent gold nanoparticles: effect of ruthenium distance for nanoprobes with enhanced lifetimes.
The photophysical properties of gold nanoparticles, AuNPs, with sizes of 13, 50 and 100 nm in diameter, coated with surface-active ruthenium complexes have been studied to investigate the effect of the distance of the ruthenium luminescent centre from the gold surface. Luminescence lifetimes of the three ruthenium probes, RuS1, RuS6 and RuS12, with different length spacer units between the surface active groups and the ruthenium centre were taken. The metal complexes were attached to AuNP13, AuNP50 and AuNP100 via thiol groups using a method of precoating the nanoparticles with a fluorinated surfactant. The luminescence lifetime of the longer spacer unit complex, RuS12, was enhanced by 70% upon attachment to the AuNP when compared to the increase of the short and medium linker unit complexes, RuS1 (20%) and (RuS6 40%) respectively. The effect of the surfactant in the lifetime increase of the ruthenium coated AuNPs was shown to be larger for the medium spacer probe, RuS6. There was no effect of the change of the size of the AuNPs from 13 to 50 or 100 nm.


Low serum vitamin D is associated with high risk of diabetes in Korean adults.
Vitamin D may play a role in glucose metabolism. A low vitamin D level has been associated with increased risk of diabetes mellitus, but the association has not been confirmed in Asians. Our objective was to examine the association of serum 25-hydroxyvitamin D [25(OH)D] levels with insulin resistance and diabetes mellitus in Korean adults based on a large population-based survey. Cross-sectional analyses were carried out on 5787 Korean adults (2453 men and 3334 women) who were 20 y or older and participated in the Fourth Korea NHANES conducted in 2008. Diabetes mellitus was defined as fasting plasma glucose ≥7 mmol/L or current use of oral hypoglycemic agents or insulin. Insulin resistance was estimated by homeostatic model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI). Compared to individuals with a sufficient serum 25(OH)D concentration ≥75 nmol/L, the OR (95% CI) for diabetes mellitus were 1.73 (1.09-2.74), 1.30 (0.91-1.84), and 1.40 (0.99-1.98) for serum 25(OH)D concentrations <25, 25 to <50, and 50 to <75 nmol/L, respectively, after multiple adjustments (P-trend < 0.0001). Furthermore, the serum 25(OH)D level was inversely associated with HOMA-IR (β = -0.061; P = 0.001) and positively associated with QUICKI (β = 0.059; P = 0.001) in overweight or obese participants. In conclusion, a low serum vitamin D concentration is associated with a high risk of diabetes mellitus in Korean adults and the concentration is inversely associated with insulin resistance in those who are overweight or obese.


Modelling of strategies for genetic control of scrapie in sheep: The importance of population structure.
Scrapie is a transmissible spongiform encephalopathy in sheep and an example of a disease that may be controlled through breeding for disease resistance. Member states of the European Union have introduced strategies for breeding against scrapie based on the selection of genetically resistant breeding rams. An ambitious strategy adopted in The Netherlands consisted of selecting resistant rams for breeding throughout both breeding and production sectors. Mathematical modelling of the effect of a breeding program on the spreading capacity of scrapie in a national flock is needed for making assessments on how long a breeding strategy needs to be maintained to achieve disease control. Here we describe such a model applied to the Dutch situation, with the use of data on the genetic content of the Dutch sheep population as well as on scrapie occurrence in this population. We show that the time needed for obtaining scrapie control depends crucially on two parameters measuring sheep population structure: the between-flock heterogeneity in genotype frequencies, and the heterogeneity of mixing (contact rates) between sheep flocks. Estimating the first parameter from Dutch genetic survey data and assuming scenario values for the second one, enables model prediction of the time needed to achieve scrapie control in The Netherlands.


A nationwide survey on the knowledge and attitudes of Malaysian optometry students on patients' visual experiences during cataract surgery.
During cataract surgery under regional (retrobulbar, peribulbar or sub- Tenon's) or topical anaesthesia, many patients experience a variety of visual sensations in their operated eye intraoperatively. Between 3% and 16.2% of patients are frightened by their intraoperative visual experiences, which may increase the risk of intraoperative complications and affect patients' satisfaction with the surgery. This study aims to determine optometry students' beliefs and knowledge of visual sensations experienced by patients during cataract surgery under regional and topical anaesthesia. A nationwide survey of all Malaysian optometry students using a standardised, self-administered questionnaire. All 129 optometry students participated in the survey, giving a 100% response rate. Overall, 26.4% and 29.5% of the students believed that patients undergoing cataract surgery under regional and topical anaesthesia, respectively, may experience no light perception, while 78.3% and 72.9%, respectively, thought that patients would experience light perception. Many respondents also believed that patients might experience a variety of other visual sensations. Of all respondents, 70.5% and 74.4% of students believed that patients undergoing cataract surgery under regional and topical anaesthesia, respectively, may be frightened by their visual experience and 93.0% and 85.3%, respectively, felt that preoperative counselling might help to alleviate this fear. Many optometry students are aware that patients might encounter a variety of visual sensations during cataract surgery under local anaesthesia. A high proportion of students believe that patients may experience fear as a result of the intraoperative visual sensations and felt that preoperative counselling would be helpful.


Nurses' widespread job dissatisfaction, burnout, and frustration with health benefits signal problems for patient care.
Job dissatisfaction among nurses contributes to costly labor disputes, turnover, and risk to patients. Examining survey data from 95,499 nurses, we found much higher job dissatisfaction and burnout among nurses who were directly caring for patients in hospitals and nursing homes than among nurses working in other jobs or settings, such as the pharmaceutical industry. Strikingly, nurses are particularly dissatisfied with their health benefits, which highlights the need for a benefits review to make nurses' benefits more comparable to those of other white-collar employees. Patient satisfaction levels are lower in hospitals with more nurses who are dissatisfied or burned out-a finding that signals problems with quality of care. Improving nurses' working conditions may improve both nurses' and patients' satisfaction as well as the quality of care.


Natural cellulose fibers from switchgrass with tensile properties similar to cotton and linen.
We report the production and characteristics of natural cellulose fibers obtained from the leaves and stems of switchgrass. In this paper, the composition, structure and properties of fibers obtained from the leaves and stem of switchgrass have been studied in comparison to the common natural cellulose fibers, such as cotton, linen and kenaf. The leaves and stems of switchgrass have tensile properties intriguingly similar to that of linen and cotton, respectively. Fibers were obtained from the leaves and stems of switchgrass using a simple alkaline extraction and the structure and properties of the fibers were studied. Fibers obtained from switchgrass leaves have crystallinity of 51%, breaking tenacity of 5.5 g per denier (715 MPa) and breaking elongation of 2.2% whereas the corresponding values for fibers obtained from switchgrass stems are 46%, 2.7 g per denier and 6.8%, respectively. Switchgrass is a relatively easy to grow and high yield biomass crop that can be source to partially substitute the natural and synthetic fibers currently in use. We hope that this research will stimulate interests in using switchgrass as a novel fiber crop in addition to being promoted as a potential source for biofuels.


Expressive behavior in Parkinson's disease as a function of interview context.
Parkinson's disease affects the ability to express motivation through face, body, and voice; contextual factors may facilitate or inhibit expressive behavior. The purpose of this study was to determine whether qualities of the interview context are associated with client motivational behavior in Parkinson's disease. Men and women with Parkinson's disease (N = 106) discussed 2 topics (enjoyable activity vs. frustrating activity) during an assessment with a female or male interviewer. From videotaped clips, displays of 4 categories of motivation and 12 verbal and 18 nonverbal, behavioral patterns were rated. During the discussion of enjoyable activities, participants used more positive words, smiled more, and were more facially expressive. Participants were less talkative about their negative feelings and appeared to be more apathetic with the same-gender interviewer. Occupational therapy practitioners should vary the emotional tone of their questions to improve the validity of motivation assessments.


Sex-specific difference in migration schedule as a precursor of protandry in a long-distance migratory bird.
Protandry, the earlier arrival of males at the breeding grounds relative to females, is common in migratory birds. However, due to difficulties in following individual birds on migration, we still lack knowledge about the spatiotemporal origin of protandry during the annual cycle, impeding our understanding of the proximate drivers of this phenomenon. Here, we use full annual cycle tracking data of red-backed shrikes Lanius collurio to investigate the occurrence of sex-related differences in migratory pattern, which could be viewed as precursors (proximate causes) to protandry. We find protandry with males arriving an estimated 8.3 days (SE = 4.1) earlier at the breeding area than females. Furthermore, we find that, averaged across all departure and arrival events throughout the annual cycle, males migrate an estimated 5.3 days earlier than females during spring compared to 0.01 days in autumn. Event-wise estimates suggest that a divergence between male and female migratory schedules is initiated at departure from the main non-breeding area, thousands of kilometres from-, and several months prior to arrival at the breeding area. Duration of migration, flight speed during migration and spatial locations of stationary sites were similar between sexes. Our results reveal that protandry might arise from sex-differential migratory schedules emerging at the departure from the main non-breeding area in southern Africa and retained throughout spring migration, supporting the view that sex-differential selection pressure operates during spring migration rather than autumn migration.


Zirconia-coated carbonyl-iron-particle-based magnetorheological fluid for polishing optical glasses and ceramics.
We report on magnetorheological finishing (MRF) spotting experiments performed on glasses and ceramics using a zirconia-coated carbonyl-iron (CI)-particle-based magnetorheological (MR) fluid. The zirconia-coated magnetic CI particles were prepared via sol-gel synthesis in kilogram quantities. The coating layer was approximately 50-100 nm thick, faceted in surface structure, and well adhered. Coated particles showed long-term stability against aqueous corrosion. "Free" nanocrystalline zirconia polishing abrasives were cogenerated in the coating process, resulting in an abrasive-charged powder for MRF. A viable MR fluid was prepared simply by adding water. Spot polishing tests were performed on a variety of optical glasses and ceramics over a period of nearly three weeks with no signs of MR fluid degradation or corrosion. Stable material removal rates and smooth surfaces inside spots were obtained.


Effectiveness of propolis on oral health: a meta-analysis.
The use of propolis mouth rinse or gel as a supplementary intervention has increased during the last decade in Taiwan. However, the effect of propolis on oral health is not well understood. The purpose of this meta-analysis was to present the best available evidence regarding the effects of propolis use on oral health, including oral infection, dental plaque, and stomatitis. Researchers searched seven electronic databases for relevant articles published between 1969 and 2012. Data were collected using inclusion and exclusion criteria. The Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument was used to evaluate the quality of the identified articles. Eight trials published from 1997 to 2011 with 194 participants had extractable data. The result of the meta-analysis indicated that, although propolis had an effect on reducing dental plaque, this effect was not statistically significant. The results were not statistically significant for oral infection or stomatitis. Although there are a number of promising indications, in view of the limited number and quality of studies and the variation in results among studies, this review highlights the need for additional well-designed trials to draw conclusions that are more robust.


Camera-based detection and removal of shadows from interactive multiprojector displays.
Front-projection displays are a cost-effective and increasingly popular method for large format visualization and immersive rendering of virtual models. New approaches to projector tiling, automatic calibration, and color balancing have made multiprojector display systems feasible without undue infrastructure changes and maintenance. As a result, front-projection displays are being used to generate seamless, visually immersive worlds for virtual reality and visualization applications with reasonable cost and maintenance overhead. However, these systems suffer from a fundamental problem: Users and other objects in the environment can easily and inadvertently block projectors, creating shadows on the displayed image. Shadows occlude potentially important information and detract from the sense of presence an immersive display may have conveyed. We introduce a technique that detects and corrects shadows in a multiprojector display while it is in use. Cameras observe the display and compare observations with an expected image to detect shadowed regions. These regions are transformed to the appropriate projector frames, where corresponding pixel values are increased and/or attenuated. In display regions where more than one projector contributes to the image, shadow regions are eliminated.


Pesticide exposure in children.
This statement presents the position of the American Academy of Pediatrics on pesticides. Pesticides are a collective term for chemicals intended to kill unwanted insects, plants, molds, and rodents. Children encounter pesticides daily and have unique susceptibilities to their potential toxicity. Acute poisoning risks are clear, and understanding of chronic health implications from both acute and chronic exposure are emerging. Epidemiologic evidence demonstrates associations between early life exposure to pesticides and pediatric cancers, decreased cognitive function, and behavioral problems. Related animal toxicology studies provide supportive biological plausibility for these findings. Recognizing and reducing problematic exposures will require attention to current inadequacies in medical training, public health tracking, and regulatory action on pesticides. Ongoing research describing toxicologic vulnerabilities and exposure factors across the life span are needed to inform regulatory needs and appropriate interventions. Policies that promote integrated pest management, comprehensive pesticide labeling, and marketing practices that incorporate child health considerations will enhance safe use.


Increasing cesarean section rates in very low-birth weight infants. Effect on outcome.
Examination of a linked birth and death certificate file from Missouri revealed a remarkable increase in the use of cesarean section for very low-birth weight infants (500 to 1499 g) from 24% to 44% in the years 1980 to 1984. In the same years the rate for 1500- to 2499-g infants went from 21% to 26% and the rate for 2500- to 7000-g infants went from 14% to 18%. We studied first-day death rates in very low-birth weight infants as an indicator of potential benefit from this increase in cesarean sections. During the 5-year period first-day deaths averaged 10% and 22% in the cesarean and vaginal birth groups, respectively. This difference was explained almost entirely by deaths in the 500- to 740-g birth weight group, where the death rates were 33% and 59%, respectively. Although this difference remained statistically significant after adjustment for gestational age and other factors that differed between the groups, it was nullified by an excess of deaths in the succeeding 6 days of life. Overall, the odds of death in the first week in these infants weighing 500 to 749 g was 0.85 (95% confidence interval, 0.52 to 1.39) in the cesarean vs vaginal deliveries. We conclude that there is little evidence that the use of cesarean section for the delivery of very low-birth weight infants, independent of maternal or fetal compromise, improves overall survival. We were unable to find reasons to justify the sharp increase in the use of cesarean sections for these small infants.


Overlap graph-based generation of haplotigs for diploids and polyploids.
Haplotype-aware genome assembly plays an important role in genetics, medicine and various other disciplines, yet generation of haplotype-resolved de novo assemblies remains a major challenge. Beyond distinguishing between errors and true sequential variants, one needs to assign the true variants to the different genome copies. Recent work has pointed out that the enormous quantities of traditional NGS read data have been greatly underexploited in terms of haplotig computation so far, which reflects that methodology for reference independent haplotig computation has not yet reached maturity. We present POLYploid genome fitTEr (POLYTE) as a new approach to de novo generation of haplotigs for diploid and polyploid genomes of known ploidy. Our method follows an iterative scheme where in each iteration reads or contigs are joined, based on their interplay in terms of an underlying haplotype-aware overlap graph. Along the iterations, contigs grow while preserving their haplotype identity. Benchmarking experiments on both real and simulated data demonstrate that POLYTE establishes new standards in terms of error-free reconstruction of haplotype-specific sequence. As a consequence, POLYTE outperforms state-of-the-art approaches in various relevant aspects, where advantages become particularly distinct in polyploid settings. POLYTE is freely available as part of the HaploConduct package at https://github.com/HaploConduct/HaploConduct, implemented in Python and C++. Supplementary data are available at Bioinformatics online.


Anomalous dynamics of an elastic membrane in an active fluid.
Using numerical simulations, we characterized the behavior of an elastic membrane immersed in an active fluid. Our findings reveal a nontrivial folding and re-expansion of the membrane that is controlled by the interplay of its resistance to bending and the self-propulsion strength of the active components in solution. We show how flexible membranes tend to collapse into multifolded states, whereas stiff membranes fluctuate between an extended configuration and a singly folded state. This study provides a simple example of how to exploit the random motion of active particles to perform mechanical work at the microscale.


Evaluation of the potential therapeutic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of endometriosis.
To assess the therapeutic potential of polyinosine-polycytidylic acid, a double-stranded RNA molecule with selective proapoptotic and antiangiogenic activity, complexed with polyethyleneimine (pIC(PEI)) in treating endometriosis. A heterologous mouse model of endometriosis was created by injecting human endometrial fragments into the peritoneum. Endometrial fragments were engineered to express the fluorescent protein mCherry as a reporter to monitor status over the course of the 4-week study. University-affiliated infertility center. Ovariectomized and hormone-replaced nude mice (n = 30) injected with fluorescent-labeled human endometrial fragments at 4-6 weeks of age. Animals (n = 10 per group) were injected with vehicle (control), the anti-VEGF compound CBO-P11 (0.6 mg/kg), or pIC(PEI) (0.6 mg/kg) twice weekly over the course of 4 weeks. Variations in the size of endometriotic implants were estimated by quantifying the expression of mCherry throughout the course of the experiment. Neovascularization, cellular proliferation, and apoptosis were estimated by quantitative immunofluorescence detection of PECAM, α-SMA, Ki67, and TUNEL. pIC(PEI) promoted a significant increase in apoptosis and a decrease in neovascularization in human fragments, but did not reduce the size of endometriotic implants. While pIC(PEI) treatment had significant antiangiogenic and pro-apoptotic effects in this setting, longer periods of exposure than the ones supported by our heterologous model and/or assays in homologous mouse models of endometriosis may be necessary to detect an effect of this compound on lesion size.


Relevance of neuroimaging for neurocognitive and behavioral outcome after pediatric traumatic brain injury.
This study aims to (1) investigate the neuropathology of mild to severe pediatric TBI and (2) elucidate the predictive value of conventional and innovative neuroimaging for functional outcome. Children aged 8-14 years with trauma control (TC) injury (n = 27) were compared to children with mild TBI and risk factors for complicated TBI (mildRF+, n = 20) or moderate/severe TBI (n = 17) at 2.8 years post-injury. Neuroimaging measures included: acute computed tomography (CT), volumetric analysis on post-acute conventional T1-weighted magnetic resonance imaging (MRI) and post-acute diffusion tensor imaging (DTI, analyzed using tract-based spatial statistics and voxel-wise regression). Functional outcome was measured using Common Data Elements for neurocognitive and behavioral functioning. The results show that intracranial pathology on acute CT-scans was more prevalent after moderate/severe TBI (65%) than after mildRF+ TBI (35%; p = .035), while both groups had decreased white matter volume on conventional MRI (ps ≤ .029, ds ≥ -0.74). The moderate/severe TBI group further showed decreased fractional anisotropy (FA) in a widespread cluster affecting all white matter tracts, in which regional associations with neurocognitive functioning were observed (FSIQ, Digit Span and RAVLT Encoding) that consistently involved the corpus callosum. FA had superior predictive value for functional outcome (i.e. intelligence, attention and working memory, encoding in verbal memory and internalizing problems) relative to acute CT-scanning (i.e. internalizing problems) and conventional MRI (no predictive value). We conclude that children with mildRF+ TBI and moderate/severe TBI are at risk of persistent white matter abnormality. Furthermore, DTI has superior predictive value for neurocognitive out-come relative to conventional neuroimaging.


Alkaline-earth metal phenylphosphonates and their intercalation chemistry.
The intercalation chemistry of layered alkaline-earth metal phenylphosphonates with the general formula MeC6H5PO3·2H2O (Ca, Sr, Ba) is reviewed. The preparation of the host materials is described and their behavior in dependence on the relative humidity and pH of the reaction medium is discussed. Mutual relationships between MeC6H5PO3·2H2O and Me(C6H5PO3H)2 were investigated using a method of computer-controlled addition of reagents. The MeC6H5PO3·2H2O compounds are able to intercalate species having a free electron pair through the so-called coordination intercalation. In this way, 1-alkylamines, 1-alkanols, 1,n-diols and 1,2-diols were intercalated. In the case of the ethanol and methanol intercalates of strontium phenylphosphonate we were able to determine the structure of the host part by single-crystal X-ray diffraction. By combination of the data obtained from the diffraction with molecular modeling we suggested the arrangement of the host molecules in the interlayer space of the host. The arrangement of the shorter diols in the interlayer space of strontium phenylphosphonate was also proposed on the basis of molecular modeling calculations. These models help us to understand the structure of the prepared intercalates.


Microengineered peripheral nerve-on-a-chip for preclinical physiological testing.
The use of advanced in vitro testing is a powerful tool to develop predictive cellular assays suitable for improving the high attrition rates of novel pharmaceutical compounds. A microscale, organotypic model of nerve tissue with physiological measures that mimic clinical nerve compound action potential (CAP) and nerve fiber density (NFD) tests may be more predictive of clinical outcomes, enabling a more cost-effective approach for selecting promising lead compounds with higher chances of late-stage success. However, the neurological architecture, physiology, and surrounding extracellular matrix are hard to mimic in vitro. Using a dual hydrogel construct and explants from rat embryonic dorsal root ganglia, the present study describes an in vitro method for electrophysiological recording of intra- and extra-cellular recordings using a spatially-controlled, microengineered sensory neural fiber tract. Specifically, these 3D neural cultures exhibit both structural and functional characteristics that closely mimic those of afferent sensory peripheral fibers found in vivo. Our dual hydrogel system spatially confines growth to geometries resembling nerve fiber tracts, allowing for a high density of parallel, fasciculated neural growth. Perhaps more importantly, outputs resembling clinically relevant test criteria, including the measurement of CAP and NFD are possible through our advanced model. Moreover, the 3D hydrogel constructs allow flexibility in incorporated cell type, geometric fabrication, and electrical manipulation, providing a viable assay for systematic culture, perturbation, and testing of biomimetic neural growth for mechanistic studies necessitating physiologically-relevant readouts.


Cigarette smoking in middle age and a long-term risk of impaired activities of daily living: NIPPON DATA80.
Few studies have reported the relationship between smoking in middle age and long-term risk of impaired activities of daily living (ADL). We analyzed 2,276 men and women aged 47-59 years at the baseline survey of NIPPON DATA80 in 1980. At the follow-up survey in 1999, ADL was surveyed among 1890 survivors. Multivariate-adjusted odds ratio (AOR) and 95% CI of impaired ADL or of composite outcome of either death or impaired ADL according to baseline smoking status were calculated by multiple logistic regression analyses. In 1999, 386 participants were dead, and 75 participants had impaired ADL. Compared with nonsmokers, AOR (95% CI) of impaired ADL was significantly higher in current smokers at baseline (odds ratio [OR] 2.11 [1.09-4.06]). Compared with nonsmokers, AOR of impaired ADL was higher as the number of cigarettes increased (OR 2.04 [1.02-4.06] for <20 cigarettes/day and OR 2.35 [0.94-5.88] for >20 cigarettes/day; p for trend = .04). AOR of composite outcome for current smoking was 1.83 (1.37-2.41). Smoking in middle age would increase future risks of impaired ADL. Smoking cessation may be important to prevent future impairment of ADL as well as death.


A systems biology approach to analyse leaf carbohydrate metabolism in Arabidopsis thaliana.
Plant carbohydrate metabolism comprises numerous metabolite interconversions, some of which form cycles of metabolite degradation and re-synthesis and are thus referred to as futile cycles. In this study, we present a systems biology approach to analyse any possible regulatory principle that operates such futile cycles based on experimental data for sucrose (Scr) cycling in photosynthetically active leaves of the model plant Arabidopsis thaliana. Kinetic parameters of enzymatic steps in Scr cycling were identified by fitting model simulations to experimental data. A statistical analysis of the kinetic parameters and calculated flux rates allowed for estimation of the variability and supported the predictability of the model. A principal component analysis of the parameter results revealed the identifiability of the model parameters. We investigated the stability properties of Scr cycling and found that feedback inhibition of enzymes catalysing metabolite interconversions at different steps of the cycle have differential influence on stability. Applying this observation to futile cycling of Scr in leaf cells points to the enzyme hexokinase as an important regulator, while the step of Scr degradation by invertases appears subordinate.


The Acute Effects of Real-World Physical Activity on Glycemia in Adolescents With Type 1 Diabetes: The Type 1 Diabetes Exercise Initiative Pediatric (T1DEXIP) Study.
Data from the Type 1 Diabetes Exercise Initiative Pediatric (T1DEXIP) study were evaluated to understand glucose changes during activity and identify factors that may influence changes. In this real-world observational study, adolescents with type 1 diabetes self-reported physical activity, food intake, and insulin dosing (multiple-daily injection users) using a smartphone application. Heart rate and continuous glucose monitoring data were collected, as well as pump data downloads. Two hundred fifty-one adolescents (age = 14 ± 2 years [mean ± SD]; HbA1c = 7.1 ± 1.3% [54 ± 14.2 mmol/mol]; 42% female) logged 3,738 activities over ∼10 days of observation. Preactivity glucose was 163 ± 66 mg/dL (9.1 ± 3.7 mmol/L), dropping to 148 ± 66 mg/dL (8.2 ± 3.7 mmol/L) by end of activity; median duration of activity was 40 min (20, 75 [interquartile range]) with a mean and peak heart rate of 109 ± 16 bpm and 130 ± 21 bpm. Drops in glucose were greater in those with lower baseline HbA1c levels (P = 0.002), shorter disease duration (P = 0.02), less hypoglycemia fear (P = 0.04), and a lower BMI (P = 0.05). Event-level predictors of greater drops in glucose included self-classified "noncompetitive" activities, insulin on board >0.05 units/kg body mass, glucose already dropping prior to the activity, preactivity glucose >150 mg/dL (>8.3 mmol/L) and time 70-180 mg/dL >70% in the 24 h before the activity (all P < 0.001). Participant-level and activity event-level factors can help predict the magnitude of drop in glucose during real-world physical activity in youths with type 1 diabetes. A better appreciation of these factors may improve decision support tools and self-management strategies to reduce activity-induced dysglycemia in active adolescents living with the disease.


Personalized Radiation Oncology: Epidermal Growth Factor Receptor and Other Receptor Tyrosine Kinase Inhibitors.
Molecular biomarkers are currently evaluated in preclinical and clinical studies in order to establish predictors for treatment decisions in radiation oncology. The receptor tyrosine kinases (RTK) are described in the following text. Among them, the most data are available for the epidermal growth factor receptor (EGFR) that plays a major role for prognosis of patients after radiotherapy, but seems also to be involved in mechanisms of radioresistance, specifically in repopulation of tumour cells between radiotherapy fractions. Monoclonal antibodies against the EGFR improve locoregional tumour control and survival when applied during radiotherapy, however, the effects are heterogeneous and biomarkers for patient selection are warranted. Also other RTK´s such as c-Met and IGF-1R seem to play important roles in tumour radioresistance. Beside the potential to select patients for molecular targeting approaches combined with radiotherapy, studies are also needed to evluate radiotherapy adaptation approaches for selected patients, i.e. adaptation of radiation dose, or, more sophisticated, of target volumes.


Prevalence of comorbid psychiatric disorders among people with autism spectrum disorder: An umbrella review of systematic reviews and meta-analyses.
With ever-increasing prevalence of various mental disorders worldwide, a comprehensive evaluation of the prevalence of co-occurring psychiatric disorders among individuals with autism spectrum disorder (ASD) is needed to strengthen the knowledge base. This umbrella review aims to summarize the current evidence on the prevalence of comorbid psychiatric disorders among people with ASD. A systematic search of 12 major databases and additional sources was conducted. Any systematically conducted narrative, qualitative, or meta-analytic review reporting the prevalence of psychiatric disorders among people with ASD with no age or geographical restriction were included. From a total of 2755 records, 26 articles representing 14 systematic reviews and 12 meta-analyses met the criteria of this review. The synthesized findings reveal a high burden of comorbid psychiatric disorders among people with ASD, including anxiety disorders, depressive disorders, bipolar and mood disorders, schizophrenia spectrum, suicidal behavior disorders, attention-deficit/hyperactivity disorder, disruptive, impulse-control and conduct disorders amongst diverse age groups, with a majority in younger participants. Most studies were conducted in developed nations, with limited evidence from low and middle-income countries. These synthesized findings provide high-quality evidence for clinical and policy-level decision-making from a global overview of the status of comorbid psychiatric disorders among people with ASD.