Physiologic Responses, Liking and Motivation for Playing the Same Video Game on an Active Versus a Traditional, Non-Active Gaming System.
Evidence suggests that individuals playing certain video games on the Nintendo Wii® (Wii) exhibit increased energy expenditure versus traditional video games, although little research examines non-Wii Sports/Fit games. The purpose of this study is to assess physiologic responses, liking, and the relative reinforcing value (RRV) of a popular, non-Wii sports video game for the Wii relative to the same game played on a traditional, non-active system. Twenty-four college-aged students participated. Heart rate and oxygen consumption (V̇O2) was assessed during rest and when playing the following games: Madden NFL 2011® for Playstation 2 (PS2 Madden) and the Wii (Wii Madden), and Wii Sports Boxing. The RRV was assessed for Wii Madden versus PS2 Madden. Analysis of variance demonstrated a main effect for condition (p ≤ 0.01) as V̇O2 (5.2 ± 0.2 ml·kg-1·min-1 Wii, 4.1 ± 0.1 ml·kg-1·min-1 PS2, 3.7 ± 0.1 ml·kg-1·min-1, rest) and heart rate (89.2 · 2.7 bpm Wii, 79.7 ± 2.5 bpm PS2, 79.1 ± 2.5 bpm, rest) was greater for Wii Madden than PS2 Madden and rest. Heart Rate (105.4 ± 5.3 bpm) and V̇O2 (10.4 ml·kg-1·min-1) for Wii Sports Boxing was significantly greater than all other conditions (p ≤ 0.003). The RRV was not significantly different between Wii Madden and PS2 Madden (p = 0.50). Compared to the same game on a traditional system, Wii Madden is more physiologically challenging and equally reinforcing. However, Wii Madden would not be categorized as moderate-intensity physical activity.


Anisakis simplex as a risk factor for relapsing acute urticaria: a case-control study.
IgE-mediated hypersensitivity reactions to Anisakis simplex have been described after ingestion of fish, suggesting that sensitisation to this parasite may induce acute urticaria and anaphylaxis. Anisakis simplex allergens are highly resistant to heat and freezing, and sensitisation may occur even in populations with low consumption of raw/undercooked fish. This study aimed to quantify the association between sensitisation to A. simplex and relapsing acute urticaria. This is the first case-control study on this topic. Cases (n = 200) were patients with a clinical diagnosis of relapsing acute urticaria, consecutively approached at the immunoallergology unit of Porto's largest paediatric hospital. Controls (n = 200) were consecutively selected at the surgery department of the same hospital, from subjects undergoing programmed orthopaedic, maxillofacial or general surgical procedures. Specific IgE measurements (Anisakis and Ascaris) were taken, and skin-prick tests (A simplex, common aeroallergens, fish, and Ascaris) were done. Sensitisation to A simplex (OR 3.86, 95% CI 2.04% to 7.29%), Ascaris (OR 3.37, 95% CI 1.89% to 6.02%), fish (OR 4.62, 95% CI 1.85% to 11.52%), and at least one aeroallergen (OR 4.59, 95% CI 2.99% to 7.05%) were associated with increased risk of acute urticaria. Regarding the sensitisation to A simplex, the aeroallergen sensitisation-adjusted OR was 2.61 (95% CI 1.33% to 5.12%) for the whole sample, and 2.72 (95% CI 0.99% to 7.47%) for those not sensitised to Ascaris or fish. Sensitisation to A simplex increases the risk of relapsing acute urticaria in subjects not sensitised to Ascaris or fish, and this is independent of aeroallergen sensitisation.


Decreased BDNF in patients with antipsychotic naïve first episode schizophrenia.
Brain-derived neurotrophic factor (BDNF) is a key factor known to mediate neuronal proliferation, differentiation, survival and response to stress. Decreases in BDNF levels have been reported in schizophrenia, but studies in treatment naïve patients are few. Herein we report on serum BDNF levels in a series of patients with first-episode treatment naïve psychoses in comparison to age matched healthy controls. Fasting serum BDNF levels were measured in 41 patients with treatment naive first episode psychosis (24 with schizophrenia, schizoaffective disorder or schizophreniform disorder, and 17 with non-schizophrenia psychotic disorders) and 41 age-matched healthy controls. A three group analyses of covariance (ANCOVA) showed a diagnosis effect (p=.038) in which patients with schizophrenia had lesser serum BDNF levels than patient with non-schizophrenia psychosis, who in turn had lesser BDNF levels than matched healthy controls. Planned two-group ANCOVAs suggested that patients with schizophrenia had lower serum BDNF level than matched controls (p=.016), whereas patients with non-schizophrenia psychosis did not differ from controls. There were no age effects on BDNF, but there was a trend (p=.08) for a gender by group interaction with greater reductions in female patients with schizophrenia. The BDNF levels did not correlate with magnitude of smoking, body mass index, severity of positive and negative symptoms or overall functioning. Serum BDNF may be reduced at the onset of psychosis but its role in the pathogenesis of schizophrenia remains unclear. Elucidating the role of BDNF in schizophrenia and related psychotic disorders may provide an important therapeutic target. Further studies are also needed to examine if patients with schizophrenia have more pronounced reductions in BDNF than those with affective psychosis.


A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype.
AUTS2 syndrome is an 'intellectual disability (ID) syndrome' caused by genomic rearrangements, deletions, intragenic duplications or mutations disrupting AUTS2. So far, 50 patients with AUTS2 syndrome have been described, but clinical data are limited and almost all cases involved young children. We present a detailed clinical description of 13 patients (including six adults) with AUTS2 syndrome who have a pathogenic mutation or deletion in AUTS2. All patients were systematically evaluated by the same clinical geneticist. All patients have borderline to severe ID/developmental delay, 83-100% have microcephaly and feeding difficulties. Congenital malformations are rare, but mild heart defects, contractures and genital malformations do occur. There are no major health issues in the adults; the oldest of whom is now 59 years of age. Behaviour is marked by it is a friendly outgoing social interaction. Specific features of autism (like obsessive behaviour) are seen frequently (83%), but classical autism was not diagnosed in any. A mild clinical phenotype is associated with a small in-frame 5' deletions, which are often inherited. Deletions and other mutations causing haploinsufficiency of the full-length AUTS2 transcript give a more severe phenotype and occur de novo. The 13 patients with AUTS2 syndrome with unique pathogenic deletions scattered around the AUTS2 locus confirm a phenotype-genotype correlation. Despite individual variations, AUTS2 syndrome emerges as a specific ID syndrome with microcephaly, feeding difficulties, dysmorphic features and a specific behavioural phenotype.


A regulatory role for cAMP in phosphatidylinositol 3-kinase/p70 ribosomal S6 kinase-mediated DNA synthesis in platelet-derived-growth-factor-stimulated bovine airway smooth-muscle cells.
In bovine airway smooth-muscle cells platelet-derived growth factor (PDGF) and endothelin (Et-1) stimulate sustained and comparable activation of mitogen-activated protein kinase (MAP kinase) but display very different mitogenic efficacies, with PDGF inducing 50 times more DNA synthesis than Et-1. To examine additional signalling pathways which may be involved in this response, we investigated the role of phosphatidylinositol 3-kinase (PtdIns 3-kinase)/p70 ribosomal protein S6 kinase (p70s6k) in mediating PDGF- and Et-1-induced mitogenesis, and whether inhibition of this pathway may underly the ability of cAMP to inhibit cell proliferation. PDGF stimulated an increase in PtdIns 3-kinase activity and a sustained 15-fold increase in p70s6k activity that was abolished by both wortmannin and rapamycin. Et-1, however, stimulated only a 2-fold increase in p70s6k activity that was rapamycin-sensitive but wortmannin-insensitive. DNA synthesis stimulated by PDGF (50-fold) and Et-1 (2-fold) followed a similar pattern of inhibition. Pretreatment with phorbol ester did not affect p70s6k activation in response to PDGF. Raising intracellular cAMP levels using forskolin, however, resulted in a marked time-dependent inhibition of p70s6k activity, a decrease in the tyrosine phosphorylation of the PtdIns 3-kinase p85 subunit and reduced PtdIns 3-kinase activity. Forskolin also inhibited PDGF-stimulated DNA synthesis. These results suggest that PtdIns 3-kinase-dependent activation of p70s6k may determine mitogenic efficacy of agonists that generate comparable MAP kinase signals. Negative regulation of PtdIns 3-kinase by cAMP may play an important role in the inhibition of airway smooth-muscle cell proliferation.


Detecting knowledge of incidentally acquired, real-world memories using a P300-based concealed-information test.
Autobiographical memory for events experienced during normal daily life has been studied at the group level, but no studies have yet examined the ability to detect recognition of incidentally acquired memories among individual subjects. We present the first such study here, which employed a concealed-information test in which subjects were shown words associated with activities they had experienced the previous day. Subjects wore a video-recording device for 4 hr on Day 1 and then returned to the laboratory on Day 2, where they were shown words relating to events recorded with the camera (probe items) and words of the same category but not relating to the subject's activities (irrelevant items). Electroencephalograms were recorded, and presentation of probe items was associated with a large peak in the amplitude of the P300 component. We were able to discriminate perfectly between 12 knowledgeable subjects who viewed stimuli related to their activities and 12 nonknowledgeable subjects who viewed only irrelevant items. These results have strong implications for the use of memory-detection paradigms in criminal contexts.


Bracing Scoliosis - State of the Art (Mini-Review).
Spinal bracing is indicated in moderate to severe curves during growth. Brace effectiveness in halting progression of adolescent idiopathic scolisosis has been shown in a Cochrane review and in a randomized controlled trial (RCT). The outcome of brace treatment is dependent on the extent of in-brace correction and compliance. We have reviewed the literature on bracing to determine the types of brace that offer the best in-brace correction. The literature has been searched for papers on bracing with documented in-brace corrections and long-term results. The in-brace percentage of correction of asymmetric braces is generally higher than that of the symmetric braces. According to the literature found in our search, long-term corrections are possible when starting treatment early, at an immature stage and with asymmetric braces of recent standards. Bracing today is supported by high quality evidence (Level I). Asymmetric braces have led to better corrections than that described for symmetric braces. An improvement of the average corrective effect has been described due to the latest CAD / CAM development. Long-term corrections are possible when starting brace treatment early, at an immature stage and with asymmetric braces of recent standards.


Cost-effectiveness of orbital atherectomy compared to rotational atherectomy in treating patients with severely calcified coronary artery lesions in Japan.
Compared to rotational atherectomy (RA), orbital atherectomy (OA) has been shown to decrease procedure failure and reintervention rates in the treatment of severely calcified coronary artery lesions. Our objective was to explore the cost-effectiveness of OA compared to RA in the Japanese healthcare system. A decision-analytic model calculated reintervention rates and consequent total 1-year costs. Effectiveness inputs were therapy-specific target lesion revascularization (TLR) rates and all-cause mortality, pooled from clinical studies. Index and reintervention costs were determined based on claims data analysis of n = 33,628 subjects treated in 2014-2016. We computed incremental cost-effectiveness in Japanese Yen (JPY) per life year (LY) gained based on differences in 1-year cost and projected long-term survival, assuming OA device cost between JPY 350,000 and JPY 550,000. OA was found to be associated with improved clinical outcomes (12-month TLR rate 5.0 vs. 15.7%) and projected survival gain (8.34 vs. 8.16 LYs (+0.17), based on 1-year mortality of 5.5 vs. 6.8%). Total 1-year costs were lower for device cost of JPY 430,000 or less, and reached a maximum ICER of JPY 753,445 per LY at the highest assumed device cost, making OA dominant or cost-effective across the tested range, at ICERs substantially below the willingness-to-pay threshold. In conclusion, orbital atherectomy for the treatment of severely calcified coronary artery lesions, compared to rotational atherectomy, is a cost-effective treatment approach in the Japanese healthcare system due to improved clinical performance.


The appropriateness of using laboratories and student participants in gambling research.
Increased recognition of the risks associated with gambling has resulted in a greater focus on empirical research to increase the understanding of gambling and design appropriate response strategies. Laboratory studies are a popular mode of research due to their relative ease and lower costs compared to field research; however such studies may be limited in the extent to which results can be generalized to real gambling scenarios. The current research investigated the validity of a laboratory research study using 127 university students (male = 97, mean age = 20.4) investigating the impact of harm-minimisation measures by replicating the study in gambling venues with 124 club patrons (male = 89, mean age = 44.1). The main results and effects of both studies were in the same direction, but fewer significant results were found in the venue study. Venue participants provided much less information in response to survey questions than student participants and were less likely to return follow-up questionnaires. It was concluded that both laboratory and field studies provide valuable contributions to the field, but caution should be taken in interpreting results, and where possible both methodologies should be used to verify conclusions.


Plant-Based Diets for Personal, Population, and Planetary Health.
Worldwide, the burden of morbidity and mortality from diet-related chronic diseases is increasing, driven by poor diet quality and overconsumption of calories. At the same time, the global food production system is draining our planet's resources, jeopardizing the environment and future food security. Personal, population, and planetary health are closely intertwined and will all continue to be vulnerable to these threats unless action is taken. Fortunately, shifting current global dietary patterns towards high-quality, plant-based diets could alleviate these health and environmental burdens. Compared with typical Western diets with high amounts of animal products, healthy plant-based diets are not only more sustainable, but have also been associated with lower risk of chronic diseases such as obesity, type 2 diabetes, cardiovascular disease, and some cancers. For personalized disease management and prevention, precision nutrition has the potential to offer more effective approaches tailored to individual characteristics such as the genome, metabolome, and microbiome. However, this area of research is in the early stages and is not yet ready for widespread clinical use. Therefore, it must not overshadow public health nutrition strategies, which have the power to improve health and sustainability on a larger scale. If widely implemented, interventions and policy changes that shift the globe towards healthy plant-based dietary patterns could be instrumental in ensuring future personal, population, and planetary health.


Not in Education, Employment, or Training status among young Swiss men. Longitudinal associations with mental health and substance use.
Not in Education, Employment, or Training (NEET) youth are youth disengaged from major social institutions and constitute a worrying concern. However, little is known about this subgroup of vulnerable youth. This study aimed to examine if NEET youth differ from other contemporaries in terms of personality, mental health, and substance use and to provide longitudinal examination of NEET status, testing its stability and prospective pathways with mental health and substance use. As part of the Cohort Study on Substance Use Risk Factors, 4,758 young Swiss men in their early 20s answered questions concerning their current professional and educational status, personality, substance use, and symptomatology related to mental health. Descriptive statistics, generalized linear models for cross-sectional comparisons, and cross-lagged panel models for longitudinal associations were computed. NEET youth were 6.1% at baseline and 7.4% at follow-up with 1.4% being NEET at both time points. Comparisons between NEET and non-NEET youth showed significant differences in substance use and depressive symptoms only. Longitudinal associations showed that previous mental health, cannabis use, and daily smoking increased the likelihood of being NEET. Reverse causal paths were nonsignificant. NEET status seemed to be unlikely and transient among young Swiss men, associated with differences in mental health and substance use but not in personality. Causal paths presented NEET status as a consequence of mental health and substance use rather than a cause. Additionally, this study confirmed that cannabis use and daily smoking are public health problems. Prevention programs need to focus on these vulnerable youth to avoid them being disengaged.


Somatosensory evoked potentials in rat cerebral cortex before and after middle cerebral artery occlusion.
We recorded somatosensory evoked potentials in pentobarbital-anesthetized rats before and after middle cerebral artery occlusion. Trigeminal (vibrissae), median (forelimb), and sciatic (hind limb) nerve stimuli produced consistent, robust, and sharply localized responses in the trigeminal, forelimb, and hind limb regions of the somatosensory cortex of 18 rats. These regions are situated at sequentially greater distances from the center of infarcts produced by middle cerebral artery occlusion. In eight rats, occlusion 1-2 mm below the rhinal fissure abolished somatosensory evoked potentials in all three cortical region within minutes. Positive wavelets preceding the primary cortical response were also diminished by the occlusion, suggesting that ischemia affected the thalamocortical white matter. Four of these eight rats did not show histologically apparent ischemic involvement of the hind limb cortical region at 3 hours after occlusion; sciatic nerve evoked potentials recovered substantially in all four rats, and the amplitudes exceeded baseline (129 +/- 30% at 1 hour, 173 +/- 33% at 3 hours) in three of the four rats. Three of the eight rats did not have gross ischemic involvement of the forelimb cortical region; median nerve evoked potentials recovered fully in all eight rats, but the amplitudes did not exceed baseline. All eight rats had evidence of ischemic damage in the trigeminal cortex; no rat showed full recovery in this region, and all but one had trigeminal evoked potentials that were less than 20% of baseline amplitudes by 3 hours after occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)


The status of health promotion in Botswana.
Health education and promotion remains an integral part of public health. This paper details health promotion activities in Botswana since the establishment of the profession in 1988. It further describes health promotion infrastructure, investment in health promotion, human resource training and collaborations within the country. Infrastructure and services for health promotion in the country are mainly provided by government through educational institutions, faith based organizations, non-governmental organizations, general medical practitioners and mining companies complementing the Ministry's efforts. More than 1000 health promotion cadres have been trained at certificate, diploma and degree levels by Boitekanelo College and the Ministry of Health through Serowe Institute of Health Sciences.


Attitudes to outcomes measured in clinical trials of cardiovascular prevention.
Selecting outcome measures in cardiovascular prevention trials should be informed by their importance to selected populations. Major vascular event outcomes are usually prioritized in these trials with considerably less attention paid to cognitive and functional outcomes. To examine views on importance of outcome measures used in clinical trials. Cross-sectional survey. Of 367 individuals approached, 280 (76%) participated: outpatients attending cardiovascular prevention clinics (n = 97), active retirement groups members (n = 75), medical students (n = 108). Participants were asked to rank, in order of importance, outcome measures, which may be included in cardiovascular prevention trials. Results were compared between two groups: <65s (n = 157) and ≥65s (n = 104). When asked what outcomes were most important to measure in cardiovascular prevention trials, respondents reported: death (31.6%) stroke (28.5%), dementia (26.9%), myocardial infarction (MI) (7.9%) and requiring nursing home (NH) care (5.1%). When asked the most relevant outcomes regarding successful ageing respondents reported; maintaining independence (32.4%), avoiding major illness (24.3%), good family life (23.6%), living as long as possible (15.8%), avoiding NH care (3.1%) and contributing to society (0.8%) as most important. When asked what outcome concerned them most about the future, respondents reported: dementia (32.6%), dependence (30.4%), death (12.8%), stroke (12.5%), cancer (6.2%) requiring NH care (4.8%) and MI (0.7%). Maintaining independence was considered most important in younger and older cohorts. Cognitive and functional outcomes are important patient-relevant outcomes, sometimes more important than major vascular events. Incorporating these outcomes into trials may encourage patient participation and adherence to preventative regimens.


Microbiota-Derived Extracellular Vesicles Detected in Human Blood from Healthy Donors.
The microbiota constitutes an important part of the holobiont in which extracellular vesicles (EVs) are key players in health, especially regarding inter- and intra-kingdom communications. Analysis of EVs from the red blood cell concentrates of healthy donors revealed variable amounts of OmpA and LPS in 12 of the 14 analyzed samples, providing indirect experimental evidence of the presence of microbiota EVs in human circulating blood in the absence of barrier disruption. To investigate the role of these microbiota EVs, we tracked the fusion of fluorescent Escherichia coli EVs with blood mononuclear cells and showed that, in the circulating blood, these EVs interacted almost exclusively with monocytes. This study demonstrates that bacterial EVs constitute critical elements of the host-microbiota cellular communication. The analysis of bacterial EVs should thus be systematically included in any characterization of human EVs.


Ovarian cancer risk factors by histologic subtypes in the NIH-AARP Diet and Health Study.
Data suggest that risk factors for ovarian carcinoma vary by histologic type, but findings are inconsistent. We prospectively evaluated risk factors by histological subtypes of incident ovarian cancer (n = 849) in a cohort of 169,391 women in the NIH-AARP Diet and Health Study. We constructed Cox models of individual exposures by comparing case subtypes to the entire non-case group and assessed p-heterogeneity in case-case comparisons using serous as the reference category. Substantial risk differences between histologic subtypes were observed for menopausal hormone therapy (MHT) use, oral contraceptive (OC) use, parity and body mass index (p-heterogeneity = 0.01, 0.03, 0.05, 0.03, respectively). MHT users were at increased risk for all histologic subtypes except for mucinous carcinomas, where risk was reduced (relative risk (RR) = 0.37; 95% confidence interval (CI): 0.18, 0.80). OC users were only at significantly decreased risk for serous cancers (RR = 0.69; 95% CI: 0.55, 0.85). Although parity was inversely associated with risk of all subtypes, the RRs ranged from 0.28 (clear cell) to 0.83 (serous). Obesity was a significant risk factor only for endometrioid cancers (RR = 1.64; 95% CI: 1.00, 2.70). Our findings support a link between etiological factors and histological heterogeneity in ovarian carcinoma.


Mortality of workers exposed to 2 methyl-4 chlorophenoxyacetic acid.
The authors examined the mortality and cancer incidence of employees at a company which has manufactured, formulated, and sprayed 2 methyl-4 chlorophenoxyacetic acid (MCPA) and other phenoxy acid herbicides. Ninety-eight percent of the 5,784 men employed by the company during 1947-1975 was traced to the end of 1983. The overall mortality of the cohort was less than that of the national population, as was mortality from cancer. When allowance was made for rural residence, the deficit of cancer deaths became a slight excess, but not statistically significantly so. Among workers whose jobs entailed potential exposure to MCPA, there was one death from soft tissue sarcoma (0.6 expected). No further cases of soft tissue sarcoma were registered among living members of the cohort. Three potentially exposed workers died from nasal carcinoma, but this tumor has not previously been associated with phenoxy herbicides and the cluster of cases may have occurred by chance. The findings do not exclude the possibility that MCPA is a human carcinogen, but they suggest that any risk of soft tissue sarcoma is less than that indicated by earlier studies of 2,4,5-T (2,4,5-trichlorophenoxyacetic acid) and 2,4,5-trichlorophenol and is small in absolute terms.


Genetic overlap between impulsivity and alcohol dependence: a large-scale national twin study.
Alcohol dependence is associated with increased levels of impulsivity, but the genetic and environmental underpinnings of this overlap remain unclear. The purpose of the current study was to investigate the degree to which genetic and environmental factors contribute to the overlap between alcohol dependence and impulsivity. Univariate and bivariate twin model fitting was conducted for alcohol dependence and impulsivity in a national sample of 16 819 twins born in Sweden from 1959 to 1985. The heritability estimate for alcohol dependence was 44% [95% confidence interval (CI) 31-57%] for males and 62% (95% CI 52-72%) for females. For impulsivity, the heritability was 33% (95% CI 30-36%) in males and females. The bivariate twin analysis indicated a statistically significant genetic correlation between alcohol dependence and impulsivity of 0.40 (95% CI 0.23-0.58) in males and 0.20 (95% CI 0.07-0.33) in females. The phenotypic correlation between alcohol dependence and impulsivity was 0.20 and 0.17 for males and females, respectively, and the bivariate heritability was 80% (95% CI 47-117%) for males and 53% (95% CI 19-86%) for females. The remaining variance in all models was accounted for by non-shared environmental factors. The association between alcohol dependence and impulsivity can be partially accounted for by shared genetic factors. The genetic correlation was greater in men compared with women, which may indicate different pathways to the development of alcohol dependence between sexes. The observed genetic overlap has clinical implications regarding treatment and prevention, and partially explains the substantial co-morbidity between alcohol dependence and psychiatric disorders characterized by impulsive behaviour.


What is an arousal and how should it be quantified?
Pathologically severe daytime sleepiness is one of the main symptoms seen in a respiratory sleep clinic and is due to repeated arousal from sleep. Which types of arousal are most important in causing this is uncertain and most studies have only found loose relationships between indices of arousal frequency and the severity of the ensuing daytime sleepiness. Recent attempts to improve these disappointing correlations have concentrated on detecting more minor arousal events through the use of novel EEG signal analysis techniques and non-EEG based signals such as blood pressure and heart rate. To date there are no good data sets which allow the relative merits of these various techniques to be compared and it is unclear whether these efforts to increase the sensitivity of arousal detection will lead to improvements in the clinical usefulness of sleep fragmentation scoring. Studies which relate both the traditional indices of sleep fragmentation and the newer methodologies to clinically relevant reference standards (such as measured excessive daytime sleepiness) are needed to clarify these issues.


Excellent, Lightweight and Flexible Electromagnetic Interference Shielding Nanocomposites Based on Polypropylene with MnFe2O4 Spinel Ferrite Nanoparticles and Reduced Graphene Oxide.
In this work, various tunable sized spinel ferrite MnFe2O4 nanoparticles (namely MF20, MF40, MF60 and MF80) with reduced graphene oxide (RGO) were embedded in a polypropylene (PP) matrix. The particle size and structural feature of magnetic filler MnFe2O4 nanoparticles were controlled by sonochemical synthesis time 20 min, 40 min, 60 min and 80 min. As a result, the electromagnetic interference shielding characteristics of developed nanocomposites MF20-RGO-PP, MF40-RGO-PP, MF60-RGO-PP and MF80-RGO-PP were also controlled by tuning of magnetic/dielectric loss. The maximum value of total shielding effectiveness (SET) was 71.3 dB for the MF80-RGO-PP nanocomposite sample with a thickness of 0.5 mm in the frequency range (8.2-12.4 GHz). This lightweight, flexible and thin nanocomposite sheet based on the appropriate size of MnFe2O4 nanoparticles with reduced graphene oxide demonstrates a high-performance advanced nanocomposite for cutting-edge electromagnetic interference shielding application.


Prevalence of restless legs syndrome in patients with irritable bowel syndrome.
To determine the prevalence of restless legs syndrome (RLS) in patients with irritable bowel syndrome (IBS). Patients with diarrhea-predominant IBS (n = 30), constipation-predominant IBS (n = 30), or mixed-symptom IBS (n = 30) were recruited from the community between March 2008 and February 2009. Rifaximin 200 mg three times daily was administered empirically to alleviate small intestinal bowel overgrowth in all patients. The presence of RLS was assessed via an RLS questionnaire and polysomnography. Twenty-six patients with IBS (29%) were diagnosed with RLS using the RLS questionnaire. Twenty-four of the 26 patients (92%) underwent polysomnography, and all had confirmation of RLS. A greater percentage of patients with RLS had diarrhea-predominant IBS (62%) compared with patients with constipation-predominant IBS (4%) or mixed-symptom IBS (33%). Restless legs syndrome is prevalent in patients with IBS, especially those with diarrheal symptoms. Assessment of concomitant disorders may improve diagnosis and expand relevant treatment options for patients.


English language proficiency, health literacy, and trust in physician are associated with shared decision making in rheumatoid arthritis.
Treat-to-target guidelines promote shared decision making (SDM) in rheumatoid arthritis (RA). Also, because of high cost and potential toxicity of therapies, SDM is central to patient safety. Our objective was to examine patterns of perceived communication around decision making in 2 cohorts of adults with RA. Data were derived from patients enrolled in 1 of 2 longitudinal, observational cohorts [University of California, San Francisco (UCSF) RA Cohort and RA Panel Cohort]. Subjects completed a telephone interview in their preferred language that included a measure of patient-provider communication, including items about decision making. Measures of trust in physician, education, and language proficiency were also asked. Logistic regression was performed to identify correlates of suboptimal SDM communication. Analyses were performed on each sample separately. Of 509 patients across 2 cohorts, 30% and 32% reported suboptimal SDM communication. Low trust in physician was independently associated with suboptimal SDM communication in both cohorts. Older age and limited English proficiency were independently associated with suboptimal SDM in the UCSF RA Cohort, as was limited health literacy in the RA Panel Cohort. This study of over 500 adults with RA from 2 demographically distinct cohorts found that nearly one-third of subjects report suboptimal SDM communication with their clinicians, regardless of cohort. Lower trust in physician was independently associated with suboptimal SDM communication in both cohorts, as was limited English language proficiency and older age in the UCSF RA Cohort and limited health literacy in the RA Panel Cohort. These findings underscore the need to examine the influence of SDM on health outcomes in RA.


Identification and characterization of the Trichoplusia ni single capsid nuclear polyhedrosis virus p10 gene.
The p10 gene was identified and characterized from the Trichoplusia ni single capsid nuclear polyhedrosis virus (TniSNPV). The p10 open reading frame (ORF) sequence was identified following sequencing of the ends of the EcoRI-G clone. Subsequent sequencing of an EcoRI-SmaI subclone identified the entire p10 and a portion of a p26 homologue. The p10 ORF of 264 basepairs (bps), encoded a predicted protein of 88 amino acids (aas) with Mr 9527 Da. The putative late transcription initiation motif (TAAG) was found upstream of the translation initiation codon at position -46. Downstream of the translation stop codon, a putative poly(A) signal was identified. The p10 amino acid sequence contained the three conserved domains reported for all other p10 genes. The p10 amino acid sequence was most homologous (85% similarity and 67% identity) to that of Buzura suppresaria NPV p10 sequence.


An Analysis of State Autism Educational Assessment Practices and Requirements.
States differ in the procedures and criteria used to identify ASD. These differences are likely to impact the prevalence and age of identification for children with ASD. The purpose of the current study was to examine the specific state variations in ASD identification and eligibility criteria requirements. We examined variations by state in autism assessment practices and the proportion of children eligible for special education services under the autism category. Overall, our findings suggest that ASD identification practices vary across states, but most states use federal guidelines, at least in part, to set their requirements. Implications and recommendations for policy and practice are discussed.


ATM is a redox sensor linking genome stability and carbon metabolism.
In response to oxidative stress, central carbohydrate metabolism is reconfigured so that the metabolic flux reroutes from glycolysis into the pentose phosphate pathway (PPP), which allows cells to mount an effective response to this cellular stress. The kinase ataxia telangiectasia mutated (ATM) regulates this metabolic shift in mammalian cells. Upon ATM activation, the rate-limiting PPP enzyme glucose 6-phosphate dehydrogenase (G6PDH) formed a complex with heat shock protein 27 that increased G6PDH activity, augmented NADP(+) to NADPH reduction, and stimulated nucleotide synthesis. As such, ATM antagonizes the tumor suppressor p53, which is a direct inhibitor of G6PDH and the PPP. In addition to its role in DNA repair and the cell cycle, ATM is thus a component of the eukaryotic redox-sensing system. By linking genome stability, the cell cycle, and carbon catabolism, ATM emerges as a central regulator of cellular metabolism with implications for cancer.


The Effects of Adding Different Stabilizers in Brine on the Physicochemical, Sensory, Microbiological and Textural Properties of White Cheese.
The aim of the present study was to determine the effect of four different thickening agents (guar gum, carrageenan, xanthan gum, and gelatin) on the textural and sensory properties of white cheese. For this purpose, various white cheeses were manufactured with brines (the salt ratio was 8% and 12%) that contained different types and concentrations of gums; white cheese textural and sensory properties were studied during storage (at 4 °C). Also, microbiological properties including lactic acid bacteria (LAB) and mesophilic aerobic bacteria were investigated. The physicochemical, textural, microbiological, and sensory properties of the cheeses were determined on the 1st, 15th, and 30th days of storage. During the storage period of cheese, the top-rated samples in terms of sensory properties were cheeses with gelatin and carrageenan gum. The microbiological data displayed that there was an inverse relationship between the number of bacteria and the amount of gum used, although it was not precisely linear. At the same time, the highest values were generally determined in the control samples, and although not to a very great extent, gelatinous examples were found to contain a lower number of lactic acid bacteria than others. Regarding the textural properties, the hardness value of all samples containing gelatin showed a continuous increasing trend, while the springiness values increased only in the samples with xanthan gum and guar gum. At the end of storage, it was observed that the inherent adhesiveness of the samples decreased by more than half and the use of gelatin resulted in an increase in the gumminess of the cheeses. As a result, it was determined that reducing the salt used in the brine by up to 8% did not cause any defect since stabilizers were preventing water passage into the cheese by holding water.


Effects of extracorporeal shock-wave lithotripsy directed at the parotid gland on oxidative stress parameters and some trace element levels in facial nerve of rats.
This study was designed to assess the effect of extracorporeal shock-wave lithotripsy (ESWL) exposure of the parotid gland on oxidative stress and some trace element levels in the facial nerves of rats. Twelve male Wistar albino rats were divided into two groups, each consisting of 6 animals. The rats in the first group served as controls. The left parotid glands of animals in the second group were treated with 1000 18-kV shock waves while anesthetized with ketamine. The animals in both groups were euthanized 72 h after the ESWL treatment, and the right facial nerve was harvested for determination of oxidant/antioxidant status and trace element levels. Lipid peroxidation product malondialdehyde (MDA) and antioxidant glutathione (GSH) levels increased, and the activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), decreased in the facial nerves of ESWL-treated rats. The levels of iron, lead, manganese, and cobalt increased, and magnesium, cadmium, and copper levels decreased. ESWL treatment of the parotid gland may increase lipid peroxidation and decrease antioxidant enzyme activity in adjacent tissues such as the facial nerve. It also causes a decrease or increase in many mineral levels of the facial nerve, which is an undesirable condition for normal physiological function.


[Anesthesia breathing systems with CO2 absorption, circle valve circuit: comparison of thermal behavior of coaxial system and conventional system with different fresh gas flows.].
The adequate maintenance of inhaled gases temperature during anesthetic procedures is critical to prevent perioperative respiratory complications. This study aimed at comparing the ability to warm up inhaled gases of coaxial breathing system and conventional system, by varying fresh gas flows (FGF). Breathing systems were tested in a lung simulator ventilated with 600 mL tidal volume and respiratory frequency of 10 bpm. The model simulated human CO2 production by delivering 250 mL.min-1 of CO2 flow. Then, exhaled gas from the model was directed to a pre-warmed humidifier to simulate human exhaled gas. Both systems were classified as circle, valve circuits with CO2 absorption. In the coaxial system (model A), the inspiratory branch was enveloped by the expiratory branch, whereas the conventional one (model B) presented separated respiratory branches. Inhaled gas temperature was measured at the following moments: 0, 5, 10, 20, 30, 40, 50, 60 and 90 minutes, with low (0.5 and 1 L.min-1) and high (3 and 6 L.min-1) FGF. Model A presented significant thermal variation between beginning and end of experiment (22.47 +/- 1.77 masculineC and 24.27 +/- 3.52 masculineC respectively, p < 0.05). Both models A and B produced similar temperatures at the end of the study (24.27 +/- 3.52 masculineC and 23.61 +/- 1.93 masculineC respectively). There was no difference between final temperatures of both models and environmental temperature (21.25 +/- 1.20 masculineC and 21.81 +/- 1,87 masculineC respectively). Low FGF has produced similar temperatures to those observed at the end of the study with higher flows in both models (A: 25.53 +/- 4.78 masculineC and 23.02 +/- 0.80 masculineC; B: 24.50 +/- 0.85 masculineC and 22.72 +/- 2.36 masculineC, respectively). The coaxial system presented significant thermal variation between beginning and end of experiment, while this was not observed in the conventional one. No difference was observed in final temperatures when comparing both systems, regardless of the FGF.


Plasma self-q switching in far infrared lasers.
The plasma electrons in pulsed far ir lasers constitute a temporary divergent refractive element. This lens element can be strong enough to prohibit stable laser modes and serves to explain the delay commonly reported between current and laser pulses. With electron recombination the cavity rapidly becomes stable, Q switching the laser pulse. The lens effect and Q-switching rate are calculated in terms of tube dimensions, laser frequency, electron density, and radial electron density distribution. Higher laser frequencies appear earlier when this effect is operative. A simple criterion is given to distinguish this delay effect from other sources of laser pulse delay. Experimental measurements are presented of cavity stability as a function of mirror curvature and electron density; wall reflections are shown to be important. The radial electron density distribution is compared with plasma theory results. Lens effects associated with the laser gain are shown to be negligible.


Identification of phosphorylcholine epitope-containing antigens in Brugia malayi and relation of serum epitope levels to infection status of jirds with brugian filariasis.
The Gib 13 monoclonal antibody was raised against eggs of Onchocerca gibsoni and subsequently found to react with a phosphorylcholine epitope designated as the T15 idiotype. Since an immunoradiometric assay based on the Gib 13 monoclonal antibody holds promise for serodiagnosis of filariasis, the goals of the current study were to evaluate phosphorylcholine epitope production and release by various parasite stages and to assess changes in serum epitope levels during different phases of Brugia malayi infection in jirds. Extracts of B. malayi adult male worms, female worms, and microfilariae contained Gib 13 monoclonal antibody-reactive antigens of Mr 25-30,000, 57-90,000, and approximately equal to 200,000. Adult female worms secreted ten-fold more epitope than microfilariae on a weight basis. Phosphorylcholine-containing antigens were localized in female and male worms, respectively, in egg-bearing regions and the intestines. Assessment of the relationship between serum levels of Gib 13 antibody-binding epitope and parasitologic status of B. malayi-infected jirds showed that the immunoradiometric assay distinguishes patent infected from uninfected control animals, detects a significant rise in epitope level during the prepatent phase of infection, and is unaffected by diethylcarbamazine-induced reduction in the intensity of microfilaremia. There was a direct positive correlation between serum epitope level and female adult worm load. Quantification of serum phosphorylcholine epitope of the T15 idiotype may be useful as an indirect measure of parasite burden in humans with lymphatic filariasis that is independent of microfilaremia.


Genome-Based Characterization of Emergent Invasive Neisseria meningitidis Serogroup Y Isolates in Sweden from 1995 to 2012.
Invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup Y has increased in Europe, especially in Scandinavia. In Sweden, serogroup Y is now the dominating serogroup, and in 2012, the serogroup Y disease incidence was 0.46/100,000 population. We previously showed that a strain type belonging to sequence type 23 was responsible for the increased prevalence of this serogroup in Sweden. The objective of this study was to investigate the serogroup Y emergence by whole-genome sequencing and compare the meningococcal population structure of Swedish invasive serogroup Y strains to those of other countries with different IMD incidence. Whole-genome sequencing was performed on invasive serogroup Y isolates from 1995 to 2012 in Sweden (n = 186). These isolates were compared to a collection of serogroup Y isolates from England, Wales, and Northern Ireland from 2010 to 2012 (n = 143), which had relatively low serogroup Y incidence, and two isolates obtained in 1999 in the United States, where serogroup Y remains one of the major causes of IMD. The meningococcal population structures were similar in the investigated regions; however, different strain types were prevalent in each geographic region. A number of genes known or hypothesized to have an impact on meningococcal virulence were shown to be associated with different strain types and subtypes. The reasons for the IMD increase are multifactorial and are influenced by increased virulence, host adaptive immunity, and transmission. Future genome-wide association studies are needed to reveal additional genes associated with serogroup Y meningococcal disease, and this work would benefit from a complete serogroup Y meningococcal reference genome.


Sediment flux and the Anthropocene.
Data and computer simulations are reviewed to help better define the timing and magnitude of human influence on sediment flux--the Anthropocene epoch. Impacts on the Earth surface processes are not spatially or temporally homogeneous. Human influences on this sediment flux have a secondary effect on floodplain and delta-plain functions and sediment dispersal into the coastal ocean. Human impact on sediment production began 3000 years ago but accelerated more widely 1000 years ago. By the sixteenth century, societies were already engineering their environment. Early twentieth century mechanization has led to global signals of increased sediment flux in most large rivers. By the 1950s, this sediment disturbance signal reversed for many rivers owing to the proliferation of dams, and sediment load reduction below pristine conditions is the dominant signal today. A delta subsidence signal began in the 1930s and is now a dominant signal in terms of sea level for many coastal environments, overwhelming even the global warming imprint on sea level. Humans have engineered how most water and sediment are discharged into the coastal ocean. Hyperpycnal flow events have become more common for some rivers, and less common for other rivers. Bottom trawling is now widespread, suggesting that even continental shelves have received a significant but as yet quantified Anthropocene impact. The Anthropocene attains the level of a geological climate event, such as that seen in the transition between the Pleistocene and the Holocene.


Identification of novel growth phase- and media-dependent small non-coding RNAs in Streptococcus pyogenes M49 using intergenic tiling arrays.
Small non-coding RNAs (sRNAs) have attracted attention as a new class of gene regulators in both eukaryotes and bacteria. Genome-wide screening methods have been successfully applied in Gram-negative bacteria to identify sRNA regulators. Many sRNAs are well characterized, including their target mRNAs and mode of action. In comparison, little is known about sRNAs in Gram-positive pathogens. In this study, we identified novel sRNAs in the exclusively human pathogen Streptococcus pyogenes M49 (Group A Streptococcus, GAS M49), employing a whole genome intergenic tiling array approach. GAS is an important pathogen that causes diseases ranging from mild superficial infections of the skin and mucous membranes of the naso-pharynx, to severe toxic and invasive diseases. We identified 55 putative sRNAs in GAS M49 that were expressed during growth. Of these, 42 were novel. Some of the newly-identified sRNAs belonged to one of the common non-coding RNA families described in the Rfam database. Comparison of the results of our screen with the outcome of two recently published bioinformatics tools showed a low level of overlap between putative sRNA genes. Previously, 40 potential sRNAs have been reported to be expressed in a GAS M1T1 serotype, as detected by a whole genome intergenic tiling array approach. Our screen detected 12 putative sRNA genes that were expressed in both strains. Twenty sRNA candidates appeared to be regulated in a medium-dependent fashion, while eight sRNA genes were regulated throughout growth in chemically defined medium. Expression of candidate genes was verified by reverse transcriptase-qPCR. For a subset of sRNAs, the transcriptional start was determined by 5' rapid amplification of cDNA ends-PCR (RACE-PCR) analysis. In accord with the results of previous studies, we found little overlap between different screening methods, which underlines the fact that a comprehensive analysis of sRNAs expressed by a given organism requires the complementary use of different methods and the investigation of several environmental conditions. Despite a high conservation of sRNA genes within streptococci, the expression of sRNAs appears to be strain specific.


Silicon and bone health.
Low bone mass (osteoporosis) is a silent epidemic of the 21st century, which presently in the UK results in over 200,000 fractures annually at a cost of over one billion pounds. Figures are set to increase worldwide. Understanding the factors which affect bone metabolism is thus of primary importance in order to establish preventative measures or treatments for this condition. Nutrition is an important determinant of bone health, but the effects of the individual nutrients and minerals, other than calcium, is little understood. Accumulating evidence over the last 30 years strongly suggest that dietary silicon is beneficial to bone and connective tissue health and we recently reported strong positive associations between dietary Si intake and bone mineral density in US and UK cohorts. The exact biological role(s) of silicon in bone health is still not clear, although a number of possible mechanisms have been suggested, including the synthesis of collagen and/or its stabilization, and matrix mineralization. This review gives an overview of this naturally occurring dietary element, its metabolism and the evidence of its potential role in bone health.


Extracts from Brassica oleracea L. convar. acephala var. sabellica inhibit TNF-α stimulated neutrophil adhesion in vitro under flow conditions.
The beneficial effects of vegetables such as leafy cabbage (Brassica oleracea) on health are attributed to their anti-oxidative and anti-inflammatory potential. Therefore, we investigated whether curly kale extracts affect cytokine induced expression of endothelial cell adhesion molecules as well as the adhesion of leukocytes to endothelial cells depending on their polyphenol content and composition. Curly kale leaves were extracted applying two solvents with different polarities (methanolic extracts (ME) and aqueous water extracts (WE)). The anti-oxidant capacity (TEAC-assay (Trolox Equivalent Antioxidant Capacity)), the polyphenol content and the composition were determined colorimetrically. The anti-inflammatory effects were measured in vitro using human umbilical vein endothelial cells (HUVECs). HUVECs were pre-incubated with extracts for 24 h and thereafter stimulated for 5 h with TNF-α (10 ng mL(-1)). Finally, the expression of cell adhesion molecules E-selectin, VCAM-1 and ICAM-1 was determined by semi-quantitative RT-PCR and leukocyte adhesion was observed using a flow adhesion assay. ME have the highest anti-oxidant activity (ME, 66.5 ± 10.9 vs. WE, 45.5 ± 6.7 mmol L(-1) TEAC), polyphenol (ME, 25.8 ± 2.4. vs. WE, 10.8 ± 1.8 mmol L(-1) GAE), flavonoid (ME, 17.9 ± 1.7 vs. WE, 5.3 ± 2.7 mmol L(-1) RE) and flavonol concentrations (ME, 5.8 ± 0.6 vs. WE, 2.1 ± 0.5 mmol L(-1) RE) in comparison to WE. The TEAC and polyphenol values well-correlated with their effect on cell adhesion. Using 10% ME, reduced adhesion of leukocytes to HUVECs was measured (36 ± 13%), whereas 10% WE reduced cell adhesion to 57 ± 5% of the TNF-α stimulated controls (100%). Concomitant with the reduced leukocyte cell adhesion in the flow assay, ME and WE significantly reduced the TNF-α induced expression of cell adhesion molecules: E-selectin (ME, 51.3 ± 10.7 vs. WE, 76.3 ± 11.9%), ICAM-1 (ME, 74.6 ± 10.2 vs. WE, 81.6 ± 7.9%) and VCAM-1 mRNA expression (ME, 35.0 ± 14.0 vs. WE, 76.6 ± 7.9%) were significantly reduced with 10% extracts. The inhibitory effect of water and methanolic soluble ingredients of curly kale leaves on cell-cell interaction and gene expression events supports their health promoting effect under inflammatory conditions.


Experimental masseter muscle pain alters jaw-neck motor strategy.
A functional integration between the jaw and neck regions has been demonstrated during normal jaw function. The effect of masseter muscle pain on this integrated motor behaviour in man is unknown. The aim of this study was to investigate the effect of induced masseter muscle pain on jaw-neck movements during a continuous jaw opening-closing task. Sixteen healthy men performed continuous jaw opening-closing movements to a target position, defined as 75% of the maximum jaw opening. Each subject performed two trials without pain (controls) and two trials with masseter muscle pain, induced with hypertonic saline as a single injection. Simultaneous movements of the mandible and the head were registered with a wireless optoelectronic three-dimensional recording system. Differences in movement amplitudes between trials were analysed with Friedman's test and corrected Wilcoxon matched pairs test. The head movement amplitudes were significantly larger during masseter muscle pain trials compared with control. Jaw movement amplitudes did not differ significantly between any of the trials after corrected Wilcoxon tests. The ratio between head and jaw movement amplitudes was significantly larger during the first pain trial compared with control. Experimental masseter muscle pain in humans affected integrated jaw-neck movements by increasing the neck component during continuous jaw opening-closing tasks. The findings indicate that pain can alter the strategy for jaw-neck motor control, which further underlines the functional integration between the jaw and neck regions. This altered strategy may have consequences for development of musculoskeletal pain in the jaw and neck regions.


Review. Hybrid trait speciation and Heliconius butterflies.
Homoploid hybrid speciation (HHS) is the establishment of a novel species through introgressive hybridization without a change in chromosome number. We discuss different routes by which this might occur and propose a novel term, 'hybrid trait speciation', which combines the idea that hybridization can generate adaptive novelty with the 'magic trait' model of ecological speciation. Heliconius butterflies contain many putative examples of hybrid colour patterns, but only recently has the HHS hypothesis been tested explicitly in this group. Molecular data has shown evidence for gene flow between many distinct species. Furthermore, the colour pattern of Heliconius heurippa can be recreated in laboratory crosses between Heliconius melpomene and Heliconius cydno and, crucially, plays a role in assortative mating between the three species. Nonetheless, although the genome of H. heurippa shows evidence for hybridization, it is not a mosaic of the two parental species. Instead, ongoing hybridization has likely blurred any signal of the original speciation event. We argue that where hybridization leads to novel adaptive traits that also cause reproductive isolation, it is likely to trigger speciation.


Evaluation of different fluids for detection of Clostridium perfringens type D epsilon toxin in sheep with experimental enterotoxemia.
Enterotoxemia caused by Clostridium perfringens type D is a highly lethal disease of sheep, goats and other ruminants. The diagnosis of this condition is usually confirmed by detection of epsilon toxin, a major exotoxin produced by C. perfringens types B and D, in the intestinal content of affected animals. It has been suggested that other body fluids can also be used for detection of epsilon toxin. This study was performed to evaluate the usefulness of intestinal content versus other body fluids in detecting epsilon toxin in cases of sheep enterotoxemia. Samples of duodenal, ileal and colon contents, pericardial and abdominal fluids, aqueous humor and urine from 15 sheep with experimentally induced enterotoxemia, were analysed for epsilon toxin using a capture ELISA. Epsilon toxin was detected in 92% of the samples of ileal content, 64% of the samples of duodenal content, 57% of the samples of colon content and in 7% of the samples of pericardial fluid and aqueous humor. No epsilon toxin was found in samples of abdominal fluid or urine from the animals with enterotoxemia or in any samples from six clinically healthy sheep used as negative controls. The results of this study indicate that with the diagnostic capture ELISA used, intestinal content (preferably ileum) should be used for C. perfringens type D epsilon toxin detection in suspected cases of sheep enterotoxemia.


Changes in work schedule affect the prevalence of shift work disorder among Norwegian nurses - a two year follow-up study.
This study aimed to explore how changes in the work schedule would affect the prevalence of Shift Work Disorder (SWD) over time. Two-year follow-up data from 1076 nurses participating in the longitudinal SUrvey of Shift work, Sleep and Health among Norwegian nurses (SUSSH) were included in the study. The questionnaires included measures of work-related factors, i.e., work schedule and numbers of night shifts and quick returns (QRs) worked the last year, as well as questions related to SWD according to the ICSD-3 diagnostic criteria at both baseline and at 2-year follow-up. Data were analyzed with paired samples t-tests, chi-square tests, and logistic regression analyses adjusting for sex and age. Terminating night work was the strongest predictor for recovering from SWD from baseline to follow-up (OR 10.91, 95% CI 6.11-19.46). Additionally, changing the work schedule from day work to night work from baseline to follow-up was the strongest predictor for developing SWD in the same period (OR 4.75, 95% CI 2.39-9.47). Reductions in number of nights (more than 10) and QRs (more than 10) worked the last year were associated with recovering from SWD between baseline and follow-up. Nurses who recovered from SWD had significantly reduced the mean number of night shifts worked the last year from 32.3 at baseline to 20.4 at follow-up (p = .001). Furthermore, an increase of more than 10 nights or more than 10 QRs worked the last year between baseline and follow-up predicted developing SWD. Nurses developing SWD between baseline and follow-up had significantly increased the mean number of nights worked the last year from 25.8 at baseline to 31.0 at follow-up (p =-.043). Changes in night work exposure were the strongest predictors for both recovering from or developing SWD from baseline to follow-up. Reducing exposure to night work and QRs were associated with recovering from SWD and increasing exposure to night work and QRs were associated with developing SWD. The results imply that unfavorable work schedules play a role in the development of sleep problems among nurses. These results may be useful when designing healthy working schedules.


Universal hidden order in amorphous cellular geometries.
Partitioning space into cells with certain extreme geometrical properties is a central problem in many fields of science and technology. Here we investigate the Quantizer problem, defined as the optimisation of the moment of inertia of Voronoi cells, i.e., similarly-sized 'sphere-like' polyhedra that tile space are preferred. We employ Lloyd's centroidal Voronoi diagram algorithm to solve this problem and find that it converges to disordered states associated with deep local minima. These states are universal in the sense that their structure factors are characterised by a complete independence of a wide class of initial conditions they evolved from. They moreover exhibit an anomalous suppression of long-wavelength density fluctuations and quickly become effectively hyperuniform. Our findings warrant the search for novel amorphous hyperuniform phases and cellular materials with unique physical properties.


Aging and the neural correlates of successful picture encoding: frontal activations compensate for decreased medial-temporal activity.
We investigated the hypothesis that increased prefrontal activations in older adults are compensatory for decreases in medial-temporal activations that occur with age. Because scene encoding engages both hippocampal and prefrontal sites, we examined incidental encoding of scenes by 14 young and 13 older adults in a subsequent memory paradigm using functional magnetic resonance imaging (fMRI). Behavioral results indicated that there were equivalent numbers of remembered and forgotten items, which did not vary as a function of age. In an fMRI analysis subtracting forgotten items from remembered items, younger and older adults both activated inferior frontal and lateral occipital regions bilaterally; however, older adults showed less activation than young adults in the left and right parahippocampus and more activation than young adults in the middle frontal cortex. Moreover, correlations between inferior frontal and parahippocampal activity were significantly negative for old but not young, suggesting that those older adults who showed the least engagement of the parahippocampus activated inferior frontal areas the most. Because the analyses included only the unique activations associated with remembered items, these data suggest that prefrontal regions could serve a compensatory role for declines in medial-temporal activations with age.


Acute hyperglycemia and hyperinsulinemia enhance adrenergic vasoconstriction and decrease calcitonin gene-related peptide-containing nerve-mediated vasodilation in pithed rats.
Recent clinical studies have demonstrated that transient postprandial hyperglycemia and hyperinsulinemia may contribute to the development of hypertension. Therefore, we investigated the influence of acute hyperglycemia and/or hyperinsulinemia induced by glucose or insulin infusion on neuronal and humoral control of vascular tone in rats. Euglycemic male Wistar rats were pithed under anesthesia and arterial blood pressure was measured. Changes in vascular responses to spinal cord stimulation (SCS) and intravenous bolus injections of noradrenaline, angiotensin II, calcitonin gene-related peptide (CGRP), acetylcholine and sodium nitroprusside (SNP) were studied by infusing various concentrations of glucose or insulin. Continuous glucose infusion, which increased both blood glucose and serum insulin levels, significantly augmented adrenergic nerve-mediated pressor responses to SCS without affecting pressor responses to injection of noradrenaline or angiotensin II. In pithed rats with artificially increased blood pressure and blockade of autonomic outflow, glucose infusion attenuated CGRPergic nerve-depressor responses to SCS without affecting depressor responses to injection of CGRP, acetylcholine or SNP. In pithed rats treated with octreotide, which increased blood glucose without increasing serum insulin levels, glucose infusion caused only significant augmentation of adrenergic nerve-mediated pressor responses. Combined infusion of insulin and glucose, which resulted in increased serum insulin levels with euglycemia, significantly augmented adrenergic nerve-mediated pressor responses and attenuated CGRPergic nerve-mediated depressor responses. The present results suggest that acute hyperglycemia and hyperinsulinemia increase adrenergic nerve-mediated vasoconstriction, which in turn blunts CGRPergic nerve function, and that the increase in plasma insulin concentration associated with hyperglycemia may be responsible for the alteration of neuronal vascular regulation.


Keepin' it R.E.A.L.!: results of a mother-adolescent HIV prevention program.
The concern that adolescents may be placing themselves at risk for contracting HIV has led to widespread public and parental support for HIV prevention programs. Several programs on increasing communication between parents and teenagers have been tested, but the study of the impact of these programs on resulting sexual behavior is lacking. To test the efficacy of two interventions for mothers and their adolescents in delaying initiation of sexual intercourse for youth who are not sexually active and encouraging the use of condoms among sexually active youth. Employed were a control group and two treatment groups: one based on social cognitive theory (SCT) and the other a life skills program (LSK) based on problem behavior theory. Assessments were conducted before the intervention (baseline) and at 4, 12, and 24 months after the baseline assessment. Adolescents and their mothers (total N = 582) enrolled in the trial. At baseline, the adolescents ranged in age 11-14 years and were mostly male and African American. The mean age of the mothers was 37.9 years, and most were African American and single. The primary analyses showed no difference among groups in abstinence rates for adolescents. However, adolescents in the LSK group demonstrated an increase in the condom use rate, and those in the SCT and control groups scored higher on human immunodeficiency virus (HIV) knowledge than those in the LSK group. Mothers showed substantial increases over time in comfort talking about sex and self-efficacy. For HIV knowledge, mothers in the SCT group scored significantly higher than those in the LSK and control groups. The results of this study are comparable to previous studies that have included mothers in the HIV education of their adolescents. Although the program did not demonstrate a substantial effect on abstinence rates, increases were observed in condom use among adolescents and in mother's sex-based discussions and comfort in talking about sexual issues.


Polarization demultiplexing in stokes space for coherent optical PDM-OFDM.
We propose a polarization demultiplexing method for coherent optical PDM-OFDM based on Stokes space, without inserting training symbols. The proposed approach performs well for different modulation formats of OFDM subcarrier, and shows comparable performances with that of conventional methods, but with a fast convergence speed and reduced overhead. The OFDM signal in the time domain cannot satisfy the conditions of SS-PDM accurately. Therefore, we first digitally convert the received OFDM signals to the frequency domain using fast Fourier transform (FFT). Each subcarrier of the OFDM signal has a much lower speed and narrower bandwidth, the polarization effects that it experiences can be treated as flat. Consequently, we can apply the polarization demultiplexing in Stokes space (SS-PDM) on per subcarrier basis. We verify this method in experiment by transmitting 66.6-Gb/s PDM-OFDM signal with 4QAM subcarrier modulation over 5440km SSMF and 133.3-Gb/s PDM-OFDM signal with 16QAM subcarrier modulation over 960km SSMF respectively. We also compare the results with those of training symbols. Finally, we analyze of the convergence speed of this method.


Interacting loci cause severe iris atrophy and glaucoma in DBA/2J mice.
Glaucomas are a major cause of blindness. Visual loss typically involves retinal ganglion cell death and optic nerve atrophy subsequent to a pathologic elevation of intraocular pressure (IOP). Some human glaucomas are associated with anterior segment abnormalities such as pigment dispersion syndrome (PDS) and iris atrophy with associated synechiae. The primary causes of these abnormalities are unknown, and their aetiology is poorly understood. We recently characterized a mouse strain (DBA/2J) that develops glaucoma subsequent to anterior segment changes including pigment dispersion and iris atrophy. Using crosses between mouse strains DBA/2J (D2) and C57BL/6J (B6), we now show there are two chromosomal regions that contribute to the anterior segment changes and glaucoma. Progeny homozygous for the D2 allele of one locus on chromosome 6 (called ipd) develop an iris pigment dispersion phenotype similar to human PDS. ipd resides on a region of mouse chromosome 6 with conserved synteny to a region of human chromosome 7q that is associated with human PDS. Progeny homozygous for the D2 allele of a different locus on chromosome 4 (called isa) develop an iris stromal atrophy phenotype (ISA). The Tyrpl gene is a candidate for isa and likely causes ISA via a mechanism involving pigment production. Progeny homozygous for the D2 alleles of both ipd and isa develop an earlier onset and more severe disease involving pigment dispersion and iris stromal atrophy.


Inter-rater Agreement for the Clinical Dysphagia Scale.
To investigate the inter-rater agreement for the clinical dysphagia scale (CDS). Sixty-seven subjects scheduled to participate in a video-fluoroscopic swallowing study (VFSS) were pre-examined by two raters independently within a 24-hour interval. Each item and the total score were compared between the raters. In addition, we investigated whether subtraction of items showing low agreement or modification of rating methods could enhance inter-rater agreement without significant compromise of validity. Inter-rater agreement was excellent for the total score (intraclass correlation coefficient (ICC): 0.886). Four items (lip sealing, chewing and mastication, laryngeal elevation, and reflex coughing) did not show excellent agreement (ICC: 0.696, 0.377, 0.446, and κ: 0.723, respectively). However, subtraction of each item either compromised validity, or did not improve agreement. When redefining 'history of aspiration' and 'lesion location' items, the inter-rater agreement (ICC: 0.912, 0.888, respectively) and correlation with new videofluoroscopic dysphagia score (PCC: 0.576, 0.577, respectively) were enhanced. The CDS showed better agreement and validity in stroke patients compared to non-stroke patients (ICC: 0.917 vs 0.835, PCC: 0.663 vs 0.414). The clinical dysphagia scale is a reliable bedside swallowing test. We can improve inter-rater agreement and validity by refining the 'history of aspiration' and 'lesion location' item.


Cdc42p and Fus2p act together late in yeast cell fusion.
Cell fusion is the key event of fertilization that gives rise to the diploid zygote and is a nearly universal aspect of eukaryotic biology. In the yeast Saccharomyces cerevisiae, several mutants have been identified that are defective for cell fusion, and yet the molecular mechanism of this process remains obscure. One obstacle has been that genetic screens have mainly focused on mating-specific factors, whereas the process likely involves housekeeping proteins as well. Here we implicate Cdc42p, an essential protein with roles in multiple aspects of morphogenesis, as a core component of the yeast cell fusion pathway. We identify a point mutant in the Rho-insert domain of CDC42, called cdc42-138, which is specifically defective in cell fusion. The cell fusion defect is not a secondary consequence of ineffective signaling or polarization. Genetic and morphological data show that Cdc42p acts at a late stage in cell fusion in concert with a key cell fusion regulator, Fus2p, which contains a Dbl-homology domain. We find that Fus2p binds specifically with activated Cdc42p, and binding is blocked by the cdc42-138 mutation. Thus, in addition to signaling and morphogenetic roles in mating, Cdc42p plays a role late in cell fusion via activation of Fus2p.


Interim Performance Progression (IPP) During Consecutive Season Best Performances of Talented Swimmers.
Objective: The main goal of the present study was to investigate the interim performance progression (IPP) of talented swimmers. Part of this group ultimately made it to the top (referred to as elite swimmers) whereas others did not make it to the top (referred to as high-competitive swimmers). Rather than investigating performance progression based solely on season best performances, we included the first swim performance of the season in the metrics of IPP. Knowledge about the IPP of talented swimmers from and toward their season best performances relative to the first swim performance of the season will enhance our understanding of changes in season best performances during the talent trajectory and provide valuable insights for talent development and selection processes in competitive swimming. Methods: Fifteen thousand nine hundred and forty four swim performances (first swim performances of the season and season best performances) between 1993 and 2019 of 3,199 talented swimmers (of whom 556 reached elite level and 2,643 reached high-competitive level) were collected from Swimrankings and related to the prevailing world record of the corresponding sex. The pattern of IPP was represented by two phases: phase A and phase B. Phase A reflected the performance progression between the previous season best performance and the first swim performance of the current season (PPA) and phase B reflected the performance progression between the first swim performance of the current season and the season best performance of the current season (PPB). Depending on the normality check, we used independent sample t-tests or Mann Whitney tests to establish significant differences in PPA and PPB between elite and high competitive swimmers per age category per sex (p < 0.05). Results: Without denying individual differences, male elite swimmers improved more during phase B from age 15 till 24 compared to high-competitive swimmers (20.5% vs. 13.1%, respectively, p < 0.05). Female elite swimmers improved more during phase B from age 13 till 23 compared to high-competitive swimmers (21.1% vs. 14.6%, respectively, p < 0.05). Except for age 14 in males, there were no significant differences between performance groups in PPA. Conclusion: Talented swimmers who ultimately made it to the top (elite swimmers) are characterized with different patterns of IPP compared to talented swimmers who did not make it to the top (high-competitive swimmers). After puberty, elite and high-competitive swimmers performed in general ~1% slower at the start of their season compared to their previous season best performance (PPA). However, elite swimmers improved more in the period between their first swim performance of the season and their season best performance (PPB) from age 13 (females) and age 15 (males) onwards.


Presymptomatic diagnosis of nonsyndromic hearing loss by genotyping.
Nonsyndromic hearing loss (NSHL) is the most common type of hereditary hearing impairment (HHI). It is genetically heterogeneous, and although the exact number of genes is not known, 38 loci have been identified. By cloning the relevant genes and studying the function of the encoded proteins at the molecular level, it may be possible to impact the habitation of persons at risk for HHI. Currently, for select families, presymptomatic diagnosis of NSHL by genotyping is possible. To provide presymptomatic diagnosis of HHI to individuals in select families who have participated in linkage studies. In 2 large families with autosomal dominant HHI, genes for NSHL were mapped to chromosomes 6 (DFNA10) and 19 (DFNA4). In each family, the phenotype is one of progressive sensorineural hearing loss that begins in the individual's mid-30s and progresses to a severe-to-profound loss requiring amplification. Presymptomatic diagnosis was requested by, and provided to, 19 at-risk persons in these kindreds. By reconstructing haplotypes through the use of short tandem repeat polymorphisms tightly linked to the disease gene, risk calculations and genetic counseling were provided to these persons. By simple Mendelian genetics, the risk of inheriting a fully penetrant autosomal dominant NSHL gene from a single affected parent is 50% for each offspring. However, by reconstructing haplotypes in families in which an HHI gene has been localized, this risk can be changed substantially.


Reduced frameshift fidelity and processivity of HIV-1 reverse transcriptase mutants containing alanine substitutions in helix H of the thumb subdomain.
We have analyzed two human immunodeficiency virus (HIV-1) reverse transcriptase mutants of helix H in the thumb subdomain suggested by x-ray crystallography to interact with the primer strand of the template-primer. These enzymes, G262A and W266A, were previously shown to have greatly elevated dissociation rate constants for template-primer and to be much less sensitive to inhibition by 3'-azidodeoxythymidine 5'-triphosphate. Here we describe their processivity and error specificity. The results reveal that: (i) both enzymes have reduced processivity and lower fidelity for template-primer slippage errors, (ii) they differ from each other in sequence-dependent termination of processive synthesis and in error specificity, and (iii) the magnitude of the mutator effect relative to wild-type enzyme for deletions in homopolymeric sequences decreases as the length of the run increases. Thus amino acid substitutions in a subdomain thought to interact with the duplex template-primer confer a strand slippage mutator phenotype to a replicative DNA polymerase. This suggests that interactions between specific amino acids and the primer stem at positions well removed from the active site are critical determinants of processivity and fidelity. These effects, obtained in aqueous solution during catalytic cycling, are consistent with and support the existing crystallographic structural model.


Molecular estimation of alteration in intestinal microbial composition in Hashimoto's thyroiditis patients.
The gut microbiota has a crucial effect on human health and physiology. Hypothyroid Hashimoto's thyroiditis (HT) is an autoimmune disorder manifested with environmental and genetic factors. However, it is hypothesized that intestinal microbes might play a vital role in the pathogenesis of HT. The aim of current was to investigate and characterize the gut microbial composition of HT patients both quantitatively and qualitatively. The fecal samples from 29 HT patients and 12 healthy individuals were collected. The PCR-DGGE targeted V3 site of 16S rRNA gene and real time PCR for Bifidobacterium Lactobacillus, Bacteroides vulgatus and Clostridium leptum were performed. Pyrosequencing of 16S rRNA gene with V4 location was performed on 20 randomly selected samples. The comparative analysis of diversity and richness indices revealed diversification of gut microbiota in HT as compared to control. The statistical data elucidate the alterations in phyla of HT patients which was also affirmed at the family level. We observed the declined abundance of Prevotella_9 and Dialister, while elevated genera of the diseased group included Escherichia-Shigella and Parasutterella. The alteration in gut microbial configuration was also monitored at the species level, which showed an increased abundance of E. coli in HT. Therefore, the current study is in agreement with the hypothesis that HT patients have intestinal microbial dysbiosis. The taxa statistics at species-level along with each gut microbial community were modified in HT. Thus, the current study may offer the new insights into the treatment of HT patients, disease pathway, and mechanism.


Fiber-based lensless polarization holography for measuring Jones matrix parameters of polarization-sensitive materials.
We report a fiber-based lensless holographic imaging system to realize a single-shot measurement of two dimensional (2-D) Jones matrix parameters of polarization-sensitive materials. In this system, a multi-source lensless off-axis Fresnel holographic recording geometry is adopted, and two optical fiber splitters are used to generate the multiple reference and illumination beams required for recording a four-channel angular-multiplexing polarization hologram (AMPH). Using this system and the method described in this paper, spatially resolved Jones matrix parameters of a polarization-sensitive material can be retrieved from one single-shot AMPH. We demonstrate the feasibility of the method by extracting a 2-D Jones matrix of a composite polarizer. Applications of the method to measure the Jones matrix maps of a stressed polymethyl methacrylate sample and a mica fragment are also presented. Benefit from the fiber-based and lensless off-axis holographic design, the system possesses a quite compact configuration, which provides a feasible approach for development of an integrated and portable system to measure Jones matrix parameters of polarization-sensitive materials.


Do CEC guidelines under-utilise the full potential of increasing kVp as a dose-reducing tool?
Increasing beam energies are well established as a radiation dose-reducing tool in diagnostic radiology. This has led to useful recommendations by the Commission of European Communities (CEC) for appropriate kVp values to be employed for a variety of examinations. The current work tests the hypothesis that kVp levels above those recommended by the CEC will result in reduced patient dose while still producing images of acceptable quality. This study explored the effect of a range of kVp levels within and above CEC recommendations for lumbar spine radiology. A phantom investigation facilitated selection of appropriate kVp levels for a patient study ( n=59): 81 kVp (CEC) and 96 kVp (non-CEC) for the AP projection and 90 kVp (CEC) and 102 kVp (non-CEC) for the lateral projection. Entrance surface and effective dose were calculated and image quality quantified using CEC image criteria and images of a detail contrast test tool. Data analysis demonstrated significant reduction in effective radiation dose for AP (29.9%) and lateral (24.6%) when a kVp value above the CEC range was employed compared with a kVp recommended by the CEC. Although significant reductions in total image quality of 18.3% and 10.1% for the antero-posterior and lateral projections, respectively, were noted, all patient images produced with all kVp values were considered acceptable by each member of the evaluative panel with all image criteria receiving a score of 2 (out of 3) or better. The psychophysical tests revealed minor non-significant reductions in visualisation scores. The current study demonstrated that kVp values outside the CEC recommended range offer reductions in dose while producing acceptable images. Practitioners should be guided, rather than constrained, by the CEC recommendations on good radiographic technique. The need for further work exploring the effect of higher energies on visualisation of subtle pathological lesions has been identified.


Overt diabetes mellitus among newly diagnosed Ugandan tuberculosis patients: a cross sectional study.
There is a documented increase of diabetes mellitus in Sub Saharan Africa, a region where tuberculosis is highly endemic. Currently, diabetes mellitus is one of the recognised risk factors of tuberculosis. No study has reported the magnitude of diabetes mellitus among tuberculosis patients in Uganda, one of the countries with a high burden of tuberculosis. This was a cross-sectional study conducted among 260 consenting adult patients with a confirmed diagnosis of tuberculosis admitted on the pulmonology wards of Mulago national referral and teaching hospital in Kampala, Uganda to determine the prevalence of diabetes mellitus and associated clinical factors. Laboratory findings as well as the socio-demographic and clinical data collected using a validated questionnaire was obtained. Point of care random blood sugar (RBS) testing was performed on all the patients prior to initiation of anti tuberculosis treatment. Diabetes mellitus was diagnosed if the RBS level was ≥ 200mg/dl in the presence of the classical symptoms of diabetes mellitus. The prevalence of diabetes mellitus among the admitted patients with tuberculosis was 8.5%. Only 5 (1.9%) patients with TB had a known diagnosis of diabetes mellitus at enrolment. Majority of the study participants with TB-DM co-infection had type 2 diabetes mellitus (n=20, 90.9%).At bivariate analysis, raised mean ALT concentrations of ≥80 U/L were associated with DM (OR-6.1, 95% CI 1.4-26.36, p=0.032) and paradoxically, HIV co-infection was protective of DM (OR-0.32, 95% CI 0.13-0.79, P=0.016). The relationship between DM and HIV as well as that with ALT remained statistically significant at multivariate analysis (HIV: OR- 0.17 95%CI 0.06-0.51, p=0.002 and ALT: OR-11.42 95%CI 2.15-60.59, p=0.004). This study demonstrates that diabetes mellitus is common among hospitalized tuberculosis patients in Uganda. The significant clinical predictors associated with diabetes mellitus among tuberculosis patients were HIV co-infection and raised mean serum alanine transaminase concentrations.


Coupled-cavity analysis of the resonant loop mirror: closed-form expressions and simulations for enhanced performance lasing.
A coupled-cavity analysis of the resonant loop mirror with a signal flow graph technique is presented. Use of this technique has resulted in simple closed-form expressions for reflectance, transmittance, critical coupling, bandwidth, finesse, gain threshold, and mode splitting. Application of this device to enhance the single longitudinal mode operation of a fiber laser is also proposed. Detailed simulation results show a dramatic reduction in bandwidth and a threefold enhancement of the free spectral range by use of the vernier effect. The formulas and results obtained would also be useful in laser sensors and filters.


Data-Driven Goals for Curbing the U.S. HIV Epidemic by 2030.
Progress in reducing HIV infections has been suboptimal despite availability of effective prevention and treatment interventions and national strategies to bring them to scale. As part of a community-driven process, we expanded previous epidemiologic models using updated surveillance data from the Centers for Disease Control and Prevention to estimate quantitative parameters for ambitious but attainable national HIV prevention goals. We estimated new HIV infections could be reduced by up to 67% and prevalence could begin to decline by 2030 if 95% targets for diagnosis, care retention, and viral suppression are met by 2025 and an additional 20% of transmissions are averted through targeted interventions such as pre-exposure prophylaxis. Notably, this would require the percentage of diagnosed persons retained in HIV care to increase by more than 35 percentage points, which would necessitate innovative models and a substantial expansion of supportive services. Although the HIV incidence reduction goal of 90% as unveiled in the 2019 State of the Union Address is likely unachievable with the current intervention toolkit, it is possible to begin to substantially reduce HIV prevalence in the next decade with sufficient investments and innovation.


Activation of calcium entry in human carcinoma A431 cells by store depletion and phospholipase C- dependent mechanisms converge on ICRAC-like calcium channels.
Activation of phospholipase C in nonexcitable cells causes the release of calcium (Ca2+) from intracellular stores and activation of Ca2+ influx by means of Ca2+ release-activated channels (ICRAC) in the plasma membrane. The molecular identity and the mechanism of ICRAC channel activation are poorly understood. Using the patch-clamp technique, here we describe the plasma membrane Ca2+ channels in human carcinoma A431 cells, which can be activated by extracellular UTP, by depletion of intracellular Ca2+ stores after exposure to the Ca2+-pump inhibitor thapsigargin, or by loading the cells with Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate. The observed channels display the same conductance and gating properties as previously described I(min) channels, but have significantly lower conductance for monovalent cations than the ICRAC channels. Thus, we concluded that the depletion-activated Ca2+ current in A431 cells is supported by I(CRAC)-like (ICRACL) channels, identical to I(min). We further demonstrated synergism in activation of ICRACL Ca2+ channels by extracellular UTP and intracellular inositol (1,4,5)-triphosphate (IP3), apparently because of reduction in phosphatidylinositol 4,5-bisphosphate (PIP2) levels in the patch. Prolonged exposure of patches to thapsigargin renders ICRACL Ca2+ channels unresponsive to IP3 but still available to activation by the combined action of IP3 and anti-PIP2 antibody. Based on these data, we concluded that phospholipase C-mediated and store-operated Ca2+ influx pathways in A431 cells converge on the same I(CRACL) Ca2+ channel, which can be modulated by PIP2.


A comparison of hippocampal pathology in man and other animals.
Bilateral damage to the medial temporal lobe, including the hippocampus, in man is associated with a severe amnesic syndrome. It is still not clear whether the hippocampus (or its output pathways and related target projection sites) is the critical structure in producing this syndrome, especially as more severe learning deficits in animals are found with lesions in the anterior inferotemporal cortex than with hippocampal lesions per se. But the problem of trying to relate memory deficits in man and animals depends on the characterization of the amnesic syndrome itself. It was originally thought to be a failure of input into long-term memory store or a failure of consolidation. Medial temporal and hippocampal lesions in animals do not produce results that fit such a characterization. On re-examination of the human syndrome, however, for which some of the evidence is reviewed, it appears that the amnesic patients can learn and remember over long intervals if certain testing paradigms are used. The results are more readily matched to some of the results of hippocampal lesion studies in animals. Two main classes of current theories of the amnesic syndrome are discussed. A somewhat different approach is suggested here, based on the dissociation between human amnesic subjects' commentaries and their objective performance, which suggests a dissociation between levels of processing rather than a failure on any particular level.


Domesticated horses differ in their behavioural and physiological responses to isolated and group housing.
The predominant housing system used for domestic horses is individual stabling; however, housing that limits social interaction and requires the horse to live in semi-isolation has been reported to be a concern for equine welfare. The aim of the current study was to compare behavioural and physiological responses of domestic horses in different types of housing design that provided varying levels of social contact. Horses (n = 16) were divided equally into four groups and exposed to each of four housing treatments for a period of five days per treatment in a randomized block design. The four housing treatments used were single housed no physical contact (SHNC), single housed semi-contact (SHSC), paired housed full contact (PHFC) and group housed full contact (GHFC). During each housing treatment, adrenal activity was recorded using non-invasive faecal corticosterone metabolite analysis (fGC). Thermal images of the eye were captured and eye temperature was assessed as a non-invasive measure of the stress response. Behavioural analysis of time budget was carried out and an ease of handling score was assigned to each horse in each treatment using video footage. SHNC horses had significantly higher (p = 0.01) concentrations of fGC and were significantly (p = 0.003) more difficult to handle compared to the other housing types. GHFC horses, although not significantly different, had numerically lower concentrations of fGC and were more compliant to handling when compared to all other housing treatments. Eye temperature was significantly (p = 0.0001) lower in the group housed treatment when compared to all other treatments. These results indicate that based on physiological and behavioural measures incorporating social contact into the housing design of domestic horses could improve the standard of domestic equine welfare.


Phase-shift calibration errors in interferometers with spherical Fizeau cavities.
Phase-demodulation algorithms in interferometry often depend on a sequence of evenly spaced reference phase shifts. These phase shifts must be accurately calibrated and can be distorted by geometric effects, especially when spherical components with high curvature are tested. Here the resulting measurement errors are quantified through mathematical analysis, and it is shown that modern phase-estimation algorithms can be effective in a spherical Fizeau cavity with a numerical aperture as large as 0.95.


Isolation and characterization of microsatellite markers in the newly discovered invasive fruit fly pest in Africa, Bactrocera invadens (Diptera: Tephritidae).
We describe the isolation and characterization of 11 polymorphic microsatellite loci from the recently discovered fruit fly pest, Bactrocera invadens. The polymorphism of these loci was tested in individual flies from two natural populations (Sri Lanka and Democratic Republic of Congo). Allele number per locus ranged from three to 15 and eight loci displayed a polymorphic information content greater than 0.5. These microsatellite loci provide useful markers for studies of population dynamics and invasion history of this pest species.


Cerebrospinal fluid kynurenines in multiple sclerosis; relation to disease course and neurocognitive symptoms.
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system, with a high rate of neurocognitive symptoms for which the molecular background is still uncertain. There is accumulating evidence for dysregulation of the kynurenine pathway (KP) in different psychiatric and neurodegenerative conditions. We here report the first comprehensive analysis of cerebrospinal fluid (CSF) kynurenine metabolites in MS patients of different disease stages and in relation to neurocognitive symptoms. Levels of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN) were determined with liquid chromatography mass spectrometry in cell-free CSF. At the group level MS patients (cohort 1; n=71) did not differ in absolute levels of TRP, KYN, KYNA or QUIN as compared to non-inflammatory neurological disease controls (n=20). Stratification of patients into different disease courses revealed that both absolute QUIN levels and the QUIN/KYN ratio were increased in relapsing-remitting MS (RRMS) patients in relapse. Interestingly, secondary progressive MS (SPMS) displayed a trend for lower TRP and KYNA, while primary progressive (PPMS) patients displayed increased levels of all metabolites, similar to a group of inflammatory neurological disease controls (n=13). In the second cohort (n=48), MS patients with active disease and short disease duration were prospectively evaluated for neuropsychiatric symptoms. In a supervised multivariate analysis using orthogonal projection to latent structures (OPLS-DA) depressed patients displayed higher KYNA/TRP and KYN/TRP ratios, mainly due to low TRP levels. Still, this model had low predictive value and could not completely separate the clinically depressed patients from the non-depressed MS patients. No correlation was evident for other neurocognitive measures. Taken together these results demonstrate that clinical disease activity and differences in disease courses are reflected by changes in KP metabolites. Increased QUIN levels of RRMS patients in relapse and generally decreased levels of TRP in SPMS may relate to neurotoxicity and failure of remyelination, respectively. In contrast, PPMS patients displayed a more divergent pattern more resembling inflammatory conditions such as systemic lupus erythematosus. The pattern of KP metabolites in RRMS patients could not predict neurocognitive symptoms.