Liberation and containment: re-visualising the eugenic and evolutionary ideal of the "Fizkul'turnitsa" in 1944.
In July 1944 cross-country races and parades of physical culturists were prominently used to celebrate Soviet liberation from German occupation. While journalistic accounts stressed the manly health and vigour of the victorious Red Army, press photographs in Pravda and Red Sport, and Aleksandr Deneika's monumental painting 'Liberation', emphasised images of the young female physical culturist. This essay explores what a contextualised analysis of these images may have to tell historians about the connections between women, physical culture and liberation being projected. The argument suggests that, on one level, the images straightforwardly symbolised and celebrated the liberation of the Soviet 'Motherland'. On another, more complex level, the images represented a particularly nuanced notion of constricted liberation for Soviet women deriving from 1920s eugenic and evolutionary discourse, inscribed into the contemporary imperative for engagement with physical culture as a necessary stage of healthful body discipline on the path to hygienic and successful motherhood.


Searching for functional gene modules with interaction component models.
Functional gene modules and protein complexes are being sought from combinations of gene expression and protein-protein interaction data with various clustering-type methods. Central features missing from most of these methods are handling of uncertainty in both protein interaction and gene expression measurements, and in particular capability of modeling overlapping clusters. It would make sense to assume that proteins may play different roles in different functional modules, and the roles are evidenced in their interactions. We formulate a generative probabilistic model for protein-protein interaction links and introduce two ways for including gene expression data into the model. The model finds interaction components, which can be interpreted as overlapping clusters or functional modules. We demonstrate the performance on two data sets of yeast Saccharomyces cerevisiae. Our methods outperform a representative set of earlier models in the task of finding biologically relevant modules having enriched functional classes. Combining protein interaction and gene expression data with a probabilistic generative model improves discovery of modules compared to approaches based on either data source alone. With a fairly simple model we can find biologically relevant modules better than with alternative methods, and in addition the modules may be inherently overlapping in the sense that different interactions may belong to different modules.


A critical evaluation of enzyme immunoassay kits for detection of antinuclear autoantibodies of defined specificities. III. Comparative performance characteristics of academic and manufacturers' laboratories.
To analyze the performance of different commercial enzyme immunoassay (EIA) kits for measuring antinuclear antibodies (ANA) specific for dsDNA, SSB/La, Sm, and Scl-70. EIA kits for detection of ANA from 9 commercial manufacturers were evaluated. The manufacturers were advised that they would be sent coded sera containing mixtures of the Arthritis Foundation/Centers for Disease Control reference reagents, and that they were to use their own test kits to analyze the antibody specificities of these sera and to report the data, in optical density (OD) units or their equivalent. Independently, 12 investigators in academic institutions who have done research in this field agreed to participate in a parallel study. The concentration of the antibodies and the specificities were blinded to the analysts and the coefficients of variation (CV) were computed for each participant. There were statistically significant differences between laboratories in terms of CV for all 9 kits tested. With the exception of one kit, there were no significant CV differences between the various autoantibody kits provided by each manufacturer and, with the exception of kits from 2 manufacturers, there were no significant differences between the various antibody kits in terms of reproducibility (CV). From the point of view of interlaboratory variability, manufacturers could be separated into either a high or low performance group. We found a disconcertingly large range of performance characteristics in the various laboratories, which could be quite detrimental in routine utilization of EIA ANA kits. Clinicians should be aware of the performance issues raised in our study, and should know and be involved in how their service laboratory assesses its own performance and the performance of commercial testing systems utilized. Manufacturers and clinical laboratories need to exercise constant quality assurance and surveillance of kit performance in the hands of medical laboratory technologists involved in routine testing.


Long term consequences of regressed coronary aneurysms after Kawasaki disease: vascular wall morphology and function.
To investigate the long term consequences of regressed aneurysms after Kawasaki disease, using follow up coronary angiography; to assess the vascular wall morphology at the site of the aneurysms by intravascular ultrasound imaging; and to evaluate the function of the affected vessels using intracoronary infusions of acetylcholine and isosorbide dinitrate. 33 patients were studied, 27 with previous Kawasaki disease and six with congenital heart disease. All Kawasaki disease patients were followed for more than 10 years from disease onset. The 33 patients comprised four groups: group 1 included 13 Kawasaki disease patients with a total of 23 sites of regressed large sized (>/= 4 mm) coronary aneurysms; group 2 included 13 Kawasaki disease patients with 22 sites of regressed small sized (< 4 mm) coronary aneurysms (four patients had sites of both large and small sized aneurysms); group 3 included a further five Kawasaki disease patients with 25 normal coronary angiography sites in the acute stage of Kawasaki disease; and group 4 comprised the six patients with congenital heart disease as controls, with a total of 27 normal coronary angiography sites. During coronary angiography, 15 microg of acetylcholine and 0.5 mg isosorbide dinitrate were infused into the coronary artery. The luminal diameter at the sites was measured using a cine-videodensitometric analyser, to assess the distensibility of the coronary artery wall. Coronary angiography in all 22 patients in groups 1 and 2 and in all the patients in group 3 was normal, with no stenoses and no irregularity of the arterial wall. However, the intravascular ultrasound imaging in groups 1 and 2 showed various degrees of the intimal thickening. In groups 1 and 2, there was significantly more vascular constriction with acetylcholine, and poorer dilatation with isosorbide dinitrate than in groups 3 or 4 (each p < 0.05, respectively). There was no difference between group 3 and group 4 in response to either acetylcholine or isosorbide dinitrate, There is evidence of persisting abnormal vascular wall morphology and vascular dysfunction at the site of regressed coronary aneurysms in patients with previous Kawasaki disease. These patients should be counselled to avoid potential risk factors for atherosclerosis, and long term follow up is needed into adult life.


Topical NSAIDs for acute pain in adults.
Use of topical NSAIDs to treat acute musculoskeletal conditions is widely accepted in some parts of the world, but not in others. Their main attraction is their potential to provide pain relief without associated systemic adverse events. To review the evidence from randomised, double-blind, controlled trials on the efficacy and safety of topically applied NSAIDs in acute pain. We searched MEDLINE, EMBASE, The Cochrane Library, and our own in-house database to December 2009. We sought unpublished studies by asking personal contacts and searching on-line clinical trial registers and manufacturers web sites. We included randomised, double-blind, active or placebo (inert carrier)-controlled trials in which treatments were administered to adult patients with acute pain resulting from strains, sprains or sports or overuse-type injuries (twisted ankle, for instance). There had to be at least 10 participants in each treatment arm, with application of treatment at least once daily. Two review authors independently assessed trial quality and validity, and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Forty-seven studies were included; most compared topical NSAIDs in the form of a gel, spray, or cream with a similar placebo, with 3455 participants in the overall analysis of efficacy. For all topical NSAIDs combined, compared with placebo, the number needed to treat to benefit (NNT) for clinical success, equivalent to 50% pain relief, was 4.5 (3.9 to 5.3) for treatment periods of 6 to 14 days. Topical diclofenac, ibuprofen, ketoprofen, and piroxicam were of similar efficacy, but indomethacin and benzydamine were not significantly better than placebo. Local skin reactions were generally mild and transient, and did not differ from placebo. There were very few systemic adverse events or withdrawals due to adverse events. There were insufficient data to reliably compare individual topical NSAIDs with each other or the same oral NSAID. Topical NSAIDs can provide good levels of pain relief, without the systemic adverse events associated with oral NSAIDs, when used to treat acute musculoskeletal conditions.


Micro objective lens with NA 0.65 for the blue-light small-form-factor optical pickup head.
A micro objective lens with the numerical aperture (NA) of 0.65 and clear aperture of 1.1mm was designed, fabricated, and tested for the proposed blue-light small-form-factor optical pickup head system. It adopted the finite optical conjugation and could be produced by using the glass molding technique. The experimental results verify the optical performance near the diffraction-limited focus spot for the applications of high-density portable optical storage systems.


Predicting transitions in low and high levels of risk behavior from early to middle adolescence: the TRAILS study.
The present study examined the joint development of substance use and externalizing problems in early and middle adolescence. First, it was tested whether the relevant groups found in previous studies i.e., those with an early onset, a late onset, and no onset or low levels of risk behavior could be identified, while using a developmental model of a single, underlying construct of risk behavior. Second, departing from Moffitt's taxonomy of antisocial behavior, it was tested if early, but not late, onset risk behavior is predicted by a problematic risk profile in childhood. Data were used from TRAILS, a population based cohort study, starting at age 11 with two follow-ups at mean ages of 13.6 and 16.3 years. Latent transition analyses demonstrated that, both in early and middle adolescence, a single underlying construct of risk behavior, consisting of two classes (labeled as low and high risk behavior), adequately represented the data. Respondents could be clearly classified into four possible transition patterns from early to middle adolescence, with a transition from high to low being almost non-existent (2.5 %), low to low (39.4 %) and low to high (41.8 %) being the most prevalent, and high to high (16.2 %) substantial. As hypothesized, only the high-high group was characterized by a clear adverse predictor profile in late childhood, while the low-high group was not. This study demonstrates that the development of substance use is correlated with externalizing problems and underscores the theory that etiologies of early and later onset risk behavior are different.


Multinational outbreak of travel-related Salmonella Chester infections in Europe, summers 2014 and 2015.
Between 2014 and 2015, the European Centre for Disease Prevention and Control was informed of an increase in numbers of Salmonella enterica serotype Chester cases with travel to Morocco occurring in six European countries. Epidemiological and microbiological investigations were conducted. In addition to gathering information on the characteristics of cases from the different countries in 2014, the epidemiological investigation comprised a matched case-case study involving French patients with salmonellosis who travelled to Morocco that year. A univariate conditional logistic regression was performed to quantify associations. The microbiological study included a whole genome sequencing (WGS) analysis of clinical and non-human isolates of S. Chester of varied place and year of isolation. A total of 162 cases, mostly from France, followed by Belgium, the Netherlands, Spain, Denmark and Sweden were reported, including 86 (53%) women. The median age per country ranged from 3 to 38 years. Cases of S. Chester were more likely to have eaten in a restaurant and visited the coast of Morocco. The results of WGS showed five multilocus sequence types (ST), with 96 of 153 isolates analysed clustering into a tight group that corresponded to a novel ST, ST1954. Of these 96 isolates, 46 (48%) were derived from food or patients returning from Morocco and carried two types of plasmids containing either qnrS1 or qnrB19 genes. This European-wide outbreak associated with travel to Morocco was likely a multi-source outbreak with several food vehicles contaminated by multidrug-resistant S. Chester strains.


Shifts in BMI category and associated cardiometabolic risk: prospective results from HEALTHY study.
To evaluate shifts across BMI categories and associated changes in cardiometabolic risk factors over 2.5 years in an ethnically diverse middle school sample. As part of HEALTHY, a multisite school-based study designed to mitigate risk for type 2 diabetes, 3993 children participated in health screenings at the start of sixth and end of eighth grades. Assessments included anthropometric measures, blood pressure, and glucose, insulin, and lipids. Students were classified as underweight, healthy weight, overweight, obese, or severely obese. Mixed models controlling for school intervention status and covariates were used to evaluate shifts in BMI category over time and the relation between these shifts and changes in risk factors. At baseline, students averaged 11.3 (±0.6) years; 47.6% were boys, 59.6% were Hispanic, and 49.8% were overweight or obese. Shifts in BMI category over time were common. For example, 35.7% of youth who were overweight moved to the healthy weight range, but 13% in the healthy weight range became overweight. BMI shifts were not associated with school intervention condition, household education, or youth gender, race/ethnicity, pubertal status, or changes in height. Increases in BMI category were associated with worsening of cardiometabolic risk factors, and decreases were associated with improvements. Boys who increased BMI category were more vulnerable to negative risk factor changes than girls. There are substantial shifts across BMI categories during middle school that are associated with clinically meaningful changes in cardiometabolic risk factors. Programs to promote decreases in BMI and prevent increases are clearly warranted.


Platelet-rich plasma injections for the treatment of hamstring injuries: a randomized controlled trial.
A hamstring injury is one of the most common types of injury affecting athletes. Despite this, the optimal management of hamstring muscle injuries is not yet defined. The effect of autologous platelet-rich plasma (PRP) therapy on the recovery of hamstring injuries is unclear. To investigate the effect of a single PRP injection in the treatment of grade 2 hamstring muscle injuries. Randomized controlled trial; Level of evidence, 2. Twenty-eight patients diagnosed with an acute hamstring injury were randomly allocated to autologous PRP therapy combined with a rehabilitation program or a rehabilitation program only. The primary outcome of this study was time to return to play. In addition, changes in pain severity and pain interference scores over time were examined. Patients in the PRP group achieved full recovery significantly earlier than controls (P = .02). The mean time to return to play was 26.7 ± 7.0 days and 42.5 ± 20.6 days for the PRP and control groups, respectively (t(22) = 2.50, P = .02). [corrected]. Significantly lower pain severity scores were observed in the PRP group throughout the study. However, no significant difference in the pain interference score was found between the 2 groups. A single autologous PRP injection combined with a rehabilitation program was significantly more effective in treating hamstring injuries than a rehabilitation program alone.


A nationwide population-based study of low vision and blindness in South Korea.
To investigate the prevalence and associated risk factors of low vision and blindness in the Korean population. This cross-sectional, population-based study examined the ophthalmologic data of 22,135 Koreans aged ≥5 years from the fifth Korea National Health and Nutrition Examination Survey (KNHANES V, 2010-2012). According to the World Health Organization criteria, blindness was defined as visual acuity (VA) less than 20/400 in the better-seeing eye, and low vision as VA of 20/60 or worse but 20/400 or better in the better-seeing eye. The prevalence rates were calculated from either presenting VA (PVA) or best-corrected VA (BCVA). Multivariate regression analysis was conducted for adults aged ≥20 years. The overall prevalence rates of PVA-defined low vision and blindness were 4.98% and 0.26%, respectively, and those of BCVA-defined low vision and blindness were 0.46% and 0.05%, respectively. Prevalence increased rapidly above the age of 70 years. For subjects aged ≥70 years, the population-weighted prevalence rates of low vision, based on PVA and BCVA, were 12.85% and 3.87%, respectively, and the corresponding rates of blindness were 0.49% and 0.42%, respectively. The presenting vision problems were significantly associated with age (younger adults or elderly subjects), female sex, low educational level, and lowest household income, whereas the best-corrected vision problems were associated with age ≥ 70 years, a low educational level, and rural residence. This population-based study provides useful information for planning optimal public eye health care services in South Korea.


A Non-Dicer RNase III and Four Other Novel Factors Required for RNAi-Mediated Transposon Suppression in the Human Pathogenic Yeast Cryptococcus neoformans.
The human pathogenic yeast Cryptococcus neoformans silences transposable elements using endo-siRNAs and an Argonaute, Ago1. Endo-siRNAs production requires the RNA-dependent RNA polymerase, Rdp1, and two partially redundant Dicer enzymes, Dcr1 and Dcr2, but is independent of histone H3 lysine 9 methylation. We describe here an insertional mutagenesis screen for factors required to suppress the mobilization of the C. neoformans HARBINGER family DNA transposon HAR1 Validation experiments uncovered five novel genes (RDE1-5) required for HAR1 suppression and global production of suppressive endo-siRNAs. The RDE genes do not impact transcript levels, suggesting the endo-siRNAs do not act by impacting target transcript synthesis or turnover. RDE3 encodes a non-Dicer RNase III related to S. cerevisiae Rnt1, RDE4 encodes a predicted terminal nucleotidyltransferase, while RDE5 has no strongly predicted encoded domains. Affinity purification-mass spectrometry studies suggest that Rde3 and Rde5 are physically associated. RDE1 encodes a G-patch protein homologous to the S. cerevisiae Sqs1/Pfa1, a nucleolar protein that directly activates the essential helicase Prp43 during rRNA biogenesis. Rde1 copurifies Rde2, another novel protein obtained in the screen, as well as Ago1, a homolog of Prp43, and numerous predicted nucleolar proteins. We also describe the isolation of conditional alleles of PRP43, which are defective in RNAi. This work reveals unanticipated requirements for a non-Dicer RNase III and presumptive nucleolar factors for endo-siRNA biogenesis and transposon mobilization suppression in C. neoformans.


Addressing obesity in the hospitalized patient: a needs assessment.
To perform a needs assessment to determine the extent to which hospitalist providers recognize and intervene upon obese patients in the hospital setting. A chart review was performed for patients admitted to the hospitalist service at Johns Hopkins Bayview Medical Center between September 1 and October 1, 2008. Patient charts were reviewed for documentation of obesity and treatment plans were ordered and implemented. Demographic data for patients and hospitalist providers was also collected. Providers were also surveyed about their documentation practices related to obesity and any perceived barriers. Forty-nine percent (136/276) of admitted patients were obese. Obesity was documented in 19% (26/136) of admission notes and a discrete plan was made to address obesity 7% (10/136) of the time. Hospitalist providers were more likely to document obesity in patients <60 years old (85% versus 55% respectively, P <0.007), and in patients with body mass indices (BMI) >or= 35 (77% versus 44% respectively, P < 0.004). Provider survey results suggest that providers do not document obesity because it is not considered to be an acute issue (67%), and they elect not to address obesity because they lack the time (63%), skill (37%), and they believe that their efforts will be unsuccessful (33%). Documentation of obesity by hospitalist providers is poor. Because an inpatient admission has been characterized as a teachable moment when patients are willing to reflect on behavior change, this may be an ideal time to counsel and educate obese patients.


Nursing practice environment: a strategy for mental health nurse retention?
Historically, mental health services have faced challenges in their ability to attract and retain a competent nursing workforce in the context of an overall nursing shortage. The current economic downturn has provided some respite; however, this is likely to be a temporary reprieve, with significant nursing shortages predicted for the future. Mental health services need to develop strategies to become more competitive if they are to attract and retain skilled nurses and avoid future shortages. Research demonstrates that creating and maintaining a positive nursing practice environment is one such strategy and an important area to consider when addressing nurse retention. This paper examines the impact the nursing practice environment has on nurse retention within the general and mental health settings. Findings indicate, that while there is a wealth of evidence to support the importance of a positive practice environment on nurse retention in the broader health system, there is little evidence specific to mental health. Further research of the mental health practice environment is required.


Folding and misfolding of the papillomavirus E6 interacting peptide E6ap.
All-atom Langevin dynamics simulations have been performed to study the folding pathways of the 18-residue binding domain fragment E6ap of the human papillomavirus E6 interacting peptide. Six independent folding trajectories, with a total duration of nearly 2 micros, all lead to the same native state in which the E6ap adopts a fluctuating alpha-helix structure in the central portion (Ser-4-Leu-13) but with very flexible N and C termini. Simulations starting from different core configurations exhibit the E6ap folding dynamics as either a two- or three-state folder with an intermediate misfolded state. The essential leucine hydrophobic core (Leu-9, Leu-12, and Leu-13) is well conserved in the native-state structure but absent in the intermediate structure, suggesting that the leucine core is not only essential for the binding activity of E6ap but also important for the stability of the native structure. The free energy landscape reveals a significant barrier between the basins separating the native and misfolded states. We also discuss the various underlying forces that drive the peptide into its native state.


An Algebraic Process for Visualization Design.
We present a model of visualization design based on algebraic considerations of the visualization process. The model helps characterize visual encodings, guide their design, evaluate their effectiveness, and highlight their shortcomings. The model has three components: the underlying mathematical structure of the data or object being visualized, the concrete representation of the data in a computer, and (to the extent possible) a mathematical description of how humans perceive the visualization. Because we believe the value of our model lies in its practical application, we propose three general principles for good visualization design. We work through a collection of examples where our model helps explain the known properties of existing visualizations methods, both good and not-so-good, as well as suggesting some novel methods. We describe how to use the model alongside experimental user studies, since it can help frame experiment outcomes in an actionable manner. Exploring the implications and applications of our model and its design principles should provide many directions for future visualization research.


Allocentric spatial learning and memory deficits in Down syndrome.
Studies have shown that persons with Down syndrome (DS) exhibit relatively poor language capacities, and impaired verbal and visuoperceptual memory, whereas their visuospatial memory capacities appear comparatively spared. Individuals with DS recall better where an object was previously seen than what object was previously seen. However, most of the evidence concerning preserved visuospatial memory comes from tabletop or computerized experiments which are biased toward testing egocentric (viewpoint-dependent) spatial representations. Accordingly, allocentric (viewpoint-independent) spatial learning and memory capacities may not be necessary to perform these tasks. Thus, in order to more fully characterize the spatial capacities of individuals with DS, allocentric processes underlying real-world navigation must also be investigated. We tested 20 participants with DS and 16 mental age-matched, typically developing (TD) children in a real-world, allocentric spatial (AS) memory task. During local cue (LC) trials, participants had to locate three rewards marked by local color cues, among 12 locations distributed in a 4 m × 4 m arena. During AS trials, participants had to locate the same three rewards, in absence of LCs, based on their relations to distal environmental cues. All TD participants chose rewarded locations in LC and AS trials at above chance level. In contrast, although all but one of the participants with DS exhibited a preference for the rewarded locations in LC trials, only 50% of participants with DS chose the rewarded locations at above chance level in AS trials. As a group, participants with DS performed worse than TD children on all measures of task performance. These findings demonstrate that individuals with DS are impaired at using an AS representation to learn and remember discrete locations in a controlled environment, suggesting persistent and pervasive deficits in hippocampus-dependent memory in DS.


Prevalence, determinants and systems-thinking approaches to optimal hypertension control in West Africa.
In West Africa, hypertension, once rare, has now emerged as a critical health concern and the trajectory is upward and factors are complex. The true magnitude of hypertension in some West African countries, including in-depth knowledge of underlying risk factors is not completely understood. There is also a paucity of research on adequate systems-level approaches designed to mitigate the growing burden of hypertension in the region. In this review, we thematically synthesize available literature pertaining to the prevalence of hypertension in West Africa and discuss factors that influence its diagnosis, treatment and control. We aimed to address the social and structural determinants influencing hypertension in the sub-region including the effects of urbanization, health infrastructure and healthcare workforce. The prevalence of hypertension in West Africa has increased over the past decade and is rising rapidly with an urban-rural gradient that places higher hypertension prevalence on urban settings compared to rural settings. Overall levels of awareness of one's hypertension status remain consistently low in West African. Structural and economic determinants related to conditions of poverty such as insufficient finances have a direct impact on adherence to prescribed antihypertensive medications. Urbanization contributes to the increasing incidence of hypertension in the sub-region and available evidence indicates that inadequate health infrastructure may act as a barrier to optimal hypertension control in West Africa. Given that optimal hypertension control in West Africa depends on multiple factors that go beyond simply modifying the behaviors of the individuals alone, we conclude by discussing the potential role systems-thinking approaches can play to achieve optimal control in the sub-region. In the context of recent advances in hypertension management including new therapeutic options and innovative solutions to expand health workforce so as to meet the high demand for healthcare, the success of these strategies will rely on a new understanding of the complexity of human behaviors and interactions most aptly framed from a systems-thinking perspective.


Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study.
Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. We retrospectively retrieved data for paediatric patients (aged 0-16 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. From Jan 17 to March 1, 2020, 36 children (mean age 8·3 [SD 3·5] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38·5°C or higher, and nine (25%) had a body temperature of 37·5-38·5°C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir-ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou.


Theory of the field-induced BEC in the frustrated spin-1/2 dimer compound BaCuSi2O6.
Building on recent neutron and NMR experiments, we investigate the field-induced exotic criticality observed in the frustrated compound BaCuSi2O6 using a frustrated model with two types of bilayers. A semiclassical treatment of the effective hard-core boson model shows that perfect interlayer frustration leads to a 2D-like critical exponent varphi=1 without logarithmic corrections and to a 3D low temperature phase with different but nonvanishing triplet populations in both types of bilayers. These further suggest a simple phenomenology in terms of a field-dependent transverse coupling in the context of which we reproduce the entire field-temperature phase diagram with quantum Monte Carlo simulations.


The effect of humic and glutamic acids in nutrient solution on the N metabolism in lettuce.
This paper reports for the first time the influence of partially replacing the nitrogen (N) source of a nutrient solution with amino acids and humic acid on the physiological and antioxidant activities and N metabolism in lettuce. A hydroponic experiment was designed to replace 25 and 50% of the N in nutrient solutions (NSs) with glutamic acid (GA) and humic acid (HA) and evaluate the effects on growth, nitrate (NO(3)) assimilation, protein content, nitrate reductase (NR) activity and antioxidant changes in lettuce. The results showed that, when a portion of the N was replaced with GA and HA, the fresh and dry weights of lettuce shoots did not change significantly compared with the full NO(3) treatment. The titratable acidity was not affected by adding HA and/or GA to the NS. The nitrite concentration and NR activity decreased with reductions in the N concentration of the NS and improved with the addition of GA and HA. GA enhanced the NO(3) uptake and protein content more than HA. Changes in the superoxide dismutase (SOD) and peroxidase (POD) activities and malondialdehyde content were inconclusive: SOD and POD activities decreased with decreasing N content of the NS, and HA addition improved the SOD and POD activities. When HA and GA were substituted for NO(3) in an NS, the acids effectively adjusted the N metabolism and growth in lettuce and decreased the N consumption of the NS.


Neural correlates of top-down guidance of attention to food: An fMRI study.
We investigated the neural correlates of working memory guided attentional selection of food versus non-food stimuli in young women. Participants were thirty-two women, aged 20.6y (± 0.5) who were presented with a cue (food or non-food item) to hold in working memory. Subsequently, they had to search for a target in a 2-item display where target and distractor stimuli were each flanked by a picture of a food or a non-food item. The behavioural data showed that attention is particularly efficiently drawn to food stimuli when thinking about food. Using fMRI, we found that holding a non-food versus food stimulus in working memory was associated with increased activity in occipital gyrus, fusiform, inferior and superior frontal gyrus. In the posterior cingulum, retrosplenial cortex, a food item that re-appeared in the search array when it was held in memory led to a reduced response, compared to when it did not re-appear. The reverse effect was found for non-food stimuli. The extent of the reappearance effect correlated with the attentional capture of food as measured behaviourally. In conclusion, these results suggest that holding food in mind may bias attention because thinking of food facilitated neuronal responses to sensory input related to food stimuli and because holding food-related information in mind is less taxing on memory.


Acquisition and Loss of CTX-M-Producing and Non-Producing Escherichia coli in the Fecal Microbiome of Travelers to South Asia.
Over 80% of travelers from the United Kingdom to the Indian subcontinent acquire CTX-M-producing Escherichia coli (CTX-M-EC), but the mechanism of CTX-M-EC acquisition is poorly understood. We aimed to investigate the dynamics of CTX-M-EC acquisition in healthy travelers and how this relates to populations of non-CTX-M-EC in the fecal microbiome. This is a prospective observational study of healthy volunteers traveling from the United Kingdom to South Asia. Fecal samples were collected pre- and post-travel at several time points up to 12 months post-travel. A toothpicking experiment was used to determine the proportion of cephalosporin-sensitive E. coli in fecal samples containing CTX-M-EC. MLST and SNP type of pre-travel and post-travel E. coli were deduced by WGS. CTX-M-EC was acquired by 89% (16/18) of volunteers. Polyclonal acquisition of CTX-M-EC was seen in 8/15 volunteers (all had >3 STs across post-travel samples), suggesting multiple acquisition events. Indistinguishable CTX-M-EC clones (zero SNPs apart) are detectable in serial fecal samples up to 7 months after travel, indicating stable maintenance in the fecal microbiome on return to the United Kingdom in the absence of selective pressure. CTX-M-EC-containing samples were often co-colonized with novel, non-CTX-M strains after travel, indicating that acquisition of non-CTX-M-EC occurs alongside CTX-M-EC. The same pre-travel non-CTX-M strains (<10 SNPs apart) were found in post-travel fecal samples after CTX-M-EC had been lost, suggesting return of the fecal microbiome to the pre-travel state and long-term persistence of minority strains in travelers who acquire CTX-M-EC.IMPORTANCEEscherichia coli strains which produce CTX-M extended-spectrum beta-lactamases are endemic as colonizers of humans and in the environment in South Asia. This study demonstrates that acquisition of CTX-M-producing E. coli (CTX-M-EC) in travelers from the United Kingdom to South Asia is polyclonal, which is likely due to multiple acquisition events from contaminated food and drinking water during travel. CTX-M-EC frequently persists in the fecal microbiome for at least 1 year after acquisition, often alongside newly acquired non-CTX-M E. coli strains. In travelers who acquire CTX-M-EC, pre-travel non-CTX-M E. coli remains as a minority population in the gut until the CTX-M-EC strains are lost. The non-CTX-M strains are then reestablished as the predominant E. coli population. This study has shed light on the dynamics of CTX-M-EC acquisition, colonization, and loss after travel. Future work involving manipulation of nonvirulent resident E. coli could be used to prevent colonization with antibiotic-resistant E. coli.


Determining the rise in BCR-ABL RNA that optimally predicts a kinase domain mutation in patients with chronic myeloid leukemia on imatinib.
In imatinib-treated chronic myeloid leukemia (CML), secondary drug resistance is often caused by mutations in the BCR-ABL kinase domain (KD). As alternative therapies are available for imatinib resistance, early identification of mutations may prevent disease progression. Because most patients are routinely monitored by BCR-ABL quantitative polymerase chain reaction (PCR), it is important to define the optimal increase in BCR-ABL that should trigger mutation testing. Expert panels have provisionally recommended a 10-fold BCR-ABL increase as the trigger for mutation screening, acknowledging the lack of consensus. To address this question, we monitored 150 CML patients by quantitative PCR and DNA sequencing. Thirty-five different mutations were identified in 53 patients, and, during 22.5 months (median) of follow-up after sequencing, mutations were significantly predictive of shorter progression-free survival. An unbiased receiver operating characteristic analysis identified a 2.6-fold increase in BCR-ABL RNA as the optimal cutoff for predicting a concomitant KD mutation, with a sensitivity of 77% (94% if including subsequent samples). The 2.6-fold threshold approximated the analytic precision limit of our PCR assay. In contrast, transcript rise cutoffs of 5-fold or greater had poor diagnostic sensitivity and no significant association with mutations. We conclude that the currently recommended 10-fold threshold to trigger mutation screening is insensitive and not universally applicable.


Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance.
In subjects with transmitted thymidine analogue mutations (TAMs), boosted PIs (PI/b) are often chosen to overcome possible resistance to the NRTI backbone. However, data to guide treatment selection are limited. Our aim was to obtain firmer guidance for clinical practice using real-world cohort data. We analysed 1710 subjects who started a PI/b in combination with tenofovir or abacavir plus emtricitabine or lamivudine, and compared their virological outcomes with those of 4889 patients who started an NNRTI (predominantly efavirenz), according to the presence of ≥1 TAM as the sole form of transmitted drug resistance. Participants with ≥1 TAM comprised predominantly MSM (213 of 269, 79.2%), subjects of white ethnicity (206 of 269, 76.6%) and HIV-1 subtype B infections (234 of 269, 87.0%). Most (203 of 269, 75.5%) had singleton TAMs, commonly a revertant of T215Y or T215F (112 of 269, 41.6%). Over a median of 2.5 years of follow-up, 834 of 6599 (12.6%) subjects experienced viraemia (HIV-1 RNA >50 copies/mL). The adjusted HR for viraemia was 2.17 with PI/b versus NNRTI-based therapy (95% CI 1.88-2.51; P < 0.001). Other independent predictors of viraemia included injecting drug use, black ethnicity, higher viral load and lower CD4 cell count at baseline, and receiving abacavir instead of tenofovir. Resistance showed no overall impact (adjusted HR 0.77 with ≥1 TAM versus no resistance; 95% CI 0.54-1.10; P = 0.15). In this cohort, patients harbouring ≥1 TAM as the sole form of transmitted drug resistance gained no apparent virological advantage from starting first-line ART with a PI/b.


Hypoglycemic and hypolipidemic effects of a polysaccharide from Lachnum YM240 and its derivatives in mice, induced by a high fat diet and low dose STZ.
Carboxymethylated and sulfated polysaccharides (CLEP and SLEP) were prepared from an exopolysaccharide previously obtained from Lachnum YM240 (LEP) by chemical modifications. Two doses (50 mg kg-1 and 200 mg kg-1 b. w.) of LEP, CLEP and SLEP were orally administered to normal mice and type 2 diabetic mice (T2DM) that were induced by streptozotocin (STZ) and a high fat diet, respectively. The hypoglycemic effect was evaluated by testing the oral glucose tolerance, fasting blood glucose (FBG) levels, fasting serum insulin (FINS), glycosylated hemoglobin A1c (HbA1c), and the hypolipidemic effect was evaluated by the body, spleen, pancreas, liver and kidney weights, as well as serum triglycerides (TG), cholesterol (TC) and free fatty acids (FFA). After four weeks of administration, LEP, CLEP and SLEP showed a marked FBG fall rate of 11.2%, 44.0% and 42.5% for the high-dose and 7.43%, 38.5% and 33.1% for the low-dose, respectively, as compared to the DC group. Moreover, compared with DC mice, TC concentrations in the high-dose groups of LEP, CLEP and SLEP were significantly decreased by 29.6%, 38.7% (P < 0.05), 33.0% (P < 0.05), and TG concentrations decreased by 18.9%, 43.9% (P < 0.01), 29.0% (P < 0.05), respectively. In addition, LEP and the derivatives significantly upregulated the expression of glucokinase (GK) and adenosine monophosphate-activated protein kinase (AMPK) in the liver, AMPK and glucose transporter 4 (Glut4) in skeletal muscle and peroxysome proliferator-activated receptor (PPAR-γ) in adipose tissue, whereas downregulated the expression of glucose-6-phosphatase (G6P) in the liver; these were examined using ELISA detection kits. These results for FBG and serum lipids indicate that LEP and its derivatives possess significant hypoglycemic and hypolipidemic effects and carboxymethylation improved the hypoglycemic and hypolipidemic effects more effectively than sulfation. Therefore, the carboxymethylated and sulfated modifications were effective ways to enhance the hypoglycemic and hypolipidemic activities of polysaccharides.


Two years later - Revisiting autobiographical memory representations in vmPFC and hippocampus.
A long-standing question in memory neuroscience concerns how and where autobiographical memories of personal experiences are represented in the brain. In a previous high resolution multivoxel pattern analysis fMRI study, we examined two week old (recent) and ten year old (remote) autobiographical memories (Bonnici et al., 2012, J. Neurosci. 32:16982-16991). We found that remote memories were particularly well represented in ventromedial prefrontal cortex (vmPFC) compared to recent memories. Moreover, while both types of memory were represented within anterior and posterior hippocampus, remote memories were more easily distinguished in the posterior portion. These findings suggested that a change of some kind had occurred between two weeks and ten years in terms of where autobiographical memories were represented in the brain. In order to examine this further, here participants from the original study returned two years later and recalled the memories again. We found that there was no difference in the detectability of memory representations within vmPFC for the now 2 year old and 12 year old memories, and this was also the case for the posterior hippocampus. Direct comparison of the two week old memories (original study) with themselves two years later (present study) confirmed that their representation within vmPFC had become more evident. Overall, this within-subjects longitudinal fMRI study extends our understanding of autobiographical memory representations by allowing us to narrow the window within which their consolidation is likely to occur. We conclude that after a memory is initially encoded, its representation within vmPFC has stablised by, at most, two years later.


Effects of glutamine-supplemented total parenteral nutrition on cytokine production and T cell population in septic rats.
This study was designed to investigate the effects of total parenteral nutrition (TPN) enriched with glutamine (GLN) on in vivo cytokine production and cellular immune response in early and late septic stages of rats. Male Wistar rats were divided into 2 experimental groups and received TPN solution at an energy level of 270 kcal/kg body weight. The TPN solutions were isonitrogenous and identical in nutrients composition except for differences in amino acid content. One group received 2% GLN, whereas the other group received glycine (Gly) instead. TPN was maintained for 5 or 6 days according to the sacrifice schedule of the rats. On day 5, sepsis was induced by cecal ligation and puncture (CLP). Respective groups of rats were sacrificed 2, 4, 6, and 24 hours after CLP. Sepsis resulted in a negative nitrogen balance in both groups, and nitrogen loss was significantly lower in the GLN than the Gly group. Interleukin (IL)-2 and interferon (IFN)-gamma in most of the samples collected at various time points were not detectable in plasma or peritoneal lavage fluid. No differences in plasma IL-6 and TNF-alpha concentrations were observed between the GLN and Gly groups. Also, there were no significant differences in IL-1beta, IL-6, and TNF-alpha concentrations in peritoneal lavage fluid between the 2 groups at various time points. The CD4+/CD8+ ratio was significantly higher in the GLN group than in the Gly group only at 4 hours after CLP, and no difference was observed at 24 hours after CLP. TPN preinfused with a GLN-supplemented solution had a beneficial effect in ameliorating the extent of negative nitrogen balance in septic rats. However, parenterally administered GLN did not reduce the production of inflammatory mediators systemically or at the site of injury, and the influence on enhancing cellular immunity was not obvious.


Relationship between high density lipoprotein antioxidant activity and carotid arterial intima-media thickness in patients with essential hypertension.
The objective of this study was to evaluate high-density lipoprotein (HDL) antioxidative activity and its possible influencing factors in patients with essential hypertension and to investigate the correlations between HDL antioxidative activity and the carotid arterial intima-media thickness (CIMT). Thirty-three patients with essential hypertension and 32 healthy people as control were included. High- and low-density lipoprotein in plasma were isolated by one-step density gradient ultracentrifugation, and induced oxidation with external Cu(2+). Antioxidant activity of HDL, lag time, and lipid peroxidation degree were determined by spectrophotometric and thiobarbituric acid reactive substances (TBARS) methods. Paraoxonase 1 (PON1) activity in serum was measured with continuous monitoring using phenylacetate as a substrate. The CIMT was measured with a high-resolution ultrasound Doppler system. In patients with essential hypertension, the inhibitory effect of HDL on low-density lipoprotein (LDL) oxidation and the PON1 activity were reduced (72.29 +/- 2.03)% vs. (80.91 +/- 2.06)%, and (112.21 +/- 8.64)u/ml vs. (146.43 +/- 8.79)u/ml (all P < 0.05). The lag time of oxidation and the lipid peroxidation between the hypertensive group and the control group did not show a statistically significant difference. Multiple stepwise regression analysis revealed that HDL antioxidative activity might be affected by PON1 activity (P = 0.004), diastolic pressure (P = 0.004), sex (P = 0.006), and that CIMT might be affected by HDL antioxidative activity (P = 0.030), systolic pressure (P = 0.026), and total cholesterol level (P = 0.033). The HDL antioxidative activity is reduced in patients with essential hypertension and significantly affected by sex. The CIMT was negatively correlated with HDL antioxidative activity, which suggests that decreased HDL antioxidative activity may be one of the important determinants for the development of atherosclerosis in patients with essential hypertension.


Human candidate polymorphisms in sympatric ethnic groups differing in malaria susceptibility in Mali.
Malaria still remains a major public health problem in Mali, although disease susceptibility varies between ethnic groups, particularly between the Fulani and Dogon. These two sympatric groups share similar socio-cultural factors and malaria transmission rates, but Fulani individuals tend to show significantly higher spleen enlargement scores, lower parasite prevalence, and seem less affected by the disease than their Dogon neighbours. We have used genetic polymorphisms from malaria-associated genes to investigate associations with various malaria metrics between the Fulanai and Dogon groups. Two cross sectional surveys (transmission season 2006, dry season 2007) were performed. Healthy volunteers from the both ethnic groups (n=939) were recruited in a rural setting. In each survey, clinical (spleen enlargement, axillary temperature, weight) and parasitological data (malaria parasite densities and species) were collected, as well as blood samples. One hundred and sixty six SNPs were genotyped and 5 immunoassays (AMA1, CSP, MSP1, MSP2, total IgE) were performed on the DNA and serum samples respectively. The data confirm the reduced malaria susceptibility in the Fulani, with a higher level of the protective O-blood group, and increased circulating antibody levels to several malaria antigens (p<10(-15)). We identified SNP allele frequency differences between the 2 ethnic groups in CD36, IL4, RTN3 and ADCY9. Moreover, polymorphisms in FCER1A, RAD50, TNF, SLC22A4, and IL13 genes were correlated with antibody production (p-value<0.003). Further work is required to understand the mechanisms underpinning these genetic factors.


Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria.
The modulation of developmental biochemical pathways by mechanical cues is an emerging feature of animal development, but its evolutionary origins have not been explored. Here we show that a common mechanosensitive pathway involving β-catenin specifies early mesodermal identity at gastrulation in zebrafish and Drosophila. Mechanical strains developed by zebrafish epiboly and Drosophila mesoderm invagination trigger the phosphorylation of β-catenin-tyrosine-667. This leads to the release of β-catenin into the cytoplasm and nucleus, where it triggers and maintains, respectively, the expression of zebrafish brachyury orthologue notail and of Drosophila Twist, both crucial transcription factors for early mesoderm identity. The role of the β-catenin mechanosensitive pathway in mesoderm identity has been conserved over the large evolutionary distance separating zebrafish and Drosophila. This suggests mesoderm mechanical induction dating back to at least the last bilaterian common ancestor more than 570 million years ago, the period during which mesoderm is thought to have emerged.


Alkylated cellulosic membranes with enhanced albumin affinity: influence of competing proteins.
4-Vinyl pyridine was grafted to the surface of the cellulosic membrane Cuprophan, and subsequently alkylated with both non-fatty acid-like C10 (GVP-C10) and fatty acid-like C16 (GVP-C16) aliphatic chains. In vitro albumin adsorption studies from single and binary protein solutions, as well as from dilute plasma demonstrated a significant enhancement (1.4-3.89 times) of albumin binding to both the GVP-C10 and GVP-C16 surfaces, relative to unmodified Cuprophan. It is speculated that enhanced albumin adsorption to a surface may improve surface thromboresistance. Further, these results suggest that there is no difference between the enhanced albumin adsorption of the fatty acid and nonfatty like alkyl chains, C10 and C16.


Chronic ulcerative colitis and colorectal cancer.
One of the most important consequences of chronically active ulcerative colitis (UC) or Crohn's disease (CD) - the two major forms of inflammatory bowel disease (IBD) - is the development of colorectal cancer (CRC). An increased risk for the occurrence of CRC in up to 30% of affected patients after 35years of UC has been reported. Recent evidence from population based studies indicates a lower risk. Nevertheless the incidence is still significantly increased as compared to individuals without chronic colitis. Colitis-associated CRC (CAC) does not display the adenoma-carcinoma sequence which is typical for sporadic CRC and the pathophysiology appears to be different. Chronic inflammation and the increased turnover of epithelial cells contribute to the development of low- and high-grade dysplasia which may further transform into CAC. Reactive oxygen species (ROS) generated by the inflammatory infiltrate are thought to contribute to the generation of dysplastic lesions. In sporadic CRC the sequence of mutations that finally lead to malignancy involves early activation of Wnt/β-catenin pathway (in 90% of cases) including mutations in adenomatous polyposis coli (APC) tumor suppressor gene, its regulating kinase GSK3β and β-catenin itself. β-catenin mutations are rarer in CAC and mutations in APC occur rather late during the disease progression, whereas there are earlier mutations in p53 and K-ras. Recent data indicate that the intestinal microbiome and its interaction with a functionally impaired mucosal barrier may also play a role in CAC development. CACs frequently show aggressive growth and early metastases. The treatment of CAC in patients with colitis always includes proctocolectomy with ileoanal anastomosis as meta- or synchronic lesions are frequent.


Observational research on NCDs in HIV-positive populations: conceptual and methodological considerations.
Noncommunicable diseases (NCDs) account for a growing burden of morbidity and mortality among people living with HIV in low- and middle-income countries (LMICs). HIV infection and antiretroviral therapy interact with NCD risk factors in complex ways, and research into this "web of causation" has so far been largely based on data from high-income countries. However, improving the understanding, treatment, and prevention of NCDs in LMICs requires region-specific evidence. Priority research areas include: (1) defining the burden of NCDs among people living with HIV, (2) understanding the impact of modifiable risk factors, (3) evaluating effective and efficient care strategies at individual and health systems levels, and (4) evaluating cost-effective prevention strategies. Meeting these needs will require observational data, both to inform the design of randomized trials and to replace trials that would be unethical or infeasible. Focusing on Sub-Saharan Africa, we discuss data resources currently available to inform this effort and consider key limitations and methodological challenges. Existing data resources often lack population-based samples; HIV-negative, HIV-positive, and antiretroviral therapy-naive comparison groups; and measurements of key NCD risk factors and outcomes. Other challenges include loss to follow-up, competing risk of death, incomplete outcome ascertainment and measurement of factors affecting clinical decision making, and the need to control for (time-dependent) confounding. We review these challenges and discuss strategies for overcoming them through augmented data collection and appropriate analysis. We conclude with recommendations to improve the quality of data and analyses available to inform the response to HIV and NCD comorbidity in LMICs.


Targeting Carcinoembryonic Antigen with DNA Vaccination: On-Target Adverse Events Link with Immunologic and Clinical Outcomes.
We have clinically evaluated a DNA fusion vaccine to target the HLA-A*0201-binding peptide CAP-1 from carcinoembryonic antigen (CEA605-613) linked to an immunostimulatory domain (DOM) from fragment C of tetanus toxin. Twenty-seven patients with CEA-expressing carcinomas were recruited: 15 patients with measurable disease (arm-I) and 12 patients without radiological evidence of disease (arm-II). Six intramuscular vaccinations of naked DNA (1 mg/dose) were administered up to week 12. Clinical and immunologic follow-up was up to week 64 or clinical/radiological disease. DOM-specific immune responses demonstrated successful vaccine delivery. All patients without measurable disease compared with 60% with advanced disease responded immunologically, while 58% and 20% expanded anti-CAP-1 CD8+ T cells, respectively. CAP-1-specific T cells were only detectable in the blood postvaccination but could also be identified in previously resected cancer tissue. The gastrointestinal adverse event diarrhea was reported by 48% of patients and linked to more frequent decreases in CEA (P < 0.001) and improved global immunologic responses [anti-DOM responses of greater magnitude (P < 0.001), frequency (P = 0.004), and duration] compared with patients without diarrhea. In advanced disease patients, decreases in CEA were associated with better overall survival (HR = 0.14, P = 0.017). CAP-1 peptide was detectable on MHC class I of normal bowel mucosa and primary colorectal cancer tissue by mass spectrometry, offering a mechanistic explanation for diarrhea through CD8+ T-cell attack. Our data suggest that DNA vaccination is able to overcome peripheral tolerance in normal and tumor tissue and warrants testing in combination studies, for example, by vaccinating in parallel to treatment with an anti-PD1 antibody. Clin Cancer Res; 22(19); 4827-36. ©2016 AACR.


Bilayer Properties of Lipid A from Various Gram-Negative Bacteria.
Lipid A is the lipid anchor of a lipopolysaccharide in the outer leaflet of the outer membrane of Gram-negative bacteria. In general, lipid A consists of two phosphorylated N-acetyl glucosamine and several acyl chains that are directly linked to the two sugars. Depending on the bacterial species and environments, the acyl chain number and length vary, and lipid A can be chemically modified with phosphoethanolamine, aminoarabinose, or glycine residues, which are key to bacterial pathogenesis. In this work, homogeneous lipid bilayers of 21 distinct lipid A types from 12 bacterial species are modeled and simulated to investigate the differences and similarities of their membrane properties. In addition, different neutralizing ion types (Ca2+, K+, and Na+) are considered to examine the ion's influence on the membrane properties. The trajectory analysis shows that (1) the area per lipid is mostly correlated to the acyl chain number, and the area per lipid increases as a function of the acyl chain number; (2) the hydrophobic thickness is mainly determined by the average acyl chain length with slight dependence on the acyl chain number, and the hydrophobic thickness generally increases with the average acyl chain length; (3) a good correlation is observed among the area per lipid, hydrophobic thickness, and acyl chain order; and (4) although the influence of neutralizing ion types on the area per lipid and hydrophobic thickness is minimal, Ca2+ stays longer on the membrane surface than K+ or Na+, consequently leading to lower lateral diffusion and a higher compressibility modulus, which agrees well with available experiments.


Functional genomic characterization of neoblast-like stem cells in larval Schistosoma mansoni
Schistosomes infect hundreds of millions of people in the developing world. Transmission of these parasites relies on a stem cell-driven, clonal expansion of larvae inside a molluscan intermediate host. How this novel asexual reproductive strategy relates to current models of stem cell maintenance and germline specification is unclear. Here, we demonstrate that this proliferative larval cell population (germinal cells) shares some molecular signatures with stem cells from diverse organisms, in particular neoblasts of planarians (free-living relatives of schistosomes). We identify two distinct germinal cell lineages that differ in their proliferation kinetics and expression of a nanos ortholog. We show that a vasa/PL10 homolog is required for proliferation and maintenance of both populations, whereas argonaute2 and a fibroblast growth factor receptor-encoding gene are required only for nanos-negative cells. Our results suggest that an ancient stem cell-based developmental program may have enabled the evolution of the complex life cycle of parasitic flatworms. DOI:http://dx.doi.org/10.7554/eLife.00768.001.


Anti-invasive, antitumoral, and antiangiogenic efficacy of a pyrimidine-2,4,6-trione derivative, an orally active and selective matrix metalloproteinases inhibitor.
The implication of matrix metalloproteinases (MMPs) in the major stages of cancer progression has fueled interest in the design of synthetic MMP inhibitors (MMPIs) as a novel anticancer therapy. Thus far, drugs used in clinical trials are broad-spectrum MMPIs the therapeutic index of which proved disappointingly low. The development of selective MMPIs for tumor progression-associated MMPs is, thus, likely to offer improved therapeutic possibilities. The anti-invasive capacity of a series of pyrimidine-trione derivatives was tested in vitro in a chemoinvasion assay, and the most potent compound was further evaluated in vivo in different human tumor xenograft models. The activity of this novel selective MMPI was compared with BB-94, a broad-spectrum inhibitor. Ro-28-2653, an inhibitor with high selectivity for MMP-2, MMP-9, and membrane type 1 (MT1)-MMP, showed the highest anti-invasive activity in vitro. In vivo, Ro-28-2653 reduced the growth of tumors induced by the inoculation of different cell lines producing MMPs and inhibited the tumor-promoting effect of fibroblasts on breast adenocarcinoma cells. Furthermore, Ro-28-2653 reduced tumor vascularization and blocked angiogenesis in a rat aortic ring assay. In contrast, BB-94 up-regulated MMP-9 expression in tumor cells and promoted angiogenesis in the aortic ring assay. Ro-28-2653, a selective and orally bioavailable MMPI with inhibitory activity against MMPs expressed by tumor and/or stromal cells, is a potent antitumor and antiangiogenic agent. In contrast to broad-spectrum inhibitors, the administration of Ro-28-2653 was not associated with the occurrence of adverse side effects that might hamper the therapeutic potential of these drugs.


High affinity binding of epibatidine to serotonin type 3 receptors.
Epibatidine and mecamylamine are ligands used widely in the study of nicotinic acetylcholine receptors (nAChRs) in the central and peripheral nervous systems. In the present study, we find that nicotine blocks only 75% of (125)I-epibatidine binding to rat brain membranes, whereas ligands specific for serotonin type 3 receptors (5-HT(3)Rs) block the remaining 25%. (125)I-Epibatidine binds with a high affinity to native 5-HT(3)Rs of N1E-115 cells and to receptors composed of only 5-HT(3A) subunits expressed in HEK cells. In these cells, serotonin, the 5-HT(3)R-specific antagonist MDL72222, and the 5-HT(3)R agonist chlorophenylbiguanide readily competed with (125)I-epibatidine binding to 5-HT(3)Rs. Nicotine was a poor competitor for (125)I-epibatidine binding to 5-HT(3)Rs. However, the noncompetitive nAChR antagonist mecamylamine acted as a potent competitive inhibitor of (125)I-epibatidine binding to 5-HT(3)Rs. Epibatidine inhibited serotonin-induced currents mediated by endogenous 5-HT(3)Rs in neuroblastoma cell lines and 5-HT(3A)Rs expressed in HEK cells in a competitive manner. Our results demonstrate that 5-HT(3)Rs are previously uncharacterized high affinity epibatidine binding sites in the brain and indicate that epibatidine and mecamylamine act as 5-HT(3)R antagonists. Previous studies that depended on epibatidine and mecamylamine as nAChR-specific ligands, in particular studies of analgesic properties of epibatidine, may need to be reinterpreted with respect to the potential role of 5-HT(3)Rs.


High-grading bias: subtle problems with assessing power of selected subsets of loci for population assignment.
Recognition of the importance of cross-validation ('any technique or instance of assessing how the results of a statistical analysis will generalize to an independent dataset'; Wiktionary, en.wiktionary.org) is one reason that the U.S. Securities and Exchange Commission requires all investment products to carry some variation of the disclaimer, 'Past performance is no guarantee of future results.' Even a cursory examination of financial behaviour, however, demonstrates that this warning is regularly ignored, even by those who understand what an independent dataset is. In the natural sciences, an analogue to predicting future returns for an investment strategy is predicting power of a particular algorithm to perform with new data. Once again, the key to developing an unbiased assessment of future performance is through testing with independent data--that is, data that were in no way involved in developing the method in the first place. A 'gold-standard' approach to cross-validation is to divide the data into two parts, one used to develop the algorithm, the other used to test its performance. Because this approach substantially reduces the sample size that can be used in constructing the algorithm, researchers often try other variations of cross-validation to accomplish the same ends. As illustrated by Anderson in this issue of Molecular Ecology Resources, however, not all attempts at cross-validation produce the desired result. Anderson used simulated data to evaluate performance of several software programs designed to identify subsets of loci that can be effective for assigning individuals to population of origin based on multilocus genetic data. Such programs are likely to become increasingly popular as researchers seek ways to streamline routine analyses by focusing on small sets of loci that contain most of the desired signal. Anderson found that although some of the programs made an attempt at cross-validation, all failed to meet the 'gold standard' of using truly independent data and therefore produced overly optimistic assessments of power of the selected set of loci--a phenomenon known as 'high grading bias.'


Burden and costs of migraine in a Swedish defined patient population - a questionnaire-based study.
Migraine is a disabling, chronic neurological disease leading to severe headache episodes affecting 13.2% of the Swedish population. Migraine leads to an extensive socio-economic burden in terms of healthcare costs, reduced workforce and quality of life (QoL) but studies of the health-economic consequences in a Swedish context are lacking. The objective of this study is to map the health-economic consequences of migraine in a defined patient population in terms of healthcare consumption, production loss and QoL in Sweden. The study is based on data from a web-based survey to members in the Swedish patients' association suffering from migraine. The survey was conducted in May 2018 and included people with migraine aged 18 years or older. The survey included questions on health resource consumption, lost production resulting from migraine-related absenteeism and presenteeism, and QoL as measured by the EuroQol 5 dimensions questionnaire (EQ-5D-5 L) and the Headache Impact Test (HIT-6). The results are presented in yearly costs per patient and losses in quality adjusted life years (QALYs). The results are based on answers from 630 individuals with migraine and are presented by number of migraine days per month. The total cost per patient and year increased with the number of migraine days per month (p < 0.001) and varied between approximately €5000 for those with less than 3 migraine days per month and €24,000 per year for those with 21-28 migraine days per month. Production loss represented the main part of the costs, approximately 80%. The average loss in QALYs per year also increased with the monthly number of migraine days (p = 0.023). Migraine leads to significant societal costs and loss of quality of life. There appears to be an unmet need and a potential for both cost savings and QoL benefits connected with a reduction in the number of migraine days.


Oligomerization is a specific requirement for apical sorting of glycosyl-phosphatidylinositol-anchored proteins but not for non-raft-associated apical proteins.
Protein apical sorting in polarized epithelial cells is mediated by two different mechanisms, raft dependent and raft independent. In Madin-Darby canine kidney (MDCK) cells, an essential step for apical sorting of glycosyl-phosphatidylinositol (GPI)-anchored proteins (GPI-APs) is their coalescence into high-molecular-weight (HMW) oligomers. Here we show that this mechanism is also functional in Fischer rat thyroid cells, which possess a different sorting phenotype compared with MDCK cells. We demonstrate that, as in MDCK cells, both apical and basolateral GPI-APs associate with detergent-resistant microdomains, but that only the apical proteins are able to oligomerize into HMW complexes during their passage through the medial Golgi. We also show that oligomerization is a specific requirement for apical sorting of GPI-APs and is not used by transmembrane, non-raft-associated apical proteins.


The role of scene summary statistics in object recognition.
Objects that are semantically related to the visual scene context are typically better recognized than unrelated objects. While context effects on object recognition are well studied, the question which particular visual information of an object's surroundings modulates its semantic processing is still unresolved. Typically, one would expect contextual influences to arise from high-level, semantic components of a scene but what if even low-level features could modulate object processing? Here, we generated seemingly meaningless textures of real-world scenes, which preserved similar summary statistics but discarded spatial layout information. In Experiment 1, participants categorized such textures better than colour controls that lacked higher-order scene statistics while original scenes resulted in the highest performance. In Experiment 2, participants recognized briefly presented consistent objects on scenes significantly better than inconsistent objects, whereas on textures, consistent objects were recognized only slightly more accurately. In Experiment 3, we recorded event-related potentials and observed a pronounced mid-central negativity in the N300/N400 time windows for inconsistent relative to consistent objects on scenes. Critically, inconsistent objects on textures also triggered N300/N400 effects with a comparable time course, though less pronounced. Our results suggest that a scene's low-level features contribute to the effective processing of objects in complex real-world environments.


Dissociable medial temporal lobe contributions to social memory.
Medial temporal lobe structures such as the hippocampus have been shown to play a critical role in mnemonic processes, with additional recruitment of the amygdala when memories contain emotional content. Thus far, studies that have examined the relationship between amygdala activity and memory have typically relied on emotional content of the kind that is rarely encountered in day-to-day interactions. The present event-related functional magnetic resonance imaging study investigates whether amygdala activity supports emotional memory during the more subtle social interactions that punctuate everyday life. Across four training sessions, subjects learned common first names for unfamiliar faces in the presence or absence of additional contextual information that was positive, negative, and neutral in valence (e.g., "Emily helps the homeless," "Bob is a deadbeat dad," "Eric likes carrots"). During scanning, subjects performed a yes/no recognition memory test on studied and novel faces. Results revealed a functional dissociation within the medial temporal lobe. Whereas a region within the right hippocampus responded strongly to all faces that had been paired with a description, regardless of its valence, activity in the right amygdala was uniquely sensitive to faces that had been previously associated with emotional descriptions (negative and positive > neutral). This pattern of activity in the amygdala was preserved even when the emotional contexts associated with faces could not be explicitly retrieved, suggesting a role for the amygdala in providing a nonspecific arousal indicator in response to viewing individuals with emotionally colored pasts.


Single cell nanoparticle tracking to model cell cycle dynamics and compartmental inheritance.
Single cell encoding with quantum dots as live cell optical tracers for deriving proliferation parameters has been developed using modelling to investigate cell cycle and proliferative outputs of human osteosarcoma cells undergoing mitotic bypass and endocycle routing. A computer-based simulation of the evolving cell population provides information on the dilution and segregation of nanoparticle dose cell by cell division and allows quantitative assessment of patterns of division, at both single cell and including whole population level cell cycle routing, with no a-priori knowledge of the population proliferation potential. The output therefore provides a unique mitotic distribution function that represents a convolution of cell cycle kinetics (cell division) and the partitioning coefficient for the labelled cell compartment (daughter-daughter inheritance or lineage asymmetry). The current study has shown that the cellular quantum dot fluorescence reduced over time as the particles were diluted by the process of cell division and had the properties of a non-random highly asymmetric event. Asymmetric nanoparticle segregation in the endosomal compartment has major implications on cell-fate determining signaling pathways and could lead to an understanding of the origins of unique proliferation and drug-resistance characteristics within a tumour cell lineage.


Vitamin supplementation for preventing miscarriage.
Miscarriage is a common complication of pregnancy that can be caused by a wide range of factors. Poor dietary intake of vitamins has been associated with an increased risk of miscarriage, therefore supplementing women with vitamins either prior to or in early pregnancy may help prevent miscarriage. The objectives of this review are to determine the effectiveness and safety of any vitamin supplementation, on the risk of spontaneous miscarriage, maternal adverse outcomes and fetal and infant adverse outcomes. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (21 June 2010). All randomised and quasi-randomised trials comparing one or more vitamins with either placebo, other vitamins, no vitamins or other interventions, prior to conception, periconceptionally or in early pregnancy (less than 20 weeks' gestation). At least two review authors independently assessed trials for inclusion, extracted data and assessed trial quality. We identified 28 trials assessing supplementation with any vitamin(s) starting prior to 20 weeks' gestation and reporting at least one primary outcome that was eligible for the review. Overall, the included trials involved 96,674 women and 98,267 pregnancies. Three trials were cluster randomised and combined contributed data for 62,669 women and 64,210 pregnancies in total. No significant differences were seen between women taking any vitamins compared with controls for total fetal loss (relative risk (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.14), early or late miscarriage (RR 1.09, 95% CI 0.95 to 1.25) or stillbirth (RR 0.86, 95% CI 0.65 to 1.13) and most of the other primary outcomes, using fixed-effect models. Compared with controls, women given any type of vitamin(s) pre or peri-conception were more likely to have a multiple pregnancy (RR 1.38, 95% CI 1.12 to 1.70, three trials, 20,986 women). Taking any vitamin supplements prior to pregnancy or in early pregnancy does not prevent women experiencing miscarriage or stillbirth. However, women taking vitamin supplements may be more likely to have a multiple pregnancy. There is insufficient evidence to examine the effects of different combinations of vitamins on miscarriage, stillbirth or other maternal and infant outcomes.


The emergence of the vertical birth in Ecuador: an analysis of agenda setting and policy windows for intercultural health.
Maternal mortality continues to claim the lives of thousands of women in Latin America despite the availability of effective treatments to avert maternal death. In the past, efforts to acknowledge cultural diversity in birth practices had not been clearly integrated into policy. However, in Otavalo (Ecuador) a local hospital pioneered the implementation of the 'Vertical Birth'-a practical manifestation of an intercultural health policy aimed at increasing indigenous women's access to maternity care. Drawing on agenda-setting theory, this qualitative research explores how the vertical birth practice made it onto the local policy agenda and the processes that allowed actors to seize a window of opportunity allowing the vertical birth practice to emerge. Our results show that the processes that brought about the vertical birth practice took place over a prolonged period of time and resulted from the interplay between various factors. Firstly, a maternal health policy community involving indigenous actors played a key role in identifying maternal mortality as a policy problem, defining its causes and framing it as an indigenous rights issue. Secondly, previous initiatives to address maternal mortality provided a wealth of experience that gave these actors the knowledge and experience to formulate a feasible policy solution and consolidate support from powerful actors. Thirdly, the election of a new government that had incorporated the demands of the indigenous movement opened up a window of opportunity to push intercultural health policies such as the vertical birth. We conclude that the socioeconomic and political changes at both national and local level allowed the meaningful participation of indigenous actors that made a critical contribution to the emergence of the vertical birth practice. These findings can help us advance our knowledge of strategies to set the agenda for intercultural maternal health policy and inform future policy in similar settings. Our results also show that Kingdon's model was useful in explaining how the VB practice emerged but also that it needs modifications when applied to low and middle income countries.


Morinda citrifolia edible leaf extract enhanced immune response against lung cancer.
Lung cancer causes 1.4 million deaths annually. In the search for functional foods as complementary therapies against lung cancer, the immuno-stimulatory properties of the vegetable Morinda citrifolia leaves were investigated and compared with the anti-cancer drug erlotinib. Lung tumour-induced BALB/c mice were fed with 150 mg kg(-1) or 300 mg kg(-1) body weight of the leaf extract, or erlotinib (50 mg kg(-1) body-weight) for 21 days. The 300 mg kg(-1) body weight extract significantly (and dose-dependently) suppressed lung tumour growth; the extract worked more effectively than the 50 mg kg(-1) body weight erlotinib treatment. The extract significantly increased blood lymphocyte counts, and spleen tissue B cells, T cells and natural killer cells, and reduced the epidermal growth factor receptor (EGFR) which is a lung adenocarcinoma biomarker. The extract also suppressed the cyclooxygenase 2 (COX2) inflammatory markers, and enhanced the tumour suppressor gene (phosphatase and tensin homolog, PTEN). It inhibited tumour growth cellular gene (transformed mouse 3T3 cell double minute 2 (MDM2), V-raf-leukemia viral oncogene 1 (RAF1), and mechanistic target of rapamycin (MTOR)) mRNA expression in the tumours. The extract is rich in scopoletin and epicatechin, which are the main phenolic compounds. The 300 mg kg(-1)Morinda citrifolia leaf 50% ethanolic extract showed promising potential as a complementary therapeutic dietary supplement which was more effective than the 50 mg kg(-1) erlotinib in suppressing lung adenocarcinoma. Part of the mechanisms involved enhancing immune responses, suppressing proliferation and interfering with various tumour growth signalling pathways.


Population dynamics and associated factors of cereal aphids and armyworms under global change.
Studying the impacts of global change, which comprises largely climate and landscape changes, on agricultural pests is crucial for developing sustainable pest management. This research is focused on understanding the factors associated with population dynamics of cereal aphids and armyworms feeding on wheat in Henan province in China from 1987 to 2010. Association between changes in climate (temperature, precipitation, and relative humidity) and agricultural characteristics (wheat proportion, crop diversity, fertilizer input, and wheat yield per unit area) and damage from cereal aphids and armyworms were examined. Cereal aphid damage has been rising, while armyworm damage had no obvious trends, but with strong year-to-year fluctuations. The analysis indicates that the factors most strongly associated with the population dynamics of cereal aphids are fertilizer input and mean temperature in February, while the population dynamics of armyworms is significantly related to precipitation in May. By comparing the characteristics of these two agricultural pests, we identify possible reasons for the disparity between their associated factors, which are related to the differences in their foraging behaviour, host range, migration capacity, and life history. These results may contribute to developing ecologically based pest management for cereal aphids and armyworms under global change.


Infection of New- and Old-World Aedes albopictus (Diptera: Culicidae) by the intracellular parasite Wolbachia: implications for host mitochondrial DNA evolution.
Wolbachia are cytoplasmically inherited, endosymbiotic bacteria known to infect a wide variety of arthropods. Polymerase chain reaction (PCR) amplification of the Wolbachia surface protein (wsp) gene was used to assay the infection of geographically disparate populations of Aedes albopictus (Skuse) by Wolbachia. Nine North American, four South American, one Hawaiian, and four Old World populations of A. albopictus were all doubly infected with both the wAlbA and wAlbB strains of Wolbachia. A 365-bp region of the wAlbA wsp gene was sequenced from seven geographically disparate host populations, and all sequences were identical. Similarly, a 474-bp region of the wAlbB wsp gene was sequenced from the same populations, and all sequences were identical. These results suggest a role for Wolbachia infection in causing the previously established pattern of low mitochondrial DNA variability, but average nuclear gene diversity, within and among populations of A. albopictus.


Genomics of chromophobe renal cell carcinoma: implications from a rare tumor for pan-cancer studies.
Chromophobe Renal Cell Carcinoma (ChRCC) is a rare subtype of the renal cell carcinomas, a heterogenous group of cancers arising from the nephron. Recently, The Cancer Genome Atlas (TCGA) profiled this understudied disease using multiple data platforms, including whole exome sequencing, whole genome sequencing (WGS), and mitochondrial DNA (mtDNA) sequencing. The insights gained from this study would have implications for other types of kidney cancer as well as for cancer biology in general. Global molecular patterns in ChRCC provided clues as to this cancer's cell of origin, which is distinct from that of the other renal cell carcinomas, illustrating an approach that might be applied towards elucidating the cell of origin of other cancer types. MtDNA sequencing revealed loss-of-function mutations in NADH dehydrogenase subunits, highlighting the role of deregulated metabolism in this and other cancers. Analysis of WGS data led to the discovery of recurrent genomic rearrangements involving TERT promoter region, which were associated with very high expression levels of TERT, pointing to a potential mechanism for TERT deregulation that might be found in other cancers. WGS data, generated by large scale efforts such as TCGA and the International Cancer Genomics Consortium (ICGC), could be more extensively mined across various cancer types, to uncover structural variants, mtDNA mutations, themes of tumor metabolic properties, as well as noncoding point mutations. TCGA's data on ChRCC should continue to serve as a resource for future pan-cancer as well as kidney cancer studies, and highlight the value of investigations into rare tumor types to globally inform principals of cancer biology.


Temporal order judgments activate temporal parietal junction.
Perceptual temporal order judgments require an individual to determine the relative timing of two spatially separate events. Here we reveal the brain regions involved with this task. We had participants observe perceptually identical visual stimuli while conducting two different tasks: discriminating temporal order or discriminating spatial properties. By contrasting the functional magnetic resonance imaging signals during these tasks, we were able to isolate regions specifically engaged by each task. Participants observed two briefly presented rectangles. In one task, participants were instructed to report which appeared first, and, in the other, they were requested to report which rectangle was squarer. A potential confound of this study is that the temporal order judgment (TOJ) task required processing of brief events (onsets), whereas the shape task did not require temporal selectivity. To address this, we conducted a second study in which both tasks required discriminating brief events concurrent with the object onsets. The stimuli were similar to the first experiment, except a gray line was briefly superimposed on each rectangle at onset. Participants reported either which rectangle appeared first (TOJ) or which rectangle had a slightly wider gray line (shape). The first study found that the TOJ task resulted in greater bilateral activation of the temporal parietal junction (TPJ). The second revealed TOJ activation in the TPJ of the left hemisphere. This suggests that TPJ activation increases when we need to temporally sequence information. This finding supports the notion that the TPJ may be a crucial component of the "when" pathway.


An Assessment of How Nurse Practitioners Create Access to Primary Care in Canadian Residential Long-Term Care Settings.
The aim of this paper is to explore the role and activities of nurse practitioners (NPs) working in long-term care (LTC) to understand concepts of access to primary care for residents. Utilizing the "FIT" framework developed by Penchanksy and Thomas, we used a directed content analysis method to analyze data from a pan-Canadian study of NPs in LTC. Individual and focus group interviews were conducted at four sites in western, central and eastern regions of Canada with 143 participants, including NPs, RNs, regulated and unregulated nursing staff, allied health professionals, physicians, administrators and directors and residents and family members. Participants emphasized how the availability and accessibility of the NP had an impact on access to primary and urgent care for residents. Understanding more about how NPs affect access in Canadian LTC will be valuable for nursing practice and healthcare planning and policy and may assist other countries in planning for the introduction of NPs in LTC settings to increase access to primary care.


Social-Ecological Examination of Non-Consensual Sexting Perpetration among U.S. Adolescents.
Adolescent sexting is a serious public health concern and is associated with adverse psychosocial outcomes, including depression, anxiety, low self-esteem, declining academic performance, and health problems. Effective prevention of sexting requires a comprehensive and deep understanding of the multiple contexts whereby sexting is likely to occur. The present study explores individual and contextual risk and protective factors that are associated with sexting behavior among a large sample of adolescents. Participants were high school students in midwestern U.S. (N = 2501; LGB n = 309, 76.4% female; non-LGB n = 2192, 47.4% female) who completed self-report measures of sexting and risk (e.g., pornography exposure, impulsivity) and protective (e.g., social support) factors. Path analysis models were conducted with the sexting outcome for groups of LGB and non-LGB students. Among LGB students, results indicated a significant association between sexting and parental monitoring (b = -0.08, p < 0.01); pornography exposure (b = 0.13, p < 0.05); dating partners (b = 0.01, p < 0.01); bullying perpetration (b = 0.17, p < 0.001); and delinquency (b = 0.13; p < 0.001). Among non-LGB students, significant associations were found between sexting and alcohol/substance use (b = 0.05, p < 0.001); bullying (b = 0.08, p < 0.001); and delinquency (b = 0.06, p < 0.001). Moderation analyses suggest that parental monitoring may have a buffering effect between sexting and several risk factors. Recommendations for practitioners include considering the protective factors of sexting perpetration and encouraging appropriate levels of parental monitoring and the continued importance of bullying and alcohol and drug prevention programming to decrease risk factors of sexting perpetration.


Effects of electrobrightening on the fit surface of cobalt-chromium RPD frameworks.
The purpose of this study was to compare 3 different electrobrightening techniques and 3 electrolytic solutions in their effects upon the fit surface of cast cobalt-chromium frameworks. Fifty cast cobalt-chromium frameworks, which were subsequently divided into batches of 10, were prepared according to a standard protocol. Three electrobrightening techniques were tested initially using a single brand of electrolyte (Croform) and a batch of 10 frameworks per technique. The loss of metal by weight was determined from the fit surface of each casting. The least corrosive technique of these 3 was used again with 2 other brands of electrolyte (Nobilium and E501) in a repetition of the protocol. The fit surfaces of 8 random samples cut from each batch of electrobrightened castings were viewed by scanning electron microscope (SEM). Statistical analysis applying a one-way analysis of variance and Bonferroni's multiple comparison of means test demonstrated that one immersion of the framework for 10 minutes at 1 amp when used in conjunction with Nobilium electrolyte removed the least metal (P = 0.001). The SEM study suggested that the Nobilium electrolyte also produced the smoothest surface. Electrobrightening techniques affect the amount of metal removed, and the electrolytic solution used influences the resultant surface.


Infection and maturation of monocyte-derived human dendritic cells by human respiratory syncytial virus, human metapneumovirus, and human parainfluenza virus type 3.
Human respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), and human parainfluenza virus type 3 (HPIV3) are common, important respiratory pathogens, but HRSV has a substantially greater impact with regard to acute disease, long-term effects on airway function, and frequency of re-infection. It has been reported to strongly interfere with the functioning of dendritic cells (DC). We compared HRSV to HMPV and HPIV3 with regard to their effects on human monocyte-derived immature DC (IDC). Side-by-side analysis distinguished between common effects versus those specific to individual viruses. The use of GFP-expressing viruses yielded clear identification of robustly infected cells and provided the means to distinguish between direct effects of robust viral gene expression versus bystander effects. All three viruses infected inefficiently based on GFP expression, with considerable donor-to donor-variability. The GFP-negative cells exhibited low, abortive levels of viral RNA synthesis. The three viruses induced low-to-moderate levels of DC maturation and cytokine/chemokine responses, increasing slightly in the order HRSV, HMPV, and HPIV3. Infection at the individual cell level was relatively benign, such that in general GFP-positive cells were neither more nor less able to mature compared to GFP-negative bystanders, and cells were responsive to a secondary treatment with lipopolysaccharide, indicating that the ability to mature was not impaired. However, there was a single exception, namely that HPIV3 down-regulated CD38 expression at the RNA level. Maturation by these viruses was anti-apoptotic. Inefficient infection of IDC and sub-optimal maturation might result in reduced immune responses, but these effects would be common to all three viruses rather than specific to HRSV.


White paper by the Society for CSF Analysis and Clinical Neurochemistry: Overcoming barriers in biomarker development and clinical translation.
Body fluid biomarkers have great potential for different clinical purposes, including diagnosis, prognosis, patient stratification and treatment effect monitoring. This is exemplified by current use of several excellent biomarkers, such as the Alzheimer's disease cerebrospinal fluid (CSF) biomarkers, anti-neuromyelitis optica antibodies and blood neurofilament light. We still, however, have a strong need for additional biomarkers and several gaps in their development and implementation should be filled. Examples of such gaps are i) limited knowledge of the causes of neurological diseases, and thus hypotheses about the best biomarkers to detect subclinical stages of these diseases; ii) the limited success translating discoveries obtained by e.g. initial mass spectrometry proteomic low-throughput studies into immunoassays for widespread clinical implementation; iii) lack of interaction among all stakeholders to optimise and adapt study designs throughout the biomarker development process to medical needs, which may change during the long period needed for biomarker development.The Society for CSF Analysis and Clinical Neurochemistry (established in 2015) has been founded as a concerted follow-up of large standardisation projects, including BIOMARKAPD and SOPHIA, and the BioMS-consortium.The main aims of the CSF society are to exchange high level international scientific experience, to facilitate the incorporation of CSF diagnostics into clinical practice and to give advice on inclusion of CSF analysis into clinical guidelines. The society has a broad scope, as its vision is that the gaps in development and implementation of biomarkers are shared among almost all neurological diseases and thus they can benefit from the activities of the society.


Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS.
Natural killer (NK) cells provide defense in the early stages of the innate immune response against viral infections by producing cytokines and causing cytotoxicity. The killer immunoglobulin-like receptors (KIRs) on NK cells regulate the inhibition and activation of NK-cell responses through recognition of human leukocyte antigen (HLA) class I molecules on target cells KIR and HLA loci are both highly polymorphic, and some HLA class I products bind and trigger cell-surface receptors specified by KIR genes. Here we report that the activating KIR allele KIR3DS1, in combination with HLA-B alleles that encode molecules with isoleucine at position 80 (HLA-B Bw4-80Ile), is associated with delayed progression to AIDS in individuals infected with human immunodeficiency virus type 1 (HIV-1). In the absence of KIR3DS1, the HLA-B Bw4-80Ile allele was not associated with any of the AIDS outcomes measured. By contrast, in the absence of HLA-B Bw4-80Ile alleles, KIR3DS1 was significantly associated with more rapid progression to AIDS. These observations are strongly suggestive of a model involving an epistatic interaction between the two loci. The strongest synergistic effect of these loci was on progression to depletion of CD4(+) T cells, which suggests that a protective response of NK cells involving KIR3DS1 and its HLA class I ligands begins soon after HIV-1 infection.