The structure of perfectionism: a twin study.
Perfectionism may be a premorbid risk factor for eating disorders. Evidence of familial transmission suggests features of perfectionism may be genetically determined. This study examines the structure of perfectionism using classical twin design models. Independent (IP) and common (CP) pathway models are used to investigate the extent to which genetic and environmental factors can help to identify and differentiate three behavioral domains of perfectionism as measured by a shortened version of the Multidimensional Perfectionism Scale (MPS) [Frost et al. (1990). Cognit. Ther. Res. 14: 449-468]. Three of the original subscales were included: Personal standards (PS), Doubts about actions (DA), Concern over mistakes (CM). We studied a sample of 1022 paired and unpaired female twins from the Mid-Atlantic Twin Registry. MZ correlations were consistently higher than DZ twin correlations for all three composite subscales. The multivariate independent pathway model provided a better fit to the twin correlations then did the more parsimonious common pathway model suggesting the pattern of familial resemblance for the three subscales is not well characterized by a unidimensional perfectionism factor. CM phenotypic variance was completely accounted for by common heritability influences in both the IP and CP models. Based on the IP model results, there was evidence that PS and CM but not DA shared some common genetic effects, with DA and CM sharing some common environmental factors. These multivariate twin modeling results support conceptualizations of perfectionism as a multidimensional construct. The biometric structural results for the three subscales examined here suggest CM is the core feature of Perfectionism with DA and PS serving as indicators of CM. Although not the best fitting model, the common pathway model estimated this behavioral domain to be isomorphic with the construct of perfectionism. The better fitting independent pathway model provided evidence of non-trivial differences in the pattern of heritability for CM, DA, and PS.


Human bronchial epithelial cells exposed in vitro to cigarette smoke at the air-liquid interface resemble bronchial epithelium from human smokers.
Organotypic culture of human primary bronchial epithelial cells is a useful in vitro system to study normal biological processes and lung disease mechanisms, to develop new therapies, and to assess the biological perturbations induced by environmental pollutants. Herein, we investigate whether the perturbations induced by cigarette smoke (CS) and observed in the epithelium of smokers' airways are reproducible in this in vitro system (AIR-100 tissue), which has been shown to recapitulate most of the characteristics of the human bronchial epithelium. Human AIR-100 tissues were exposed to mainstream CS for 7, 14, 21, or 28 min at the air-liquid interface, and we investigated various biological endpoints [e.g., gene expression and microRNA profiles, matrix metalloproteinase 1 (MMP-1) release] at multiple postexposure time points (0.5, 2, 4, 24, 48 h). By performing a Gene Set Enrichment Analysis, we observed a significant enrichment of human smokers' bronchial epithelium gene signatures derived from different public transcriptomics datasets in CS-exposed AIR-100 tissue. Comparison of in vitro microRNA profiles with microRNA data from healthy smokers highlighted various highly translatable microRNAs associated with inflammation or with cell cycle processes that are known to be perturbed by CS in lung tissue. We also found a dose-dependent increase of MMP-1 release by AIR-100 tissue 48 h after CS exposure in agreement with the known effect of CS on this collagenase expression in smokers' tissues. In conclusion, a similar biological perturbation than the one observed in vivo in smokers' airway epithelium could be induced after a single CS exposure of a human organotypic bronchial epithelium-like tissue culture.


Nursing support for family members of critically ill adults.
Researchers have identified the needs of family members of critically ill adults, explored their experiences, and investigated interventions. To address a gap in the theoretical knowledge about how nurses help these individuals, the authors developed a grounded theory of nursing support from the perspective of family members. Results indicated that family members were initiated into a cycle of Work to meet perceived responsibilities to Get Through the experience. Supportive nurses engaged in the process of Lightening Our Load to mitigate the negative effects of the critical care experience on family members by Engaging With Us, Sustaining Us, and Disengaging From Us. No previous research has yet identified the Work of these family members, the steps they take to gain nurses' respect, and the significance to them of nurses' Welcoming us and Saying goodbye. This theory extends the understanding of nursing support beyond current knowledge of family needs, caring, comfort, supportive care, and social support.


Antifungal activity, main active components and mechanism of Curcuma longa extract against Fusarium graminearum.
Curcuma longa possesses powerful antifungal activity, as demonstrated in many studies. In this study, the antifungal spectrum of Curcuma longa alcohol extract was determined, and the resulting EC50 values (mg/mL) of its extract on eleven fungi, including Fusarium graminearum, Fusarium chlamydosporum, Alternaria alternate, Fusarium tricinctum, Sclerotinia sclerotiorum, Botrytis cinerea, Fusarium culmorum, Rhizopus oryzae, Cladosporium cladosporioides, Fusarium oxysporum and Colletotrichum higginsianum, were 0.1088, 0.1742, 0.1888, 0.2547, 0.3135, 0.3825, 0.4229, 1.2086, 4.5176, 3.8833 and 5.0183, respectively. Among them, F. graminearum was selected to determine the inhibitory effects of the compounds (including curdione, isocurcumenol, curcumenol, curzerene, β-elemene, curcumin, germacrone and curcumol) derived from Curcuma longa. In addition, the antifungal activities of curdione, curcumenol, curzerene, curcumol and isocurcumenol and the synergies of the complexes of curdione and seven other chemicals were investigated. Differential proteomics of F. graminearum was also compared, and at least 2021 reproducible protein spots were identified. Among these spots, 46 were classified as differentially expressed proteins, and these proteins are involved in energy metabolism, tRNA synthesis and glucose metabolism. Furthermore, several fungal physiological differences were also analysed. The antifungal effect included fungal cell membrane disruption and inhibition of ergosterol synthesis, respiration, succinate dehydrogenase (SDH) and NADH oxidase.


Improving the demand for birth registration: a discrete choice experiment in Ethiopia.
Birth registration remains limited in most low and middle-income countries. We investigated which characteristics of birth registration facilities might determine caregivers' decisions to register children in Ethiopia. We conducted a discrete choice experiment in randomly selected households in Addis Ababa and the Southern Nations, Nationalities, and People's Region. We interviewed caregivers of children 0-5 years old. We asked participants to make eight choices between pairs of hypothetical registration facilities. These facilities were characterised by six attributes selected through a literature review and consultations with local stakeholders. Levels of these attributes were assigned at random using a fractional design. We analysed the choice data using mixed logit models that account for heterogeneity in preferences across respondents. We calculated respondents' willingness to pay to access registration facilities with specific attributes. We analysed all data separately by place of residence (urban vs rural). Seven hundred and five respondents made 5614 choices. They exhibited preferences for registration facilities that charged lower fees for birth certificates, that required shorter waiting time to complete procedures and that were located closer to their residence. Respondents preferred registration facilities that were open on weekends, and where they could complete procedures in a single visit. In urban areas, respondents also favoured registration facilities that remained open for extended hours on weekdays, and where the presence of only one of the parents was required for registration. There was significant heterogeneity between respondents in the utility derived from several attributes of registration facilities. Willingness to pay for access to registration facilities with particular attributes was larger in urban than rural areas. In these regions of Ethiopia, changes to the operating schedule of registration facilities and to application procedures might help improve registration rates. Discrete choice experiments can help orient initiatives aimed at improving birth registration.


Covariation in frequencies of substitution, deletion, transposition, and recombination during eutherian evolution.
Six measures of evolutionary change in the human genome were studied, three derived from the aligned human and mouse genomes in conjunction with the Mouse Genome Sequencing Consortium, consisting of (1) nucleotide substitution per fourfold degenerate site in coding regions, (2) nucleotide substitution per site in relics of transposable elements active only before the human-mouse speciation, and (3) the nonaligning fraction of human DNA that is nonrepetitive or in ancestral repeats; and three derived from human genome data alone, consisting of (4) SNP density, (5) frequency of insertion of transposable elements, and (6) rate of recombination. Features 1 and 2 are measures of nucleotide substitutions at two classes of "neutral" sites, whereas 4 is a measure of recent mutations. Feature 3 is a measure dominated by deletions in mouse, whereas 5 represents insertions in human. It was found that all six vary significantly in megabase-sized regions genome-wide, and many vary together. This indicates that some regions of a genome change slowly by all processes that alter DNA, and others change faster. Regional variation in all processes is correlated with, but not completely accounted for, by GC content in human and the difference between GC content in human and mouse.


Insulin can enhance GLUT4 gene expression in 3T3-F442A cells and this effect is mimicked by vanadate but counteracted by cAMP and high glucose--potential implications for insulin resistance.
It is well-established that high levels of cAMP or glucose can produce insulin resistance. The aim of this study was to characterize the interaction between these agents and insulin with respect to adipose tissue/muscle glucose transporter isoform (glucose transporter 4, GLUT4) gene regulation in cultured 3T3-F442A adipocytes and to further elucidate the GLUT4-related mechanisms in insulin resistance. Insulin (10(4) microU/ml) treatment for 16 h clearly increased GLUT4 mRNA level in cells cultured in medium containing 5.6 mM glucose but not in cells cultured in medium with high glucose (25 mM). 8-Bromo-cAMP (1 or 4 mM) or N(6)-monobutyryl cAMP, a hydrolyzable and a non-hydrolyzable cAMP analog, respectively, markedly decreased the GLUT4 mRNA level irrespective of glucose concentrations. In addition, these cAMP analogs also inhibited the upregulating effect of insulin on GLUT4 mRNA level. Interestingly, the tyrosine phosphatase inhibitor vanadate (1-50 microM) clearly increased GLUT4 mRNA level in a time- and concentration-dependent manner. Furthermore, cAMP-induced inhibition of the insulin effect was also prevented by vanadate. In parallel to the effects on GLUT4 gene expression, both insulin, vanadate and cAMP produced similar changes in cellular GLUT4 protein content and cAMP impaired the effect of insulin to stimulate (14)C-deoxyglucose uptake. In contrast, insulin, vanadate or cAMP did not alter insulin receptor (IR) mRNA or the cellular content of IR protein. (1) Both insulin and vanadate elicit a stimulating effect on GLUT4 gene expression in 3T3-F442A cells, but a prerequisite is that the surrounding glucose concentration is low. (2) Cyclic AMP impairs the insulin effect on GLUT4 gene expression, but this is prevented by vanadate, probably by enhancing the tyrosine phosphorylation of signalling peptides and/or transcription factors. (3) IR gene and protein expression is not altered by insulin, vanadate or cAMP in this cell type. (4) The changes in GLUT4 gene expression produced by cAMP or vanadate are accompanied by similar alterations in GLUT4 protein expression and glucose uptake, suggesting a role of GLUT4 gene expression for the long-term regulation of cellular insulin action on glucose transport.


Assessment of an Antibody-in-Lymphocyte Supernatant Assay for the Etiological Diagnosis of Pneumococcal Pneumonia in Children.
New diagnostic tests for the etiology of childhood pneumonia are needed. We evaluated the antibody-in-lymphocyte supernatant (ALS) assay to detect immunoglobulin (Ig) G secretion from ex vivo peripheral blood mononuclear cell (PBMC) culture, as a potential diagnostic test for pneumococcal pneumonia. We enrolled 348 children with pneumonia admitted to Patan Hospital, Kathmandu, Nepal between December 2015 and September 2016. PBMCs sampled from participants were incubated for 48 h before harvesting of cell culture supernatant (ALS). We used a fluorescence-based multiplexed immunoassay to measure the concentration of IgG in ALS against five conserved pneumococcal protein antigens. Of children with pneumonia, 68 had a confirmed etiological diagnosis: 12 children had pneumococcal pneumonia (defined as blood or pleural fluid culture-confirmed; or plasma CRP concentration ≥60 mg/l and nasopharyngeal carriage of serotype 1 pneumococci), and 56 children had non-pneumococcal pneumonia. Children with non-pneumococcal pneumonia had either a bacterial pathogen isolated from blood (six children); or C-reactive protein <60 mg/l, absence of radiographic consolidation and detection of a pathogenic virus by multiplex PCR (respiratory syncytial virus, influenza viruses, or parainfluenza viruses; 23 children). Concentrations of ALS IgG to all five pneumococcal proteins were significantly higher in children with pneumococcal pneumonia than in children with non-pneumococcal pneumonia. The concentration of IgG in ALS to the best-performing antigen discriminated between children with pneumococcal and non-pneumococcal pneumonia with a sensitivity of 1.0 (95% CI 0.73-1.0), specificity of 0.66 (95% CI 0.52-0.78) and area under the receiver-operating characteristic curve (AUROCC) 0.85 (95% CI 0.75-0.94). Children with pneumococcal pneumonia were older than children with non-pneumococcal pneumonia (median 5.6 and 2.0 years, respectively, p < 0.001). When the analysis was limited to children ≥2 years of age, assay of IgG ALS to pneumococcal proteins was unable to discriminate between children with pneumococcal pneumonia and non-pneumococcal pneumonia (AUROCC 0.67, 95% CI 0.47-0.88). This method detected spontaneous secretion of IgG to pneumococcal protein antigens from cultured PBMCs. However, when stratified by age group, assay of IgG in ALS to pneumococcal proteins showed limited utility as a test to discriminate between pneumococcal and non-pneumococcal pneumonia in children.


Tailoring supramolecular nanotubes by bile salt based surfactant mixtures.
An approach for tailoring self-assembled tubular structures is described. By controlling the relative composition of a two-component surfactant mixture comprising the natural bile salt lithocholate and its bolamphiphilic derivative, it was possible to finely tune the nanotube cross-section of the mixed tubular aggregates that self-associated spontaneously in aqueous solution at pH 12. The diameter was found to vary up to 50% when the stoichiometric ratio of the two bile salts was changed. The tuning of supramolecular nanochannels with such remarkable precision is of significant interest for technological applications of these materials.


Theories of consciousness.
Recent years have seen a blossoming of theories about the biological and physical basis of consciousness. Good theories guide empirical research, allowing us to interpret data, develop new experimental techniques and expand our capacity to manipulate the phenomenon of interest. Indeed, it is only when couched in terms of a theory that empirical discoveries can ultimately deliver a satisfying understanding of a phenomenon. However, in the case of consciousness, it is unclear how current theories relate to each other, or whether they can be empirically distinguished. To clarify this complicated landscape, we review four prominent theoretical approaches to consciousness: higher-order theories, global workspace theories, re-entry and predictive processing theories and integrated information theory. We describe the key characteristics of each approach by identifying which aspects of consciousness they propose to explain, what their neurobiological commitments are and what empirical data are adduced in their support. We consider how some prominent empirical debates might distinguish among these theories, and we outline three ways in which theories need to be developed to deliver a mature regimen of theory-testing in the neuroscience of consciousness. There are good reasons to think that the iterative development, testing and comparison of theories of consciousness will lead to a deeper understanding of this most profound of mysteries.


The influence of a sustained multifaceted approach to improve antibiotic prescribing in Slovenia during the past decade: findings and implications.
Rising antibiotic resistance has become an increasing public health problem. There is a well-established correlation between antibiotic consumption and antimicrobial resistance. Consequently, measures to rationalize the prescribing of antibiotics should reduce the resistant strains. Following a 24% increase in antibiotic consumption at the end of the 1990s, multiple activities were designed and introduced by the Health Insurance Institute of Slovenia (ZZZS) and other organizations in Slovenia at the end of 1999. These activities reduced the antibiotic consumption by 18.7% by 2002. These measures have continued. To study changes in antibiotic utilization from 1995 to 2012 alongside the multiple interventions and their consequences, including changes in resistance patterns. This was a retrospective observational study involving all patients dispensed at least one ZZZS prescription for an antibiotic in Slovenia. Utilization was expressed in defined daily doses per thousand inhabitants per day. Multifaceted interventions were conducted over time involving all key stakeholder groups, that is, the Ministry of Health, ZZZS, physician groups and patients. These included comprehensive communication programs as well as prescribing restrictions for a number of antibiotics and classes. From 1999 to 2012, antibiotic consumption decreased by 2-9% per year, with an overall decrease of 31%. There were also appreciable structural changes. Overall antibiotic utilization and the utilization of 7 out of 10 antibiotics significantly decreased after multiple interventions. The resistance of Streptococcus pneumoniae to penicillin decreased in line with decreased utilization. However, its resistance to macrolides increased from 5.4 to 21% despite halving of its utilization. The resistance of Escherichia coli to fluoroquinolones doubled from 10 to 21% despite utilization decreasing by a third. Expenditures on antibiotics decreased by 53%. Multiple demand-side measures introduced following increased utilization significantly decreased subsequent antibiotic utilization and associated costs. However, there was variable impact on antibiotic resistance. Additional targeted activities are planned to further reduce antibiotic prescribing and resistance.


Indigenous research methodologies: decolonizing the Australian sports sciences.
To design a questionnaire that would determine an Indigenous individual's perceptions of the barriers and motivators to aerobic and anabolic exercise with a series of questions designed to elicit the factors that impact uptake and retention of regular physical activity. For this purpose, a questionnaire was designed to capture information relating to motivators and barriers, traditional physical activities, preferred exercise environments, exercise goals and levels of commitment to physical activity. This article does not report the results of the questionnaire itself but the preparation that was required in order to develop it. Indigenous standpoint theory. Participatory Action Research. A series of consultation meetings were arranged between the first author, a Noongar Aboriginal researcher, with a range of people from the same Noongar community as the author to discuss priorities and develop questions. The drafted questionnaire was shaped with continuous Noongar community feedback to ensure the language, length and appropriateness of questions. Questionnaire reliability was assessed using interclass correlation. Most questions had excellent internal consistency. A consensus was reached on the utility of the questionnaire. The personal contacts of the first author and nature of community involvement in the development of this questionnaire were helpful in assuring that it would be an acceptable tool for the Noongar community. The piloting of the questionnaire was also important in confirming its community acceptability. This article provides a model and suggestions for researching physical activity and exercise in a culturally safe manner.


Large genomic differences between Moraxella bovoculi isolates acquired from the eyes of cattle with infectious bovine keratoconjunctivitis versus the deep nasopharynx of asymptomatic cattle.
Moraxella bovoculi is a recently described bacterium that is associated with infectious bovine keratoconjunctivitis (IBK) or "pinkeye" in cattle. In this study, closed circularized genomes were generated for seven M. bovoculi isolates: three that originated from the eyes of clinical IBK bovine cases and four from the deep nasopharynx of asymptomatic cattle. Isolates that originated from the eyes of IBK cases profoundly differed from those that originated from the nasopharynx of asymptomatic cattle in genome structure, gene content and polymorphism diversity and consequently placed into two distinct phylogenetic groups. These results suggest that there are genetically distinct strains of M. bovoculi that may not associate with IBK.


Prefrontal Function Engaging in External-Focused Attention in 5- to 6-Month-Old Infants: A Suggestion for Default Mode Network.
The present study used functional near-infrared spectroscopy (fNIRS) to measure 5- to 6-month-old infants' hemodynamic response in the prefrontal cortex (PFC) to visual stimuli differing in saliency and social value. Nineteen Japanese 5- to 6-month-old infants watched video clips of Peek-a-Boo (social signal) performed by an anime character (AC) or a human, and hand movements without social signal performed by an AC. The PFC activity of infants was measured by 22-channel fNIRS, while behaviors including looking time were recorded simultaneously. NIRS data showed that infants' hemodynamic responses in the PFC generally decreased due to these stimuli, and the decrease was most prominent in the frontopolar (FP), covering medial PFC (MPFC), when infants were viewing Peek-a-Boo performed by an AC. Moreover, the decrease was more pronounced in the dorsolateral PFC (DLPFC) when infants were viewing Peek-a-Boo performed by an AC than by a human. Accordingly, behavioral data revealed significantly longer looking times when Peek-a-Boo was performed by an AC than by a human. No significant difference between Peek-a-Boo and non-Peek-a-Boo conditions was observed in either measure. These findings indicate that infants at this age may prefer stimuli with more salient features, which may be more effective in attracting their attentions. In conjunction with our previous findings on responses to self-name calling in infants of similar age, we hypothesize that the dynamic function of the MPFC and its vicinity (as part of default mode network (DMN): enhanced by self-focused stimuli, attenuated by externally focused stimuli), which is consistently observed in adults, may have already emerged in 5- to 6-month-old infants.


Plausibility and possible determinants of sudden "remissions" in borderline patients.
THIS STUDY documents dramatic improvements in patients with borderline personality disorder (BPD) and explores their possible determinants. From a sample of the 160 carefully diagnosed borderline patients on whom prospective follow-along data was collected, a subsample of 18 was identified whose DSM-IV criteria count fell to two or fewer during the course of the first 6 months of the study and retained that improvement for the next 6 months. Follow-along data including month-by-month ratings of BPD criteria; week-by-week ratings of Axis I disorders, medication changes, and life events were then used to establish concensus ratings on four hypothesized causes: Axis I remissions, situational change, misdiagnosis, and treatment effects. Follow-up data collected at 2 years was examined to see whether the improvements persisted. The results were that 18 BPD patients underwent dramatic improvements in the first 6 months. Only one had relapsed by 2 years. Though one was judged to have been misdiagnosed at baseline, the most important determinants were judged to be situational changes (n = 10) and remissions of co-occurring Axis I disorders (n = 7). In 10 patients treatment appeared to have facilitated these situational or Axis I resolutions. In conclusion, patients with BPD can make significant improvements that are rapid and of sufficient duration to be considered remissions. Determinants were identified that warrant further prospective evaluation.


Pathogenesis, clinical features, and neurological outcome of cerebral malaria.
Cerebral malaria is the most severe neurological complication of Plasmodium falciparum malaria. Even though this type of malaria is most common in children living in sub-Saharan Africa, it should be considered in anybody with impaired consciousness that has recently travelled in a malaria-endemic area. Cerebral malaria has few specific features, but there are differences in clinical presentation between African children and non-immune adults. Subsequent neurological impairments are also most common and severe in children. Sequestration of infected erythrocytes within cerebral blood vessels seems to be an essential component of the pathogenesis. However, other factors such as convulsions, acidosis, or hypoglycaemia can impair consciousness. In this review, we describe the clinical features and epidemiology of cerebral malaria. We highlight recent insights provided by ex-vivo work on sequestration and examination of pathological specimens. We also summarise recent studies of persisting neurocognitive impairments in children who survive cerebral malaria and suggest areas for further research.


The canalicular bile salt export pump BSEP (ABCB11) as a potential therapeutic target.
Bile formation is a key function of the liver and is driven by active secretion of bile salts and other organic compounds into the biliary tree. Bile salts represent the major organic constituent of bile. They are released with bile into the small intestine, where they are almost quantitatively reabsorbed and transported via the portal circulation back to the liver. In the liver, they are taken up into hepatocytes and secreted into bile. This cycling between the liver and the small intestine is called enterohepatic circulation of bile salts. Bile salts are secreted from hepatocytes into the bile by the bile salt export pump BSEP. This step constitutes the rate-limiting step of handling of bile salts in the liver and is the major driving force of the enterohepatic circulation of bile salts. Improper functioning of BSEP leads to an accumulation of bile salts within hepatocytes, where bile salts become cytotoxic. If persistent, accumulation of bile salts in hepatocytes will lead to liver disease. This review summarizes the essential concepts of bile formation and the current knowledge of mechanisms known to impair BSEP function. Finally, it sets the current therapeutic approaches for cholestatic liver disease into perspective to the pathophysiologic mechanisms of impaired BSEP function.


IL-22 signaling contributes to West Nile encephalitis pathogenesis.
The Th17 cytokine, IL-22, regulates host immune responses to extracellular pathogens. Whether IL-22 plays a role in viral infection, however, is poorly understood. We report here that Il22(-/-) mice were more resistant to lethal West Nile virus (WNV) encephalitis, but had similar viral loads in the periphery compared to wild type (WT) mice. Viral loads, leukocyte infiltrates, proinflammatory cytokines and apoptotic cells in the central nervous system (CNS) of Il22(-/-) mice were also strikingly reduced. Further examination showed that Cxcr2, a chemokine receptor that plays a non-redundant role in mediating neutrophil migration, was significantly reduced in Il22(-/-) compared to WT leukocytes. Expression of Cxcr2 ligands, cxcl1 and cxcl5, was lower in Il22(-/-) brains than wild type mice. Correspondingly, neutrophil migration from the blood into the brain was attenuated following lethal WNV infection of Il22(-/-) mice. Our results suggest that IL-22 signaling exacerbates lethal WNV encephalitis likely by promoting WNV neuroinvasion.


Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019.
Health care workers exposed to coronavirus disease 2019 (COVID-19) could be psychologically stressed. To assess the magnitude of mental health outcomes and associated factors among health care workers treating patients exposed to COVID-19 in China. This cross-sectional, survey-based, region-stratified study collected demographic data and mental health measurements from 1257 health care workers in 34 hospitals from January 29, 2020, to February 3, 2020, in China. Health care workers in hospitals equipped with fever clinics or wards for patients with COVID-19 were eligible. The degree of symptoms of depression, anxiety, insomnia, and distress was assessed by the Chinese versions of the 9-item Patient Health Questionnaire, the 7-item Generalized Anxiety Disorder scale, the 7-item Insomnia Severity Index, and the 22-item Impact of Event Scale-Revised, respectively. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes. A total of 1257 of 1830 contacted individuals completed the survey, with a participation rate of 68.7%. A total of 813 (64.7%) were aged 26 to 40 years, and 964 (76.7%) were women. Of all participants, 764 (60.8%) were nurses, and 493 (39.2%) were physicians; 760 (60.5%) worked in hospitals in Wuhan, and 522 (41.5%) were frontline health care workers. A considerable proportion of participants reported symptoms of depression (634 [50.4%]), anxiety (560 [44.6%]), insomnia (427 [34.0%]), and distress (899 [71.5%]). Nurses, women, frontline health care workers, and those working in Wuhan, China, reported more severe degrees of all measurements of mental health symptoms than other health care workers (eg, median [IQR] Patient Health Questionnaire scores among physicians vs nurses: 4.0 [1.0-7.0] vs 5.0 [2.0-8.0]; P = .007; median [interquartile range {IQR}] Generalized Anxiety Disorder scale scores among men vs women: 2.0 [0-6.0] vs 4.0 [1.0-7.0]; P < .001; median [IQR] Insomnia Severity Index scores among frontline vs second-line workers: 6.0 [2.0-11.0] vs 4.0 [1.0-8.0]; P < .001; median [IQR] Impact of Event Scale-Revised scores among those in Wuhan vs those in Hubei outside Wuhan and those outside Hubei: 21.0 [8.5-34.5] vs 18.0 [6.0-28.0] in Hubei outside Wuhan and 15.0 [4.0-26.0] outside Hubei; P < .001). Multivariable logistic regression analysis showed participants from outside Hubei province were associated with lower risk of experiencing symptoms of distress compared with those in Wuhan (odds ratio [OR], 0.62; 95% CI, 0.43-0.88; P = .008). Frontline health care workers engaged in direct diagnosis, treatment, and care of patients with COVID-19 were associated with a higher risk of symptoms of depression (OR, 1.52; 95% CI, 1.11-2.09; P = .01), anxiety (OR, 1.57; 95% CI, 1.22-2.02; P < .001), insomnia (OR, 2.97; 95% CI, 1.92-4.60; P < .001), and distress (OR, 1.60; 95% CI, 1.25-2.04; P < .001). In this survey of heath care workers in hospitals equipped with fever clinics or wards for patients with COVID-19 in Wuhan and other regions in China, participants reported experiencing psychological burden, especially nurses, women, those in Wuhan, and frontline health care workers directly engaged in the diagnosis, treatment, and care for patients with COVID-19.


Do differences in the administrative structure of populations confound comparisons of geographic health inequalities?
Geographical health inequalities are naturally described by the variation in health outcomes between areas (e.g. mortality rates). However, comparisons made between countries are hampered by our lack of understanding of the effect of the size of administrative units, and in particular the modifiable areal unit problem. Our objective was to assess how differences in geographic and administrative units used for disseminating data affect the description of health inequalities. Retrospective study of standard populations and deaths aggregated by administrative regions within 20 European countries, 1990-1991. Estimated populations and deaths in males aged 0-64 were in 5 year age bands. Poisson multilevel modelling was conducted of deaths as standardised mortality ratios. The variation between regions within countries was tested for relationships with the mean region population size and the unequal distribution of populations within each country measured using Gini coefficients. There is evidence that countries whose regions vary more in population size show greater variation and hence greater apparent inequalities in mortality counts. The Gini coefficient, measuring inequalities in population size, ranged from 0.1 to 0.5 between countries; an increase of 0.1 was accompanied by a 12-14% increase in the standard deviation of the mortality rates between regions within a country. Apparently differing health inequalities between two countries may be due to differences in geographical structure per se, rather than having any underlying epidemiological cause. Inequalities may be inherently greater in countries whose regions are more unequally populated.


Behavioral significance of motion direction causes anisotropic flash-lag, flash-drag, flash-repulsion, and movement-mislocalization effects.
Motion from periphery to central vision (foveopetal motion) causes a greater flash-lag effect than motion in the opposite direction (foveofugal motion). In order to examine the factors that contribute to the motion direction-based anisotropic flash-lag effect, we investigated the mislocalization of the flash caused by motion and the mislocalization of the moving object per se. We observed that for foveofugal motion, flashes were perceived shifted in the direction of motion but mislocalized in the opposite direction for foveopetal motion. Additionally the mislocalization of the moving object was larger in foveopetal motion than in foveofugal motion. Thus, both factors contribute to the anisotropic flash-lag effect. We interpret these findings in terms of greater behavioral significance of foveopetal motion in relation to foveofugal motion.


Assessment of the current status of playground safety in the midwestern region of Turkey: an effort to provide a safe environment for children.
This study aimed to identify and evaluate the degree of conformity to the playground standards and the level of compliance with current safety specifications of the playgrounds in the midwestern region of Turkey. An observational technique was used at a total of 57 public playgrounds. A playground safety control form was prepared based on the United States National Program for Playground Safety and the Consumer Product Safety Commission security standards, since there is no national law covering playground equipment and safety in Turkey. The study evaluated the surroundings of the playground, arrangement of equipment in the playground, and characteristics of the equipment. The percentage of playgrounds surveyed with inadequate or hard surfacing was 80.7%. Fifty-two percent of the equipment was found to be inappropriate. Equipment was higher than the recommended heights. The results of our study unfortunately point out that playgrounds for children do not meet many of the safety criteria.


Effect of insulin on fat metabolism during and after normal pregnancy.
Whereas development of resistance to the action of insulin on glucose metabolism during gestation has been recognized, it is presently not known whether there is also resistance to the action of insulin on lipid metabolism. We have, therefore, examined the effect of physiological hyperinsulinemia (during euglycemic-hyperinsulinemic clamping) on free fatty acid (FFA) turnover in seven nondiabetic overweight or obese women during and after pregnancy. Basal rates of FFA release, oxidation, and reesterification and basal plasma FFA concentrations were not significantly different from each other during the 2nd and 3rd trimester of pregnancy and postpartum. During euglycemic-hyperinsulinemic (approximately 500 pmol/l) clamping, however, lipolysis was significantly less inhibited during the 3rd trimester (from 7.0 +/- 0.9 to 4.9 +/- 0.9 micromol x kg(-1) x min(-1), -30%) than during the 2nd trimester (from 8.4 +/- 0.6 to 4.1 +/- 0.9 micromol x kg(-1) x min(-1), -51%) and postpartum (from 8.5 +/- 1.1 to 4.2 +/- 0.6 micromol x kg(-1) x min(-1), -51%). Similarly, fat oxidation was not inhibited at all (from 3.5 +/- 0.3 to 3.8 +/- 0.5 micromol x kg(-1) x min(-1)) during the 3rd trimester but was suppressed by 51% (from 3.9 +/- 0.2 to 1.9 +/- 0.3 micromol x kg(-1) x min(-1)) during the 2nd trimester and by 38% (from 2.6 +/- 0.7 to 1.6 +/- 0.5 micromol x kg(-1) x min(-1) postpartum. These data demonstrated that resistance to the action of insulin on lipolysis and on fat oxidation developed during late gestation and disappeared postpartum.


Potential epigenetic biomarkers of obesity-related insulin resistance in human whole-blood.
Obesity can increase the risk of complex metabolic diseases, including insulin resistance. Moreover, obesity can be caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are not well defined. Therefore, the identification of novel epigenetic biomarkers of obesity allows for a more complete understanding of the disease and its underlying insulin resistance. The aim of our study was to identify DNA methylation changes in whole-blood that were strongly associated with obesity and insulin resistance. Whole-blood was obtained from lean (n = 10; BMI = 23.6 ± 0.7 kg/m2) and obese (n = 10; BMI = 34.4 ± 1.3 kg/m2) participants in combination with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing on genomic DNA isolated from the blood. We identified 49 differentially methylated cytosines (DMCs; q < 0.05) that were altered in obese compared with lean participants. We identified 2 sites (Chr.21:46,957,981 and Chr.21:46,957,915) in the 5' untranslated region of solute carrier family 19 member 1 (SLC19A1) with decreased methylation in obese participants (lean 0.73 ± 0.11 vs. obese 0.09 ± 0.05; lean 0.68 ± 0.10 vs. obese 0.09 ± 0.05, respectively). These 2 DMCs identified by obesity were also significantly predicted by insulin sensitivity (r = 0.68, P = 0.003; r = 0.66; P = 0.004). In addition, we performed a differentially methylated region (DMR) analysis and demonstrated a decrease in methylation of Chr.21:46,957,915-46,958,001 in SLC19A1 of -34.9% (70.4% lean vs. 35.5% obese). The decrease in whole-blood SLC19A1 methylation in our obese participants was similar to the change observed in skeletal muscle (Chr.21:46,957,981, lean 0.70 ± 0.09 vs. obese 0.31 ± 0.11 and Chr.21:46,957,915, lean 0.72 ± 0.11 vs. obese 0.31 ± 0.13). Pyrosequencing analysis further demonstrated a decrease in methylation at Chr.21:46,957,915 in both whole-blood (lean 0.71 ± 0.10 vs. obese 0.18 ± 0.06) and skeletal muscle (lean 0.71 ± 0.10 vs. obese 0.30 ± 0.11). Our findings demonstrate a new potential epigenetic biomarker, SLC19A1, for obesity and its underlying insulin resistance.


Elicitation of broadly neutralizing influenza antibodies in animals with previous influenza exposure.
The immune system responds to influenza infection by producing neutralizing antibodies to the viral surface protein, hemagglutinin (HA), which regularly changes its antigenic structure. Antibodies that target the highly conserved stem region of HA neutralize diverse influenza viruses and can be elicited through vaccination in animals and humans. Efforts to develop universal influenza vaccines have focused on strategies to elicit such antibodies; however, the concern has been raised that previous influenza immunity may abrogate the induction of such broadly protective antibodies. We show here that prime-boost immunization can induce broadly neutralizing antibody responses in influenza-immune mice and ferrets that were previously infected or vaccinated. HA stem-directed antibodies were elicited in mice primed with a DNA vaccine and boosted with inactivated vaccine from H1N1 A/New Caledonia/20/1999 (1999 NC) HA regardless of preexposure. Similarly, gene-based vaccination with replication-defective adenovirus 28 (rAd28) and 5 (rAd5) vectors encoding 1999 NC HA elicited stem-directed neutralizing antibodies and conferred protection against unmatched 1934 and 2007 H1N1 virus challenge in influenza-immune ferrets. Indeed, previous exposure to certain strains could enhance immunogenicity: The strongest HA stem-directed immune response was observed in ferrets previously infected with a divergent 1934 H1N1 virus. These findings suggest that broadly neutralizing antibodies against the conserved stem region of HA can be elicited through vaccination despite previous influenza exposure, which supports the feasibility of developing stem-directed universal influenza vaccines for humans.


Quantitative correlation between HLA class I allele expression and recognition of melanoma cells by antigen-specific cytotoxic T lymphocytes.
MHC class I antigen expression is necessary for CD8+ T-cell-mediated recognition of tumors. Recently, several mechanisms leading to loss or decreased expression of MHC antigens on the tumor cell surface have been described that may account for tumor escape from immune recognition. It is yet unknown whether tumor recognition by CTL occurs at a threshold amount of MHC molecules or correlates with the level of HLA-allele expression. In this study, a model was developed in which clones derived from the 624-MEL melanoma cell line and expressing varying amounts of HLA-A2 molecules were lysed in a standard 51Cr release assay by an HLA-A2-restricted CTL clone (A42) or a bulk culture of tumor-infiltrating lymphocytes. The A42 clone and the tumor-infiltrating lymphocyte culture were characterized previously as specifically recognizing the melanoma antigen MART-1(27-35) peptide. A marked heterogeneity in the susceptibility to lysis by A42 was observed in tumor clones and was not due to heterogeneous expression of MART-1 by the clones or loss of accessory molecules involved in the lymphocyte-target interaction. Lysis by A42 and by the tumor-infiltrating lymphocyte culture significantly correlated with the level of HLA-A2 expression, evaluated as mean channel number of fluorescence by flow cytometry (P < 0.001). Transfection of an HLA-A2-negative clone (624.28) with the HLA-A2.1 gene produced a panel of clones expressing different levels of HLA-A2, the lysis of which was highly correlated with the expression of HLA-A2 (P < 0.001). The addition of exogenous MART-1(27-35) peptide enhanced lysis of clones expressing intermediate amounts of HLA-A2 but did not affect clones with high expression. These data suggest that the number of HLA molecules present on the surface of tumor cells can quantitatively affect their lysis by CTL in situations with borderline amounts of peptide and/or MHC.


Surgical management of cricopharyngeal dysphagia in dogs: 14 cases (1989-2001).
To determine outcome of and complications associated with cricopharyngeal myotomy or myectomy for treatment of cricopharyngeal dysphagia (CPD) in dogs. Retrospective study. 14 dogs. Medical records of dogs with CPD that underwent cricopharyngeal myotomy or myectomy were examined. Follow-up information was obtained through telephone interviews with owners and referring veterinarians and clinical examinations when feasible. 16 surgical procedures were performed on the 14 dogs. Dysphagia was completely resolved immediately after surgery in 1 dog, and clinical signs did not recur (follow-up time of 8 years); a second dog also had immediate complete resolution of dysphagia, but follow-up time was only 10 days. Three dogs had transient complete resolution with a mean time to recurrence of dysphagia of 12.3 weeks (range, 2 to 36 weeks). Three dogs had permanent partial resolution. Six dogs had no improvement after surgery. Eight of the 14 dogs were euthanatized because of problems related to CPD, including persistent dysphagia (n = 8) and aspiration pneumonia (5). The failure rate for dogs undergoing surgical treatment of CPD may be high, particularly if concurrent aspiration pneumonia or malnutrition is not addressed prior to surgery. For those dogs with concurrent diseases, more aggressive medical management, such as enteral tube feeding, may be warranted rather than surgery. In dogs with CPD complicated by other anatomic or functional conditions, such as myasthenia gravis, laryngeal paralysis, and esophageal stricture, surgery may also not be indicated.


Longer and more frequent marine heatwaves over the past century.
Heatwaves are important climatic extremes in atmospheric and oceanic systems that can have devastating and long-term impacts on ecosystems, with subsequent socioeconomic consequences. Recent prominent marine heatwaves have attracted considerable scientific and public interest. Despite this, a comprehensive assessment of how these ocean temperature extremes have been changing globally is missing. Using a range of ocean temperature data including global records of daily satellite observations, daily in situ measurements and gridded monthly in situ-based data sets, we identify significant increases in marine heatwaves over the past century. We find that from 1925 to 2016, global average marine heatwave frequency and duration increased by 34% and 17%, respectively, resulting in a 54% increase in annual marine heatwave days globally. Importantly, these trends can largely be explained by increases in mean ocean temperatures, suggesting that we can expect further increases in marine heatwave days under continued global warming.


[Release of histamine and leukotrienes C4 and B4, and bronchial hyperresponsiveness in elderly patients with asthma].
Thirty patients with atopic asthma in whose asthma IgE-mediated allergic reaction participates, were selected for this study. They were divided into three age groups: elderly patients aged 60 and over, middle-aged patients between the ages of 40 and 59, and young patients between 20 and 39, to clarify the effects of aging on the mechanism of onset of asthma. In the cellular composition of bronchoalveolar lavage (BAL) fluid, the proportion of BAL lymphocytes was increased in elderly patients, and the proportion of BAL eosinophils was increased in young patients, although there was no statistically significant difference between the proportions of these cells in the three age groups. The proportion of BAL basophilic cells (basophils and mast cells) was significantly lower in elderly patients than in young patients (p < 0.05). The release of histamine from BAL cells was significantly lower in elderly patients than in middle-aged patients (p < 0.05) and young patients (p < 0.02). There was, however, no significant difference between the release of leukotrienes C4 (LTC4) and B4 (LTB4) in the three age groups. The release of histamine, LTC4 and LTB4 from peripheral leucocytes was not significantly different between the three age groups. Finally, Bronchial reactivity to methacholine showed a tendency to decrease with aging.


Atomic hydrogen interactions with gas-phase coronene cations: hydrogenation versus fragmentation.
Sequential hydrogenation of polycyclic aromatic hydrocarbon (PAH) cations drives a gradual transition from a planar to a puckered geometry and from an aromatic to an aliphatic electronic structure. The resulting H-induced weakening of the molecular structure together with the exothermic nature of the consecutive H-attachment processes can lead to substantial molecular fragmentation. We have studied H attachment to gas-phase coronene cations in a radiofrequency ion trap using tandem mass spectrometry. With increasing hydrogenation, C2Hi loss and multifragmentation are identified as main de-excitation channels. To understand the dependence of both channels on H-exposure time, we have simulated the molecular stability and fragmentation channels of hydrogenated PAHs using a molecular dynamics approach employing potential energies determined by a density functional based tight binding method. As the coronene fragmentation patterns depend on the balance between energy deposition by H-attachment and the extent of cooling in between subsequent attachment processes, we investigate several scenarios for the energy distribution of hydrogenated PAHs. Good agreement between experiment and simulation is reached, when realistic energy distributions are considered.


Your space or mine? Mapping self in time.
While humans are capable of mentally transcending the here and now, this faculty for mental time travel (MTT) is dependent upon an underlying cognitive representation of time. To this end, linguistic, cognitive and behavioral evidence has revealed that people understand abstract temporal constructs by mapping them to concrete spatial domains (e.g. past=backward, future=forward). However, very little research has investigated factors that may determine the topographical characteristics of these spatiotemporal maps. Guided by the imperative role of episodic content for retrospective and prospective thought (i.e., MTT), here we explored the possibility that the spatialization of time is influenced by the amount of episodic detail a temporal unit contains. In two experiments, participants mapped temporal events along mediolateral (Experiment 1) and anterioposterior (Experiment 2) spatial planes. Importantly, the temporal units varied in self-relevance as they pertained to temporally proximal or distal events in the participant's own life, the life of a best friend or the life of an unfamiliar other. Converging evidence from both experiments revealed that the amount of space used to represent time varied as a function of target (self, best friend or unfamiliar other) and temporal distance. Specifically, self-time was represented as occupying more space than time pertaining to other targets, but only for temporally proximal events. These results demonstrate the malleability of space-time mapping and suggest that there is a self-specific conceptualization of time that may influence MTT as well as other temporally relevant cognitive phenomena.


Survey of clinician attitudes toward smoking cessation for psychiatric and substance abusing clients.
The current study examined mental health clinician attitudes regarding smoking cessation for psychiatric and substance abusing patients. Participants included n = 15 never smokers, n = 12 former smokers, and n = 7 current smokers. There was a trend (p = 0.08) for current smokers as compared to former and never smokers to be less likely to encourage their clients to stop smoking. Overall, clinicians strongly agreed that an individual's motivation is the most important determinant of success in quitting. Clinicians were concerned that smoking cessation would initiate a relapse to substance abuse. We suggest that mental health clinicians can be instrumental in providing information, encouragement, and opportunities for their patients to attempt smoking cessation.


Fibrous networks with incorporated macrocycles: a chiral stimuli-responsive supramolecular supergelator and its application to biocatalysis in organic media.
A new and versatile, crown ether appended, chiral supergelator has been designed and synthesized based on the bis-urea motif. The introduction of a stereogenic center improved its gelation ability significantly relative to its achiral analogue. This low-molecular-weight gelator forms supramolecular gels in a variety of organic solvents. It is sensitive to multiple chemical stimuli and the sol-gel phase transitions can be reversibly triggered by host-guest interactions. The gel can be used to trap enzymes and release them on demand by chemical stimuli. It stabilizes the microparticles in Pickering emulsions so that enzyme-catalyzed organic reactions can take place in the polar phase inside the microparticles, the organic reactants diffusing through the biphasic interface from the surrounding organic phase. Because of the higher interface area between the organic and polar phases, enzyme activity is enhanced in comparison with simple biphasic systems.


Talent goes to global cities: The world network of scientists' mobility.
Global cities boast higher rates of innovation as measured through patent and scientific production. However, the source of the location advantage of innovation hubs is still debated in the literature, with arguments ranging from localized knowledge spillovers to network effects. Thanks to an extensive data set of individual scientist career paths, we shed new light on the role of scientist location choices in determining the superior innovative performance of global cities. We analyze the career paths of around two million researchers over a decade across more than two thousand cities around the globe. First, we show that scientists active in global cities are more productive in terms of citation weighted publications. We then show that this superior performance is in part driven by highly prolific scientists moving and remaining preferentially in global cities, i.e., central cities in the international scientist mobility network. The overall picture that emerges is that global cities are better positioned to attract and retain prolific scientists than more peripheral cities.


Nato3 plays an integral role in dorsoventral patterning of the spinal cord by segregating floor plate/p3 fates via Nkx2.2 suppression and Foxa2 maintenance.
During embryogenesis, the dorsal roof plate and the ventral floor plate (FP) act as organizing centers to pattern the developing neural tube. Organizer-secreted morphogens provide signals that are interpreted via the graded expression of transcription factors. These factors establish a combinatorial code, which subsequently determines the fate of neuronal progenitors along the dorsoventral axis. To further separate the fates and promote distinct identities of the neural progenitors, mutual repression takes place among transcription factors expressed in progenitors situated along the dorsoventral axis. The molecular mechanisms acting in the developing spinal cord and underlying the segregation of the progenitor pool containing cells with a mixed FP/p3 fate into separate FP cells and V3 neurons are not fully understood. Using in vivo ectopic expression in chick, we found that Nato3 induces ectopic Foxa2-positive cells and indirectly downregulates Nkx2.2 expression. To examine the role of Nato3 in the FP, Foxa2-Nato3 signaling was blocked in Nato3 null mice and to a greater extent in Nato3 null/Foxa2 heterozygous bigenic mutants. Complementary to the findings obtained by gain of function in chick, the loss of function in mouse indicated that the segregation of the FP/p3 population into its derivatives was interrupted. Together, the data suggest that Nato3 is a novel determinant factor regulating the segregation of the FP and p3 identities, which is an essential step for establishing a definitive FP fate in the embryonic spinal cord.


Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.
Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines. Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force. The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, and suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using ultrasound and serum thyroglobulin as well as those related to management of recurrent and metastatic disease. We created evidence-based recommendations in response to our appointment as an independent task force by the American Thyroid Association to assist in the clinical management of patients with thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.


A data-driven mathematical model of CA-MRSA transmission among age groups: evaluating the effect of control interventions.
Community associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a major cause of skin and soft tissue infections (SSTIs) in the US. We developed an age-structured compartmental model to study the spread of CA-MRSA at the population level and assess the effect of control intervention strategies. We used Monte-Carlo Markov Chain (MCMC) techniques to parameterize our model using monthly time series data on SSTIs incidence in children (≤ 19 years) during January 2004 -December 2006 in Maricopa County, Arizona. Our model-based forecast for the period January 2007-December 2008 also provided a good fit to data. We also carried out an uncertainty and sensitivity analysis on the control reproduction number, Rc which we estimated at 1.3 (95% CI [1.2,1.4]) based on the model fit to data. Using our calibrated model, we evaluated the effect of typical intervention strategies namely reducing the contact rate of infected individuals owing to awareness of infection and decolonization strategies targeting symptomatic infected individuals on both [Formula: see text] and the long-term disease dynamics. We also evaluated the impact of hypothetical decolonization strategies targeting asymptomatic colonized individuals. We found that strategies focused on infected individuals were not capable of achieving disease control when implemented alone or in combination. In contrast, our results suggest that decolonization strategies targeting the pediatric population colonized with CA-MRSA have the potential of achieving disease elimination.


Spatially Explicit Models to Investigate Geographic Patterns in the Distribution of Forensic STRs: Application to the North-Eastern Mediterranean.
Human forensic STRs used for individual identification have been reported to have little power for inter-population analyses. Several methods have been developed which incorporate information on the spatial distribution of individuals to arrive at a description of the arrangement of diversity. We genotyped at 16 forensic STRs a large population sample obtained from many locations in Italy, Greece and Turkey, i.e. three countries crucial to the understanding of discontinuities at the European/Asian junction and the genetic legacy of ancient migrations, but seldom represented together in previous studies. Using spatial PCA on the full dataset, we detected patterns of population affinities in the area. Additionally, we devised objective criteria to reduce the overall complexity into reduced datasets. Independent spatially explicit methods applied to these latter datasets converged in showing that the extraction of information on long- to medium-range geographical trends and structuring from the overall diversity is possible. All analyses returned the picture of a background clinal variation, with regional discontinuities captured by each of the reduced datasets. Several aspects of our results are confirmed on external STR datasets and replicate those of genome-wide SNP typings. High levels of gene flow were inferred within the main continental areas by coalescent simulations. These results are promising from a microevolutionary perspective, in view of the fast pace at which forensic data are being accumulated for many locales. It is foreseeable that this will allow the exploitation of an invaluable genotypic resource, assembled for other (forensic) purposes, to clarify important aspects in the formation of local gene pools.


Phenotypic Characterization of Mice Carrying Homozygous Deletion of KLF11, a Gene in Which Mutations Cause Human Neonatal and MODY VII Diabetes.
We have previously shown that amino acid changes in the human Kruppel-Like Factor (KLF) 11 protein is associated with the development of maturity onset diabetes of the young VII, whereas complete inactivation of this pathway by the -331 human insulin mutation causes neonatal diabetes mellitus. Here, we report that Klf11-/- mice have decreased circulating insulin levels, alterations in the control of blood glucose and body weight, as well as serum dyslipidemia, but do not develop diabetes. Functional assays using ex vivo liver tissue sections demonstrate that Klf11-/- mice display increased insulin sensitivity. Genome-wide experiments validated by pathway-specific quantitative PCR arrays reveal that the Klf11-/- phenotype associates to alterations in the regulation of gene networks involved in lipid metabolism, in particular those regulated by peroxisome proliferator-activated receptor-γ. Combined, these results demonstrate that the major phenotype given by the whole-body deletion of Klf11 in mouse is not diabetes but increased insulin sensitivity, likely due to altered transcriptional regulation in target tissues. The absence of diabetes in the Klf11-/- mouse either indicates an interspecies difference for the role of this transcription factor in metabolic homeostasis between mouse and humans, or potentially highlights the fact that other molecular factors can compensate for its absence. Nevertheless, the data of this study, gathered at the whole-organism level, further support a role for KLF11 in metabolic processes like insulin sensitivity, which regulation is critical in several forms of diabetes.


Septo-optic dysplasia complex: Clinical and radiological manifestations in Omani children.
Septo-optic dysplasia (SOD), also known as de-Morsier's syndrome, is a rare disorder characterized by any combination of optic nerve hypoplasia (ONH), pituitary gland hypoplasia, and midline abnormalities of the brain including absence of septum pellucidum and corpus callosum dysgenesis. It is typically diagnosed in infancy and has a variable presentation that includes visual, neurologic, and/or hypothalamic-pituitary endocrine deficits. To demonstrate the ophthalmic, endocrine, and neurologic spectrum of SOD in five Omani children and address the crucial role of high-resolution neuroimaging for its early and accurate diagnosis. A retrospective chart review was performed in 2010 of all children in the pediatric ophthalmology database of Sultan Qaboos University Hospital (SQUH) who were diagnosed to have ONH. All relevantdemographic, ophthalmic, neurologic, endocrine, and neuro-radiological manifestations were recorded in a data collection form. All previous neuroimaging results were reviewed by a neuro-radiologist. Five patients (four males, one female) with the diagnosis of ONH were included in the study. They presented during the period 1998-2008. All patients were born at term, with normal birth weights to healthy mothers with insignificant antenatal history. Age at presentation ranged from three months to one year. Manifestations at presentation included severe visual impairment (5/5), neonatal hypoglycemia (3/5), seizure disorder (2/5), and failure to thrive (4/5). ONH was bilateral in 3/5 patients and unilateral in (2/5). Brain and orbit imaging revealed varying anomalies in all patients. These included absent septum pellucidum (3/5), severe corpus callosum agenesis (1/5), ectopic pituitary (5/5), falx cerebri deficiency (1/5), optic nerve hypoplasia (5/5), optic chiasmal hypoplasia (5/5), and olfactory tract hypoplasia (1/5). Endocrine deficits were detected in 4/5 patients (3 with panhypopituitarism, and 1 with growth hormone deficiency) and necessitated replacement therapy. SOD is a clinically heterogeneous disorder with a wide spectrum of ophthalmic, endocrine, and neurologic manifestations. All features might not be present in a single patient. A high consanguinity rate and lack of history of alcohol and drug use were observed in our cohort. Most affected children present first to the pediatrician with failure to thrive. Radiological confirmation of ONH necessitates high-resolution imaging and interpretation by an experienced neuro-radiologist. In our cohort, all patients with ONH had associated optic chiasmal hypoplasia. Early detection and treatment reduces disease-related morbidity, and can be life saving.


Negative Regulation of miR-375 by Interleukin-10 Enhances Bone Marrow-Derived Progenitor Cell-Mediated Myocardial Repair and Function After Myocardial Infarction.
Poor survival and function of transplanted cells in ischemic and inflamed myocardium likely compromises the functional benefit of stem cell-based therapies. We have earlier reported that co-administration of interleukin (IL)-10 and BMPAC enhances cell survival and improves left ventricular (LV) functions after acute myocardial infarction (MI) in mice. We hypothesized that IL-10 regulates microRNA-375 (miR-375) signaling in BMPACs to enhance their survival and function in ischemic myocardium after MI and attenuates left ventricular dysfunction after MI. miR-375 expression is significantly upregulated in BMPACs upon exposure to inflammatory/hypoxic stimulus and also after MI. IL-10 knockout mice display significantly elevated miR-375 levels. We report that ex vivo miR-375 knockdown in BMPAC before transplantation in the ischemic myocardium after MI significantly improve the survival and retention of transplanted BMPACs and also BMPAC-mediated post-infarct repair, neovascularization, and LV functions. Our in vitro studies revealed that knockdown of miR-375-enhanced BMPAC proliferation and tube formation and inhibited apoptosis; over expression of miR-375 in BMPAC had opposite effects. Mechanistically, miR-375 negatively regulated 3-phosphoinositide-dependent protein kinase-1 (PDK-1) expression and PDK-1-mediated activation of PI3kinase/AKT signaling. Interestingly, BMPAC isolated from IL-10-deficient mice showed elevated basal levels of miR-375 and exhibited functional deficiencies, which were partly rescued by miR-375 knockdown, enhancing BMPAC function in vitro and in vivo. Taken together, our studies suggest that miR-375 is negatively associated with BMPAC function and survival and IL-10-mediated repression of miR-375 enhances BMPAC survival and function.


Biophysical differentiation of susceptibility and chemical differences in Staphylococcus aureus.
Differentiating bacteria strains using biophysical forces has been the focus of recent studies using dielectrophoresis (DEP). The refinement of these studies has created high-resolution separations such that very subtle properties of the cells are enough to induce significant differences in measurable biophysical properties. These high-resolution capabilities build upon the advantages of DEP which include small sample sizes and fast analysis times. Studies focusing on differentiating antimicrobial resistant and susceptible bacteria potentially have significant impact on human health and medical care. A prime example is Staphylococcus aureus, which commonly colonizes adults without ill effects. However, the pathogen is an important cause of infections, including surgical site infections. Treatment of S. aureus infections is generally possible with antimicrobials, but antimicrobial resistance has emerged. Of special importance is resistance to methicillin, an antimicrobial created in response to resistance to penicillin. Here, dielectrophoresis is used to study methicillin-resistant (MRSA) and -susceptible S. aureus (MSSA) strains, both with and without the addition of a fluorescent label. The capture onset potential of fluorescently-labeled MRSA (865 ± 71 V) and thus the ratio of electrokinetic to dielectrophoretic mobility, was found to be higher than that of fluorescently-labeled MSSA (685 ± 61 V). This may be attributable to the PBP2a enzyme present in the MRSA strain and not in the MSSA bacteria. Further, unlabeled MRSA was found to have a capture onset potential of 732 ± 44 V, while unlabeled MSSA was found to have a capture onset potential of 562 ± 59 V. This shows that the fluorescently-labeled bacteria require a higher applied potential, and thus ratio of mobilities, to capture than the unlabeled bacteria.


Senescence determines the fate of activated rat pancreatic stellate cells.
In chronic pancreatitis (CP), persistent activation of pancreatic stellate cells (PSC) converts wound healing into a pathological process resulting in organ fibrosis. Here, we have analysed senescence as a novel mechanism involved in the termination of PSC activation and tissue repair. PSC senescence was first studied in vitro by establishing long-term cultures and by applying chemical triggers, using senescence-associated β-Galactosidase (SA β-Gal) as a surrogate marker. Subsequently, susceptibility of PSC to immune cell-mediated cytolysis was investigated employing cocultures. Using the model of dibutyltin dichloride-induced CP in rats, appearance of senescent cells was monitored by immunohistochemistry and immunofluorescence, and correlated with the progression of tissue damage and repair, immune cell infiltration and fibrosis. The results indicated that long-term culture and exposure of PSC to stressors (doxorubicin, H(2) O(2) and staurosporine) induced senescence. Senescent PSC highly expressed CDKN1A/p21, mdm2 and interleukin (IL)-6, but displayed low levels of α-smooth muscle actin. Senescence increased the susceptibility of PSC to cytolysis. In CP, the number of senescent cells correlated with the severity of inflammation and the extension of fibrosis. Areas staining positive for SA β-Gal overlapped with regions of fibrosis and dense infiltrates of immune cells. Furthermore, a close physical proximity of immune cells and activated PSC was observed. We conclude that inflammation, PSC activation and cellular senescence are timely coupled processes which take place in the same microenvironment of the inflamed pancreas. Lymphocytes may play a dual-specific role in pancreatic fibrogenesis, triggering both the initiation of wound healing by activating PSC, and its completion by killing senescent stellate cells.


Highly controlled electrofusion of individually selected cells in dielectrophoretic field cages.
The prospect of novel therapeutic approaches has renewed the current interest in the fusion of rare cells, like stem cells or primary immune cells. While conventional techniques are only capable of mass fusion, lab-on-a-chip systems often still lack an acceptable method for making the cells available after processing. Here, we present a microfluidic approach for electrofusion on the single-cell level that offers high control over the cells both before and after fusion. For cell pairing and fusion, we employed dielectrophoresis and AC voltage pulses, respectively. Each cell has been characterized and selected before they were paired, fused and released from the fluidic system for subsequent analysis and cultivation. The successful experimental evaluation of our system was further corroborated by numerical simulations. We obtained fusion efficiencies of more than 30% for individual pairs of mouse myeloma and B cell blasts and showed the proliferating ability of the hybrid cells 3 d after fusion. Since aggregates of more than two cells can be fused, the technique could also be developed further for generating giant cells for low-noise electrophysiology in the context of semi-automated pharmaceutical screening procedures.


Purification and characterization of assimilatory nitrite reductase from Candida utilis.
Nitrate assimilation in many plants, algae, yeasts and bacteria is mediated by two enzymes, nitrate reductase (EC 18.104.22.168) and nitrite reductase (EC 220.127.116.11). They catalyse the stepwise reduction of nitrate to nitrite and nitrite to ammonia respectively. The nitrite reductase from an industrially important yeast, Candida utilis, has been purified to homogeneity. Purified nitrite reductase is a heterodimer and the molecular masses of the two subunits are 58 and 66 kDa. The native enzyme exhibits a molecular mass of 126 kDa as analysed by gel filtration. The identify of the two subunits of nitrite reductase was confirmed by immunoblotting using antibody for Cucurbita pepo leaf nitrite reductase. The presence of two different sized transcripts coding for the two subunits was confirmed by (a) in vitro translation of mRNA from nitrate-induced C. utilis followed by immunoprecipitation of the in vitro translated products with heterologous nitrite reductase antibody and (b) Northern-blot analysis. The 66 kDa subunit is acidic in nature which is probably due to its phosphorylated status. The enzyme is stable over a range of temperatures. Both subunits can catalyse nitrite reduction, and the reconstituted enzyme, at a higher protein concentration, shows an activity similar to that of the purified enzyme. Each of these subunits has been shown to contain a few unique peptides in addition to a large number of common peptides. Reduced Methyl Viologen has been found to be as effective an electron donor as NADPH in the catalytic process, a phenomenon not commonly seen for nitrite reductases from other systems.


The distribution of tyrosine hydroxylase-immunoreactive fibers in primate neocortex is widespread but regionally specific.
An antiserum directed against tyrosine hydroxylase (TH), an enzyme involved in dopamine and norepinephrine synthesis, was used to visualize axons immunohistochemically in monkey neocortex. Labeled fibers were distributed throughout the entire neocortex, but they had striking patterns of regional and laminar specialization. For example, primary motor cortex contained the greatest density of TH-labeled fibers, whereas primary sensory regions were sparsely innervated. Marked heterogeneity of fiber density was also present among the association regions of the frontal, parietal, and temporal lobes. In addition, the laminar pattern of innervation in a given region was correlated with its fiber density. Sparsely innervated regions had labeled fibers only in layer I and sometimes layer VI. In regions of intermediate density, labeled fibers tended to be located in layers I-superficial III and layers V-VI, whereas in densely innervated motor cortex TH-immunoreactive fibers were present in all cortical layers. Comparison of these distribution patterns with those produced by an antiserum directed against dopamine-beta-hydroxylase (DBH), a specific marker of neocortical noradrenergic axons, revealed marked differences. DBH-immunoreactive fibers were observed in some cortical locations where few or no TH-labeled fibers were present. In other regions, the density of TH-immunoreactive processes far exceeded that of DBH-labeled fibers. These findings indicate that nearly all of the immunoreactive fibers revealed by this anti-TH antiserum are dopaminergic. This interpretation was further supported by lesions of the ascending noradrenergic fibers in the brain stem, which reduced DBH immunoreactivity, but not TH immunoreactivity, in neocortex. The distinctive innervation patterns of TH-immunoreactive fibers suggest a functional specialization of the dopaminergic projections to primate neocortex.


Nonlinear [Ca2+] signaling in dendrites and spines caused by activity-dependent depression of Ca2+ extrusion.
Spine Ca2+ triggers the induction of synaptic plasticity and other adaptive neuronal responses. The amplitude and time course of Ca2+ signals specify the activation of the signaling pathways that trigger different forms of plasticity such as long-term potentiation and depression. The shapes of Ca2+ signals are determined by the dynamics of Ca2+ sources, Ca2+ buffers, and Ca2+ extrusion mechanisms. Here we show in rat CA1 pyramidal neurons that plasma membrane Ca2+ pumps (PMCAs) and Na+/Ca2+ exchangers are the major Ca2+ extrusion pathways in spines and small dendrites. Surprisingly, we found that Ca2+ extrusion via PMCA and Na+/Ca2+ exchangers slows in an activity-dependent manner, mediated by intracellular Na+ and Ca2+ accumulations. This activity-dependent depression of Ca2+ extrusion is, in part, attributable to Ca2+-dependent inactivation of PMCAs. Ca2+ extrusion recovers from depression with a time constant of 0.5 s. Depression of Ca2+ extrusion provides a positive feedback loop, converting small differences in stimuli into large differences in Ca2+ concentration. Depression of Ca2+ extrusion produces Ca2+ concentration dynamics that depend on the history of neuronal activity and therefore likely modulates the induction of synaptic plasticity.


Determinants of Effective Caregiver Communication After Adolescent Traumatic Brain Injury.
To characterize the effects of caregiver mental health and coping strategies on interactions with an injured adolescent acutely after traumatic brain injury (TBI). Multi-site, cross-sectional study. Outpatient setting of 3 tertiary pediatric hospitals and 2 tertiary general medical centers. Adolescents (N = 125) aged 12-17 years, 1-6 months after being hospitalized with complicated mild to severe TBI. Data were collected as part of a multi-site clinical trial of family problem-solving therapy after TBI. Multiple regression analyses were used to examine the relationship of caregiver and environmental characteristics to the dimensions of effective communication, warmth, and negativity during caregiver-adolescent problem-solving discussions. Adolescent and caregiver interactions, as measured by the Iowa Family Interaction Rating Scales. Caregivers who utilized problem-focused coping strategies were rated as having higher levels of effective communication (P < .01), as were those with higher socioeconomic status (P < .01). Problem-focused coping style and higher socioeconomic status were also associated lower levels of negative interactions (P < .01 and P < .05, respectively). Female gender of the adolescent and fewer children in the home were associated with increased parental warmth during the interaction (P < .01 and P < .05, respectively). Neither adolescent TBI severity nor caregiver depression significantly influenced caregiver-teen interactions. Problem-focused coping strategies are associated with higher levels of effective communication and lower levels of caregiver negativity during the initial months after adolescent TBI, suggesting that effective caregiver coping may facilitate better caregiver-adolescent interactions after TBI.


Congenital choledochal cysts in adults.
Excision of the extrahepatic portion of congenital choledochal cysts (CCs) avoids the risk of cancer. The standard classification scheme is out of date. Retrospective case series and literature review. Tertiary care university hospital. Thirty-eight adult patients diagnosed as having CC from 1990 to 2004. Clinical and radiographic imaging findings, operative treatment, pathologic features, and clinical outcome. Thirty-nine adult patients were treated for CCs (mean [SD] age at diagnosis, 31 [17] years, and mean [SD] age at surgery 37 [14] years). The primary report was abdominal pain (36 of 39 patients). Eight patients had cholangitis, 5 had jaundice, and 6 had pancreatitis. Radiographic imaging studies and operative findings showed that the abnormality predominantly involved the extrahepatic bile duct in 30 patients, the intrahepatic and extrahepatic bile ducts in 7 patients; and 2 were diverticula attached to the common bile duct. Surgical treatment in 29 (90%) of 31 patients with benign cysts (regardless of intrahepatic changes) consisted of resection of the enlarged extrahepatic bile duct and gallbladder and Roux-en-Y hepaticojejunostomy. Eight patients (21%) were initially seen with associated cancer (cholangiocarcinoma of the extrahepatic duct in 6; gallbladder cancer in 2). Seven of 8 patients had a prior diagnosis of CC but had undergone a drainage operation (3 patients), expectant treatment (3 patients), or incomplete excision (1patient). In none of the patients with cancer was surgery not curative. Nine patients had previously undergone a cystoduodenostomy and/or cystojejunostomy as children. Four of them had cancer on presentation as adults. There were no postoperative deaths. Cancer subsequently developed in no patient whose benign extrahepatic cyst was excised, regardless of the extent of enlargement of the intrahepatic bile duct. Congenital CCs consist principally of congenital dilation of the extrahepatic bile duct with a variable amount of intrahepatic involvement. We believe that the standard classification scheme is confusing, unsupported by evidence, misleading, and serves no purpose. The distinction between type I and type IV CCs has to be arbitrary, for the intrahepatic ducts were never completely normal. Although Caroli disease may resemble CCs morphologically, with respect to cause and clinical course, the 2 are unrelated. The other rare anomalies (gallbladderlike diverticula; choledochocele) are also unrelated to CC. Therefore, the term "congential choledochal cyst" should be exclusively reserved for congenital dilation of the extrahepatic and intrahepatic bile ducts apart from Caroli disease, and the other conditions should be referred to by their names, for example, choledochocele, and should no longer be thought of as subtypes of CC. Our data demonstrate once again a persistent tendency to recommend expectant treatment in patients without symptoms and the extreme risk of nonexcisional treatment. The entire extrahepatic biliary tree should be removed when CC is diagnosed whether or not symptoms are present. The outcome of that approach was excellent.


Aortic stiffness in prediabetic adults: relationship to insulin resistance.
A decrease in the compliance of the arterial system, termed arterial stiffness, results in increased cardiac workload. Several studies have shown that arterial stiffness is increased in individuals with type 2 diabetes. Also, insulin resistance is generally considered to be of major importance in the pathophysiology of type 2 diabetes mellitus given that glucose intolerance and insulin resistance precede the development of overt diabetes, these factors would be associated with arterial stiffness. This study was to evaluate the state of aortic elasticity in prediabetic adults in relation to insulin resistance. A case-control study was performed. A total of 113 consecutive adults with prediabetes were enrolled for the study, 32 adults had insulin resistance (group A) and 81 had insulin sensitive (group B). Forty-five healthy (with normal fasting glucose) adults matched for age and gender were considered as control. All were subjected to full medical history and clinical examination including blood pressure and body mass index. Biochemical studies including lipids profile, fasting glucose and homeostasis model assessment of insulin resistance (HOMA IR) test. Echocardiographic studies were done for assessment of the aortic stiffness index. Significant increase in mean aortic stiffness index was seen in group A than group B. Stiffness was correlated with insulin resistance and the correlation appeared to be independent of glucose tolerance status and obesity. Similar correlations were observed with age, triglycerides and waist circumference. Prediabetic subjects have an aortic stiffness which represent pattern of cardiovascular risk factors. These changes are predominantly observed in prediabetic subjects with increased HOMA IR and visceral obesity independent of glucose levels. Prediabetes; Insulin resistance; Aortic stiffness index.


The detection of a population of submillimeter-bright, strongly lensed galaxies.
Gravitational lensing is a powerful astrophysical and cosmological probe and is particularly valuable at submillimeter wavelengths for the study of the statistical and individual properties of dusty star-forming galaxies. However, the identification of gravitational lenses is often time-intensive, involving the sifting of large volumes of imaging or spectroscopic data to find few candidates. We used early data from the Herschel Astrophysical Terahertz Large Area Survey to demonstrate that wide-area submillimeter surveys can simply and easily detect strong gravitational lensing events, with close to 100% efficiency.


Flow-dependent porosity and other biomechanical properties of mysticete baleen.
Despite its vital function in a highly dynamic environment, baleen is typically assumed to be a static material. Its biomechanical and material properties have not previously been explored. Thus I tested sections of baleen from bowhead whales, Balaena mysticetus, and humpback whales, Megaptera novaeangliae, alone or in groups representing miniature 'racks', in a flow tank through which water and buoyant particles circulated with variable flow velocity. Kinematic sequences were recorded through an endoscopic camera or viewing window. One set of experiments investigated particle capture; another series analyzed biomechanical behavior, including fringe spacing, movement and interaction. Baleen fringe porosity directly correlates, in a mostly linear fashion, with velocity of incident water flow. However, undulation and interaction of fringes (especially of bowheads) at higher flow velocities can decrease porosity. Fringe porosity depends on distance from the baleen plate. Porosity also varies, with fringe length, by position along the length of an individual plate. Plate orientation, which varied from 0 to 90 deg relative to water flow, is crucial in fringe spacing and particle capture. At all flow velocities, porosity is lowest with plates aligned parallel to water flow. Turbulence introduced when plates rotate perpendicular to flow (as in cross-flow filtration) increases fringe interaction, so that particles more easily strike fringes yet more readily dislodge. Baleen of bowhead whales, which feed by continuous ram filtration, differs biomechanically from that of humpbacks, which use intermittent lunge filtration. The longer, finer fringes of bowhead baleen readily form a mesh-like mat, especially at higher flow velocities, to trap tiny particles.


Fusion of short telomeres in human cells is characterized by extensive deletion and microhomology, and can result in complex rearrangements.
Telomere fusion is an important mutational event that has the potential to lead to large-scale genomic rearrangements of the types frequently observed in cancer. We have developed single-molecule approaches to detect, isolate and characterize the DNA sequence of telomere fusion events in human cells. Using these assays, we have detected complex fusion events that include fusion with interstitial loci adjacent to fragile sites, intra-molecular rearrangements, and fusion events involving the telomeres of both arms of the same chromosome consistent with ring chromosome formation. All fusion events were characterized by the deletion of at least one of the telomeres extending into the sub-telomeric DNA up to 5.6 kb; close to the limit of our assays. The deletion profile indicates that deletion may extend further into the chromosome. Short patches of DNA sequence homology with a G:C bias were observed at the fusion point in 60% of events. The distinct profile that accompanies telomere fusion may be a characteristic of the end-joining processes involved in the fusion event.


Why does bromine square palladium off? An ab initio study of brominated palladium and its nanomorphology.
A first-principles description and prediction of brominated nanocrystals of Pd is presented. In particular, we conducted an extensive study of the adsorption behaviour of Br on various Pd surfaces (including both low and high Miller-index surfaces) as a function of its surface coverage. By coupling our calculated surface energies with ab initio (electrochemical) thermodynamics and the Gibbs-Wulff shape model, we find that the relative stability of the Pd surfaces is strongly modified by Br, allowing high Miller-index surfaces of Pd (namely the (210) surface) to become competitively favourable at moderate concentrations of Br. We also show that Pd nanoparticles assume a cube-like crystal shape at high concentrations of Br, exposing mainly the (100) facets with a Br surface coverage of 0.5 ML. This not only confirms and explains recent solution synthesis results, but also provides a quantitative atomic picture of the exposed surface facets, which is crucial in understanding the local surface chemistry of shape-controlled nanoparticles for better nanocatalyst design.


Management of nut allergy influences quality of life and anxiety in children and their mothers.
Nut allergy is known to impact on the quality of life (QoL) and anxiety of both the allergic child and their parents, but little is known about how the management of food allergy is associated with these variables. To investigate the impact of nut allergy on QoL and anxiety in mothers and children with nut allergy in order to identify management strategies that may influence these factors. Forty-one nut allergic children (age 6-16 yrs) and their mothers completed questionnaires to assess maternal and children's QoL (PedsQL, WHOQOL-BREF, FAQL-PB), anxiety (SCAS, STAI) and perceived stress scale (PSS). Children also completed a nut allergy specific QoL questionnaire. Demographic data, details of previous reactions, test results and management plans were collected using parent-report questionnaires and hospital notes. Children with nut allergy had poorer emotional (p = 0.004), social (p = 0.043), and psychological (p = 0.006) QoL compared to healthy normative data. Maternal and child QoL and anxiety were not influenced by the severity of previous reactions. Mother and child reported lower anxiety (p = 0.043 and p < 0.001 respectively) when the child was prescribed an epinephrine auto-injector. Anxiety was not associated with whether the child carried the auto-injector or whether they strictly avoided traces of nuts in foods. Prescribing auto-injectors is associated with reduced anxiety for food allergic children and their mothers, but is not associated with improved adherence with medical management or reduced risk-taking behavior.


Disparities exist between National food group recommendations and the dietary intakes of women.
Preconception and pregnancy dietary intakes can influence the health of future generations. In this study we compared the food intakes of reproductive-aged women by pregnancy status, to current Australian recommendations. Data are from the Australian Longitudinal Study on Women's Health, younger cohort aged 25-30 years in 2003, with self-reported status as pregnant (n = 606), trying to conceive (n = 454), given birth in the last 12 months (n = 829) or other (n = 5597). Diet was assessed using a validated 74-item food frequency questionnaire. Food group servings and nutrient intakes were compared to the Australian Guide to Healthy Eating (AGHE) and Australian Nutrient Reference Values (NRVs). No women met all AGHE food group recommendations. Highest adherence rates [mean (95% CI) servings/day] were for meat [85%, 1.9(1.8-1.9)], fruit [44%, 2.1(2.1-2.2)] and dairy [35%, 1.8(1.8-1.9)], with < 14% meeting remaining recommendations. Women who achieved NRVs (folate, iron, calcium, zinc, fibre) for pregnancy, breastfeeding and adult life stages were 1.5%, 3.3% and 13.7%, respectively. Compared to AGHE, women consumed more servings of fruit (4.9 vs 4.0;P = 0.034) and dairy (3.4 vs 2.0;P = 0.006) to achieve pregnancy NRVs; more dairy (2.9 vs 2.0;P = 0.001), less fruit (3.9 vs 5.0;P < .001) and vegetables (3.4 vs 7.0;P < .001) to achieve breastfeeding NRVs; more fruit (3.6 vs 3.0;P < .001), dairy (2.5 vs 2.0;P < .001), meat (1.8 vs 1.5;P = 0.015), less vegetables (3.6 vs 5.0;P < .001) to achieve adult NRVs. The AGHE does not align with contemporary diets of Australian women or enable them to meet all NRVs. Current tools to guide food consumption by women during pregnancy require revision.


Recent Advancemnts in Biodegradable Ocular Implants.
The perpetuation of healthy vision is paramount in an individual. It has been observed that various drug delivery systems have been fabricated to develop vision quality in individuals. Systemic ocular drug therapies have limited efficacy due to poor bioavailability, systemic and toxic side effects and low patient compliance. Various drug systems which follow the ocular route of administration are manufactured to achieve optimized bioavailability along with better patient compliance. Ocular implant is one such example. It is divided into biodegradable and non-biodegradable drug delivery systems wherein the former is more beneficial. This review aims to demonstrate the current momentum in the formulation and optimization of various biodegradable ocular drug delivery systems and its characteristics.


Some simple nosocomial disease transmission models.
The SARS epidemic of 2002-2003 drew attention to nosocomial disease transmission as many of the disease cases were transmitted through hospital staff and visitors. Various types of model have been proposed to describe this, including metapopulation models. We formulate and analyze a simple compartmental model with heterogeneous mixing to describe nosocomial transmission and determine the reproduction number and final size relation.


Prevalence of hippocampal malrotation in a population without seizures.
Hippocampal malrotation (HIMAL) is a failure of hippocampal inversion that occurs during normal fetal development and has been seen on MR imaging examinations of people with epilepsy, but it has not been studied in patients without epilepsy. We intended to evaluate the prevalence of HIMAL in MR imaging examinations of patients without seizures to better understand the significance of HIMAL in the population with seizure. A total of 497 MR imaging examinations with thin-section imaging through the temporal lobes of patients referred for conditions other than seizures were reviewed. The examinations were performed on 1.5T magnets. Sagittal T1-weighted and coronal T2-weighted images were used to evaluate each MR image for the distinctive features of HIMAL. As previously described in the literature, the criteria for HIMAL include unilateral involvement and incomplete rotation of a hippocampus that is normal in size and signal intensity but abnormally rounded in shape, with blurred inner structure. In addition, ipsilateral findings of an atypical collateral sulcus angle and atypical position and size of the fornix were noted. The corpus callosum is normal, and the temporal lobe remains normal in size, though the temporal horn may appear enlarged. None of the patients' examinations fulfilled all of the HIMAL criteria. Six studies satisfied 2 or more criteria, which included an abnormally rounded hippocampus and a vertical collateral sulcus. These HIMAL findings were all seen on the left. Forniceal asymmetry was the most prevalent abnormality, with 289 patients manifesting a low position of 1 fornix. Hippocampal malrotation is a rare finding in patients without seizures. HIMAL is therefore likely to be a pathologic finding.


Parabiosis and single-cell RNA sequencing reveal a limited contribution of monocytes to myofibroblasts in kidney fibrosis.
Fibrosis is the common final pathway of virtually all chronic injury to the kidney. While it is well accepted that myofibroblasts are the scar-producing cells in the kidney, their cellular origin is still hotly debated. The relative contribution of proximal tubular epithelium and circulating cells, including mesenchymal stem cells, macrophages, and fibrocytes, to the myofibroblast pool remains highly controversial. Using inducible genetic fate tracing of proximal tubular epithelium, we confirm that the proximal tubule does not contribute to the myofibroblast pool. However, in parabiosis models in which one parabiont is genetically labeled and the other is unlabeled and undergoes kidney fibrosis, we demonstrate that a small fraction of genetically labeled renal myofibroblasts derive from the circulation. Single-cell RNA sequencing confirms this finding but indicates that these cells are circulating monocytes, express few extracellular matrix or other myofibroblast genes, and express many proinflammatory cytokines. We conclude that this small circulating myofibroblast progenitor population contributes to renal fibrosis by paracrine rather than direct mechanisms.