Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398) and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r(2) = 0.94 to 0.99) were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF) = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10(-16)). This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10(-19)), nephritis (MAF = 34.3%, OR = 1.80, p<10(-11)), and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10(-13)). An association with severe nephritis was even more striking (MAF = 39.2%, OR = 2.35, p<10(-4) in the homogeneous subset of subjects). In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease.


The effect of de-escalation of P2Y12 receptor inhibitor therapy after acute myocardial infarction in patients undergoing percutaneous coronary intervention: A nationwide cohort study.
To examine the effect of de-escalation of P2Y12 inhibitor in dual antiplatelet therapy (DAPT) on major adverse cardiovascular events (MACE) and bleeding complications after acute myocardial infarction (AMI) in Taiwanese patients undergoing percutaneous coronary intervention (PCI). Patients who had received PCI during hospitalization for AMI (between 2013 and 2016) and were initially treated with aspirin and ticagrelor and without adverse events after 3 months of treatment were retrospectively evaluated. In total, 1,901 and 8,199 patients were identified as "de-escalated DAPT" (switched to aspirin and clopidogrel) and "unchanged DAPT" (continued on aspirin and ticagrelor) cohorts, respectively. With a mean follow-up of 8 months, the incidence rates (per 100 person-year) of death, AMI readmission and MACE were 2.89, 3.68, and 4.91 in the de-escalated cohort and 2.42, 3.28, and 4.72 in the unchanged cohort, respectively, based on an inverse probability of treatment weighted approach that adjusting for baseline characteristics of the patients. Multivariate Cox regression analyses showed the two groups had no significant differences in the hazard risk of death, AMI admission, and MACE. Additionally, there was no observed difference in the risk of bleeding, including major or clinically relevant non-major bleeding. The real-world data revealed that de-escalation of P2Y12 inhibitor in DAPT was not associated with a higher risk of death or AMI readmission in Taiwanese patients with AMI undergoing successful PCI.


Building toolkits for COPD exacerbations: lessons from the past and present.
In the nineteenth century, it was recognised that acute attacks of chronic bronchitis were harmful. 140 years later, it is clearer than ever that exacerbations of chronic obstructive pulmonary disease (ECOPD) are important events. They are associated with significant mortality, morbidity, a reduced quality of life and an increasing reliance on social care. ECOPD are common and are increasing in prevalence. Exacerbations beget exacerbations, with up to a quarter of in-patient episodes ending with readmission to hospital within 30 days. The healthcare costs are immense. Yet despite this, the tools available to diagnose and treat ECOPD are essentially unchanged, with the last new intervention (non-invasive ventilation) introduced over 25 years ago.An ECOPD is 'an acute worsening of respiratory symptoms that results in additional therapy'. This symptom and healthcare utility-based definition does not describe pathology and is unable to differentiate from other causes of an acute deterioration in breathlessness with or without a cough and sputum. There is limited understanding of the host immune response during an acute event and no reliable and readily available means to identify aetiology or direct treatment at the point of care (POC). Corticosteroids, short acting bronchodilators with or without antibiotics have been the mainstay of treatment for over 30 years. This is in stark contrast to many other acute presentations of chronic illness, where specific biomarkers and mechanistic understanding has revolutionised care pathways. So why has progress been so slow in ECOPD? This review examines the history of diagnosing and treating ECOPD. It suggests that to move forward, there needs to be an acceptance that not all exacerbations are alike (just as not all COPD is alike) and that clinical presentation alone cannot identify aetiology or stratify treatment.


Geographic access to care is not a determinant of child mortality in a rural Kenyan setting with high health facility density.
Policy-makers evaluating country progress towards the Millennium Development Goals also examine trends in health inequities. Distance to health facilities is a known determinant of health care utilization and may drive inequalities in health outcomes; we aimed to investigate its effects on childhood mortality. The Epidemiological and Demographic Surveillance System in Kilifi District, Kenya, collects data on vital events and migrations in a population of 220,000 people. We used Geographic Information Systems to estimate pedestrian and vehicular travel times to hospitals and vaccine clinics and developed proportional-hazards models to evaluate the effects of travel time on mortality hazard in children less than 5 years of age, accounting for sex, ethnic group, maternal education, migrant status, rainfall and calendar time. In 2004-6, under-5 and under-1 mortality ratios were 65 and 46 per 1,000 live-births, respectively. Median pedestrian and vehicular travel times to hospital were 193 min (inter-quartile range: 125-267) and 49 min (32-72); analogous values for vaccine clinics were 47 (25-73) and 26 min (13-40). Infant and under-5 mortality varied two-fold across geographic locations, ranging from 34.5 to 61.9 per 1000 child-years and 8.8 to 18.1 per 1000, respectively. However, distance to health facilities was not associated with mortality. Hazard Ratios (HR) were 0.99 (95% CI 0.95-1.04) per hour and 1.01 (95% CI 0.95-1.08) per half-hour of pedestrian and vehicular travel to hospital, respectively, and 1.00 (95% CI 0.99-1.04) and 0.97 (95% CI 0.92-1.05) per quarter-hour of pedestrian and vehicular travel to vaccine clinics in children <5 years of age. Significant spatial variations in mortality were observed across the area, but were not correlated with distance to health facilities. We conclude that given the present density of health facilities in Kenya, geographic access to curative services does not influence population-level mortality.


Language style matching in writing: synchrony in essays, correspondence, and poetry.
Each relationship has its own personality. Almost immediately after a social interaction begins, verbal and nonverbal behaviors become synchronized. Even in asocial contexts, individuals tend to produce utterances that match the grammatical structure of sentences they have recently heard or read. Three projects explore language style matching (LSM) in everyday writing tasks and professional writing. LSM is the relative use of 9 function word categories (e.g., articles, personal pronouns) between any 2 texts. In the first project, 2 samples totaling 1,744 college students answered 4 essay questions written in very different styles. Students automatically matched the language style of the target questions. Overall, the LSM metric was internally consistent and reliable across writing tasks. Women, participants of higher socioeconomic status, and students who earned higher test grades matched with targets more than others did. In the second project, 74 participants completed cliffhanger excerpts from popular fiction. Judges' ratings of excerpt-response similarity were related to content matching but not function word matching, as indexed by LSM. Further, participants were not able to intentionally increase style or content matching. In the final project, an archival study tracked the professional writing and personal correspondence of 3 pairs of famous writers across their relationships. Language matching in poetry and letters reflected fluctuations in the relationships of 3 couples: Sigmund Freud and Carl Jung, Elizabeth Barrett and Robert Browning, and Sylvia Plath and Ted Hughes. Implications for using LSM as an implicit marker of social engagement and influence are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved).


Specific types of family support and adolescent non-school physical activity levels.
In a sample of 291 adolescents (mean age 13 yr), seven psychosocial factors, including family support, were examined in relation to accelerometry-derived physical activity (PA) measured after school and during the weekend. Gender-specific stepwise linear regression analyses determined which combinations of factors explained the variance in nonschool moderate to vigorous PA and nonschool total PA after adjusting for % BF, age, and maturity (p ≤ 0.05). Being praised by a family member and % BF explained 13% of the variance in female nonschool MVPA, while being praised and maturity explained 13% of the variance in nonschool total PA. Having a family member watch him participate, % BF, and age explained 11.5% of the variance in male nonschool MVPA, while having a family member participate with him explained 6.4% of the variance in nonschool total PA. Despite adolescents' growing independence, family support continues to influence PA levels.


Functional connectivity of the frontoparietal network predicts cognitive modulation of pain.
The experience of pain can be significantly influenced by expectancy (predictive cues). This ability to modulate pain has the potential to affect therapeutic analgesia substantially and constitutes a foundation for nonpharmacological pain relief. In this study, we investigated (1) brain regions involved in visual cue modulation of pain during anticipation of pain, pain administration, and pain rating; and (2) the association between pretest resting state functional connectivity and the magnitude of cue effects on pain ratings. We found that after cue conditioning, visual cues can significantly modulate subjective pain ratings. Functional magnetic resonance imaging results suggested that brain regions pertaining to the frontoparietal network (prefrontal and parietal cortex) and a pain/emotion modulatory region (rostral anterior cingulate cortex) are involved in cue modulation during both pain anticipation and administration stage. Most interestingly, we found that pretest resting state functional connectivity between the frontoparietal network (as identified by independent component analysis) and the rostral anterior cingulate cortex/medial prefrontal cortex was positively associated with cue effects on pain rating changes. We believe that these findings will shed new light on our understanding of variable cue/expectancy effects across individuals and how the intrinsic connectivity of the brain may influence expectancy-induced modulation of pain.


[Pleuropulmonary manifestations of rheumatoid arthritis. A casuistic reminder].
A case of pleuropulmonary manifestations of rheumatoid arthritis (RA) in the form of persistent pleuritis and effusion in a 58 year old male patient with known RA is presented. The well-known pleuropulmonary complications of RA pleurisy, interstitial fibrosis, effusion, rheumatoid nodules and Caplan's syndrome can occur in sero-negative patients without primary articular symptoms and therefore pose difficult problems in differential diagnosis. These problems can be partially overcome by thoracoscopic visualization of the often characteristic changes of the parietal pleura: hyperemia, vasculitis and rheumatoid nodules and histochemical examination of the pleural liquid will show low glucose concentration, high protein concentration, elevated lactate-dehydrogenase concentration, acid pH and a characteristic cytomorphology with mononuclear and neutrophil leucocytes in typical cases. The pleuropulmonary manifestations can sometimes be successfully treated with a combination of NSAIDs and methotrexate.


A phosphotyrosine displacement mechanism for activation of Src by PTPalpha.
Protein tyrosine phosphatase alpha (PTPalpha) is believed to dephosphorylate physiologically the Src proto-oncogene at phosphotyrosine (pTyr)527, a critical negative-regulatory residue. It thereby activates Src, and PTPalpha overexpression neoplastically transforms NIH 3T3 cells. pTyr789 in PTPalpha is constitutively phosphorylated and binds Grb2, an interaction that may inhibit PTPalpha activity. We show here that this phosphorylation also specifically enables PTPalpha to dephosphorylate pTyr527. Tyr789-->Phe mutation abrogates PTPalpha-Src binding, dephosphorylation of pTyr527 (although not of other substrates), and neoplastic transformation by overexpressed PTPalpha in vivo. We suggest that pTyr789 enables pTyr527 dephosphorylation by a pilot binding with the Src SH2 domain that displaces the intramolecular pTyr527-SH2 binding. Consistent with model predictions, we find that excess SH2 domains can disrupt PTPalpha-Src binding and can block PTPalpha-mediated dephosphorylation and activation in proportion to their affinity for pTyr789. Moreover, we show that, as predicted by the model, catalytically defective PTPalpha has reduced Src binding in vivo. The displacement mechanism provides another potential control point for physiological regulation of Src-family signal transduction pathways.


Triplet State Aromaticity: NICS Criterion, Hyperconjugation, and Charge Effects.
Aromaticity, one of the most important concepts in organic chemistry, has attracted considerable interest from both experimentalists and theoreticians. It remains unclear which NICS index is best to evaluate the triplet-state aromaticity. Here, we carry out thorough density functional theory (DFT) calculations to examine this issue. Our results indicate that among the various computationally available NICS indices, NICS(1)zz is the best for the triplet state. The correlations can be improved from 0.840 to 0.938 when only neutral species are considered, demonstrating the significant effect of the charge on the triplet-state aromaticity. In addition, calculations suggest that five-membered cyclic species with "hyperconjugative" aromaticity (and antiaromaticity) in the S0 state will become antiaromatic (and aromatic) in the T1 state, indicating an important role of hyperconjugation. Finally, a moderate correlation (r(2) =0.708) is identified between the NICS(1)zz values and spin distributions.


Speech perception and cortical event related potentials in children with auditory neuropathy.
1) To investigate the unaided and aided speech perception abilities of children with auditory neuropathy (AN) and to compare their performance to children with sensorineural hearing loss. 2) To establish whether cortical event related potentials (ERPs) could be recorded in children with AN, and to determine the relationship between the presence of these responses and speech perception. Unaided and aided speech perception assessments (PBK words), and cortical-ERP testing was carried out in a group of 18 children with AN. Data also were obtained from a cohort of age and hearing level matched children with sensorineural hearing loss. The speech perception performance of the 15 children with AN able to complete a PBK-word assessment, fell into two distinct categories. The children either showed no open-set speech perception ability (7/15 cases), or performance levels similar to their sensorineural counterparts (8/15 cases). Approximately 50% of children with AN showed ERPs of normal latency, amplitude and morphology. In all cases, response presence (at normal latencies) was consistent with reasonable speech perception ability, and response absence was consistent with negligible speech perception. In approximately 50% of children with auditory neuropathy, the provision of amplification results in significant open-set speech perception improvements. The results confirm the previously published reports that speech perception ability cannot be reliably estimated from the behavioral audiogram in children with AN. Obligatory ERP test results may offer a means of predicting perceptual skills in newly diagnosed youngsters as the presence of ERPs (with age-appropriate latency and morphology) was correlated with significant open set speech perception abilities and amplification benefit. The absence of the ERP in contrast, indicated profound hearing disability evidenced by profound hearing loss and/or extremely poor speech perception.


Relating the mechanical properties of atherosclerotic calcification to radiographic density: A nanoindentation approach.
Calcification morphology can determine atherosclerotic plaque stability and is associated with increased failures rates for endovascular interventions. Computational efforts have sought to elucidate the relationship between calcification and plaque rupture in addition to predicting tissue response during aggressive revascularisation techniques. However, calcified material properties are currently estimated and may not reflect real tissue conditions. The objective of this study is to correlate calcification mechanical properties with three radiographic density groups obtained from corresponding Computed Tomography (CT) images. Seventeen human plaques extracted from carotid (n = 10) and peripheral lower limb (n = 7) arteries were examined using micro-computed tomography (µCT), simultaneously locating the calcified deposits within their internal structure and quantifying their densities. Three radiographic density groups were defined based on the sample density distribution: (A) 130-299.99 Hounsfield Units (HU), (B) 300-449.99 HU and (C) >450 HU. Nanoindentation was employed to determine the Elastic Modulus (E) and Hardness (H) values within the three density groups. Results reveal a clear distinction between mechanical properties with respect to radiographic density groups (p < 0.0005). No significant differences exist in the density-specific behaviours observed between carotid and peripheral samples. Previously defined calcification classifications indicate an association with specific radiographic density patterns. Scanning Electron Microscopy (SEM) examination revealed that density group A regions consist of both calcified and non-calcified tissues. Further research is required to define the radiographic thresholds which identify varying degrees of tissue calcification. This study demonstrates that the mechanical properties of fully mineralised atherosclerotic calcification emulate that of bone tissues (17-25 GPa), affording computational models with accurate material parameters. STATEMENT OF SIGNIFICANCE: Global mechanical characterisation techniques disregard the heterogeneous nature of atherosclerotic lesions. Previous nanoindentation results for carotid calcifications have displayed a wide range. This study evaluates calcification properties with respect to radiographic density obtained from Micro-CT images. This is the first work to characterise calcifications from peripheral lower limb arteries using nanoindentation. Results demonstrate a strong positive correlation between radiographic density and calcification mechanical properties. Characterising calcifications using their density values provides clarity on the variation in published properties for calcified tissues. Furthermore, this study confirms the hypothesis that fully calcified plaque tissue behaviour similar to that of bone. Appropriate material parameters for calcified tissues can now be employed in computational simulations.


CARPs enhance p53 turnover by degrading 14-3-3sigma and stabilizing MDM2.
CARP1 and CARP2 proteins (CARPs) are E3 ligases that target p53 as well as phospho-p53 for degradation. Because MDM2 is a critical regulator of p53 turnover, we investigated and found that CARPs associate with MDM2. We provide evidence that CARPs stabilize MDM2 by inhibiting MDM2 self-ubiquitination. CARPs together with MDM2 enhance p53 degradation, thereby inhibiting p53-mediated cell death. CARP protein levels correlate with MDM2 levels including under hypoxia where both are reduced. CARP2 was found to target 14-3-3sigma for degradation, leading to MDM2 stabilization. MDMX, a homolog of MDM2, is not absolutely required for MDM2 stabilization by CARPs, although overexpression of CARP2 enhances MDM2/MDMX interaction. Taken together, our study identifies novel mechanisms by which CARP proteins regulate the p53 signaling pathway.


Daptomycin-resistant Enterococcus faecalis diverts the antibiotic molecule from the division septum and remodels cell membrane phospholipids.
Treatment of multidrug-resistant enterococci has become a challenging clinical problem in hospitals around the world due to the lack of reliable therapeutic options. Daptomycin (DAP), a cell membrane-targeting cationic antimicrobial lipopeptide, is the only antibiotic with in vitro bactericidal activity against vancomycin-resistant enterococci (VRE). However, the clinical use of DAP against VRE is threatened by emergence of resistance during therapy, but the mechanisms leading to DAP resistance are not fully understood. The mechanism of action of DAP involves interactions with the cell membrane in a calcium-dependent manner, mainly at the level of the bacterial septum. Previously, we demonstrated that development of DAP resistance in vancomycin-resistant Enterococcus faecalis is associated with mutations in genes encoding proteins with two main functions, (i) control of the cell envelope stress response to antibiotics and antimicrobial peptides (LiaFSR system) and (ii) cell membrane phospholipid metabolism (glycerophosphoryl diester phosphodiesterase and cardiolipin synthase). In this work, we show that these VRE can resist DAP-elicited cell membrane damage by diverting the antibiotic away from its principal target (division septum) to other distinct cell membrane regions. DAP septal diversion by DAP-resistant E. faecalis is mediated by initial redistribution of cell membrane cardiolipin-rich microdomains associated with a single amino acid deletion within the transmembrane protein LiaF (a member of a three-component regulatory system [LiaFSR] involved in cell envelope homeostasis). Full expression of DAP resistance requires additional mutations in enzymes (glycerophosphoryl diester phosphodiesterase and cardiolipin synthase) that alter cell membrane phospholipid content. Our findings describe a novel mechanism of bacterial resistance to cationic antimicrobial peptides. The emergence of antibiotic resistance in bacterial pathogens is a threat to public health. Understanding the mechanisms of resistance is of crucial importance to develop new strategies to combat multidrug-resistant microorganisms. Vancomycin-resistant enterococci (VRE) are one of the most recalcitrant hospital-associated pathogens against which new therapies are urgently needed. Daptomycin (DAP) is a calcium-decorated antimicrobial lipopeptide whose target is the bacterial cell membrane. A current paradigm suggests that Gram-positive bacteria become resistant to cationic antimicrobial peptides via an electrostatic repulsion of the antibiotic molecule from a more positively charged cell surface. In this work, we provide evidence that VRE use a novel strategy to avoid DAP-elicited killing. Instead of "repelling" the antibiotic from the cell surface, VRE diverts the antibiotic molecule from the septum and "traps" it in distinct membrane regions. We provide genetic and biochemical bases responsible for the mechanism of resistance and disclose new targets for potential antimicrobial development.


Human health impacts in a changing South African climate.
Climate change is projected to lead to warmer temperatures, especially in southern Africa, where the warming is predicted to be 2°C higher than the global increase. Given the high burden of disease already associated with environmental factors in this region, this temperature increase may lead to grave challenges for human health and quality of life. HIV/AIDS, poverty, food and water insecurity together with inequality and unemployment will further complicate the manner in which we will need to address the challenges of a changing climate. The health impacts are direct, such as increased temperatures leading to heat exhaustion, and indirect, such as likely increases in infectious diseases from contaminated water and changes in the distribution and/or magnitude of vector-borne diseases. The most effective measures for adapting to climate change to ensure healthy populations are to implement basic public health systems and services. These range from a continuous supply of clean water to adequate primary healthcare services. Support for required interventions is required not only from government, but also from healthcare professionals and communities. The need for disease surveillance, data capturing and more focused research is paramount.


Epidemiology of hepatitis B and C viruses: a global overview.
This article reviews the prevalence, disease burden, genotype distribution, and transmission patterns of hepatitis B virus (HBV) and hepatitis C virus in the 6 World Health Organization regions. The global epidemiology of hepatitis B and C demonstrates a predominantly declining prevalence of the diseases. Improvement in the control of hepatitis B has been largely achieved with implementation of a more universal HBV vaccine program, although a large gap still remains in the effort toward global prevention of hepatitis B. The transmission of hepatitis C has been greatly impacted by mandatory screening of blood donors in most countries in the world, although intravenous drug use continues to be a major source of infection. Public education regarding the risks of exposure to infected paraphernalia as well as household items such as razors is necessary in the continuing effort to curb this disease.


Activation of mitogen-activated protein kinase kinase by v-Raf in NIH 3T3 cells and in vitro.
Mitogen-activated protein (MAP) kinases are 42- and 44-kD serine-threonine protein kinases that are activated by tyrosine and threonine phosphorylation in cells stimulated with mitogens and growth factors. MAP kinase and the protein kinase that activates it (MAP kinase kinase) were constitutively activated in NIH 3T3 cells infected with viruses containing either of two oncogenic forms (p35EC12, p3722W) of the c-Raf-1 protein kinase. The v-Raf proteins purified from cells infected with EC12 or 22W viruses activated MAP kinase kinase from skeletal muscle in vitro. Furthermore, a bacterially expressed v-Raf fusion protein (glutathione S-transferase-p3722W) also activated MAP kinase kinase in vitro. These findings suggest that one function of c-Raf-1 in mitogenic signaling is to phosphorylate and activate MAP kinase kinase.


Knowledge, attitude and practices of non-oncologist physicians regarding cancer and palliative care: a multi-center study from Pakistan.
Cancer is a major cause of disease burden in Pakistan, so that knowledge of physicians about all aspects should be adequate, especially for palliative care for end stage management, given the generally late stage presentation. A cross-sectional study was conducted in three tertiary care hospitals and areas of general practice in Pakistan. A total of 236 non-oncologist physicians were assessed. Most of them claimed to have cared for cancer patients in someway and considered that cancer treatment is often long and protracted. However, one-third were unaware of the fact that cancer is a major disease burden in our society. About half of them thought that chemotherapy makes patients miserable. Oncology as a practice was considered financially of low reward by about a quarter. Most physicians, including consultants, were unaware of the term hospice. Many did not know where to refer cases of cancer and about the commonest cancers in Pakistani males. Awareness about cancer and palliative care among primary physicians needs to be improved for cancer prevention and control.


Development and initial standardization of Ayurveda child personality inventory.
Ayurveda inventories for prakriti (constitution) have been developed and validated for adults. Children, however, require different categories of quarter and questions, for example, to assess the intelligence, the questions can be related to their scholastic performances. To develop and standardize an inventory to assess the prakriti of the children, and to compare with Child Personality Questionnaire (CPQ). A 135-item Ayurveda child personality inventory (ACPI) scale was developed on the basis of translation of Sanskrit verses describing vataja (A), pittaja (B), and kaphaja prakriti (C) characteristics and by taking the opinions of experts (ten Ayurveda experts and three psychologists). Study was carried out in Maxwell public school, Bangalore. The scale was administered on parents of children of the age group 6-12 years. CPQ was administered on children of the age group 8-12 years. The ACPI was associated with excellent internal consistency. The Cronbach's alpha for A, B, and C scales were 0.77, 0.55, and 0.84, respectively, and the Split-half reliability scores were 0.66.0.39 and 0.84, respectively. Factor validity coefficient scores on each items was above 0.5. Scores on vataja, pittaja and kaphaja scales were inversely correlated. Items of V, P, and K scales showed significant correlation (values ranging from 0.39 to 0.84) with subscales of CPQ, which indicates that Eastern and Western psychology concept have good correspondence. The prakrti of the children can be measured consistently by this instrument. Scores on V and P scale showed good correlation with the anxiety primary scale of CPQ.


A Validated RP-HPLC Method for Simultaneous Estimation of Nebivolol and Hydrochlorothiazide in Tablets.
A simple, selective, rapid, precise and economical reverse phase high pressure liquid chromatographic method has been developed for the simultaneous estimation of nebivolol and hydrochlorthiazide from pharmaceutical formulation. Phenomenex Gemini C(18) (25 cm×4.6 mm i.d., 5 μ) column with a mobile phase consisting of acetonitrile: 50mM ammonium acetate (adjusted to pH 3.5 using orthophosphoric acid) (70:30 v/v) at a flow rate of 1.0 ml/min was used. Detection was carried out at 254 nm. Probenecid was used as an internal standard. The retention times of probenecid, nebivolol and hydrochlorthiazide were 13.05, 3.32 and 4.25 min, respectively. The developed method was validated in terms of accuracy, precision, linearity, limit of detection, limit of quantitation and solution stability. The proposed method can be used for the estimation of these drugs in combined dosage forms.


Molecular characterization of Swiss Ceratopogonidae (Diptera) and evaluation of real-time PCR assays for the identification of Culicoides biting midges.
Biting midges of the genus Culicoides (Diptera, Ceratopogonidae) are vectors of several viruses of veterinary relevance, and they can cause insect bite hypersensitivity. As the morphological identification of these tiny insects is a difficult task in many cases, alternative approaches are expedient. With the aim to develop real-time PCRs, we determined partial mitochondrial cytochrome oxidase I gene (mt COI) sequences from 380 Culicoides midges representing three regions of Switzerland, namely the Alps, Midland north of the Alps (Atlantic climate), and South of the Alps (Mediterranean climate). The same region was also sequenced from non-biting midges of the genera Atrichopogon, Brachypogon, Dasyhelea, Forcipomyia and Serromyia. A total of 21 Culicoides species were identified by morphology. Sequence variability (haplotypes) was observed in all species. For each of C. grisescens and C. obsoletus, a novel cryptic species was identified. Whereas all individuals of C. grisescens and of the cryptic C. obsoletus species (O2) originated only from Alpine sites, the known C. obsoletus (O1) species was found in all three regions. Further, a sister taxon to C. pulicaris was identified based on the mt COI sequences and named Culicoides sp. Alignments of available mtCOI sequences from Ceratopogonidae (GenBank, this study) were used to design real-time PCR primers and probes to distinguish C. chiopterus, C. deltus, C. dewulfi, C. grisescens (including the cryptic species), C. imicola, C. lupicaris, C. obsoletus O1, C. obsoletus O2, C. pulicaris, C. scoticus and Culicoides sp. Specificities of primers and probes was tested with cloned targets representing 1 to 4 haplotypes of 18 Culicoides spp. and 1 haplotype each from 4 other Ceratopogonidae. No cross-reactivity was observed when plasmid template representing 5 × 10(6) gene copies was tested, but it was evident (Ct values ≤ 30) in few instances when plasmid template representing 5 × 10(9) gene copies was utilized, the latter corresponding to the total gene copy number (as determined in this study) in 20 insects. The sensitivities of two assays (C. imicola, C. grisescens) were tested by spiking single insects into pools of 99 or 999, randomly selected non-target Ceratopogonidae (with approx. 90% Culicoides specimens). In the pools of 100, Ct values were in the range of those obtained with single insects when employing 1% of the isolated DNA, whereas the sensitivity with the pools of 1000 was low, presumably due to the low DNA concentrations obtained with a protocol that seems inadequate for these larger pools. Thus, the assays as described are applicable for the specific identification of biting midges in small pools. Primers and probes of this study were devised to be suitable for multiplexed assays but these evaluations await to be performed.


Curating the innate immunity interactome.
The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks. A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks. InnateDB (http://www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity. Here, we describe the InnateDB curation project, which is manually annotating the human and mouse innate immunity interactome in rich contextual detail, and present our novel curation software system, which has been developed to ensure interactions are curated in a highly accurate and data-standards compliant manner. To date, over 13,000 interactions (protein, DNA and RNA) have been curated from the biomedical literature. Here, we present data, illustrating how InnateDB curation of the innate immunity interactome has greatly enhanced network and pathway annotation available for systems-level analysis and discuss the challenges that face such curation efforts. Significantly, we provide several lines of evidence that analysis of the innate immunity interactome has the potential to identify novel signalling, transcriptional and post-transcriptional regulators of innate immunity. Additionally, these analyses also provide insight into the cross-talk between innate immunity pathways and other biological processes, such as adaptive immunity, cancer and diabetes, and intriguingly, suggests links to other pathways, which as yet, have not been implicated in the innate immune response. In summary, curation of the InnateDB interactome provides a wealth of information to enable systems-level analysis of innate immunity.


Family physicians' preferences for computerized decision-support hardware and software.
While computers are now widely used by family physicians for billing and patient registration purposes, their use as decision-support tools is still quite limited. The purpose of this study was to determine the current use of computer hardware and software by family physicians, and the characteristics these physicians desire in computerized decision-support hardware and software. A cross-sectional survey of a random sample of 250 Michigan family physicians was undertaken in mid-1995. These physicians were asked about their current use of a variety of computer hardware and software. They were also asked to rate the value of different kinds of decision-support information potentially available by computer. The survey instrument also gathered the family physicians' preferences for design factors (both hardware and software), such as the size of a computer, the time needed to access information, and the frequency of updates. Word processing on desktop computers and hospital information systems are the most widely used computer applications by family physicians. Physicians are most interested in computer-based information on drugs, storage and generation of patient education materials, and accessing treatment recommendations. Most feel that semiannual or annual updates of information are adequate, and would like a uniform interface. A high percentage of physicians (84.5% of all physicians and 94.1% of younger physicians) stated that they would consider carrying a handheld computer. There is significant interest in several types of clinical decision-support software. Based on the results of this study, such software should have following characteristics: (1) be available for handheld as well as networked and desktop computers, (2) include drug information (particularly warnings, interactions, and side effects), (3) include overviews of treatment recommendations, (4) include patient education materials, and (5) have a uniform user interface and be updated at least annually.


Expression of a functional Kir4 family inward rectifier K+ channel from a gene cloned from mouse liver.
1. A low stringency polymerase chain reaction (PCR) homology screening procedure was used to probe a mouse liver cDNA library to identify novel inward rectifier K+ channel genes. A single gene (mLV1) was identified that exhibited extensive sequence homology with previously cloned inward rectifier K+ channel genes. The mLV1 gene showed greatest sequence identity with genes belonging to the Kir4 subfamily. The amino acid sequence of mLV1 was 96 % identical to a Kir channel cloned from human kidney (hKir4.2), and approximately 60 % identical to the Kir4.1 channel cloned from human and rat, so that mLV1 was classified as mKir4.2. 2. Xenopus oocytes injected with cRNA encoding mKir4.2 displayed a large inwardly rectifying K+ current, while control oocytes injected with H2O displayed no similar K+ current. The current was blocked by Ba2+ and Cs+ in a voltage-dependent fashion and displayed inward rectification that was intermediate between that of the strong inward rectifier Kir2.1 and the weak inward rectifier Kir1.1. The current was weakly blocked by TEA in a voltage-independent fashion. 3. mKir4.2 current was subject to modulation by several distinct mechanisms. Intracellular acidification decreased mKir4.2 current in a reversible fashion, while activation of protein kinase C decreased mKir4.2 current in a manner that was not rapidly reversible. Incubation of oocytes in elevated [K+] produced a slowly developing enhancement of current. 4. Oocytes co-injected with cRNA for mKir4.2 and Kir5.1, a protein that does not form functional homomeric channels, displayed membrane currents with properties distinct from those expressing mKir4.2 alone. Co-injected oocytes displayed larger currents than mKir4.2, with novel kinetic properties and an increased sensitivity to Ba2+ block at negative potentials, suggesting that mKir4.2 forms functional heteromultimeric channels with Kir5.1, as has been shown for Kir4.1 5. These results demonstrate for the first time that a Kir4.2 channel gene product forms functional channels in Xenopus oocytes, that these Kir channels display novel properties, and that Kir4.2 subunits may be responsible for physiological modulation of functional Kir channels.


Climate impacts on human settlement and agricultural activities in northern Norway revealed through sediment biogeochemistry.
Disentangling the effects of climate change and anthropogenic activities on the environment is a major challenge in paleoenvironmental research. Here, we used fecal sterols and other biogeochemical compounds in lake sediments from northern Norway to identify both natural and anthropogenic signals of environmental change during the late Holocene. The area was first occupied by humans and their grazing animals at ∼2,250 ± 75 calendar years before 1950 AD (calendar years before present). The arrival of humans is indicated by an abrupt increase in coprostanol (and its epimer epicoprostanol) in the sediments and an associated increase in 5β-stigmastanol (and 5β-epistigmastanol), which resulted from human and animal feces washing into the lake. Human settlement was accompanied by an abrupt increase in landscape fires (indicated by the rise in pyrolytic polycyclic aromatic hydrocarbons) and a decline in woodland (registered by a change in n-alkane chain lengths from leaf waxes), accelerating a process that began earlier in the Holocene. Human activity and associated landscape changes in the region over the last two millennia were mainly driven by summer temperatures, as indicated by independent tree-ring reconstructions, although there were periods when socioeconomic factors played an equally important role. In this study, fecal sterols in lake sediments have been used to provide a record of human occupancy through time. This approach may be useful in many archeological studies, both to confirm the presence of humans and grazing animals, and to distinguish between anthropogenic and natural factors that have influenced the environment in the past.


A novel flexible capacitive load sensor for use in a mobile unicompartmental knee replacement bearing: An in vitro proof of concept study.
Instrumented knee replacements can provide in vivo data quantifying physiological loads acting on the knee. To date instrumented mobile unicompartmental knee replacements (UKR) have not been realised. Ideally instrumentation would be embedded within the polyethylene bearing. This study investigated the feasibility of an embedded flexible capacitive load sensor. A novel flexible capacitive load sensor was developed which could be incorporated into standard manufacturing of compression moulded polyethylene bearings. Dynamic experiments were performed to determine the characteristics of the sensor on a uniaxial servo-hydraulic material testing machine. The instrumented bearing was measured at sinusoidal frequencies between 0.1 and 10Hz, allowing for measurement of typical gait load magnitudes and frequencies. These correspond to frequencies of interest in physiological loading. The loads that were applied were a static load of 390N, corresponding to an equivalent body weight load for UKR, and a dynamic load of ±293N. The frequency transfer response of the sensor suggests a low pass filter response with a -3dB frequency of 10Hz. The proposed embedded capacitive load sensor was shown to be applicable for measuring in vivo loads within a polyethylene mobile UKR bearing.


Microbial diversity in the midguts of field and lab-reared populations of the European corn borer Ostrinia nubilalis.
Insects are associated with microorganisms that contribute to the digestion and processing of nutrients. The European Corn Borer (ECB) is a moth present world-wide, causing severe economical damage as a pest on corn and other crops. In the present work, we give a detailed view of the complexity of the microorganisms forming the ECB midgut microbiota with the objective of comparing the biodiversity of the midgut-associated microbiota and explore their potential as a source of genes and enzymes with biotechnological applications. A high-throughput sequencing approach has been used to identify bacterial species, genes and metabolic pathways, particularly those involved in plant-matter degradation, in two different ECB populations (field-collected vs. lab-reared population with artificial diet). Analysis of the resulting sequences revealed the massive presence of Staphylococcus warneri and Weissella paramesenteroides in the lab-reared sample. This enabled us to reconstruct both genomes almost completely. Despite the apparently low diversity, 208 different genera were detected in the sample, although most of them at very low frequency. By contrast, the natural population exhibited an even higher taxonomic diversity along with a wider array of cellulolytic enzyme families. However, in spite of the differences in relative abundance of major taxonomic groups, not only did both metagenomes share a similar functional profile but also a similar distribution of non-redundant genes in different functional categories. Our results reveal a highly diverse pool of bacterial species in both O. nubilalis populations, with major differences: The lab-reared sample is rich in gram-positive species (two of which have almost fully sequenced genomes) while the field sample harbors mainly gram-negative species and has a larger set of cellulolytic enzymes. We have found a clear relationship between the diet and the midgut microbiota, which reveals the selection pressure of food on the community of intestinal bacteria.


A novel interface for the telementoring of robotic surgery.
To prospectively evaluate the feasibility and safety of a novel, second-generation telementoring interface (Connect(™) ; Intuitive Surgical Inc., Sunnyvale, CA, USA) for the da Vinci robot. Robotic surgery trainees were mentored during portions of robot-assisted prostatectomy and renal surgery cases. Cases were assigned as traditional in-room mentoring or remote mentoring using Connect. While viewing two-dimensional, real-time video of the surgical field, remote mentors delivered verbal and visual counsel, using two-way audio and telestration (drawing) capabilities. Perioperative and technical data were recorded. Trainee robotic performance was rated using a validated assessment tool by both mentors and trainees. The mentoring interface was rated using a multi-factorial Likert-based survey. The Mann-Whitney and t-tests were used to determine statistical differences. We enrolled 55 mentored surgical cases (29 in-room, 26 remote). Perioperative variables of operative time and blood loss were similar between in-room and remote mentored cases. Robotic skills assessment showed no significant difference (P > 0.05). Mentors preferred remote over in-room telestration (P = 0.05); otherwise no significant difference existed in evaluation of the interfaces. Remote cases using wired (vs wireless) connections had lower latency and better data transfer (P = 0.005). Three of 18 (17%) wireless sessions were disrupted; one was converted to wired, one continued after restarting Connect, and the third was aborted. A bipolar injury to the colon occurred during one (3%) in-room mentored case; no intraoperative injuries were reported during remote sessions. In a tightly controlled environment, the Connect interface allows trainee robotic surgeons to be telementored in a safe and effective manner while performing basic surgical techniques. Significant steps remain prior to widespread use of this technology.


Use of hypertonic saline injection in trauma.
The use of hypertonic saline injection in trauma patients is discussed. Patients with hemorrhage, burns, and traumatic brain injury (TBI) may develop hypovolemic shock and require resuscitation. Compared with conventional isotonic crystalloids, hypertonic saline has several advantages, including hemodynamic, immune-modulating, and antiinflammatory effects, for use in trauma patients for resuscitation. In addition, hypertonic saline is also used in patients with TBI to reduce intracranial pressure (ICP). Overall, studies have not shown a difference in mortality or other clinically important outcomes with the use of hypertonic saline for resuscitation in trauma patients; however, most of these studies were not adequately powered to show significant differences. A recent Cochrane review concluded that there is no evidence that hypertonic crystalloids are better than isotonic or near-isotonic crystalloids for fluid resuscitation in trauma patients. Two recent trials that were adequately powered to investigate a mortality endpoint were halted for futility. A few small randomized controlled studies found that hypertonic saline was more effective than mannitol as a hyperosmolar agent for ICP reduction. Recent guidelines from the American Burn Association have suggested that hypertonic saline may be used for burn shock resuscitation by experienced providers with close monitoring to avoid excessive hypernatremia. One of the main concerns with the use of hypertonic saline is its potential to cause central pontine myelinolysis due to a rapid increase in serum sodium levels. There is no evidence that hypertonic saline provides any additional benefit over isotonic crystalloid solutions for trauma resuscitation. Hypertonic saline may be more effective than mannitol at reducing ICP in patients with TBI.


Towards a common methodology for developing logistic tree mortality models based on ring-width data.
Tree mortality is a key process shaping forest dynamics. Thus, there is a growing need for indicators of the likelihood of tree death. During the last decades, an increasing number of tree-ring based studies have aimed to derive growth-mortality functions, mostly using logistic models. The results of these studies, however, are difficult to compare and synthesize due to the diversity of approaches used for the sampling strategy (number and characteristics of alive and death observations), the type of explanatory growth variables included (level, trend, etc.), and the length of the time window (number of years preceding the alive/death observation) that maximized the discrimination ability of each growth variable. We assess the implications of key methodological decisions when developing tree-ring based growth-mortality relationships using logistic mixed-effects regression models. As examples, we use published tree-ring datasets from Abies alba (13 different sites), Nothofagus dombeyi (one site), and Quercus petraea (one site). Our approach is based on a constant sampling size and aims at (1) assessing the dependency of growth-mortality relationships on the statistical sampling scheme used, (2) determining the type of explanatory growth variables that should be considered, and (3) identifying the best length of the time window used to calculate them. The performance of tree-ring-based mortality models was reasonably high for all three species (area under the receiving operator characteristics curve, AUC > 0.7). Growth level variables were the most important predictors of mortality probability for two species (A. alba, N. dombeyi), while growth-trend variables need to be considered for Q. petraea. In addition, the length of the time window used to calculate each growth variable was highly uncertain and depended on the sampling scheme, as some growth-mortality relationships varied with tree age. The present study accounts for the main sampling-related biases to determine reliable species-specific growth-mortality relationships. Our results highlight the importance of using a sampling strategy that is consistent with the research question. Moving towards a common methodology for developing reliable growth-mortality relationships is an important step towards improving our understanding of tree mortality across species and its representation in dynamic vegetation models.


Central Venous Catheter Salvage in Home Parenteral Nutrition Catheter-Related Bloodstream Infections: Long-Term Safety and Efficacy Data.
Catheter-related bloodstream infections (CRBSIs) are a serious complication in the provision of home parenteral nutrition (HPN). Antibiotic salvage of central venous catheters (CVCs) in CRBSI is recommended; however, this is based on limited reports. We assessed the efficacy of antibiotic salvage of CRBSIs in HPN patients. All confirmed CRBSIs occurring in patients receiving HPN in a national intestinal failure unit (IFU), between 1993 and 2011, were analyzed. A standardized protocol involving antibiotic and urokinase CVC locks and systemic antibiotics was used. In total, 588 patients were identified with a total of 2134 HPN years, and 297 CRBSIs occurred in 137 patients (65 single and 72 multiple CRBSIs). The overall rate of CRBSI in all patients was 0.38 per 1000 catheter days. Most (87.9%) infections were attributable to a single microorganism. In total, 72.5% (180/248) of CRBSIs were salvaged when attempted (coagulase-negative staphylococcus, 79.8% [103/129], Staphylococcus aureus, 56.7% [17/30]; polymicrobial infections, 67.7% [21/30]; and miscellaneous, 66.1% [39/59]). CVC salvage was not attempted in 49 episodes because of life-threatening sepsis (n = 18), fungal infection (n = 7), catheter problems (n = 20), and CVC tunnel infection (n = 4). Overall, the CVC was removed in 33.7% (100/297) of cases. There were 5 deaths in patients admitted to the IFU for management of the CRBSI (2 severe sepsis at presentation, 3 metastatic infection). This is the largest reported series of catheter salvage in CRBSIs and demonstrates successful catheter salvage in most cases when using a standardized protocol.


Relationship between xerostomia and gingival condition in young adults.
Xerostomia is a subjective symptom of dryness in the mouth. Although a correlation between xerostomia and oral conditions in the elderly has been reported, there are few such studies in the young adults. The aim of this study was to examine the relationship of xerostomia with the gingival condition in university students. A total of 2077 students (1202 male subjects and 875 female subjects), 18-24 years of age, were examined. The disease activity and severity of the gingival condition were assessed as the percentage of teeth with bleeding on probing (%BOP) and the presence of teeth with probing pocket depth of ≥ 4 mm, respectively. Additional information on xerostomia, oral health behaviors, coffee/tea intake and nasal congestion was collected via a questionnaire. Path analysis was used to test pathways from xerostomia to the gingival condition. One-hundred and eighty-three (8.8%) students responded that their mouths frequently or always felt dry. Xerostomia was related to %BOP and dental plaque formation, but was not related to the presence of probing pocket depth ≥ 4 mm. In the structural model, xerostomia was related to dental plaque formation (p < 0.01), and a lower level of dental plaque formation was associated with a lower %BOP. Xerostomia was associated with coffee/tea intake (p < 0.01) and nasal congestion (p < 0.001). Xerostomia was indirectly related to gingival disease activity through the accumulation of dental plaque. Nasal congestion and coffee/tea intake also affected xerostomia. These findings suggest that xerostomia should be considered in screening for gingivitis risk in young adults.


Using Smartphones and Health Apps to Change and Manage Health Behaviors: A Population-Based Survey.
Chronic conditions are an increasing challenge for individuals and the health care system. Smartphones and health apps are potentially promising tools to change health-related behaviors and manage chronic conditions. The aim of this study was to explore (1) the extent of smartphone and health app use, (2) sociodemographic, medical, and behavioral correlates of smartphone and health app use, and (3) associations of the use of apps and app characteristics with actual health behaviors. A population-based survey (N=4144) among Germans, aged 35 years and older, was conducted. Sociodemographics, presence of chronic conditions, health behaviors, quality of life, and health literacy, as well as the use of the Internet, smartphone, and health apps were assessed by questionnaire at home visit. Binary logistic regression models were applied. It was found that 61.25% (2538/4144) of participants used a smartphone. Compared with nonusers, smartphone users were younger, did more research on the Internet, were more likely to work full-time and more likely to have a university degree, engaged more in physical activity, and less in low fat diet, and had a higher health-related quality of life and health literacy. Among smartphone users, 20.53% (521/2538) used health apps. App users were younger, less likely to be native German speakers, did more research on the Internet, were more likely to report chronic conditions, engaged more in physical activity, and low fat diet, and were more health literate compared with nonusers who had a smartphone. Health apps focused on smoking cessation (232/521, 44.5%), healthy diet (201/521, 38.6%), and weight loss (121/521, 23.2%). The most common app characteristics were planning (264/521, 50.7%), reminding (188/521, 36.1%), prompting motivation (179/521 34.4%), and the provision of information (175/521, 33.6%). Significant associations were found between planning and the health behavior physical activity, between feedback or monitoring and physical activity, and between feedback or monitoring and adherence to doctor's advice. Although there were many smartphone and health app users, a substantial proportion of the population was not engaged. Findings suggest age-related, socioeconomic-related, literacy-related, and health-related disparities in the use of mobile technologies. Health app use may reflect a user's motivation to change or maintain health behaviors. App developers and researchers should take account of the needs of older people, people with low health literacy, and chronic conditions.


Overexpression of MUC1 reconfigures the binding properties of tumor cells.
Although it is known that adhesion and antiadhesion are essential to the metastatic spread of tumor cells, little is known about the molecules that regulate these processes. MUC1 is overexpressed and aberrantly glycosylated by a variety of tumor cells. Studies described here examined whether tumor-associated MUC1 conferred new binding properties on tumor cell lines. Flow cytometry analysis with soluble P-, E- and L-selectin/IgM chimeric proteins was performed on human pancreatic (S2-013 and Panc-1) and colon (Caco-2) tumor cells. S2-013 cells bound E- and P-selectin and Caco-2 cells bound P-selectin. Epitope-tagged MUC1 (MUC1F) expressed by S2-013, Panc-1 and Caco-2 tumor cells did not bind to P-, E- or L-selectin. Overexpression of MUC1F on the surface of S2-013 cells blocked the interactions of E-selectin to tumor-associated ligand(s) but did not affect accessibility of monoclonal antibodies to other cell surface glycoproteins (CD9, CD44). Cell aggregation assays revealed that MUC1F expressed by S2-013 cells was able to bind to intracellular adhesion molecule-1 expressed on B cells. Overexpression of MUC1F containing a targeted mutation (the tandem repeat domain entirely or partially deleted) did not block the binding of E-selectin to its S2-013-associated ligand. These results demonstrate for the first time that the heavily O-glycosylated tandem repeat domain of MUC1 can simultaneously mediate and block binding to adhesion molecules with some molecular specificity and further support the hypothesis that MUC1 plays a dual role in the metastatic spread of tumor cells.


Testing the quality of a carrier: a field experiment on lizard signalers.
In the Australian painted dragon lizard (Ctenophorus pictus), males occur in two different morphs with respect to gular color, with or without a yellow bib. Males without a bib lost within-clutch paternity significantly more often to rivals than bibbed males. Thus, it appears that bibs identify some phenotypic advantage linked to competitive ability. To test whether this could be related to whole-organism capacity to withstand an increased workload (due to better health and vigor, or evolved differences in self-maintenance), we implanted males with a lead pellet (loaded), Styrofoam pellet (controls), or sham-operated males without implants (shams), and compared male categories with respect to how they maintained body mass during the mating season. Somewhat unexpectedly, bibbed males consistently lost more body weight across all treatments and controls, although we could not verify that this translated into higher mortality in this short-lived animal (about 80% survive for one year only). However, bibbed males may invest more into "mating success" than nonbibbed males, which agrees with our experimental results and paternity data.


Preventing child abuse and neglect: a randomized trial of nurse home visitation.
A program of prenatal and infancy home visitation by nurses was tested as a method of preventing a wide range of health and developmental problems in children born to primiparas who were either teenagers, unmarried, or of low socioeconomic status. Among the women at highest risk for care-giving dysfunction, those who were visited by a nurse had fewer instances of verified child abuse and neglect during the first 2 years of their children's lives (P = .07); they were observed in their homes to restrict and punish their children less frequently, and they provided more appropriate play materials; their babies were seen in the emergency room less frequently during the first year of life. During the second year of life, the babies of all nurse-visited women, regardless of the families' risk status, were seen in the emergency room fewer times, and they were seen by physicians less frequently for accidents and poisonings than comparison group babies (P less than or equal to .05 for all findings, except where indicated.) Treatment differences for child abuse and neglect and emergency room visits were more significant among women who had a lower sense of control over their lives.


Vitamin B12 intramuscular injections versus oral supplements: a budget impact analysis.
Vitamin B12 deficiency can lead to adverse health effects such as anemia and, in some cases, permanent neurologic damage. In Canada, patients with vitamin B12 deficiency are typically given intramuscular injections, which incur considerable cost and inconvenience. The clinical evidence-based analysis has found that oral supplementation is as effective as intramuscular injections. This economic analysis aimed to estimate the cost savings of switching from intramuscular injections to high-dose oral supplements for patients aged 18 years and older with confirmed vitamin B12 deficiency. Population-based administrative databases for Ontario were used to identify patients receiving vitamin B12 intramuscular injections in any fiscal year between 2006 and 2011. The Ontario Drug Benefit (ODB) database was used to identify patients who were prescribed vitamin B12 injections, and the Ontario Health Insurance Plan database was used to identify all physician claims for intramuscular injections as well as laboratory tests assessing vitamin B12 levels. The Registered Physicians Database was used to identify the type of physician; the analysis was restricted to family physicians and internists. Two cohorts of patients were identified. For cohort 1, the ODB database was used to identify patients who were prescribed vitamin B12 injections. Those covered under the ODB are 65 years of age or older and are economically deprived. A second cohort was created to capture those 18 to 64 years of age receiving injections. Cohort 2 consisted of patients (not in cohort 1) who received 6 or more intramuscular injections within 1 year and had a laboratory test 2 months before the intramuscular injection claim. Physician experts were consulted to estimate the resources and costs of converting patients to oral supplements. The Ministry of Health and Long-Term Care perspective was taken, and all costs are expressed in 2013 Canadian dollars. The budget impact analysis demonstrated costs of $2.8 million to the Ministry of Health and Long-Term Care in the first year of conversion; however, in subsequent years there are savings of $4.2 million per year. The cumulative 5-year budget impact demonstrates savings of $14.2 million to the health care system. This analysis represents the cost of conversion for those currently receiving intramuscular injections. There are no conversion costs for those who are prescribed oral supplements as an initial therapy, and so the savings could be even greater than reported. As well, an underlying assumption of this analysis is that patients will comply with oral supplementation. Over 5 years, there are savings of $14.2 million to the health care system from switching to vitamin B12 oral supplements. Vitamin B12 deficiency has long been thought to be associated with dementia and other neurocognitive disorders. In a separate report, Health Quality Ontario (HQO) reviewed the published research on this issue and found only weak evidence that vitamin B12 deficiency is associated with the onset of dementia. That review also found moderate evidence that treatment with vitamin B12 does not improve dementia and that oral supplements are as effective as injections of vitamin B12. In 2010, more than 2.9 million serum vitamin B12 tests were performed in Ontario at a cost of $40 million. Each year, approximately 110,000 residents receive vitamin B12 injections to boost their levels of vitamin B12. HQO commissioned an economic analysis to estimate the cost savings of switching from vitamin B12 injections to high-dose oral supplements for patients aged 18 years and older with confirmed B12 deficiency. This study concluded that the Ontario health care system could save $14.5 million in 5 years by switching to oral supplements, assuming that patients took the oral supplements as required.


Genetic counseling, genetic testing, and risk perceptions for breast and colorectal cancer: Results from the 2015 National Health Interview Survey.
We examined what proportion of the U.S. population with no personal cancer history reported receiving either genetic counseling or genetic testing for cancer risk, and also the association of these behaviors with cancer risk perceptions. We used data from the 2015 National Health Interview Survey. Objective relative risk scores for breast (women) and colorectal (men and women) cancer risk were generated for individuals without a personal history of cancer. Participants' risk perceptions were compared with their objective relative risk. Of 12,631 women, 1.2% reported receiving genetic counseling and 0.8% genetic testing for hereditary breast cancer risk. Of 15,085 men and women, 0.8% reported receiving genetic counseling and 0.3% genetic testing for hereditary colorectal cancer risk. Higher breast cancer risk perception was associated with genetic counseling (OR: 4.31, 95%CI: 2.56, 7.26) and testing (OR: 3.56, 95%CI: 1.80, 7.03). Similarly, higher perception of colorectal cancer risk was associated with genetic counseling (OR: 5.04, 95%CI: 2.57, 9.89) and testing (OR: 5.92, 95%CI: 2.40, 14.63). A higher proportion of individuals with colorectal cancer risk perceptions concordant with their objective risk (vs. discordant) had undergone genetic counseling or testing for colorectal cancer risk. Concordant risk perceptions for breast cancer were not associated with breast cancer genetic counseling or testing. Given frequent dialogue about implementing population level programs involving genetic services for cancer risk, policy makers and investigators should consider the role of risk perceptions in the effectiveness and design of such programs and potential strategies for addressing inaccuracies in risk perceptions.


Polymer grafting to single-walled carbon nanotubes: effect of chain length on solubility, graft density and mechanical properties of macroscopic structures.
Single-walled carbon nanotubes are grafted with polystyrene chains employing a graft-to protocol. Thermogravimetric analysis allows calculation of the grafted chain density and average interchain separation on the nanotube surface as a function of molecular weight. The separation scales with molecular weight as a power law with an exponent of ca. 0.588, showing the grafted chains to be in a swollen random walk conformation. This implies that chain packing is controlled by coil size in solution. In addition, the dispersed concentration of functionalized nanotubes scales with the size of the steric potential barrier that prevents aggregation of polymer functionalized nanotubes. It is also shown that the molecular weight of the grafted chains significantly affects the mechanical properties of nanotube films.


Molecular dynamics simulation of the M2 helices within the nicotinic acetylcholine receptor transmembrane domain: structure and collective motions.
Multiple nanosecond duration molecular dynamics simulations were performed on the transmembrane region of the Torpedo nicotinic acetylcholine receptor embedded within a bilayer mimetic octane slab. The M2 helices and M2-M3 loop regions were free to move, whereas the outer (M1, M3, M4) helix bundle was backbone restrained. The M2 helices largely retain their hydrogen-bonding pattern throughout the simulation, with some distortions in the helical end and loop regions. All of the M2 helices exhibit bending motions, with the hinge point in the vicinity of the central hydrophobic gate region (corresponding to residues alphaL251 and alphaV255). The bending motions of the M2 helices lead to a degree of dynamic narrowing of the pore in the region of the proposed hydrophobic gate. Calculations of Born energy profiles for various structures along the simulation trajectory suggest that the conformations of the M2 bundle sampled correspond to a closed conformation of the channel. Principal components analyses of each of the M2 helices, and of the five-helix M2 bundle, reveal concerted motions that may be relevant to channel function. Normal mode analyses using the anisotropic network model reveal collective motions similar to those identified by principal components analyses.


Association between limiting longstanding illness in mothers and their children: findings from the UK Millennium Cohort Study.
To explore the association between maternal disability as measured by the presence of a limiting longstanding illness (LLI) 9 months postpartum and subsequent child health at the age of 7 years. Nationally representative prospective longitudinal study. England, Scotland, Wales and Northern Ireland. Secondary analysis of data on 11 807 mother-child pairs recruited to the UK Millennium Cohort Study. Baseline interviews with mothers were carried out in 2001-2002. When the children were 7 years old, the follow-up survey included questions about limiting longstanding health conditions in the child. Any longstanding condition that was reported to limit the children's activities in any way. Nearly 7% of all children were reported to have an LLI at the age of 7 years. The majority (88.1%, 95% CI 85.6% to 90.2%) of children whose mother was disabled did not have an LLI themselves. The children of disabled mothers, however, had higher odds of LLI (OR=1.9, 95% CI 1.5 to 2.5) independently of different maternal, pregnancy and birth characteristics and breast feeding duration. Inclusion of poverty measures in the model did not significantly affect the odds (OR=1.8, 95% CI 1.4 to 2.4), suggesting that maternal LLI around the time of birth increases the odds of child LLI at the age of 7 years independently of starting life in poverty. There is a strong positive association between maternal and child LLI. Health professionals should work together with social care and other relevant service providers to identify the individual needs of disabled parents and provide adequate support throughout the pregnancy and after the child is born. Further research is important to clarify the exact nature of the associations for different types of maternal and child disability.


Rituximab and immune deficiency: case series and review of the literature.
As the indications and use of rituximab continue to expand, the reports of long-term effects of anti-CD20--mediated B-cell depletion on the immune system accumulate. We report a group of patients with immunodeficiency who were treated with rituximab and present their immunologic data. A retrospective chart review identified patients with immunodeficiency who received rituximab for treatment of their primary disease and required immunoglobulin replacement therapy (IGRT). Pre-IGRT immunoglobulins, specific antibodies, B-cells, and B-cell phenotype were recorded and analyzed. We identified 11 patients with immunodeficiency who received rituximab and required IGRT. Two of these patients were diagnosed with common variable immunodeficiency before rituximab treatment. Nine other patients had hypogammaglobulinemia and did not achieve an adequate response to polysaccharide vaccine. There was a significant delay in B-cell recovery. B-cell phenotypes identified predominantly naive B cells in the blood of these patients with significant decrease in switched and memory B cells. There are patients with persistent B-cell dysfunction long after rituximab treatment was discontinued. Some of these patients required IGRT. These patients should be distinguished from patients with primary immunodeficiency diseases. Routine baseline B-cell numbers and serum immunoglobulin levels before starting immunomodulatory therapy are required to help distinguish primary immunodeficiency diseases from secondary rituximab-induced, transient, and, at times, prolonged immune suppression. Periodic monitoring is prudent to identify immune recovery. Post-rituximab B-cell phenotyping may help identify the patients who will develop persistent immune dysfunction caused by an unidentified underlying disease or the prolonged effect of rituximab treatment.


Survey Response Styles, Acculturation, and Culture Among a Sample of Mexican American Adults.
A number of studies have investigated use of extreme (ERS) and acquiescent (ARS) response styles across cultural groups. However, due to within-group heterogeneity, it is important to also examine use of response styles, acculturation, and endorsement of cultural variables at the individual level. This study explores relationships between acculturation, six Mexican cultural factors, ERS, and ARS among a sample of 288 Mexican American telephone survey respondents. Three aspects of acculturation were assessed: Spanish use, the importance of preserving Mexican culture, and interaction with Mexican Americans versus Anglos. These variables were hypothesized to positively associate with ERS and ARS. Participants with higher Spanish use did utilize more ERS and ARS; however, value for preserving Mexican culture and interaction with Mexican Americans were not associated with response style use. In analyses of cultural factors, endorsement of familismo and simpatia were related to more frequent ERS and ARS, machismo was associated with lower ERS among men, and la mujer was related to higher ERS among women. Caballerismo was marginally associated with utilization of ERS among men. No association was found between la mujer abnegada and ERS among women. Relationships between male gender roles and ARS were nonsignificant. Relationships between female gender roles and ARS were mixed but trended in the positive direction. Overall, these findings suggest that Mexican American respondents vary in their use of response styles by acculturation and cultural factors. This usage may be specifically influenced by participants' valuing of and engagement with constructs directly associated with social behavior.


Comparison of the complications in vertical rectus abdominis musculocutaneous flap with non-reconstructed cases after pelvic exenteration.
Perineal reconstruction following pelvic exenteration is a challenging area in plastic surgery. Its advantages include preventing complications by obliterating the pelvic dead space and minimizing the scar by using the previous abdominal incision and a vertical rectus abdominis musculocutaneous (VRAM) flap. However, only a few studies have compared the complications and the outcomes following pelvic exenteration between cases with and without a VRAM flap. In this study, we aimed to compare the complications and the outcomes following pelvic exenteration with or without VRAM flap coverage. We retrospectively reviewed the cases of nine patients for whom transpelvic VRAM flaps were created following pelvic exenteration due to pelvic malignancy. The complications and outcomes in these patients were compared with those of another nine patients who did not undergo such reconstruction. Flap reconstruction was successful in eight cases, with minor complications such as wound infection and dehiscence. In all cases in the reconstructed group (n=9), structural integrity was maintained and major complications including bowel obstruction and infection were prevented by obliterating the pelvic dead space. In contrast, in the control group (n=9), peritonitis and bowel obstruction occurred in 1 case (11%). Despite the possibility of flap failure and minor complications, a VRAM flap can result in adequate perineal reconstruction to prevent major complications of pelvic exenteration.


Tumor-homing photosensitizer-conjugated glycol chitosan nanoparticles for synchronous photodynamic imaging and therapy based on cellular on/off system.
Herein, we developed the photosensitizer, protoporphyrin IX (PpIX), conjugated glycol chitosan (GC) nanoparticles (PpIX-GC-NPs) as tumor-homing drug carriers with cellular on/off system for photodynamic imaging and therapy, simultaneously. In order to prepare PpIX-GC-NPs, hydrophobic PpIXs were chemically conjugated to GC polymer and the amphiphilic PpIX-GC conjugates formed a stable nanoparticle structure in aqueous condition, wherein conjugated PpIX molecules formed hydrophobic inner-cores and they were covered by the hydrophilic GC polymer shell. Based on the nanoparticle structure, PpIX-GC-NPs showed the self-quenching effect that is 'off' state with no fluorescence signal and phototoxicity with light exposure. It is due to the compact crystallized PpIX molecules in the nanoparticles as confirmed by dynamic light scattering and X-ray diffraction methods. However, after cellular uptake, compact nanoparticle structure gradually decreased to generate strong fluorescence signal and singlet oxygen generation when irradiated. Importantly, PpIX-GC-NPs-treated mice presented prolonged blood circulation, enhanced tumor targeting ability, and improved in vivo therapeutic efficiency in tumor-bearing mice, compared to that of free PpIX-treated mice. These results proved that this tumor-homing cellular 'on/off' nanoparticle system of PpIX-GC-NPs has a great potential for synchronous photodynamic imaging and therapy in cancer treatment.


Emotion in obesity discourse: understanding public attitudes towards regulations for obesity prevention.
Intense concern about obesity in the public imagination and in political, academic and media discourses has catalysed advocacy efforts to implement regulatory measures to reduce the occurrence of obesity in Australia and elsewhere. This article explores public attitudes towards the possible implementation of regulations to address obesity by analysing emotions within popular discourses. Drawing on reader comments attached to obesity-relevant news articles published on Australian news and current affairs websites, we examine how popular anxieties about the 'obesity crisis' and vitriol directed at obese individuals circulate alongside understandings of the appropriate role of government to legitimise regulatory reform to address obesity. Employing Ahmed's theorisation of 'affective economies' and broader literature on emotional cultures, we argue that obesity regulations achieve popular support within affective economies oriented to neoliberal and individualist constructions of obesity. These economies preclude constructions of obesity as a structural problem in popular discourse; instead positioning anti-obesity regulations as a government-endorsed vehicle for discrimination directed at obese people. Findings implicate a new set of ethical challenges for those championing regulatory reform for obesity prevention.


Kinetic and inhibition studies on substrate channelling in the bifunctional enzyme catalysing C-terminal amidation.
A series of experiments has been conducted to investigate the possibility that substrate channelling might occur in the bifunctional forms of enzymes carrying out C-terminal amidation, a post-translational modification essential to the biological activity of many neuropeptides. C-terminal amidation entails sequential action by peptidylglycine mono-oxygenase (PAM, EC 188.8.131.52) and peptidylamidoglycolate lyase (PGL, EC 184.108.40.206), with the mono-oxygenase catalysing conversion of a glycine-extended pro-peptide into the corresponding alpha-hydroxyglycine derivative, which is then converted by the lyase into amidated peptide plus glyoxylate. Since the mono-oxygenase and lyase reactions exhibit tandem reaction stereospecificities, channelling of the alpha-hydroxy intermediate might occur, as is the case for some other multifunctional enzymes. Selective inhibition of the mono-oxygenase domain by competitive ester inhibitors, as well as mechanism-based mono-oxygenase inactivation by the novel olefinic inhibitor 5-acetamido-4-oxo-6-phenylhex-2-enoate (N-acetylphenylalanyl acrylate), has little to no effect on the kinetic parameters of the lyase domain of the AE from Xenopus laevis. Similarly, inhibition of the lyase domain by the potent dioxo inhibitor 2,4-dioxo-5-acetamido-6-phenylhexanoate has little effect on the activity of the monooxygenase domain in the bifunctional enzyme. A series of experiments on intermediate accumulation and conversion were also carried out, along with kinetic investigations of the reactivities of the monofunctional and bifunctional forms of PAM and PGL towards substrates and inhibitors. Taken together, the results demonstrate the kinetic independence of the mono-oxygenase and lyase domains, and provide no evidence for substrate channelling between these domains in the bifunctional amidating enzyme.


Quantitative objective assessment of peripheral nociceptive C fibre function.
A technique is described for the quantitative assessment of peripheral nociceptive C fibre function by measurement of the axon reflex flare. Acetylcholine, introduced by electrophoresis, is used to stimulate a ring of nociceptive C fibre endings at the centre of which the increase in blood flow is measured with a laser Doppler flowmeter. This flare (neurogenic vasodilatation) has been compared with mechanically or chemically stimulated non-neurogenic cutaneous vasodilation. The flare is abolished by local anaesthetic and is absent in denervated skin. The flare has been measured on the sole of the foot of 96 healthy subjects; its size decreases with age in males, but not in females.


Advantage of the subcutaneous immunoglobulin replacement therapy in primary immunodeficient patients with or without secondary protein loss.
Gür-Çetinkaya P, Çağdaş-Ayvaz DN, Öksüz AB, Ertoy A, Hayran U, Özkan F, Erol M, Tezcan İ. Advantage of the subcutaneous immunoglobulin replacement therapy in primary immunodeficient patients with or without secondary protein loss. Turk J Pediatr 2018; 60: 270-276. In recent years subcutaneous immunoglobulin is widely used for primary immunodeficient patients. Subcutaneous administration provides a more stable and higher serum immunoglobulin levels due to continuous and steady transition from lymphatics to the systemic circulation. We aimed to evaluate the changes in serum immunoglobulin levels under subcutaneous immunoglobulin therapy in patients with primary immunodeficiency with or without secondary protein loss. Nine patients with primary immunodeficiency who switched to subcutaneous immunoglobulin were enrolled. Age, gender, diagnosis, reasons of transition to subcutaneous route, reasons of secondary protein loss were recorded. A questionnaire consisting of frequencies and types of infections, side effects observed with intravenous and subcutaneous routes; date and reason of transition to subcutaneous route were asked to all participants. Serum immunoglobulin levels at the 3rd and the 6th months before and after subcutaneous route were recorded. Of the 9 patients (M/F=4/5) the median age was 12 years (6.1-28.7) and 5 of them had protein loss. In total, 444 injections were applied, and all patients experienced local reactions. Infections were more frequent under intravenous than subcutaneous route (p=0.004). We observed an increase in immunoglobulin levels under subcutaneous route (p=0.069 at 3rd; p=0.13 at 6th month). This increase was evident at the 3rd month of transition to subcutaneous route in patients with protein loss (p=0.080). There was an increase in serum immunoglobulin levels under subcutaneous route. However, increase was not statistically significant since the study group was small. This increment was prominent in patients with protein loss. Subcutaneous administration may be a good alternative for primary immunodeficient patients with protein loss who have persistent low serum immunoglobulin levels despite increments in the intravenous immunoglobulin doses.


Invasion genetics of the silver carp Hypophthalmichthys molitrix across North America: Differentiation of fronts, introgression, and eDNA metabarcode detection.
In the 1970s, the introduced silver carp Hypophthalmichthys molitrix (which is indigenous to eastern Asia) escaped from southern U.S. aquaculture to spread throughout the Mississippi River basin, and since has steadily moved northward. This large, prolific filter-feeder reduces food availability for other fishes. It now has reached the threshold of the Laurentian Great Lakes, where it likely will significantly impact food chains and fisheries. Our study evaluates population genetic variability and differentiation of the silver carp using 10 nuclear DNA microsatellite loci, and sequences of two mitochondrial genes-cytochrome b and cytochrome c oxidase subunit 1, along with the nuclear ribosomal protein S7 gene intron 1. We analyze population samples from: two primary Great Lakes' invasion fronts (at the Illinois River outside of Chicago, IL in Lake Michigan and in the Wabash River, which leads into the Maumee River and western Lake Erie), the original establishment "core" in the Lower Mississippi River, and expansion areas in the Upper Mississippi and Missouri rivers. We analyze and compare our results with bighead and other invasive carps, and cyprinid relatives. Results reveal that the silver carp invasion possesses moderate levels of genetic diversity, with more mtDNA haplotypes and unique microsatellite alleles in the "core" Lower Mississippi River population, which also diverges the most. The two invasion fronts also significantly genetically differ. About 3% of individuals (including all populations except the Illinois River) contain a unique and very divergent mtDNA haplotype, which likely stems from historic introgression in Asia with female largescale silver carp H. harmandi. The nuclear microsatellites and S7 sequences of the introgressed individuals do not differ from silver carp and are very distant from bighead carp. These sequence variation data are employed to design and evaluate a targeted high-throughput metabarcoding sequence assay that identifies and distinguishes among species of invasive carps (i.e., silver, bighead, grass, black, and common carps, along with goldfish), as well as native cyprinids, using cytochrome b. Our assay further differentiates among selected silver carp haplotypes (including between H. molitrix and H. harmandi), for use in population genetics and future analyses of spread pathways. We test and evaluate this assay on environmental (e)DNA water samples from 48 bait shops in the Great Lakes' region (along the Lake Erie, Lake St. Clair, and Wabash River watersheds), using positive and negative controls and custom bioinformatic processing. Test results discern silver carp eDNA in four of the shops-three in Lake Erie and one in the Wabash River watershed-and bighead carp from one of the same Lake Erie venues, suggesting that retailers (who often source from established southerly populations) comprise another introduction vector. Our overall findings thus provide key population genetic and phylogenetic data for understanding and tracing introductions, vectors, and spread pathways for silver carp, their variants, and their relatives.


Knockdown of selenocysteine-specific elongation factor in Amblyomma maculatum alters the pathogen burden of Rickettsia parkeri with epigenetic control by the Sin3 histone deacetylase corepressor complex.
Selenocysteine is the 21st naturally-occurring amino acid. Selenoproteins have diverse functions and many remain uncharacterized, but they are typically associated with antioxidant activity. The incorporation of selenocysteine into the nascent polypeptide chain recodes the TGA stop codon and this process depends upon a number of essential factors including the selenocysteine elongation factor (SEF). The transcriptional expression of SEF did not change significantly in tick midguts throughout the blood meal, but decreased in salivary glands to 20% at the end of the fast feeding phase. Since selenoprotein translation requires this specialized elongation factor, we targeted this gene for knockdown by RNAi to gain a global view of the role selenoproteins play in tick physiology. We found no significant differences in tick engorgement and embryogenesis but detected no antioxidant capacity in tick saliva. The transcriptional profile of selenoproteins in R. parkeri-infected Amblyomma maculatum revealed declined activity of selenoprotein M and catalase and increased activity of selenoprotein O, selenoprotein S, and selenoprotein T. Furthermore, the pathogen burden was significantly altered in SEF-knockdowns. We then determined the global impact of SEF-knockdown by RNA-seq, and mapped huge shifts in secretory gene expression that could be the result of downregulation of the Sin3 histone deacetylase corepressor complex.


Health promotion and work: prevention of shift work disorders in companies.
Workplace health promotion is a strategy to improve the health and well-being of people at work. The measures aim at the personal, organisational and work environment. Shift work is one of many reasons provoking increased job stress. According to worldwide epidemiological data, up to 30% of the working population are employed in shifts. Taking into consideration that shift work causes a large number of somatic and psychiatric diseases which bear considerable negative consequences for the health status and the quality of life, it seems to be important to initiate health promotion strategies for shift workers in the companies. The results of recent studies indicate that well-scheduled und targeted health programmes can change the lifestyle of shift working employees and have an impact on the risk factors involved. One problem, though, is a considerable time lag till effects become apparent; therefore, the long-term economic effects of workplace health promotion have not been evaluated sufficiently to date. These definitely positive effects highlight the demand for trainings and workshops for people in shift work. We urgently suggest a speedy implementation of the recommended strategies by companies with shift work systems. In our view, this poses a challenge to the "infant" interdisciplinary field of sleep medicine that should be solved.


Analysis of Risk Factors Associated With Poor Outcome in Posterior Reversible Encephalopathy Syndrome After Treatment in Children: Systematic Review and Meta-Analysis.
Objective: Chemotherapy and hematopoietic stem cell transplantation (HSCT) play important roles in clinical etiology, symptoms, signs, imaging findings, and biochemical parameters for inducing posterior reversible encephalopathy syndrome (PRES) in pediatric oncologic diseases. We aimed to evaluate various risk factors of pediatric oncologic diseases after conducting chemotherapy and HSCT to induce PRES for predicting the clinical prognosis frequency. Methods: The literature was performed on PubMed, Web of Science, and Embase databases to recognize the qualified studies. The odds ratios (ORs) of related risk factors and their corresponding 95% confidence intervals (CIs) were used to compute the pooled assessments of the outcomes. Results: Six studies were included in the meta-analysis, involving 828 records. The risk of female children has a significantly higher incidence than male children in oncologic age groups of PRES. Children over the age of 10 years old in oncologic age groups develop a significantly increased risk of PRES. Acute graft-versus-host disease (GVHD) has a significant promotion effect on the occurrence of PRES. Hypertension can promote the occurrence of PRES in children. The risk of PRES in immunodeficient children increases significantly. Children with sickle cell disease (SCD) have a significantly increased risk of PRES. The risk of PRES in children with T-cell leukemia rises considerably. The central nervous system (CNS) leukemia/involvement has a significant role in promoting the occurrence of PRES in children. The pooled OR for the factors male, ≥ 10 years old of age, acute GVHD, hypertension, immunodeficiency, SCD, T-cell leukemia, CNS leukemia/involvement was 0.66 (95% CI: 0.58, 0.76; P < 0.00001), 2.06 (95% CI: 1.23, 3.43; P < 0.006), 1.32 (95% CI: 1.14, 1.53; P < 0.0003), 8.84 (95% CI: 7.57, 10.32; P < 0.00001), 2.72 (95% CI: 1.81, 4.08; P < 0.00001), 2.87 (95% CI: 2.15, 3.83; P < 0.00001), 2.84 (95% CI: 1.65, 4.88; P < 0.0002), and 3.13 (95% CI: 1.43, 6.84; P < 0.004), respectively. Conclusions: The result of this meta-analysis suggests that female children, age over 10 years old, acute GVHD, hypertension, immunodeficiency, SCD, T-cell leukemia, and CNS leukemia/involvement are likely to have the poor outcome in pediatric oncologic/hematologic diseases in PRES.


Rat metallothionein-2 contains N(alpha)-acetylated and unacetylated isoforms.
Mammalian metallothioneins (MT), are characteristically N(alpha)-acetylated and the presence of an unblocked N-terminus has not previously been reported. On-line capillary electrophoresis-electrospray mass spectrometry of hepatic MT-2 from rats injected with zinc revealed two isoforms differing by a mass equivalent to that of a single acetyl group. The lower mass component constituted > 20% of total MT-2 protein and both MT-2 isoforms were separated by reversed-phase high-performance liquid chromatography. The identity of each fraction was confirmed by matrix-assisted laser desorption ionisation mass spectrometry, and amino acid analysis and N-terminal sequencing revealed that the lower mass isoform was unblocked at the N-terminus and had an amino acid composition and sequence which is characteristic of rat MT-2. Thus the complementary techniques of mass spectrometry and N-terminal sequencing demonstrated conclusively that purified MT-2 from zinc-treated rats contains an unacetylated isoform. We propose that the cotranslational acetylation of rat MT-2 may under some circumstances be inefficient compared to that in other nonrodent species, where we have detected only trace levels of unacetylated MT isoforms.


Pediatric ocular injuries from airsoft toy guns.
To report ocular injuries caused by airsoft guns in children. A retrospective chart review of pediatric patients who sustained ocular injuries related to airsoft guns between November 2005 and December 2007. Place of trauma, presenting symptoms and signs, surgical interventions performed, and final visual outcome were reviewed. Thirty-two patients with a mean age of 8.8 ± 4.0 years (range: 1.5 to 18 years) were examined; 28 were boys (87.5%). Presenting visual acuity ranged from hand motions to 20/20 and could not be assessed in 2 patients. Hyphema was a common finding that was present in 24 cases, corneal abrasions were present in 10 cases, and raised intraocular pressure was present in 7 cases. Seven patients presented with traumatic cataract, and two had iridodialysis. Immediate surgical intervention was performed in 7 patients and 7 patients were scheduled for elective surgery. The patients presented after an average of 1.9 ± 1.9 days (range: 4 hours to 6 days) after the injury. Average follow-up was 18 days (range: 7 days to 5 months). Final visual acuity was 20/200 or worse in 5 patients, 20/40 or better in 23 patients, and could not be assessed in 2 cases. Airsoft guns can cause a variety of serious injuries, sometimes necessitating operative intervention. The long-term morbidity from some of these injuries is significant. Airsoft guns are capable of inflicting serious and permanent ocular damage.