The role of employee perceptions of safety priorities on safety outcomes across organisational levels.
Research has shown that safety climate predicts safety outcomes in various occupational settings. One important component of safety climate is employees' perceived priorities of safety in an organisation relative to other operational demands (e.g. productivity or efficiency). The relationships between three dimensions of employee perceptions of safety priorities (company, supervisor, worker), employee safety behaviour and self-reported injury outcomes were examined in the current study. Survey data were collected from 858 field workers (a response rate of 89%) at a TV-cable installation company. Results showed that all three dimensions of employee perceptions of safety priorities had significant and unique positive relationships with employee safety behaviour. Furthermore, safety behaviour was a significant mediator of the relationship between the three types of perceived safety priorities and missed work days due to workplace injury. The results showed the value of addressing employee perceptions of safety priorities across organisational levels when trying to improve workplace safety and reduce costly injuries. Practitioner Summary: The study examined relationships between the three different organisational levels of employee perceptions of safety priorities and employee safety behaviour and injury outcomes. The results demonstrated the value of addressing employee perceptions of safety priorities held by different levels of management as well as the worker level to improve workplace safety and reduce costly injuries. Abbreviations: AIC: Akaike Information Criterion; BIC: Bayesian Information Criterion; CFA: confirmatory factor analysis; CFI: comparative fit index; CI: confidence interval; NAICS: the North American Industry Classification System; RMSEA: root mean square errors of approximation; SB: safety behavior; SD: standard deviation; SE: standard error; SIC: the standard industrial class; SP: safety priority.


Personality patterns of people with medically refractory epilepsy - Does the epileptogenic zone matter?
The aims of this study were to determine the rate of dysfunctional personality patterns before and after epilepsy surgery, their types, and the importance of the epileptogenic zone in a sample of people with refractory epilepsy. We conducted an ambispective observational study, including refractory epilepsy surgery candidates. Demographic, psychiatric, and neurological data were recorded. Evaluation of personality was made using the Millon Clinical Multiaxial Inventory-II (MCMI-II). Presurgical predictors of personality patterns were determined using a linear regression model. The proportion of patients with dysfunctional personality patterns, before and after surgery, was compared using the Mcnemar's test. Then a generalized estimating equation model was performed to include predictors of changes in this rate. One hundred and ninety-nine participants were included. Seventy percent had a dysfunctional personality pattern before surgery. After surgery, this percentage dropped to 58%. The difference was statistically significant after adjusting for potential confounders (p = 0.013). The most common types were Cluster C personality patterns. Temporal epileptogenic zone was a significant predictor of higher scores of the Avoidant (Coef. 11.8; Confidence Interval (CI) -0.59 23.7; p = 0.051) and Compulsive (Coef. 9.55; CI 2.48 16.6; p = 0.008) personality patterns and lower scores of Histrionic (Coef. -11.4; CI -21.2 -1.55; p = 0.024) and Antisocial (Coef. -8.4; CI -15.6 -1.25; p = 0.022) personality patterns, compared to extratemporal epileptogenic zone. People with refractory epilepsy have high rates of dysfunctional personality patterns. These patterns differ according to the epileptogenic zone.


Whole Genome-Derived Tiled Peptide Arrays Detect Prediagnostic Autoantibody Signatures in Non-Small-Cell Lung Cancer.
The majority of non-small-cell lung cancer (NSCLC) cases are diagnosed at advanced stages, primarily because earlier stages of the disease are either asymptomatic or may be attributed to other causes such as infection or long-term effects from smoking. Therefore, early detection of NSCLC would likely increase response and survival rates due to timely intervention. Here, we utilize a novel approach based on whole genome-derived tiled peptide arrays to identify epitopes associated with autoantibody reactivity in NSCLC as a potential means for early detection. Arrays consisted of 2,781,902 tiled peptides representing 20,193 proteins encoded in the human genome. Analysis of 86 prediagnostic samples and 86 matched normal controls from a high-risk cohort revealed 48 proteins with three or more reactive epitopes in NSCLC samples relative to controls. Independent mass spectrometry analysis identified 40 of the 48 proteins in prediagnostic sera from NSCLC samples, of which, 21 occurred in the immunoglobulin-bound fraction. In addition, 63 and 34 proteins encompassed three or more epitopes that were distinct for squamous cell lung cancer and lung adenocarcinoma, respectively. Collectively, these data show that tiled peptide arrays provide a means to delineate epitopes encoded across the genome that trigger an autoantibody response associated with tumor development. SIGNIFICANCE: This study provides a modality for early diagnosis of NSCLC for precision oncology that can be applied to other cancer types.


Structure and nucleotide sequence of the heavy chain gene of HLA-DR.
We have used a 175-nucleotide-long primer extension product corresponding to the 5' end of HLA-DR alpha-chain mRNA to isolate a genomic clone from a human DNA library. The entire HLA-DR alpha gene is contained in two contiguous EcoRI fragments spanning about 7.5 kilobases (kb); most of the sequence has been determined. The 5' end of the gene is contained in a 4.4-kb fragment, and the coding segments and the 3' untranslated region are contained in a 3.1-kb fragment. The gene is split into five exons. The 5' untranslated region, the leader peptide, and the first two NH2-terminal amino acids are fused into the first exon. Exons 2 and 3 represent two extracellular coding domains of mature p34. The transmembrane domain, cytoplasmic domain, and part of the 3' untranslated region are merged into a fourth exon. The rest of the 3' untranslated region is in exon 5. The predicted amino acid sequence of mature p34, as deduced from its gene structure, has 229 residues and reveals a single potential disulfide loop (between cysteine residues 107 and 163) as well as a 22-amino acid residue membrane integrated segment (residues 193-214). Fifteen amino acids (residues 215-229) reside on the cytoplasmic side of the plasma membrane. There is considerable amino acid sequence homology between the second external domains of p34 and p29, as well as the immunoglobulin-like third domain of HLA-B7, and beta 2-microglobulin and the homologous constant region domains of the light and heavy chains of immunoglobulins.


Basal and stimulated protein S-nitrosylation in multiple cell types and tissues.
There is substantial evidence that protein S-nitrosylation provides a significant route through which nitric oxide (NO)-derived bioactivity is conveyed. However, most examples of S-nitrosylation have been characterized on the basis of analysis in vitro, and relatively little progress has been made in assessing the participant forms of nitric-oxide synthase (NOS) or the dynamics of protein S-nitrosylation in situ. Here we utilize antibodies specific for the nitrosothiol (SNO) moiety to provide an immunohistochemical demonstration that protein S-nitrosylation is coupled to the activity of each of the major forms of NOS. In cultured endothelial cells, SNO-protein immunoreactivity increases in response to Ca(2+)-stimulated endothelial NOS (eNOS) activity, and in aortic rings, endothelium-derived and eNOS-mediated relaxation (EDRF) is coupled to increased protein S-nitrosylation in both endothelial and associated smooth muscle cells. In cultured macrophages, SNO-protein levels increase upon cytokine induction of induced NOS (iNOS), and in PC12 cells, increased protein S-nitrosylation is linked to nerve growth factor induction of neuronal NOS (nNOS). In addition, we describe developmental and pathophysiological increases in SNO-protein immunoreactivity within human lung. These results, which demonstrate Ca(2+), neurohumoral, growth factor, cytokine, and developmental regulation of protein S-nitrosylation that is coupled to NOS expression and activity, provide unique evidence for the proposition that this ubiquitous NO-derived post-translational protein modification serves as a major effector of NO-related bioactivity.


Compassionate Hearts Protect Against Wandering Minds: Self-compassion Moderates the Effect of Mind-Wandering on Depression.
Depression is associated with high levels of mind-wandering and low levels of self-compassion. However, little is known about whether and how these two factors interact with one another to influence depressive symptoms. The current study examined the interaction between mind-wandering, self-compassion and depressive symptoms in a depressed sample and tested the effects of an eight-week Mindfulness Based Cognitive Therapy (MBCT) program on these constructs. At baseline, mind-wandering was associated with higher depressive symptoms only among individuals with low self-compassion. Self-compassion additionally predicted depressive improvement. As expected, MBCT increased self-compassion and reduced mind-wandering compared to a treatment-as-usual control group. Overall, longitudinal changes in self-compassion produced a moderation effect similar to the one at baseline so that increases in mind-wandering were associated with increases in depressive symptoms only among those who decreased in self-compassion. Results provide the first evidence that self-compassion can protect against the deleterious effects of mind-wandering among depressed participants, both at baseline and longitudinally. Findings also suggest that self-compassion is an effective predictor of depressive improvement. Finally, MBCT is effective not only at reducing depressive symptoms, but also at targeting protective and risk factors associated with depression.


Development of a disease-specific quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-QoL): Spanish multi-centre research project.
There is a need for a disease-specific instrument for assessing health-related quality of life in adults with hereditary angioedema due to C1 inhibitor deficiency, a rare, disabling and life-threatening disease. In this paper we report the protocol for the development and validation of a specific questionnaire, with details on the results of the process of item generation, domain selection, and the expert and patient rating phase. Semi-structured interviews were completed by 45 patients with hereditary angioedema and 8 experts from 8 regions in Spain. A qualitative content analysis of the responses was carried out. Issues raised by respondents were grouped into categories. Content analysis identified 240 different responses, which were grouped into 10 conceptual domains. Sixty- four items were generated. A total of 8 experts and 16 patients assessed the items for clarity, relevance to the disease, and correct dimension assignment. The preliminary version of the specific health-related quality of life questionnaire for hereditary angioedema (HAE-QoL v 1.1) contained 44 items grouped into 9 domains. To the best of our knowledge, this is the first multi-centre research project that aims to develop a specific health-related quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency. A preliminary version of the specific HAE-QoL questionnaire was obtained. The qualitative analysis of interviews together with the expert and patient rating phase helped to ensure content validity. A pilot study will be performed to assess the psychometric properties of the questionnaire and to decide on the final version.


Postsynaptic density-93 clusters Kv1 channels at axon initial segments independently of Caspr2.
Postsynaptic density-93 (PSD-93)/Chapsyn-110 is a PDZ (PSD-95/Discs large/zona occludens-1) domain-containing membrane-associated guanylate kinase (MAGUK) that functions as a scaffold to assemble channels, receptors, and other signaling proteins at cell membranes. PSD-93 is highly enriched at synapses, but mice lacking this protein have no synaptic structural abnormalities, probably because of overlapping expression and redundancy with other MAGUKs. Consequently, the function of PSD-93 is not well understood. Here, we show that PSD-93, but not other MAGUKs, is enriched at the axon initial segment (AIS), where it colocalizes with Kv1.1, Kv1.2, Kv1.4, and Kvbeta2 subunit-containing K(+) channels, Caspr2, and TAG-1 (transient axonal glycoprotein-1). When coexpressed with Kv1 channels in heterologous cells, PSD-93 induces formation of large cell-surface clusters. Knockdown of PSD-93 in cultured hippocampal neurons by RNA interference disrupted Kv1 channel localization at the AIS. Similarly, PSD-93-/- mice failed to cluster Kv1 channels at the AIS of cortical and hippocampal neurons. In contrast, Caspr2, which mediates Kv1 channel clustering at the juxtaparanode, is not required for localization of Kv1 channels at the AIS. These results show PSD-93 mediates AIS accumulation of Kv1 channels independently of Caspr2.


Dietary patterns and risk of self-reported activity limitation in older adults from the Three-City Bordeaux Study.
Few studies have been interested in the relationship between dietary patterns and activity limitation in older adults yet. We analysed the association between dietary patterns and the risk of self-reported activity limitation - that is mobility restriction, limitation in instrumental activities in daily living (IADL) and in activities in daily living (ADL) - in community-dwellers aged 67+ years initially free of activity limitation in 2001-2002 and re-examined at least once over 10 years - that is 583 participants for mobility restriction, 1114 for IADL limitation and 1267 for ADL limitation. At baseline, five sex-specific dietary clusters were derived by hybrid clustering method from weekly frequency of intake of twenty food and beverage items. Self-reported mobility restriction, limitations in IADL and in ADL were assessed using the Rosow-Breslau, the Lawton-Brody and the Katz scales, respectively. Associations between dietary clusters and the risk of each activity limitation were assessed using Cox proportional hazard models. In models adjusted for socio-demographic and health-related covariates, compared with the 'Healthy' cluster the 'Biscuits and snacking' cluster was associated with a higher risk of mobility restriction (hazard ratio (HR)=3·0; 95 % CI 1·6, 5·8) and limitation in IADL (HR=2·1; 95 % CI 1·1, 4·2) in men and limitation in ADL in women (HR=2·3; 95 % CI 1·3, 4·0). In this French cohort of community-dwellers aged 67+ years, some unhealthy dietary patterns may increase the risk of activity limitation all along the disablement process in older adults.


Decoding locomotion from population neural activity in moving C. elegans.
We investigated the neural representation of locomotion in the nematode C. elegans by recording population calcium activity during movement. We report that population activity more accurately decodes locomotion than any single neuron. Relevant signals are distributed across neurons with diverse tunings to locomotion. Two largely distinct subpopulations are informative for decoding velocity and curvature, and different neurons' activities contribute features relevant for different aspects of a behavior or different instances of a behavioral motif. To validate our measurements, we labeled neurons AVAL and AVAR and found that their activity exhibited expected transients during backward locomotion. Finally, we compared population activity during movement and immobilization. Immobilization alters the correlation structure of neural activity and its dynamics. Some neurons positively correlated with AVA during movement become negatively correlated during immobilization and vice versa. This work provides needed experimental measurements that inform and constrain ongoing efforts to understand population dynamics underlying locomotion in C. elegans.


Rabies: epidemiological tendencies and control tools.
Rabies encephalitis still generates 50,000 human deaths/year. It is due to neuron infection by lyssaviruses. Seven genotypes (GT) are currently distinguished within the Lyssavirus genus which segregate in two phylogroups (PG). This classification is constantly evolving due to isolation of new lyssaviruses within bat populations. Functional differences exist between GTs in term of neurotropism, pathogenesis, induction of apoptosis, immunogenicity, and their molecular basis are starting to be elucidated. Lyssavirus vectors are mammals, preferentially from the Carnivora and Chiroptera orders. Phylogenetic reconstruction strongly supports that lyssaviruses evolved in chiropters long before the emergence of carnivoran rabies which very likely occurred through host-switchings from bats to carnivores. If dog rabies control is possible by vaccination and population control, if oral vaccination demonstrated its potential to eliminate rabies from a terrestrial wildlife reservoir (fox in Western Europe), it is unrealistic today to clear lyssaviruses from bats, while bat rabies is a growing concern for both public and animal health. As bat transmit divergent lyssavirus GTs which are not well prevented by available vaccine strains, there is a need to increase the protection spectrum of vaccines. DNA-based immunization with plasmids expressing chimeric G proteins (fusion of two halves from different GTs) was shown to be effective in inducing a complete immune response and to broaden the spectrum of rabies vaccines toward lyssavirus vaccines. Further, the lyssavirus G protein can carry foreign epitopes/antigens in the perspective of multivalent vaccines against various zoonoses of carnivores.


Atrioventricular nodal function in the immature canine heart [corrected and republished article orginally printed in Pediatr Res 1987 Nov;22(5):616-20].
Previous studies have suggested that the atrioventricular nodal functional refractory period in the neonate is equal to or shorter than that of the ventricle, providing little or no protection to the ventricle against rapid atrial rates and allowing closely coupled atrial beats to fall within the ventricular vulnerable period. We evaluated atrioventricular node function in 21 mongrel neonatal puppies, 3-15 days old, and 15 adult dogs utilizing intracardiac His bundle recording and stimulation techniques. The mean atrioventricular nodal functional refractory period (173.1 +/- 20.0 ms) exceeded both the ventricular effective refractory period (139.5 +/- 14.3) and ventricular functional refractory period (163.3 +/- 14.5) in the neonates. Furthermore, the atrioventricular node was the site of limiting antegrade conduction in all neonates. No ventricular arrhythmias were induced by atrial extrastimulation in any of the neonates. The site of conduction delay during atrial extrastimulation was confined to the atrioventricular node in 15/16 neonates (94%) while 1/16 (6%) had combined nodal and infranodal delay. The neonates developed Wenckebach, at significantly faster heart rates than the adults, but both groups developed Wenckebach at approximately twice the resting heart rate. Retrograde conduction was a consistent finding in the neonates. However, antegrade Wenckebach occurred at a significantly faster heart rate than retrograde Wenckebach suggesting different functional properties. Our data suggest that in the neonatal canine, the atrioventricular node functional refractory period is longer than both the ventricular effective refractory period and ventricular functional refractory period. Furthermore, the degree of protection offered by the neonatal atrioventricular node to the ventricle appears to be comparable to that of the adult.


CHAMP: Cognitive behaviour therapy for health anxiety in medical patients, a randomised controlled trial.
Abnormal health anxiety, also called hypochondriasis, has been successfully treated by cognitive behaviour therapy (CBT) in patients recruited from primary care, but only one pilot trial has been carried out among those attending secondary medical clinics where health anxiety is likely to be more common and have a greater impact on services. The CHAMP study extends this work to examine both the clinical and cost effectiveness of CBT in this population. The study is a randomized controlled trial with two parallel arms and equal randomization of 466 eligible patients (assuming a 20% drop-out) to an active treatment group of 5-10 sessions of cognitive behaviour therapy and to a control group. The aim at baseline, after completion of all assessments but before randomization, was to give a standard simple explanation of the nature of health anxiety for all participants. Subsequently the control group was to receive whatever care might usually be available in the clinics, which is normally a combination of clinical assessment, appropriate tests and reassurance. Those allocated to the active treatment group were planned to receive between 5 and 10 sessions of an adapted form of cognitive behaviour therapy based on the Salkovskis/Warwick model, in which a set of treatment strategies are chosen aimed at helping patients understand the factors that drive and maintain health anxiety. The therapy was planned to be given by graduate research workers, nurses or other health professionals trained for this intervention whom would also have their competence assessed independently during the course of treatment. The primary outcome is reduction in health anxiety symptoms after one year and the main secondary outcome is the cost of care after two years. This represents the first trial of adapted cognitive behaviour therapy in health anxiety that is large enough to test not only the clinical benefits of treatment but also whether the cost of treatment is offset by savings from reduced use of other health services in comparison to the control group.Cognitive behaviour therapy for Health Anxiety in Medical Patients (CHAMP) TRIAL REGISTRATION: Current Controlled Trials ISRCTN14565822.


Differences in impact of long term caregiving for mentally ill older adults on the daily life of informal caregivers: a qualitative study.
Owing to the policy of extramuralization of care in most Western countries older people with severe mental illness have to rely more and more on informal caregivers for daily care. Caregivers themselves are often aged, and although caregiving implies an impact on daily life that exceeds the boundaries of usual informal care, the impact differs across caregivers. Some caregivers seem to suffer more than others, and the differences cannot be fully understood by factors currently known to exacerbate the burden of caregiving. In order to help caregivers reduce the impact of caregiving it is important to gain a deeper understanding of factors influencing the burden and its impact on the caregiver's life. With this in mind, the aim of the study is to explore and understand differences in the impact of long-term caregiving on the quality of life of caregivers who look after older adults with severe mental illness. A qualitative, associative, inductive strategy and continuous simultaneous coding were used to interpret the data of 19 semi-structured interviews. We identified an underlying psychological factor "perceived freedom of choice" which explains the gross differences in impact, leading to a definition of two main types of caregivers. Depending on how people perceive freedom of choice to provide care, the consequences of caregiving can be characterized as a process of gain (type 1) or loss (type 2). Four influential factors deepen the impact of caregiving for the type 2 caregivers, and two subtypes are identified for this category. Consequences of caregiving are most readily seen in a deteriorating quality of the relationship with the care recipient and in the psychosocial well-being of the caregiver. The concept of freedom of choice adds to our understanding of the differences and explains the variation in impact on the caregivers' life. The type 1 caregiver generally experiences gain whereas type 2 generally experiences loss, which puts the latter group typically at risk of becoming overloaded. Whether people perceive that they have freedom of choice in caregiving is an important consideration in evaluating the type of intervention needed to support caregivers.


Xenopus as a model organism in developmental chemical genetic screens.
Chemical genetics is a potentially powerful tool for studying developmental processes in vertebrate systems. We present data showing Xenopus laevis as a model organism in which systematic chemical genetic screens can be carried out. Previous forward chemical genetic screens, including those with developing zebrafish embryos, have demonstrated the nature and value of biological information gained with this approach. We show how amenable Xenopus is to chemical genetics by investigating a series of compounds either with known biochemical effects, or previously identified to give developmental phenotypes, on a range of biological functions, including the development of pigmentation, the heart and the central nervous system in zebrafish. We have found that the compounds give comparable phenotypes when applied to developing Xenopus embryos. We have also studied the penetrance and expressivity of these chemical genetic phenotypes in relation to genetic variation and the developmental window during which the compound is present. Finally, we assess the feasibility and the potential throughput of a screen in this vertebrate species.


Incidental findings on brain magnetic resonance imaging of children with sickle cell disease.
We describe the prevalence and range of incidental intracranial abnormalities identified through MRI of the brain in a large group of children screened for a clinical trial. We included 953 children between 5 and 14 years of age who were screened with MRI of the brain for the Silent Infarct Transfusion Trial. All had sickle cell anemia or sickle beta-null thalassemia. MRI scans were interpreted by 3 neuroradiologists. MRI scans reported to have any abnormality were reviewed by 2 study neuroradiologists. Incidental findings were classified into 4 categories, that is, no, routine, urgent, or immediate referral recommended. Cerebral infarctions and vascular lesions were not considered incidental and were excluded. We identified 63 children (6.6% [95% confidence interval: 5.1%-8.4%]) with 68 incidental intracranial MRI findings. Findings were classified as urgent in 6 cases (0.6%), routine in 25 cases (2.6%), and no referral required in 32 cases (3.4%). No children required immediate referral. Two children with urgent findings underwent surgery in the subsequent 6 months. In this large cohort of children, incidental intracranial findings were identified for 6.6%, with potentially serious or urgent findings for 0.6%.


Age effects in emotional prospective memory: cue valence differentially affects the prospective and retrospective component.
While first studies suggested that emotional task material may enhance prospective memory performance in young and older adults, the extent and mechanisms of this effect are under debate. The authors explored possible differential effects of cue valence on the prospective and retrospective component of prospective memory in young and older adults. Forty-five young and 41 older adults performed a prospective memory task in which emotional valence of the prospective memory cue was manipulated (positive, negative, neutral). The multinomial model of event-based prospective memory was used to analyze effects of valence and age on the two prospective memory components separately. Results revealed an interaction indicating that age differences were smaller in both emotional valence conditions. For older adults positive cues improved the prospective component, while negative cues improved the retrospective component. No main effect of valence was found for younger adults on an overt accuracy measure, but model-based analyses showed that the retrospective component was enhanced in the positive compared with the negative cue condition. The study extends the literature in demonstrating that processes underlying emotional effects on prospective memory may differ depending on valence and age.


Paeoniflorin regulates macrophage activation in dimethylnitrosamine-induced liver fibrosis in rats.
Macrophages in other organs (e.g. kidneys, lungs, and spleen, et. al) have rarely been reported in the development of liver fibrosis. Therefore, it is important to investigate macrophage activation in the main organs in liver fibrosis. We investigated the potential antifibrogenic effects of paeoniflorin (PF) in a dimethylnitrosamine (DMN)-induced rat model with special focus on inhibiting macrophage activation in the main organs. Rat hepatic fibrosis was induced by treatment with DMN three times weekly over a 4-week period. DMN rats were treated with water, PF, or gadolinium chloride (GdCl3) from the beginning of the 3rd week. The expression of CD68, marker of macrophage, was investigated using immunohistochemical, real-time PCR, and western blot analysis. Hepatic hydroxyproline content markedly decreased and histopathology improved in the DMN-PF rats. Expression of desmin and collagen 1 decreased notably in DMN-PF liver. CD68 expression in the liver, spleen and kidney increased markedly after 2 weeks but decreased in DMN-water rats. PF and GdCl3 decreased CD68 expression in the liver and spleen and there was no effect on kidney. CD68 expression in the lung increased gradually during the course of DMN-induced liver fibrosis, and PF inhibited CD68 expression in the lung significantly while GdCl3 increased CD68 markedly. Expression of tumor necrosis factor (TNF-α) was decreased significantly by GdCl3 in the liver, as revealed by real-time PCR analysis. However, GdCl3 could not decrease TNF-α level in the serum by enzyme linked immunosorbent assay (ELISA). Macrophage activation was disrupted in the liver, spleen, lung and kidney during development of DMN-induced liver fibrosis. PF administration attenuated DMN-induced liver fibrosis at least in part by regulating macrophage disruption in the main organs.


Factors influencing full immunization coverage among 12-23 months of age children in Ethiopia: evidence from the national demographic and health survey in 2011.
Immunization remains one of the most important public health interventions to reduce child morbidity and mortality. The 2011 national demographic and health survey (DHS) indicated low full immunization coverage among children aged 12-23 months in Ethiopia. Factors contributing to the low coverage of immunization have been poorly understood. The aim of this study was to identify factors associated with full immunization coverage among children aged 12-23 months in Ethiopia. This study used the 2011 Ethiopian demographic and health survey data. The survey was cross sectional by design and used a multistage cluster sampling procedure. A total of 1,927 mothers with children of 12-23 months of age were extracted from the children's dataset. Mothers' self-reported data and observations of vaccination cards were used to determine vaccine coverage. An adjusted odds ratio (AOR) with 95% confidence intervals (CI) was used to outline the independent predictors. The prevalence of fully immunized children was 24.3%. Specific vaccination coverage for three doses of DPT, three doses of polio, measles and BCG were 36.5%, 44.3%, 55.7% and 66.3%, respectively. The multivariable analysis showed that sources of information from vaccination card [AOR 95% CI; 7.7 (5.95-10.06)], received postnatal check-up within two months after birth [AOR 95% CI; 1.8 (1.28-2.56)], women's awareness of community conversation program [AOR 95% CI; 1.9 (1.44-2.49)] and women in the rich wealth index [AOR 95% CI; 1.4 (1.06-1.94)] were the predictors of full immunization coverage. Women from Afar [AOR 95% CI; 0.07 (0.01-0.68)], Amhara [AOR 95% CI; 0.33 (0.13-0.81)], Oromiya [AOR 95% CI; 0.15 (0.06-0.37)], Somali [AOR 95% CI; 0.15 (0.04-0.55)] and Southern Nation and Nationalities People administrative regions [AOR 95% CI; 0.35 (0.14-0.87)] were less likely to fully vaccinate their children. The overall full immunization coverage in Ethiopia was considerably low as compared to the national target set (66%). Health service use and access to information on maternal and child health were found to predict full immunization coverage. Appropriate strategies should be devised to enhance health information and accessibility for full immunization coverage by addressing the variations among regions.


Quantitative passive soil vapor sampling for VOCs--part 2: laboratory experiments.
Controlled laboratory experiments were conducted to demonstrate the use of passive samplers for soil vapor concentration monitoring. Five different passive samplers were studied (Radiello, SKC Ultra, Waterloo Membrane Sampler, ATD tubes and 3M OVM 3500). Ten different volatile organic compounds were used of varying classes (chlorinated ethanes, ethanes, and methanes, aliphatics and aromatics) and physical properties (vapor pressure, solubility and sorption). Samplers were exposed in randomized triplicates to concentrations of 1, 10 and 100 ppmv, with a relative humidity of ∼80%, a temperature of ∼24 °C, and a duration of 30 minutes in a chamber with a face velocity of about 5 cm min(-1). Passive samplers are more commonly used for longer sample durations (e.g., 8 hour workday) and higher face velocities (>600 cm min(-1)), so testing to verify the performance for these conditions was needed. Summa canister samples were collected and analyzed by EPA Method TO-15 to establish a baseline for comparison for all the passive samplers. Low-uptake rate varieties of four of the samplers were also tested at 10 ppmv under two conditions; with 5 cm min(-1) face velocity and stagnant conditions to assess whether low or near-zero face velocities would result in a low bias from the starvation effect. The results indicate that passive samplers can provide concentration measurements with accuracy (mostly within a factor of 2) and precision (RSD < 15%) comparable to conventional Summa canister samples and EPA Method TO-15 analysis. Some compounds are challenging for some passive samplers because of uncertainties in the uptake rates, or challenges with retention or recovery.


BIMA, a TPR-containing protein required for mitosis, localizes to the spindle pole body in Aspergillus nidulans.
The Aspergillus nidulans bimA gene is required for mitosis. Loss of function mutations in bimA cause cells to arrest growth with condensed chromatin and a short, metaphaselike mitotic spindle. bimA is a member of a gene family defined by a repeated motif called the Tetratrico Peptide Repeat (TPR), which is found in genes from bacteria, yeast and insects. Several yeast TPR genes are also required for mitosis, including Saccharomyces cerevisiae CDC27 and Schizosaccharomyces pombe nuc2+, which appear to be functional homologs of bimA. We have developed antisera specific to the bimA protein (BIMA) and have characterized BIMA by western blot and immunocytochemical analyses. BIMA is heterogeneous in apparent molecular weight, consisting of a major 90-kD species and at least two minor species of approximately 105 kD. The results of BIMA localization by immunofluorescence microscopy depend on the level of BIMA expression. Overexpression of BIMA, which had no deleterious affect on growth or mitosis, resulted in localization of BIMA on or throughout most nuclei. Nuclear staining was granular, and overlapped but was not completely coincident with DNA staining by DAPI. In contrast, when expressed at normal levels, BIMA colocalized with the spindle pole body (SPB). BIMA localized to the SPB in a cell cycle independent manner. These results show that BIMA is either associated with or is a component of the SPB, and they suggest that BIMA functions at the spindle poles to promote the onset of anaphase.


Risk Factors and Clinical Outcomes Associated with Perioperative Transfusion-associated Circulatory Overload.
Transfusion-associated circulatory overload remains underappreciated in the perioperative environment. The authors aimed to characterize risk factors for perioperative transfusion-associated circulatory overload and better understand its impact on patient-important outcomes. In this case-control study, 163 adults undergoing noncardiac surgery who developed perioperative transfusion-associated circulatory overload were matched with 726 transfused controls who did not develop respiratory complications. Univariate and multivariable logistic regression analyses were used to evaluate potential risk factors for transfusion-associated circulatory overload. The need for postoperative mechanical ventilation, lengths of intensive care unit and hospital stay, and mortality were compared. For this cohort, the mean age was 71 yr and 56% were men. Multivariable analysis revealed the following independent predictors of transfusion-associated circulatory overload: emergency surgery, chronic kidney disease, left ventricular dysfunction, previous β-adrenergic receptor antagonist use, isolated fresh frozen plasma transfusion (vs. isolated erythrocyte transfusion), mixed product transfusion (vs. isolated erythrocyte transfusion), and increasing intraoperative fluid administration. Patients who developed transfusion-associated circulatory overload were more likely to require postoperative mechanical ventilation (73 vs. 33%; P < 0.001) and experienced prolonged intensive care unit (11.1 vs. 6.5 days; P < 0.001) and hospital lengths of stay (19.9 vs. 9.6 days; P < 0.001). Survival was significantly reduced (P < 0.001) in transfusion recipients who developed transfusion-associated circulatory overload (1-yr survival 72 vs. 84%). Perioperative transfusion-associated circulatory overload was associated with a protracted hospital course and increased mortality. Efforts to minimize the incidence of transfusion-associated circulatory overload should focus on the judicious use of intraoperative blood transfusions and nonsanguineous fluid therapies, particularly in patients with chronic kidney disease, left ventricular dysfunction, chronic β-blocker therapy, and those requiring emergency surgery.


Demonstration of high opioid-like activity in isolated peptides from wheat gluten hydrolysates.
Because of a possible relationship between schizophrenia and celiac disease, a condition in some individuals who are sensitive to wheat gluten proteins in the diet, there has been interest in observations that peptides derived from wheat gluten proteins exhibit opioid-like activity in in vitro tests. To determine the origin of the peptides exhibiting opioid activity, wheat proteins were fractionated by size (gel filtration), by charge differences (ion exchange chromatography) and by differences in hydrophobicity (reversed-phase HPLC). These fractions were hydrolyzed by pepsin or pepsin and trypsin and the resulting peptides separated by gel filtration chromatography. The separated peptides were tested for opioid-like activity by competitive binding to opioid receptor sites in rat brain tissue in the presence of tritium-labeled dihydromorphine. The peptides showed considerable differences in activity; while some peptides exhibited no activity, 0.5 mg of the most active peptides were equivalent to 1 nM of morphine in the binding assay. The most active peptides were derived from the gliadin fraction of the gluten complex.


Improving Outcomes for Esophageal Cancer using Proton Beam Therapy.
Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT.


A Quantitative, Risk-Based Approach to the Management of Neonatal Early-Onset Sepsis.
Current algorithms for management of neonatal early-onset sepsis (EOS) result in medical intervention for large numbers of uninfected infants. We developed multivariable prediction models for estimating the risk of EOS among late preterm and term infants based on objective data available at birth and the newborn's clinical status. To examine the effect of neonatal EOS risk prediction models on sepsis evaluations and antibiotic use and assess their safety in a large integrated health care system. The study cohort includes 204 485 infants born at 35 weeks' gestation or later at a Kaiser Permanente Northern California hospital from January 1, 2010, through December 31, 2015. The study compared 3 periods when EOS management was based on (1) national recommended guidelines (baseline period [January 1, 2010, through November 31, 2012]), (2) multivariable estimates of sepsis risk at birth (learning period [December 1, 2012, through June 30, 2014]), and (3) the multivariable risk estimate combined with the infant's clinical condition in the first 24 hours after birth (EOS calculator period [July 1, 2014, through December 31, 2015]). The primary outcome was antibiotic administration in the first 24 hours. Secondary outcomes included blood culture use, antibiotic administration between 24 and 72 hours, clinical outcomes, and readmissions for EOS. The study cohort included 204 485 infants born at 35 weeks' gestation or later: 95 343 in the baseline period (mean [SD] age, 39.4 [1.3] weeks; 46 651 male [51.0%]; 37 007 white, non-Hispanic [38.8%]), 52 881 in the learning period (mean [SD] age, 39.3 [1.3] weeks; 27 067 male [51.2%]; 20 175 white, non-Hispanic [38.2%]), and 56 261 in the EOS calculator period (mean [SD] age, 39.4 [1.3] weeks; 28 575 male [50.8%]; 20 484 white, non-Hispanic [36.4%]). In a comparison of the baseline period with the EOS calculator period, blood culture use decreased from 14.5% to 4.9% (adjusted difference, -7.7%; 95% CI, -13.1% to -2.4%). Empirical antibiotic administration in the first 24 hours decreased from 5.0% to 2.6% (adjusted difference, -1.8; 95% CI, -2.4% to -1.3%). No increase in antibiotic use occurred between 24 and 72 hours after birth; use decreased from 0.5% to 0.4% (adjusted difference, 0.0%; 95% CI, -0.1% to 0.2%). The incidence of culture-confirmed EOS was similar during the 3 periods (0.03% in the baseline period, 0.03% in the learning period, and 0.02% in the EOS calculator period). Readmissions for EOS (within 7 days of birth) were rare in all periods (5.2 per 100 000 births in the baseline period, 1.9 per 100 000 births in the learning period, and 5.3 per 100 000 births in the EOS calculator period) and did not differ statistically (P = .70). Incidence of adverse clinical outcomes, including need for inotropes, mechanical ventilation, meningitis, and death, was unchanged after introduction of the EOS calculator. Clinical care algorithms based on individual infant estimates of EOS risk derived from a multivariable risk prediction model reduced the proportion of newborns undergoing laboratory testing and receiving empirical antibiotic treatment without apparent adverse effects.


Establishment of stably transfected cells constitutively expressing the full-length and truncated antigenic proteins of two genetically distinct mink astroviruses.
Astroviruses are becoming a growing concern in veterinary and public health. To date there are no registered vaccines against astrovirus-induced disease, mostly due to the difficulty to cultivate astroviruses to high titer for vaccine development using conventional techniques. As means to circumvent this drawback, we have developed stably transfected mink fetal cells and BHK21 cells constitutively expressing the full-length and truncated capsid proteins of two distinct genotypes of mink astrovirus. Protein expression in these stably transfected cells was demonstrated by strong signals as evaluated by in-situ PLA and IFA, and confirmed by Western blotting. The recombinant full-length and truncated proteins induced a high level of antibodies in mink, evaluated by ELISA, demonstrating their immunogenicity. In a challenge experiment in mink, a reduction in presentation clinical signs and virus shedding was observed in mink kits born from immunized females. The gene integration and protein expression were sustained through cell passage, showing that the used approach is robust and reliable for expression of functional capsid proteins for vaccine and diagnostic applications.


Atmospheric transmittance of an absorbing gas. 7. Further improvements to the OPTRAN 6 approach.
We present recent improvements in accuracy to the fast transmittance-calculation procedure, Optical Path Transmittance (OPTRAN), which is used for satellite data assimilation at the National Oceanic and Atmospheric Administration. These improvements are (1) to change the absorber space used for ozone, (2) to add new predictors for each gas, and (3) to treat the water vapor line absorption and water continuum absorption as separate terms. Significant improvements in the accuracy of the OPTRAN algorithm for High-Resolution Infrared Radiation Sounders (HIRS) and the Atmospheric Infrared Sounder (AIRS) are demonstrated. The results that we show here extend a recent paper of Xiong and McMillin (2004) that describes the use of a polychromatic correction term to replace the effective transmittance concept to include additional changes that improve accuracy.


Reduced Cardiac Index Reserve and Hypovolemia in Severe Falciparum Malaria.
Impaired microvascular perfusion is central to the development of coma and lactic acidosis in severe falciparum malaria. Refractory hypotension is rare on admission but develops frequently in fatal cases. We assessed cardiac function and volume status in severe falciparum malaria and its prognostic significance. Patients with severe (N = 101) or acute uncomplicated falciparum malaria (N = 83) were recruited from 2 hospitals in India and Bangladesh, and healthy participants (N = 44) underwent echocardiography. Patients with severe malaria had 38% shorter left ventricular (LV) filling times and 25% shorter LV ejection times than healthy participants because of tachycardia; however, stroke volume, LV internal diameter in diastole (LVIDd), and LV internal diameter in systole (LVIDs) indices were similar. A low endocardial fraction shortening (eFS) was present in 17% (9 of 52) of severe malaria patients. Adjusting for preload and afterload, eFS was similar in health and severe malaria. Fatal cases had smaller baseline LVIDd and LVIDs indices, more collapsible inferior vena cavae (IVC), and higher heart rates than survivors. The LVIDs and IVC collapsibility were independent predictors for mortality, together with base excess and Glasgow Coma Scale. Patients with severe malaria have rapid ejection of a normal stroke volume. Fatal cases had features of relative hypovolemia and reduced cardiac index reserve.


Regulatory T cells promote a protective Th17-associated immune response to intestinal bacterial infection with C. rodentium.
Intestinal infection with the mouse pathogen Citrobacter rodentium induces a strong local Th17 response in the colon. Although this inflammatory immune response helps to clear the pathogen, it also induces inflammation-associated pathology in the gut and thus, has to be tightly controlled. In this project, we therefore studied the impact of Foxp3(+) regulatory T cells (Treg) on the infectious and inflammatory processes elicited by the bacterial pathogen C. rodentium. Surprisingly, we found that depletion of Treg by diphtheria toxin in the Foxp3(DTR) (DEREG) mouse model resulted in impaired bacterial clearance in the colon, exacerbated body weight loss, and increased systemic dissemination of bacteria. Consistent with the enhanced susceptibility to infection, we found that the colonic Th17-associated T-cell response was impaired in Treg-depleted mice, suggesting that the presence of Treg is crucial for the establishment of a functional Th17 response after the infection in the gut. As a consequence of the impaired Th17 response, we also observed less inflammation-associated pathology in the colons of Treg-depleted mice. Interestingly, anti-interleukin (IL)-2 treatment of infected Treg-depleted mice restored Th17 induction, indicating that Treg support the induction of a protective Th17 response during intestinal bacterial infection by consumption of local IL-2.


Conifer root and butt rot caused by Heterobasidion annosum (Fr.) Bref. s.l.
SUMMARY The root and butt rot caused by Heterobasidon annosum is one of the most destructive diseases of conifers in the northern temperate regions of the world, particularly in Europe. Economic losses attributable to Heterobasidion infection in Europe are estimated at 800 million euros annually. The fungus has been classified into three separate European intersterile species P (H. annosum), S (H. parviporum) and F (H. abietinum) based on their main host preferences: pine, spruce and fir, respectively. In North America, two intersterile groups are present, P and S/F, but these have not been given scientific names. The ecology of the disease spread has been intensively studied but the genetics, biochemistry and molecular aspects of pathogen virulence have been relatively little examined. Recent advances in transcript profiling, molecular characterization of pathogenicity factors and establishment of DNA-transformation systems have paved the way for future advances in our understanding of this pathosystem. Heterobasidion annosum (Fr.) Bref., H. parviporum Niemelä & Korhonen and H. abietinum Niemelä & Korhonen; kingdom Fungi; class Basidiomycotina; order Aphyllophorales; family Bondarzewiaceae; genus Heterobasidion. presence of the fungus fruit bodies, basidiocarps whitish in the margins, upper surface is tan to dark brown, usually irregular shaped, 3.5 (-7) cm thick and up to 40 cm in diameter; pores 5-19, 7-22 and 13-26 mm(2) for the P, F and S groups, respectively. Small brownish non-sporulating postules develop on the outside of infected roots. Asexual spores (conidiospores) are 3.8-6.6 x 2.8-5.0 microm in size. Mating tests are necessary for identification of intersterility groups. The fungus attacks many coniferous tree species. In Europe, particularly trees of the genera Pinus and Juniperus (P), Picea (S), Abies (F) and in North America Pinus (P) and Picea, Tsuga and Abies (S/F). To a lesser extent it causes root rot on some decidous trees (Betula and Quercus). Disease symptoms: symptoms (e.g. exhudation of resin, crown deterioration) due to Heterobasidion root rot in living trees are not particularly characteristic and in most cases cannot be distinguished from those caused by other root pathogens. Heterobasidion annosum s.l. is a white rot fungus. Initial growth in wood causes a stain that varies in colour depending on host tree species. Incipient decay is normally pale yellow and it develops into a light brown decay to become a white pocket rot with black flecks in its advanced stage. silvicultural methods (e.g. stump removal), chemicals (urea, borates) and biological control agent (Phlebiopsis gigantea, marketed as PG Suspension(R) in the UK, PG IBL(R) in Poland and Rotstop(R) in Fennoscandia) are commonly used approaches for minimizing the disease spread.


Inhibition of hypochlorous acid by lidocaine and native components of alveolar epithelial lining fluid.
Alveolar epithelial lining fluid (ELF) contains several antioxidant substances that may provide in vivo protection. We studied the ability of ELF and ELF components to inhibit the neutrophil oxidant hypochlorous acid (HOCI). Normal bronchoalveolar lavage fluid containing ELF was incubated with physiologically relevant concentrations of HOCI (0.04 mM). After incubation, residual HOCI activity was titered by the iodide method. The inhibitory activity of lavage fluid was unexpectedly strong. For example, lavage fluid diluted 20-fold in the assay system quenched 49% of starting HOCI. We initially postulated that ELF total protein and glutathione would account for most of the inhibition of HOCI. However, several experimental approaches demonstrated that the total protein and glutathione concentrations in diluted lavage fluid were too low to explain the observed inhibition. Instead, the majority of HOCI inhibition was due to the lidocaine used for upper airway anesthesia. Reagent lidocaine exhibited strong reactivity in the HOCI assay system. Furthermore, the lavage fluid lidocaine concentration (32.4 +/- 6.9 micrograms/ml) was sufficient to explain most of the observed quenching activity. Additional experiments explored the hypothetical quenching activity of ELF components devoid of lidocaine. These findings demonstrate the technical problems posed by lidocaine in antioxidant studies involving lavage fluid or ELF.


Methane Activations by Titanium Neopentylidene Complexes: Electronic Resilience and Steric Control.
The titanium neopentylidene complex (PNP)Ti═CHtBu(CH2tBu) (PNP = N[2-PiPr2-4-methylphenyl]2-) is capable of activating both sp2 and sp3 C-H bonds under mild conditions. In addition to methane C-H activation, competition between the initial hydrogen abstraction reaction to form the methane activation product and the tautomerization reaction of this product to form a terminal methylidene was also explored. Several modifications of the PNP and CHtBu ligands were explored to determine the effect of these changes on C-H bond activation. In general, on the one hand, the modifications involving electronic effects have small and inconsistent influence on the stability of the intermediates and products and on the reaction barriers. On the other hand, the use of bulky groups in the ligands favors the methane activation process. By replacing the iPr groups in the PNP ligand with tBu groups, both methane activation and tautomerization reactions become more energetically favorable than in the unmodified complex. On the one hand, the largest acceleration of the methane C-H activation occurs when tBu groups in the phosphine are combined with an extra CH2 linker between the aromatic ring and the phosphine. On the other hand, replacing the nitrogen in the PNP ligand by phosphorus results in lower barriers for the tautomerization reaction and the stabilization of the product of the tautomerization although it remains slightly less stable than product of methane C-H activation. While several ligand modifications related to the electronic effects were examined, it is interesting that most of them did not make a significant change on the barriers for either reaction, indicating a significant resilience of this titanium complex, which could be used to enhance the practical aspects of the complex without a significant loss of its activity.


Molecular mimicry between a monoclonal antibody and one subunit of crotoxin, a heterodimeric phospholipase A2 neurotoxin.
Crotoxin is a heterodimeric phospholipase A2 neurotoxin formed by the non-covalent association of an acidic and non-toxic subunit, CA, and a basic and weakly toxic phospholipase A2, CB. The two subunits behave in a synergistic manner. CA enhances the lethal potency of CB by increasing its selectivity of action. The mAb A-56.36, directed against the non-toxic subunit CA, was previously shown to neutralize crotoxin toxicity by dissociating the crotoxin complex. In the present report, a polypeptide sequence similarity was observed between some CDRs of mAb A-56.36 and two regions of CB (pos. 60-80 and 95-110). Phage displayed peptides corresponding to VH2 and VH3 of mAb A-56.36 and to their homologous sequences in CB bind CA to different extents. This observation shows that mAb A-56.36 interacts with a region of CA involved in its interaction with CB, therefore mimicking the binding of CB to CA. A similar approach was used to determine the regions of ammodytoxin A and of agkistrodotoxin, two phospholipase A2 neurotoxins similar to CB, which are involved in the formation of heterocomplexes with CA. The analysis of these data contributes to the determination of stretches of amino acids which could constitute the paratope of mAb A-56.36, as well as the region of association of CB with CA in crotoxin.


Millifluidic culture improves human midbrain organoid vitality and differentiation.
Human midbrain-specific organoids (hMOs) serve as an experimental in vitro model for studying the pathogenesis of Parkinson's disease (PD). In hMOs, neuroepithelial stem cells (NESCs) give rise to functional midbrain dopaminergic (mDA) neurons that are selectively degenerating during PD. A limitation of the hMO model is an under-supply of oxygen and nutrients to the densely packed core region, which leads eventually to a "dead core". To reduce this phenomenon, we applied a millifluidic culture system that ensures media supply by continuous laminar flow. We developed a computational model of oxygen transport and consumption in order to predict oxygen levels within the hMOs. The modelling predicts higher oxygen levels in the hMO core region under millifluidic conditions. In agreement with the computational model, a significantly smaller "dead core" was observed in hMOs cultured in a bioreactor system compared to those ones kept under conventional shaking conditions. Comparing the necrotic core regions in the organoids with those obtained from the model allowed an estimation of the critical oxygen concentration necessary for ensuring cell vitality. Besides the reduced "dead core" size, the differentiation efficiency from NESCs to mDA neurons was elevated in hMOs exposed to medium flow. Increased differentiation involved a metabolic maturation process that was further developed in the millifluidic culture. Overall, bioreactor conditions that improve hMO quality are worth considering in the context of advanced PD modelling.


GLP-1 and changes in glucose tolerance following gastric bypass surgery in morbidly obese subjects.
It has been proposed, that the dramatic amelioration of type 2 diabetes following Roux-en-Y gastric bypass (RYGBP) could by accounted for, at least in part, by changes in glucagon-like peptide-1 (GLP-1) secretion. However, human data supporting this hypothesis is scarce. A 12-month prospective study on the changes in glucose homeostasis, and active GLP-1 in response to a standard test meal (STM) was conducted in 34 obese subjects (BMI 49.1+/-1.0 kg/m(2)) who had different degrees of glucose tolerance: normal glucose tolerance (NGT, n=12), impaired glucose tolerance (IGT, n=12), and type 2 diabetes (n=10). At 6 weeks after RYGBP, despite the subjects still being markedly obese (BMI 43.5+/-0.9 kg/m(2)), fasting plasma glucose and HbA1c decreased in the 3 study groups (P<0.05). Insulin sensitivity improved, but was still abnormal in a comparable proportion of subjects among groups (P=0.717). When insulin secretion was accounted for the prevailing insulin sensitivity, an increase was found in subjects with diabetes (P<0.05) although it remained lower compared to NGT- and IGT-subjects (P<0.01). At 12 months follow-up, no differences among groups were found in the evaluated glucose homeostasis parameters. Compared to baseline, at 6 weeks the incremental AUC(0-120') of active GLP-1 in response to the STM increased in NGT and IGT (P<0.05) but not in subjects with diabetes (P=0.285). However, the GLP-1 response to a STM was comparable among groups at 12 months follow-up (P=0.887). 1) RYGBP was associated with an improvement but not complete restoration of glucose homeostasis at 6 weeks after surgery. 2) GLP-1 is not a critical factor for the early changes in glucose tolerance.


Disentangling the Contemporaneous and Dynamic Effects of Human and Health Capital on Wages over the Life Cycle.
We quantify the life-cycle effects of human and health capital on the wage distribution of women, with a focus on health capital measured by body mass. We use NLSY79 data on women followed annually up to twenty years during the time of their lives when average annual weight gain is greatest. We measure the wage impact of current body mass (i.e., the contemporaneous or direct effect) while controlling for observed measures of human capital (namely, educational attainment, employment experience, marital status tenure, and family size) and the impacts of an evolving body mass (i.e., the dynamic or indirect effects) on the endogenous histories of behaviors that produce these human capital stocks. We find significant differences in the contemporaneous and dynamic effects of body mass on wages by age, by race, and by wage level.


Polymerase chain reaction for detection of Mycoplasma genitalium in clinical samples.
We have used the polymerase chain reaction to detect Mycoplasma genitalium in artificially seeded human throat swab samples as well as in clinical material. On the basis of the published nucleotide sequence of the M. genitalium 140-kDa adhesin gene, primers were chosen to produce an amplified fragment of 281 bp. Five different previously isolated strains, including the type strain of M. genitalium, could all be detected by the polymerase chain reaction, and DNAs from other mycoplasmal and bacterial species yielded negative results. The detection limits were estimated to be approximately 50 organisms by inspection of ethidium bromide-stained agarose gels and 4 organisms when a biotinylated oligonucleotide probe was used in filter hybridization. The amplified DNA fragments were subjected to restriction enzyme analysis. DNAs from the five different isolates all possessed EcoRI, SspI, AluI, Sau3AI, and DdeI restriction sites, as predicted from the published sequence. A total of 150 urogenital swabs collected from 100 patients for culturing of Chlamydia trachomatis were tested for the presence of M. genitalium DNA. Ten samples from eight patients were found positive. The amplified DNA fragments from all of our clinical samples possessed the AluI, Sau3AI, and DdeI restriction sites, but three samples from two patients did not contain the SspI site and none of the samples contained the EcoRI site.


Indirect photometric detection of anions in nonaqueous capillary electrophoresis employing Orange G as probe and a light-emitting diode-based detector.
A method based on indirect photometric detection (IPD) in CE employing a blue LED (473 nm) as a light source and the highly absorbing (478 nm) anionic dye, Orange G, as the probe ion was developed for the sensitive analysis of inorganic and organic anions. The use of nonaqueous solvents was examined as a simple way to reduce the adsorption of the dye onto the capillary wall and to thereby improve the baseline stability. The benefits of this approach were confirmed by experiments using BGEs in methanol (MeOH) and DMSO in which superior baselines were obtained relative to those achieved using aqueous electrolyte systems. A range of commercial LEDs was tested to improve the detection performance, with a difference of 25% in sensitivity being observed between the best and worst performing LED. The final system (4 mM Orange G, 0.05% w/v hydroxypropylcellulose (HPC), 20 mM triethanolamine (TEA) in pure MeOH) exhibited stable baselines and very low LODs (0.10-0.18 microM) for a test mixture comprising nine inorganic and organic anions. These values represent a two- to six-fold improvement over previous studies and the proposed method provides the most sensitive IPD method for the determination of anions using CE published to date. RSDs for ten replicates were in the ranges of 0.42-0.62% for migration time, 1.41-3.46% for peak area and 3.20-5.78% for peak height.


Preparation and characterization of biomimetic silk fibroin/chitosan composite nanofibers by electrospinning for osteoblasts culture.
In this study, we have successfully fabricated electrospun bead-free silk fibroin [SF]/chitosan [CS] composite nanofibers [NFs] covering the whole range of CS content (0%, 25%, 50%, 75%, and 100%). SF/CS spinning solutions were prepared in a mixed solvent system of trifluoroacetic acid [TFA] and dichloromethane. The morphology of the NFs was observed by scanning electron microscope, and the average fiber diameter ranges from 215 to 478 nm. Confocal laser scanning microscopy confirms the uniform distribution of SF and CS within the composite NFs. To increase biocompatibility and preserve nanostructure when seeded with cells in culture medium, NFs were treated with an ethanol/ammonia aqueous solution to remove residual TFA and to change SF protein conformation. After the chemical treatment, SF/CS NFs could maintain the original structure for up to 54 days in culture medium. Properties of pristine and chemically treated SF/CS NFs were investigated by Fourier transform infrared spectroscopy [FT-IR], X-ray diffraction [XRD], and thermogravimetry/differential scanning calorimetry [TG/DSC]. Shift of absorption peaks in FT-IR spectra confirms the conformation change of SF from random coil to β-sheet by the action of ethanol, which is also consistent with the SF crystalline diffraction patterns measured by XRD. From TG/DSC analysis, the decomposition temperature peaks due to salt formation from TFA and protonated amines disappeared after chemical treatment, indicating complete removal of TFA by binding with ammonium ions during the treatment. This was also confirmed with the disappearance of F1s peak in X-ray photoelectron spectroscopy spectra and disappearance of TFA salt peaks in FT-IR spectra. The composite NFs could support the growth and osteogenic differentiation of human fetal osteoblastic [hFOB] cells, but each component in the composite NF shows distinct effect on cell behavior. SF promotes hFOB proliferation while CS enhances hFOB differentiation. The composite SF/CS NFs will be suitable for bone tissue engineering applications by choosing a suitable blend composition.PACS: 87.85.jf; 87.85.Rs; 68.37.Hk.


Selective corneal imaging using combined second-harmonic generation and two-photon excited fluorescence.
A multiphoton microscope employing second-harmonic generation (SHG) and two-photon excited fluorescence (TPF) is used for high-resolution ex vivo imaging of rabbit cornea in a backscattering geometry. Endogenous TPF and SHG signals from corneal cells and extracellular matrix, respectively, are clearly visible without exogenous dyes. Spectral characterization of these upconverted signals provides confirmation of the structural origin of both TPF and SHG, and spectral imaging facilitates the separation of keratocyte and epithelial cells from the collagen-rich corneal stroma. The polarization dependence of collagen SHG is used to highlight fiber orientation, and three-dimensional SHG tomography reveals that approximately 88% of the stromal volume is occupied by collagen lamellae.


Molecular cloning, sequencing, and expression of lytM, a unique autolytic gene of Staphylococcus aureus.
A gene encoding an autolytic activity was identified in an autolysis-deficient mutant (Lyt-) of Staphylococcus aureus which produces only a single band in autolytic-activity gels (N. Mani, P. Tobin, and R. K. Jayaswal, J. Bacteriol. 175:1493-1499, 1993). An open reading frame, designated lytM, of 948 bp that could encode a polypeptide of 316 amino acid residues was identified. The calculated molecular mass of the lytM gene product (34.4 kDa) corresponded to that of the autolytic activity detected (approximately 36 kDa) in the Lyt- mutant. Results deduced from amino acid sequence analysis and N-terminal amino acid sequencing data suggest that LytM is a secreted protein. The C-terminal region of the putative protein encoded by lytM showed 51% identity with the N-terminal region of the mature lysostaphin from Staphylococcus simulans and 50% identity with the N-terminal region of ALE-1 from Staphylococcus capitis EPK1. Northern blot analysis showed that lytM expresses a transcript of approximately 955 bp, as predicted from the DNA sequence. Escherichia coli clones carrying the lytM gene exhibited autolytic-activity bands of approximately 36 kDa as well as of 19 and 22 kDa in activity gels. The lytM gene was mapped to the SmaI-D fragment on the S. aureus chromosome. Mapping data and results of hybridization experiments with primers generated from gene sequences of known autolytic genes of S. aureus clearly indicate that the lytM gene is distinct from other staphylococcal autolytic genes reported to date.


XPO1/CRM1 Inhibition Causes Antitumor Effects by Mitochondrial Accumulation of eIF5A.
XPO1 inhibitors have shown promise for cancer treatment, and yet the underlying mechanisms for the antitumor effects are not well understood. In this study, we explored the usefulness of selective inhibitors of nuclear export (SINE) compounds that are specific inhibitors of XPO1. We used proteomic analysis in XPO1 inhibitor-treated ovarian cancer cell lines and examined antitumor effects in ovarian and breast cancer mouse models. We also studied the effects of XPO1 inhibitor in combination with chemotherapeutic agents. XPO1 inhibitor treatment substantially increased the percentage of apoptotic cells (60%) after 72 hours of incubation. XPO1 inhibitor promoted the accumulation of eIF5A in mitochondria, leading to cancer cell death. Topotecan showed the greatest synergistic effect with XPO1 inhibitor. XPO1 inhibitors prevented the translocation of IGF2BP1 from the nucleus to the cytoplasm, thereby permitting the localization of eIF5A in the mitochondria. This process was p53, RB, and FOXO independent. Significant antitumor effects were observed with XPO1 inhibitor monotherapy in orthotopic ovarian (P < 0.001) and breast (P < 0.001) cancer mouse models, with a further decrease in tumor burden observed in combination with topotecan or paclitaxel (P < 0.05). This mitochondrial accumulation of eIF5A was highly dependent on the cytoplasmic IGF2BP1 levels. We have unveiled a new understanding of the role of eIF5A and IGF2BP1 in XPO1 inhibitor-mediated cell death and support their clinical development for the treatment of ovarian and other cancers. Our data also ascertain the combinations of XPO1 inhibitors with specific chemotherapy drugs for therapeutic trials.


Tobacco and alcohol sponsorship of sporting events provide insights about how food and beverage sponsorship may affect children's health.
Determining children's exposure to food and beverage company sponsorship, and the effect of this exposure, is important in establishing the extent to which there may be health and societal consequences. This paper aimed to provide preliminary evidence on the scope and potential effects on children of unhealthy food and beverage sponsorship. A review of published literature and media and marketing reports was conducted to determine the types of food and beverage sponsorship campaigns that children are exposed to, and the effect of corporate sponsorship (including tobacco and alcohol) on children and adolescents. A large range of food and beverage sponsorship activities, in Australia and internationally, were identified for both school and sport settings. In particular, food and beverage companies have attempted to develop a marketing presence at all levels of professional and community sport. No information was identified measuring the effect of food and beverage company sponsorship on children and adolescents. However, empirical evidence from consumer studies relating to tobacco and alcohol sponsorship has repeatedly demonstrated that sponsorship has an impact on children's product recall and product-related attitudes and behavioural intentions. While there is no available research on the direct effect of food and beverage sponsorship, the demonstrated effects of tobacco and alcohol sponsorship on children's product awareness, preferences and consumption are likely to be applicable to food companies.


Progressive Resistance Training in End-Stage Renal Disease: Systematic Review.
This systematic review provides an overview of the extant literature on progressive resistance training (PRT) in patients with end-stage renal disease (ESRD) and outlines recommendations for future trials. A systematic review of all published literature evaluating the chronic (>6 weeks) application of PRT in patients with ESRD using electronic databases. The search yielded 16 clinical trials, including 11 randomized controlled trials (RCT), 4 uncontrolled trials and one trial involving a within-subjects control period plus RCT. RCT quality, assessed via the CONSORT statement, ranged from low (4/10) to high (10/10) with a mean score of 7.3/10; 7/11 RCT had a quality score ≥7.5. All trials evaluated chronic adaptation to PRT across a range of important outcomes. PRT can induce muscle hypertrophy and improve aspects of physical functioning and health-related quality of life in ESRD. There is preliminary evidence that PRT may reduce protein-energy malnutrition and cardiovascular disease risk factors, including C-reactive protein, total cholesterol, triglyceride, and measures of insulin resistance in patients with or at-risk of comorbid type 2 diabetes. The evidence base for PRT adapting some of the endpoints investigated to date remains inconsistent (e.g. physical performance tests, obesity outcomes), and many other pertinent clinical outcomes remain to be investigated. RCT are required to investigate a range of novel research questions related to the benefits and application of PRT in this cohort and its patient subgroups (e.g. diabetes, depression, dyslipidemia, etc.). Future studies must be of high methodological quality to inform clinical practice guidelines.


Cortical areas involved in virtual movement of phantom limbs: comparison with normal subjects.
To demonstrate that amputees performing "virtual" movements of their amputated limb activate cortical areas previously devoted to their missing limb, we studied amputees with functional magnetic resonance imaging (fMRI) and positron emission tomographic (PET) scans and compared the results with those of normal volunteers performing imaginary movements during fMRI acquisitions. Ten amputees (age range, 33-92 yr; average age, 49 yr; six men and four women; eight upper-limb and two lower-limb amputations) able to move their phantom limb at will were studied by fMRI (all patients) and PET scan (seven patients). The time between amputation and fMRI and PET studies ranged from 1 to 27 years (average, 13 yr). Patients were asked to perform virtual movements of the amputated limb and normal movements of the contralateral normal limb according to the functional images acquisition procedure. Movements of the stump were also used to differentiate stump cortical areas from virtual movement-activated areas. Ten right-handed volunteers, age- and sex-matched to the amputees, were also studied by fMRI. All volunteers were asked to perform four tasks during their fMRI study: imaginary movements of their right arm (1 task) and foot (1 task) and real movements of their left arm (1 task) and foot (1 task). In amputees, virtual movements of the missing limbs produced contralateral primary sensorimotor cortex activation on both fMRI and PET scans. These activation areas, different from the stump activation areas, were similar in location to contralateral normal limb-activated areas. Quantitatively, in two amputees who claimed to be able to perform both slow and fast virtual movements, regional cerebral blood flow measured by PET scan in the precentral gyrus increased significantly during fast movements in comparison with slow virtual movements. In normal subjects, significant differences between real versus imaginary fMRI activations were found (for both foot and hand movements); imaginary right hand and foot tasks activated primarily the contralateral supplementary motor areas, with no significant activation detected in the contralateral precentral or postcentral gyri. Primary sensorimotor cortical areas can be activated by phantom-limb movements and thus can be considered functional for several years or decades after amputation. In this study, we found that the location of the activation of these areas is comparable to that of activations produced by normal movements in control subjects or in amputees.


Superior Parietal Lobule: A Role in Relative Localization of Multiple Different Elements.
Simultanagnosia is an impairment in processing multiple visual elements simultaneously consecutive to bilateral posterior parietal damage, and neuroimaging data have specifically implicated the superior parietal lobule (SPL) in multiple element processing. We previously reported that a patient with focal and bilateral lesions of the SPL performed slower than controls in visual search but only for stimuli consisting of separable lines. Here, we further explored this patient's visual processing of plain object (colored disk) versus object consisting of separable lines (letter), presented in isolation (single object) versus in triplets. Identification of objects was normal in isolation but dropped to chance level when surrounded by distracters, irrespective of eccentricity and spacing. We speculate that this poor performance reflects a deficit in processing objects' relative locations within the triplet (for colored disks), aggravated by a deficit in processing the relative location of each separable line (for letters). Confirming this, performance improved when the patient just had to detect the presence of a specific colored disk within the triplets (visual search instruction), while the inability to identify the middle letter was alleviated when the distracters were identical letters that could be grouped, thereby reducing the number of ways individual lines could be bound.


Elbow injuries in athletes.
Throwing and racquet sports produce large stresses at the elbow joint consisting of tension on the medial or ulnar side, and compression on the lateral or radial side. Medial tension can lead to tears of the common flexor origin or medial collateral ligament, ulnar nerve subluxation, or pronator teres syndrome. Bony lesions include fragmentation and partial avulsion of the medial humeral epicondyle (little league elbow) or even complete avulsion of the epicondyle. The possible sequelae of excessive lateral compression include osteochondritis dissecans of the capitellum, osteochondral fractures of the capitellum and radius, and loose bodies. Early and accurate diagnosis is essential to initiate proper treatment.


Spatially distinct Raman scattering characteristics of individual ZnO nanorods under controlled polarization: intense end scattering from forbidden modes.
In this study, we characterize incident/scattered polarization-specific and NR position-resolved Raman scattering behaviors of individual zinc oxide nanorods (ZnO NRs). We quantify Raman signals from the five key ZnO phonon modes of E2L, E2H-2L, A1T, E1T, and E2H, and reveal the NR position-dependent Raman scattering characteristics of the phonon modes per given light-matter interaction geometry. We then present Raman intensity maps and elucidate Raman behaviors consistent and incongruous with Raman selection rules. In particular, we identify an intriguing Raman scattering phenomenon from the forbidden modes, distinctively occurring at the two NR ends. Their unexpectedly strong and localized scattering signals at the NR termini are contrasted by the scattering behaviors from the rest of the NR positions agreeing with the selection predictions. By carrying out control measurements on isotropic ZnO microparticles (MPs), we ascertain that the unique NR position-specific Raman responses observed on ZnO NRs originate from their high shape anisotropy. Owing to the superior optical property coupled with reduced dimensionality and high geometric anisotropy, ZnO NRs have gained much attention recently for use in optoelectronic, photonic, and biosensor technologies. Raman scattering has been increasingly exploited as a noninvasive and sensitive analytical tool to investigate NR properties pertinent to these applications. Hence, our endeavors, explicitly providing the spatially distinct, polarized Raman scattering behaviors from individual ZnO NRs, will be central to the correct interpretation of Raman data of both the individual and ensemble NRs as well as to the accurate correlation of the measurement outcomes to their chemical/physical/optical properties. Our efforts may also promote novel applications for polarized Raman scattering whose optical outputs on the various positions along the ZnO NRs can be selectively modulated.


Piecewise Regression Analysis of Secular Change in the Maximum Femoral Vertical Head Diameter of American White Males and Females.
Osteometric measurements of the femur are consistently used to estimate stature, sex, and race in constructing demographic profiles. The presence of positive or negative changes in the size of the maximum vertical diameter of the femoral head could potentially affect the validity of such profiles. Additionally, changes in femoral head size may be an indicator of the socioeconomic status, health, and nutrition of a population over periods of time. Two large data sets consisting of white male and white female femoral vertical head diameter measurements with birth years spanning 1841-1990 are used in this study. A combination of both LOESS and piecewise regression models determined the presence of secular changes in femoral head size. Tests of the residuals were also conducted to assess normality of the data and goodness of fit of the nonlinear models. The results indicate that white males and females experienced nonsignificant increases in femoral head diameter size before 1920 and significant decreases in size thereafter. The results of this study are consistent with other studies that have identified changes in body and skeletal morphology. Considerable changes and improvements in environmental conditions that humans have experienced since the mid-nineteenth century likely contribute to the decrease in femoral head size observed in this study.


Kinematics and muscle dynamics of C- and S-starts of carp (Cyprinus carpio L.).
An analysis is presented of body curvature, acceleration and muscle strain during fast-starts in the common carp (Cyprinus carpio L.). C- and S-starts were filmed at 200 frames s-1 at 23 degreesC. Curvatures and accelerations of mid-body axes were calculated from digitised outlines. Maximum accelerations at 0.3 FL (fork length) from the snout were 54 m s-2 for C-starts and 40 m s-2 for S-starts. The total turning angle was approximately 150 degrees in C-starts. This angle was 70 degrees during escape S-starts, significantly larger than for predatory S-starts in other species. Sarcomere strains of axial muscle fibres were calculated at 0.4 and 0.8 FL. During C-starts, white muscle fibres were exposed to maximum sarcomere strains of up to approximately 16 %, and posterior fibres had similar strains to anterior fibres (red 27 %; white 16 %). During S-starts, however, maximum strains in anterior fibres (red 39 %; white 24 %) were more than twice those in posterior fibres (red 17 %; white 10 %). In a C-start, the fish made a large turning angle directed away from the stimulus by bending its tail strongly and thereby producing a large thrust. A larger anterior peak curvature of the fish during S-starts enabled the carp to control the direction of escape better than during C-starts, but with lower accelerations and smaller turning angles. During cyclic and intermittent swimming, red posterior fibres experienced the largest strains. Interestingly, previous studies have shown these fibres to have the lowest passive stiffness and the largest titin isoform, allowing them to attain large strain amplitudes with relatively low passive tensions.


Atomistic interpretation of solid solution hardening from spectral analysis.
From analysis of a series of vibrational spectra of ir energy absorption and laser Raman, an attempt is made to interpret solid solution hardening from an atomistic point of view for the system CaF(2)/SrF(2). It is shown to be caused by the combined action of three atomic characteristics, i.e., their changes as a function of composition. They are deformation of the atomic coordination polyhedrons, overlap of the outer electron shells of the atom pairs, and the ratio of the ionic to covalent share of binding. A striking nonlinear behavior of the three characteristics, as a function of composition, gives maximum atomic bond strength to the 55/45 position of the system CaF(2)/SrF(2), in agreement with the measured data of the solid solution hardening. The curve for atomic bond strength, derived from the three characteristics, is almost identical to the curve for measured microhardness data. This result suggests that the atomistic interpretation, put forward in this paper, is correct.


Diving into old age: muscular senescence in a large-bodied, long-lived mammal, the Weddell seal (Leptonychotes weddellii).
Classic aging theory postulates the absence of pronounced organismal senescence in wild animals since mortality probably occurs first. Large-bodied, long-lived mammals are a recognized exception to this tenet, yet organismal senescence has not been investigated to date in such mammals in the wild. Furthermore, oxidative stress theory of aging supports the suggestion that exercise hypoxia, as regularly incurred during apneustic foraging in diving mammals might lead to cellular dysfunction and accelerated aging. To determine if an aspect of organismal senescence occurs in wild marine mammals, we examined the pattern of skeletal muscle aging (contractile and connective tissue components of longissimus dorsi and pectoralis muscles) in free-ranging adult Weddell seals (9-26 years). The average myocyte cross-sectional area was 22% greater with age in the longissiums dorsi, but no significant increase occurred in the pectoralis. Cross-sectional area was not related to body mass. Changes in myocyte number per area were consistent with the 35-40% age-increase in extracellular space in both muscle groups. Also consistent with extracellular space remodeling, total and relative collagen contents were significantly elevated in older seals (115% in longissimus dorsi; 65% in pectoralis). The ratio of muscle myocyte to collagen declined with age (50-63%) at both sites. Additionally, a shift towards a higher ratio of type I to type III collagen occurred with advancing age in both muscle groups (79% increase in pectoralis; 49% in longissimus dorsi). We reject the classic tenet and null-hypothesis that Weddell seals do not survive to an age where muscular senescence becomes detectable.


The Effects of Hyperhydrating Supplements Containing Creatine and Glucose on Plasma Lipids and Insulin Sensitivity in Endurance-Trained Athletes.
The addition of carbohydrate (CHO) in the form of simple sugars to creatine (Cr) supplements is central. The study aimed to determine whether ingestion of glucose (Glu) simultaneously with Cr and glycerol (Cr/Gly) supplement is detrimental to plasma lipids of endurance-trained individuals and find out whether modification arising can be attenuated by replacing part of the Glu with alpha lipoic acid (Ala). Twenty-two endurance-trained cyclists were randomized to receive Cr/Gly/Glu (11.4 g Cr-H2O, 1 g Gly/kg BM, and 150 g Glu) or Cr/Gly/Glu/Ala (11.4 g Cr-H2O, 1 g Gly/kg BM, 100 g Glu, and 1 g Ala) for 7 days. Fasting concentration of TAG increased significantly (P < 0.01) after supplementation with Cr/Gly/Glu (before: 0.9 ± 0.2 mmol/L; after: 1.3 ± 0.4 mmol/L) and Cr/Gly/Glu/Ala (before: 0.8 ± 0.2 mmol/L; after: 1.2 ± 0.5 mmol/L) but changes were not different between the groups. Supplementation significantly (P < 0.05) increased the TAG to HDL-cholesterol ratio but had no effect on fasting concentration of total, HDL-, and LDL-cholesterol and insulin resistance. Thus, addition of Glu to Cr containing supplements enhances plasma TAG concentration and the TAG to HDL-cholesterol ratio and this enhancement cannot be attenuated by partial replacement of Glu with Ala.


Similarities of Drosophila rab GTPases based on expression profiling: completion and analysis of the rab-Gal4 kit.
We recently generated rab-Gal4 lines for 25 of 29 predicted Drosophila rab GTPases. These lines provide tools for the expression of reporters, mutant rab variants or other genes, under control of the regulatory elements of individual rab loci. Here, we report the generation and characterization of the remaining four rab-Gal4 lines. Based on the completed 'rab-Gal4 kit' we performed a comparative analysis of the cellular and subcellular expression of all rab GTPases. This analysis includes the cellular expression patterns in characterized neuronal and non-neuronal cells and tissues, the subcellular localization of wild type, constitutively active and dominant negative rab GTPases and colocalization with known intracellular compartment markers. Our comparative analysis identifies all Rab GTPases that are expressed in the same cells and localize to the same intracellular compartments. Remarkably, similarities based on these criteria are typically not predicted by primary sequence homology. Hence, our findings provide an alternative basis to assess potential roles and redundancies based on expression in developing and adult cell types, compartment identity and subcellular localization.


The effects of a supervised resistance-training program on Special Olympics athletes.
To examine the effects of a resistance-training program on athletes with intellectual disabilities (ID). 2-way (2 x 2), repeated-measures analysis of variance on 2 groups (males and females); 30 Special Olympics (SO) athletes, age 16-22 (16 males, 14 females). INTERVENTION/OUTCOME MEASURES: Resistance training, twice per week, for 3 months on Med-X weight equipment. Exercises tested: chest press, abdominal crunch, seated row, overhead press, seated dip, lower back extension, and biceps curl. The weight lifted and the number of repetitions performed were used to determine predicted 1-repetition max (1RM). All participants as a group increased significantly in predicted 1RM for each exercise performed. Males were stronger than females for 5 of the 7 exercises. A significant interaction effect between genders was demonstrated for the seated dip. Significant strength gains can be accomplished by adolescents with ID via a supervised resistance-training program.


Population genetic structure of Earth's largest fish, the whale shark (Rhincodon typus).
Large pelagic vertebrates pose special conservation challenges because their movements generally exceed the boundaries of any single jurisdiction. To assess the population structure of whale sharks (Rhincodon typus), we sequenced complete mitochondrial DNA control regions from individuals collected across a global distribution. We observed 51 single site polymorphisms and 8 regions with indels comprising 44 haplotypes in 70 individuals, with high haplotype (h = 0.974 +/- 0.008) and nucleotide diversity (pi = 0.011 +/- 0.006). The control region has the largest length variation yet reported for an elasmobranch (1143-1332 bp). Phylogenetic analyses reveal no geographical clustering of lineages and the most common haplotype was distributed globally. The absence of population structure across the Indian and Pacific basins indicates that oceanic expanses and land barriers in Southeast Asia are not impediments to whale shark dispersal. We did, however, find significant haplotype frequency differences (AMOVA, Phi(ST) = 0.107, P < 0.001) principally between the Atlantic and Indo-Pacific populations. In contrast to other recent surveys of globally distributed sharks, we find much less population subdivision and no evidence for cryptic evolutionary partitions. Discovery of the mating and pupping areas of whale sharks is key to further population genetic studies. The global pattern of shared haplotypes in whale sharks provides a compelling argument for development of broad international approaches for management and conservation of Earth's largest fish.


The effect of ultrafast fiber laser application on the bond strength of resin cement to titanium.
The purpose of this study was to investigate the effect of ultrafast fiber laser treatment on the bond strength between titanium and resin cement. A total of 60 pure titanium discs (15 mm × 2 mm) were divided into six test groups (n = 10) according to the surface treatment used: group (1) control, machining; group (2) grinding with a diamond bur; group (3) ultrafast fiber laser application; group (4) resorbable blast media (RBM) application; group (5) electro-erosion with copper; and group (6) sandblasting. After surface treatments, resin cements were applied to the treated titanium surfaces. Shear bond strength testing of the samples was performed with a universal testing machine after storing in distilled water at 37 °C for 24 h. One-way ANOVA and Tukey's HSD post hoc test were used to analyse the data (P < 0.05). The highest bond strength values were observed in the laser application group, while the lowest values were observed in the grinding group. Sandblasting and laser application resulted in significantly higher bond strengths than control treatment (P < 0.05). Ultrafast fiber laser treatment and sandblasting may improve the bond strength between resin cement and titanium.


Complex patterns in a simple system.
Numerical simulations of a simple reaction-diffusion model reveal a surprising variety of irregular spatiotemporal patterns. These patterns arise in response to finite-amplitude perturbations. Some of them resemble the steady irregular patterns recently observed in thin gel reactor experiments. Others consist of spots that grow until they reach a critical size, at which time they divide in two. If in some region the spots become overcrowded, all of the spots in that region decay into the uniform background.


Convalescent COVID-19 Patients Without Comorbidities Display Similar Immunophenotypes Over Time Despite Divergent Disease Severities.
COVID-19, the disease caused by SARS-CoV-2 infection, can assume a highly variable disease course, ranging from asymptomatic infection, which constitutes the majority of cases, to severe respiratory failure. This implies a diverse host immune response to SARS-CoV-2. However, the immunological underpinnings underlying these divergent disease courses remain elusive. We therefore set out to longitudinally characterize immune signatures of convalescent COVID-19 patients stratified according to their disease severity. Our unique convalescent COVID-19 cohort consists of 74 patients not confounded by comorbidities. This is the first study of which we are aware that excludes immune abrogations associated with non-SARS-CoV-2 related risk factors of disease severity. Patients were followed up and analyzed longitudinally (2, 4 and 6 weeks after infection) by high-dimensional flow cytometric profiling of peripheral blood mononuclear cells (PBMCs), in-depth serum analytics, and transcriptomics. Immune phenotypes were correlated to disease severity. Convalescence was overall associated with uniform immune signatures, but distinct immune signatures for mildly versus severely affected patients were detectable within a 2-week time window after infection.


Tetragonal and trigonal Mo2B2 monolayers: two new low-dimensional materials for Li-ion and Na-ion batteries.
In this study, we report two new Mo2B2 monolayers and investigate their stabilities, electronic structures, lattice dynamics, and properties as anode materials for energy storage by using the crystal structure prediction technique and first-principles method. The calculated phonon spectra and electrical structures indicate that our predicted tetragonal and trigonal Mo2B2 (tetr- and tri-Mo2B2) monolayers possess excellent electronic conductivity and great stability. The adsorption energies of Li/Na on them are negative enough to ensure stability and safety under operating conditions. Besides, tetr-Mo2B2 possesses a theoretical specific capacity of ∼251 mA h g-1 for both Li- and Na-ion batteries (LIBs and NIBs), while tri-Mo2B2 possesses ∼251 and ∼188 mA h g-1 for LIBs and NIBs, respectively. The diffusion energy barriers of Li/Na over tetr- (0.029/0.010 eV) and tri- (0.023/0.013 eV) Mo2B2 are very small, indicating their excellent charge/discharge capability. In addition, the low electrode potential of Li/Na-intercalated tetr- and tri-Mo2B2 is beneficial to their performance as anode materials. This work is of great importance for widening the families of both anode materials for LIBs/NIBs and two-dimensional transition metal borides.


Fv-1 restriction and its effects on murine leukemia virus integration in vivo and in vitro.
We have investigated the mechanisms by which alleles at the mouse Fv-1 locus restrict replication of murine leukemia viruses. Inhibition of productive infection is closely paralleled by reduced accumulation of integrated proviral DNA as well as by reduced levels of linear viral DNA in a cytoplasmic fraction. Nevertheless, viral DNA is present at nearly normal levels in a nuclear fraction, and total amounts of viral DNA are only mildly affected in restrictive infections, suggesting a block in integration to account for reduced levels of proviral DNA. However, integrase (IN)-dependent trimming of 3' ends of viral DNA occurs normally in vivo during restrictive infections, demonstrating that not all IN-mediated events are prevented in vivo. Furthermore, viral integration complexes present in nuclear extracts of infected restrictive cells are fully competent to integrate their DNA into a heterologous target in vitro. Thus, the Fv-1-dependent activity that restricts integration in vivo may be lost in vitro; alternatively, Fv-1 restriction may prevent a step required for integration in vivo that is bypassed in vitro.