The association of stride length to ball velocity and elbow varus torque in professional pitchers.
Professional basebal pitchers (n =315) were divided into quartiles based on increasing stride length and random intercept linear mixed-effect models were used to correlate stride length with ball velocity, pelvis and trunk rotation at foot contact, and throwing arm kinetics. Average stride length among all pitchers was 78.3±5.3%body height (%BH). For every 10% increase in stride length, ball velocity increased by 0.9 m/s (B =0.089, β =0.25, p <0.001) and trunk rotation initiation occurred 4.23 ms earlier (B =-0.42, β =-0.14, p <0.001). When divided into quartiles pelvis rotation was less towards home plate in Q1 compared to Q3 and Q4 (70.0±10.7° vs. 60.9±8.9° and 58.6±9.1°, p <0.001). No significant differences in shoulder internal rotation torque (p =0.173) or elbow varus torque (p =0.072) were noted between quartiles. Professional baseball pitchers who reached stride lengths of 80%BH or greater achieved faster ball velocity without an increase in elbow varus torque. This may, be a byproduct of rotating the pelvis for a greater proportion of the pitching motion and thereby more effectively utilising the lower extremities in the kinetic chain. Encouraging players to achieve this threshold of stride length may enhance ball velocity outcomes.


Non-Invasive Intracranial Pressure Estimation During Combined Exposure to CO₂ and Head-Down Tilt.
Exposure to carbon dioxide (CO2) and cephalad fluid shift are considered factors that affect intracranial pressure (ICP) during spaceflight. Increases in ICP were reported during cephalad fluid shift induced by head-down tilt (HDT), while little is known regarding the effect of additional CO2 during HDT on ICP. Therefore, we tested the hypothesis that this combination increases ICP more than HDT alone. There were 15 healthy male volunteers who underwent 4 types of 10-min interventions consisting of Placebo/Supine (air and supine), CO2/Supine (3% CO2 and supine, CO2 alone), Placebo/HDT (air and -10° HDT, HDT alone), and CO2/HDT (3% CO2 and -10° HDT, combination). Using arterial blood pressure (ABP) and cerebral blood flow velocity waveforms, ICP was estimated noninvasively before and during the four interventions. Two calculation methods were employed. One is based on the signal transformation from ABP to ICP with the intracranial component as a "black box" system (nICP_BB), and the other is based on the equation ICP = ABP - cerebral perfusion pressure, reflecting critical closing pressure (nICP_CrCP). Both nICP_BB and nICP_CrCP significantly increased during Placebo/HDT and CO2/HDT, although there was no statistically significant difference between the nICP indexes of these two interventions. Increases in ICP were observed during both Placebo/HDT and CO2/HDT. Contrary to our hypothesis, the combination of 3% CO2 and -10° HDT did not increase ICP remarkably compared to -10° HDT alone. Therefore, the addition of 3% CO2 is considered to have little effect on increasing ICP during cephalad fluid shift.Kurazumi T, Ogawa Y, Yanagida R, Morisaki H, Iwasaki K. Non-invasive intracranial pressure estimation during combined exposure to CO2 and head-down tilt. Aerosp Med Hum Perform. 2018; 89(4):365-370.


Genomic prediction in biparental tropical maize populations in water-stressed and well-watered environments using low-density and GBS SNPs.
One of the most important applications of genomic selection in maize breeding is to predict and identify the best untested lines from biparental populations, when the training and validation sets are derived from the same cross. Nineteen tropical maize biparental populations evaluated in multienvironment trials were used in this study to assess prediction accuracy of different quantitative traits using low-density (~200 markers) and genotyping-by-sequencing (GBS) single-nucleotide polymorphisms (SNPs), respectively. An extension of the Genomic Best Linear Unbiased Predictor that incorporates genotype × environment (GE) interaction was used to predict genotypic values; cross-validation methods were applied to quantify prediction accuracy. Our results showed that: (1) low-density SNPs (~200 markers) were largely sufficient to get good prediction in biparental maize populations for simple traits with moderate-to-high heritability, but GBS outperformed low-density SNPs for complex traits and simple traits evaluated under stress conditions with low-to-moderate heritability; (2) heritability and genetic architecture of target traits affected prediction performance, prediction accuracy of complex traits (grain yield) were consistently lower than those of simple traits (anthesis date and plant height) and prediction accuracy under stress conditions was consistently lower and more variable than under well-watered conditions for all the target traits because of their poor heritability under stress conditions; and (3) the prediction accuracy of GE models was found to be superior to that of non-GE models for complex traits and marginal for simple traits.


Mutation of mitochondrial DNA G13513A presenting with Leigh syndrome, Wolff-Parkinson-White syndrome and cardiomyopathy.
Mutation of mitochondrial DNA (mtDNA) G13513A, encoding the ND5 subunit of respiratory chain complex I, can cause mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) and Leigh syndrome. Wolff-Parkinson-White (WPW) syndrome and optic atrophy were reported in a high proportion of patients with this mutation. We report an 18-month-old girl, with an 11-month history of psychomotor regression who was diagnosed with WPW syndrome and hypertrophic cardiomyopathy, in association with Leigh syndrome. Supplementation with coenzyme Q10, thiamine and carnitine prevented further regression in gross motor function but the patient's heart function deteriorated and dilated cardiomyopathy developed 11 months later. She was found to have a mutation of mtDNA G13513A. We suggest that mtDNA G13513A mutation is an important factor in patients with Leigh syndrome associated with WPW syndrome and/or optic atrophy, and serial heart function monitoring by echocardiography is recommended in this group of patients.


Once-a-week psychiatric ward round or daily inpatient team meeting? A multidisciplinary mental health team's experience of new ways of working.
Evidence indicates that while service users are dissatisfied with current ward round practices, studies of how professionals experience this practice are sparse. This study highlights staff view of the once-a-week psychiatric ward round compared to a reformed ward round taking place every weekday. Interviews were conducted at one acute psychiatric ward in north-west England. Our analysis revealed a core theme, 'forming a new way of working', which could be understood from three themes. The theme, 'bound by tradition', emphasized how the traditional ward round represented a double-edged sword: it provided a safe structure, but it also highlighted a shared awareness of an urgent need to leave old ways of working behind. The process of change became discernable in the themes 'juggling the change' and 'light at the end of the tunnel', which showed that restructuring the traditional ward round was both possible and valued. We found that staff views on ward rounds are more complex than had been earlier understood, but new ways of working can be implemented, if the impact of tradition, the process of change, and the time to bed down are taken into account.


A chimeric Ty3/Moloney murine leukemia virus integrase protein is active in vivo.
This report describes the results of experiments to determine whether chimeras between a retrovirus and portions of Ty3 are active in vivo. A chimera between Ty3 and a Neo(r)-marked Moloney murine leukemia virus (M-MuLV) was constructed. The C-terminal domain of M-MuLV integrase (IN) was replaced with the C-terminal domain of Ty3 IN. The chimeric retroviruses were expressed from an amphotrophic envelope packaging cell line. The virus generated was used to infect the human fibrosarcoma cell line HT1080, and cells in which integration had occurred were selected by G418 resistance. Three independently integrated viruses were rescued. In each case, the C-terminal Ty3 IN sequences were maintained and short direct repeats of the genomic DNA flanked the integration site. Sequence analysis of the genomic DNA flanking the insertion did not identify a tRNA gene; therefore, these integration events did not have Ty3 position specificity. This study showed that IN sequences from the yeast retrovirus-like element Ty3 can substitute for M-MuLV IN sequences in the C-terminal domain and contribute to IN function in vivo. It is also one of the first in vivo demonstrations of activity of a retrovirus encoding an integrase chimera. Studies of chimeras between IN species with distinctive integration patterns should complement previous work by expanding our understanding of the roles of nonconserved domains.


The Effectiveness of a New Hemostatic Agent (Ankaferd Blood Stopper) for the Control of Bleeding following Tooth Extraction in Hemophilia: A Controlled Clinical Trial.
To assess the hemostatic efficacy of a new local hemostatic agent, Ankaferd Blood Stopper (ABS), for the control of bleeding following tooth extraction in hemophiliacs. Simple tooth extractions were performed in 27 hemophilia A patients. In the treatment group (n=17) local hemostasis was achieved via application of ABS to the extraction sockets, whereas in the control group (n=10) local hemostasis was achieved via direct packing with gauze. In all, 57 (21 primary and 36 permanent) teeth extractions were performed in 27 hemophilia A patients. There were no significant differences in age or factor VIII level distribution between the 2 groups (p>0.05). The most significant clinical difference between the groups was associated with the use of ABS; those in the treatment group had significantly shorter duration of bleeding (p=0.002). This is the first study to evaluate the efficacy of ABS for the control of bleeding following tooth extraction in hemophiliacs. ABS can be considered an alternative local hemostatic agent for reducing clotting factor concentrates in hemophilia patients. None declared.


Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf.
Legionella pneumophila is an intracellular bacterium that causes an acute form of pneumonia called Legionnaires' disease. After infection of human macrophages, the Legionella-containing phagosome (LCP) avoids fusion with the lysosome allowing intracellular replication of the bacterium. In macrophages derived from most mouse strains, the LCP is delivered to the lysosome resulting in Legionella degradation and restricted bacterial growth. Mouse macrophages lacking the NLR protein Ipaf or its downstream effector caspase-1 are permissive to intracellular Legionella replication. However, the mechanism by which Ipaf restricts Legionella replication is not well understood. Here we demonstrate that the presence of flagellin and a competent type IV secretion system are critical for Legionella to activate caspase-1 in macrophages. Activation of caspase-1 in response to Legionella infection also required host Ipaf, but not TLR5. In the absence of Ipaf or caspase-1 activation, the LCP acquired endoplasmic reticulum-derived vesicles, avoided fusion with the lysosome, and allowed Legionella replication. Accordingly a Legionella mutant lacking flagellin did not activate caspase-1, avoided degradation, and replicated in wild-type macrophages. The regulation of phagosome maturation by Ipaf occurred within 2 h after infection and was independent of macrophage cell death. In vivo studies confirmed that flagellin and Ipaf play an important role in the control of Legionella clearance. These results reveal that Ipaf restricts Legionella replication through the regulation of phagosome maturation, providing a novel function for NLR proteins in host defense against an intracellular bacterium.


In vitro excystation of Haplorchis taichui (Trematoda: Heterophyidae).
The effects of trypsin, bile extract, temperature and acid-based condition for the in vitro excystation of Haplorchis taichui metacercariae were studied. At 37 degrees C, approximately half the number of metacercariae excysted when exposed to 1% trypsin for 15 minutes with no more excystation found beyond this time. Increasing trypsin concentration seemed to reduce the excystation rate while bile extract was, however, unlikely to be an absolute requirement. A temperature of 37 degrees-41 degrees C yielded a similar excystation result in combination with 1% trypsin; however, less excystation occurred at a lower temperature of 35 degrees C. The acid-based environment of pH 8 gave the best excystation result in association with 1% trypsin at a temperature of 39 degrees C. Higher and lower basicity produced a smaller excystation rate. An environmental condition of 1% trypsin at pH 8 and a temperature of between 37 degrees-41 degrees C was recommended for the in vitro excystation of H. taichui metacercariae. The relatively broad temperature and pH range condition for the excystation of H. taichui corresponded with various definitive hosts that were infected naturally by this fluke.


Mapping in pig of genes involved in sexual differentiation: AMH, WT1, FTZF1, SOX2, SOX9, AHC, and placental and embryonic CYP19.
Intersexuality has been reported in pigs and investigations are in progress to identify and physically map the genes involved in sex-reversal. In this study we have mapped on porcine chromosomes seven genes which might be implicated in this developmental pathway. Four genes were mapped by radioactive in situ hybridization: AMH (Anti-Müllerian Hormone) and WT1 (Wilms' Tumor gene 1) were both mapped to pig chromosome 2 (SSC2) in the q14-->q21 and p14-->q11 regions, placental CYP19 (cytochrome P450, subfamily XIX) and FTZF1 (fushi tarazu factor [Drosophila] homolog 1, alias SF1 [steroidogenic factor 1]) to pig chromosome 1 (SSC1) in the q14-->q17 and q210-->q211 regions respectively. Four other genes were regionally located by PCR analysis on a cytogenetically characterized porcine somatic cell hybrid panel: a second CYP19 gene (expressed in embryo) was mapped to porcine 1q12-->q17, AHC (alias DAX1, adrenal hypoplasia congenital) to porcine Xp24, SOX2 and SOX9 (SRY sex determining region Y-box 2 and 9) to 13q23-->q41 and 12p13-->p11 respectively. These results are in global agreement with mapping data available in other mammalian species.


Aminocarbonylation of aryl halides using a nickel phosphite catalytic system.
The nickel and phosphite catalytic system with sodium methoxide enables a very efficient aminocarbonylation reaction to be performed between aryl iodides or bromides and N,N-dimethylformamide (DMF). Phosphite ligand 1, which is very stable to air and moisture and, furthermore, inexpensive, afforded the highest reaction yield.


Affinity labeling of Escherichia coli glucosamine-6-phosphate synthase with a fructose 6-phosphate analog--evidence for proximity between the N-terminal cysteine and the fructose-6-phosphate-binding site.
Glucosamine-6-phosphate synthase (GlcNP-synthase) catalyzes the formation of glucosamine 6-phosphate from fructose 6-phosphate using the gamma-amide functionality of glutamine as the nitrogen source. In the absence of glutamine, GlcNP-synthase was recently found to catalyze the formation of glucose 6-phosphate corresponding to a phosphoglucoisomerase-like activity. Here we report active-site directed, irreversible inhibition of Escherichia coli GlcNP-synthase (k(inact) = 0.60 +/- 0.05 min(-1), Kirr = 1.40 +/- 0.20 mM) by anhydro-1,2-hexitol 6-phosphates previously known as irreversible inhibitors of phosphoglucoisomerase. Enzyme inactivation with the tritiated affinity label, followed by tryptic digestion and purification of the radioactive fragments, allowed identification of three peptides. Two of them, accounting for 54% of the recovered radioactivity, are believed to result from the nucleophilic attack of side-chain carboxylates of Glu255 and Glu258 and thiol of Cys300 of the fructose-6-phosphate-binding site on the epoxide functionality of the inhibitor. The major peptide corresponds to derivatization of the N-terminal cysteine from the glutamine-binding site by the inhibitor. These results provide evidence for the close proximity of glutamine and fructose-6-phosphate-binding sites recently suggested by Bearne [Bearne, S. L. (1996) J. Biol. Chem. 271, 3052-3057].


Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study.
For most patients, asthma is not controlled as defined by guidelines; whether this is achievable has not been prospectively studied. A 1-year, randomized, stratified, double-blind, parallel-group study of 3,421 patients with uncontrolled asthma compared fluticasone propionate and salmeterol/fluticasone in achieving two rigorous, composite, guideline-based measures of control: totally and well-controlled asthma. Treatment was stepped-up until total control was achieved (or maximum 500 microg corticosteroid twice a day). Significantly more patients in each stratum (previously corticosteroid-free, low- and moderate-dose corticosteroid users) achieved control with salmeterol/fluticasone than fluticasone. Total control was achieved across all strata: 520 (31%) versus 326 (19%) patients after dose escalation (p < 0.001) and 690 (41%) versus 468 (28%) at 1 year for salmeterol/fluticasone and fluticasone, respectively. Asthma became well controlled in 1,071 (63%) versus 846 (50%) after dose escalation (p < 0.001) and 1,204 (71%) versus 988 (59%) at 1 year. Control was achieved more rapidly and at a lower corticosteroid dose with salmeterol/fluticasone versus fluticasone. Across all strata, 68% and 76% of the patients receiving salmeterol/fluticasone and fluticasone, respectively, were on the highest dose at the end of treatment. Exacerbation rates (0.07-0.27 per patient per year) and improvement in health status were significantly better with salmeterol/fluticasone. This study confirms that the goal of guideline-derived asthma control was achieved in a majority of the patients.


Biarylpyrazole inverse agonists at the cannabinoid CB1 receptor: importance of the C-3 carboxamide oxygen/lysine3.28(192) interaction.
The biarylpyrazole, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716; 1) has been shown to act as an inverse agonist/antagonist at the cannabinoid CB1 receptor. Our previous mutant cycle study suggested that K3.28(192) is involved in a direct interaction with the C-3 substituent of 1 in wild-type (WT) CB1.(1) However, these results did not establish what part of the C-3 substituent of 1 is involved in the K3.28(192) hydrogen bond, the carboxamide oxygen or the piperidine nitrogen. Furthermore, our previous calcium channel assay results for 5-(4- chlorophenyl)-3-[(E)-2-cyclohexylethenyl]-1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole (VCHSR; 2) (an analogue of 1 that lacks hydrogen-bonding capability in its C-3 substituent) showed that this compound acts as a neutral antagonist, a result that is in contrast to 1, which acts as an inverse agonist in this same assay.(1) These results suggested a relationship between biarylpyrazole interaction with K3.28(192) at CB1 and inverse agonism, but these results were for a single pair of compounds (1 and 2). The work presented here was designed to test two hypotheses derived from our modeling and mutant cycle results. The hypotheses are as follows: (1) it is the carboxamide oxygen of the C-3 substituent of 1 that interacts directly with K3.28(192) and (2) the interaction with K3.28(192) is crucial for the production of inverse agonism for biarylpyrazoles such as 1. To determine whether the carboxamide oxygen or the piperidine nitrogen of the C-3 substituent may be the interaction site for K3.28(192), we designed, synthesized, and evaluated a new set of analogues of 1 (3-6, Chart 1) in which modifications only to the C-3 substituent of 1 have been made. In each case, the modifications that were made preserved the geometry of this substituent in 1. The absence of the piperidine nitrogen was not found to affect affinity, whereas the absence of the carboxamide oxygen resulted in a reduction in affinity. CB1 docking studies in an inactive state model of CB1 resulted in the trend, 3,1<5,4<2<6 for ligand/CB1 interaction energies. This trend was consistent with the trend in WT CB1 Ki values versus [3H]CP55,940 reported here. In calcium channel assays, all analogues with carboxamide oxygens (1, 3, and 4) were found to be inverse agonists, whereas those that lacked this group (2, 5, and 6) were found to be neutral antagonists. Taken together, these results support the hypothesis that it is the carboxamide oxygen of the C-3 substituent of 1 that engages in a hydrogen bond with K3.28(192) in WT CB1. Furthermore, functional results for 1-6 support the hypothesis that the interaction of 1 with K3.28(192) may be key to its inverse agonism.


Medical data capture and display: the importance of clinicians' workstation design.
The Department of Veterans Affairs is developing, testing and evaluating the benefits of physicians' workstations as an aid to medical data capture in an outpatient clinic setting. The physician's workstation uses a graphical user interface to aid the clinician in recording encounter data. Various input devices including keyboard, mouse, pen, voice, barcode reader, and tablet are available on the workstations, and user preferences will be examined. Access to general services such as electronic mail and reference databases is also available. The workstation provides a wide variety of patient specific data from the hospital information system, including image data. The single data collection process by the clinician will also provide data for the cost recovery process.


[Subacute anti-N-methyl-D-aspartate receptor encephalitis. A serie of 13 paediatric cases].
Subacute anti-NMDA receptor encephalitis was recognised in 2007 as a clinical entity, and was first described in young women with ovarian teratoma. The first paediatric series unrelated with tumours was reported in 2009. To present the clinical features, treatment, and prognosis of 13 patients with anti-NMDA receptor encephalitis in Chile. A description is presented of 13 children, 9 males, aged between 1 and 16 years, diagnosed between 2009 and 2016 in 7 hospitals. All patients were evaluated with cerebral magnetic resonance and electroencephalogram. Cytochemical, oligoclonal bands and virus studies (PCR and antibodies) were performed in cerebrospinal fluid. All patients were evaluated in search of anti NMDA receptor in serum and cerebrospinal fluid. Tumor imaging studies were performed in all children. All children began the disease with psychiatric symptoms, and 11/13 had seizures. All of them subsequently presented with psychomotor agitation, dystonia, and bucolingual dyskinesias, with 11/13 loss of language and 6/13 autonomic disorders. All of them (13/13) had positive anti-NMDA receptor antibodies. CSF was normal in 12/13 children, positive oligoclonal bands in 6/10 patients, normal brain resonance in 13/13 children, EEG changes in 11/13 children, and abnormal SPECT in 6/6 children. A methylprednisolone bolus of 30mg/kg was given for 3-5 days to 12/13 children, and 6 received immunoglobulin 2g/kg. The large majority (12/13) of children recovered 1-4 months after disease onset. One child had a recurrence one year later, and recovered quickly. Subacute encephalitis due to NMDA anti-receptor antibodies should be suspected in children with psychiatric disorders and abnormal movements. Functional studies, such as EEG and SPECT are valuable diagnostic support. Early detection of this encephalitis leads to a faster recovery of patients.


Profile of young people's advice clinic in reproductive health, 1988-93.
For an unprepared sexually active teenager the 1990s present a minefield of potential problems in addition to the most obvious problems of unplanned pregnancy and sexually transmitted disease. Promoting the importance of a healthy sexual and reproductive life to young people requires openness, better sex education, realistic discussion of related issues, and provision of contraception, as well as support if things go wrong. The Woodhouse Park Clinic in south Manchester opened in October 1988 with the aim of providing weekly advice sessions to young people up to the age of 18. Advice is given on topics such as substance misuse and smoking as well as on family planning. Attendance has steadily increased over the years; from April to June 1993 the average number of attenders per session was 39, one third of whom were young men.


Pharmacokinetic Characteristics and Clinical Outcomes of Vancomycin in Young Children With Various Degrees of Renal Function.
Although vancomycin pharmacokinetics are affected by age and renal function in adults and older children, its pharmacokinetics in children aged 1 month to 2 years remained unclear. We investigated clinical outcome and nephrotoxicity in younger children with renal insufficiency who were treated with vancomycin. One hundred and ten children aged 1 month to 2 years were enrolled, and they were divided into 3 groups: normal renal function (group A), mild renal insufficiency (group B), and moderate renal insufficiency (group C). A population pharmacokinetic model was established. Significant differences were observed for trough concentration, AUC0-24 h , CL, and t1/2 in the 3 groups. When given at 40 mg/kg per day, 36.4%, 62.5%, and 85.0% of children achieved the target of AUC/MIC ≥ 400, and 47.0%, 70.8%, and 95% of children obtained early good clinical outcomes in groups A, B, and C (P < .05), respectively. One child in group A and 4 children in group C suffered from acute kidney injury. These results indicated that children with renal insufficiency readily achieved the target AUC/MIC but were at increased risk of nephrotoxicity. Vancomycin clearance and creatinine clearance were not correlated with each other in children with renal insufficiency, indicating that both renal function and serum concentration should be monitored during vancomycin therapy.


Changes in protein structure and dynamics as a function of hydration from (1)H second moments.
We report the proton second moment obtained directly from the Free Induction Decay (FID) of the NMR signal of variously hydrated bovine serum albumin (BSA) and hen egg white lysozyme (HEWL) and from the width of the NMR Z-spectrum of the cross-linked protein gels of different concentrations. The second moment of the proteins decreases in a continuous stepwise way as a function of increasing water content, which suggests that the structural and dynamical changes occur in small incremental steps. Although the second moment is dominated by the short range distances of nearest neighbors, the changes in the second moment show that the protein structure becomes more open with increasing hydration level. A difference between the apparent liquid content of the sample as found from decomposition of the FID and the analytically determined water content demonstrates that water absorbed in the early stages of hydration is motionally immobilized and magnetically indistinguishable from rigid protein protons while at high hydration levels some protein side-chain protons move rapidly contributing to liquid-like component of the NMR signal.


Weekly low-dose methotrexate therapy for sarcoidosis.
Low-dose methotrexate therapy has been used to treat a variety of chronic inflammatory diseases; a few studies have discussed the efficacy of this therapy for sarcoidosis. We present a patient with symptomatic sarcoidosis who was successfully treated with low-dose methotrexate after being refractory to steroids. This patient showed significant clinical improvement without development of any severe side effects. These findings suggest that low-dose methotrexate therapy may be a useful alternative treatment for sarcoidosis.


MOGSA: Integrative Single Sample Gene-set Analysis of Multiple Omics Data.
Gene-set analysis (GSA) summarizes individual molecular measurements to more interpretable pathways or gene-sets and has become an indispensable step in the interpretation of large-scale omics data. However, GSA methods are limited to the analysis of single omics data. Here, we introduce a new computation method termed multi-omics gene-set analysis (MOGSA), a multivariate single sample gene-set analysis method that integrates multiple experimental and molecular data types measured over the same set of samples. The method learns a low dimensional representation of most variant correlated features (genes, proteins, etc.) across multiple omics data sets, transforms the features onto the same scale and calculates an integrated gene-set score from the most informative features in each data type. MOGSA does not require filtering data to the intersection of features (gene IDs), therefore, all molecular features, including those that lack annotation may be included in the analysis. Using simulated data, we demonstrate that integrating multiple diverse sources of molecular data increases the power to discover subtle changes in gene-sets and may reduce the impact of unreliable information in any single data type. Using real experimental data, we demonstrate three use-cases of MOGSA. First, we show how to remove a source of noise (technical or biological) in integrative MOGSA of NCI60 transcriptome and proteome data. Second, we apply MOGSA to discover similarities and differences in mRNA, protein and phosphorylation profiles of a small study of stem cell lines and assess the influence of each data type or feature on the total gene-set score. Finally, we apply MOGSA to cluster analysis and show that three molecular subtypes are robustly discovered when copy number variation and mRNA data of 308 bladder cancers from The Cancer Genome Atlas are integrated using MOGSA. MOGSA is available in the Bioconductor R package "mogsa."


Remote ischemic postconditioning confers neuroprotective effects via inhibition of the BID-mediated mitochondrial apoptotic pathway.
Ischemic postconditioning has been demonstrated to alleviate brain ischemia/reperfusion-induced neuronal apoptosis; however, the protective mechanisms underlying the improved and more convenient method of remote ischemic postconditioning (RIPostC) are only recently beginning to be elucidated. Mitochondria are important in the regulation of cell apoptosis, and the B‑cell lymphoma 2 (Bcl‑2) homology 3 interacting‑domain death agonist (BID) promotes the insertion/oligomerization of Bcl‑2‑associated X protein into the mitochondrial outer membrane, leading to the release of proapoptotic proteins from the mitochondria. The present study hypothesized that RIPostC targets the BID‑mediated mitochondrial apoptotic pathway to exert neuroprotective effects, and the optimal time window for RIPostC application was investigated. RIPostC was conducted as follows: Three 10‑min cycles of bilateral femoral artery occlusion with intervals of 10 min reperfusion after 0, 10 or 30 min of brain reperfusion. The results revealed that reperfusion induced significant activation of BID, via proteolytic cleavage and translocation to the mitochondria, as determined using western blot analysis and immunofluorescence staining. Mitochondrial release of cytochrome c was additionally detected during BID activation, all of which were inhibited by the application of RIPostC. When RIPostC was applied during reperfusion, it demonstrated a significant protective effect. Furthermore, the infarct volume, neurological function and the degree of neuronal apoptosis were improved with application of RIPostC. These results suggested that the protective mechanisms of RIPostC may be associated with inhibition of the BID‑mediated mitochondrial apoptotic pathway, which may act as a potential molecular target for therapeutic intervention in the future.


['Open season in the hunt for poliovirus' (continued)].
Global eradication of poliomyelitis was started in 1988. Polio eradication is considered feasible on theoretical and practical grounds, is cost-effective and is endorsed at the highest political levels. The strategy is based on (a) increasing vaccination coverage through routine immunization, national immunization days and so-called mopping-up campaigns, (b) improving surveillance, and (c) polio-free certification. Since the start of the programme global vaccination coverage increased from 67% in 1988 to 83% in 1995; the number of reported cases--an estimated 10% of the total number--decreased by 90% from 35,251 (1988) to 3,755 (1996). A rapid further decrease is expected with the start of national immunization days on the Indian subcontinent. In the next years the emphasis will be strongly on surveillance i.e. detection of possible polio patients and (wild) poliovirus circulation. All countries will need to implement reliable surveillance to show their polio-free status. Only then can the world be declared polio-free.


Analysis of corticosteroids in urine by HPLC and thermospray LC/MS.
The method for simultaneous determination and confirmation of nine corticosteroids in urine by high-performance liquid chromatography with a diode array detector and thermospray liquid chromatography-mass spectrometry was studied. HPLC was performed on a C18 column with a gradient mobile phase system of water and acetonitrile. The calibration curve was linear from 20 ng/mL to 1.0 micrograms/mL for each corticosteroid, and the detection limit was 10 ng/mL in 5 mL of urine. The extraction recovery of each corticosteroid from the spiked urine was equal to or greater than 85% by liquid-liquid extraction (LLE) at pH 9 using diethyl ether and approximately 79% or more by solid-phase extraction (SPE) with a Sep-Pak C18 cartridge. The mass spectra obtained with the positive ion mode showed protonated molecular species [M + H]+, ammonium adduct ion [M + NH4]+, [MH-60]+, [MH-30]+, and [MH-18]+. The LC/MS detection limits ranged from 10 to 50 ng in the scan mode and from 1 to 5 ng in the selected ion monitoring (SIM) mode.


Microbiome disruption and recovery in the fish Gambusia affinis following exposure to broad-spectrum antibiotic.
Antibiotics are a relatively common disturbance to the normal microbiota of humans and agricultural animals, sometimes resulting in severe side effects such as antibiotic-associated enterocolitis. Gambusia affinis was used as a vertebrate model for effects of a broad-spectrum antibiotic, rifampicin, on the skin and gut mucosal microbiomes. The fish were exposed to the antibiotic in the water column for 1 week, and then monitored during recovery. As observed via culture, viable counts from the skin microbiome dropped strongly yet returned to pretreatment levels by 1.6 days and became >70% resistant. The gut microbiome counts dropped and took longer to recover (2.6 days), and became >90% drug resistant. The resistance persisted at ~20% of skin counts in the absence of antibiotic selection for 2 weeks. A community biochemical analysis measuring the presence/absence of 31 activities observed a 39% change in results after 3 days of antibiotic treatment. The antibiotic lowered the skin and gut microbiome community diversity and altered taxonomic composition, observed by 16S rRNA profiling. A 1-week recovery period did not return diversity or composition to pretreatment levels. The genus Myroides dominated both the microbiomes during the treatment, but was not stable and declined in abundance over time during recovery. Rifampicin selected for members of the family Comamonadaceae in the skin but not the gut microbiome. Consistent with other studies, this tractable animal model shows lasting effects on mucosal microbiomes following antibiotic exposure, including persistence of drug-resistant organisms in the community.


Hypokalemic periodic paralysis: a 3-year follow-up study.
Primary hypokalemic periodic paralysis (HypoPP) is an inherited channelopathy most commonly caused by mutations in CACNA1S. HypoPP can present with different phenotypes: periodic paralysis (PP), permanent muscle weakness (PW), and mixed weakness (MW) with both periodic and permanent weakness. Little is known about the natural history of HypoPP. In this 3-year follow-up study, we used the MRC scale for manual muscle strength testing and whole-body muscle MRI (Mercuri score) to assess disease progression in individuals with HypoPP-causing mutations in CACNA1S. We included 25 men (mean age 43 years, range 18-76 years) and 12 women (mean age 42 years, range 18-76 years). Two participants were asymptomatic, 21 had PP, 12 MW, and two PW. The median number of months between baseline and follow-up was 42 (range 26-52). Muscle strength declined in 11 patients during follow-up. Four of the patients with a decline in muscle strength had no attacks of paralysis during follow-up, and two of these patients had never had attacks of paralysis. Fat replacement of muscles increased in 27 patients during follow-up. Eight of the patients with increased fat replacement had no attacks of paralysis during follow-up, and two of these patients had never had attacks of paralysis. The study demonstrates that HypoPP can be a progressive myopathy in both patients with and without attacks of paralysis.


Transient receptor potential vanilloid 4 as a regulator of induced pluripotent stem cell chondrogenesis.
Transient receptor potential vanilloid 4 (TRPV4) is a polymodal calcium-permeable cation channel that is highly expressed in cartilage and is sensitive to a variety of extracellular stimuli. The expression of this channel has been associated with the process of chondrogenesis in adult stem cells as well as several cell lines. Here, we used a chondrogenic reporter (Col2a1-GFP) in murine induced pluripotent stem cells (iPSCs) to examine the hypothesis that TRPV4 serves as both a marker and a regulator of chondrogenesis. Over 21 days of chondrogenesis, iPSCs showed significant increases in Trpv4 expression along with the standard chondrogenic gene markers Sox9, Acan, and Col2a1, particularly in the green fluorescent protein positive (GFP+) chondroprogenitor subpopulation. Increased gene expression for Trpv4 was also reflected by the presence of TRPV4 protein and functional Ca2+ signaling. Daily activation of TRPV4 using the specific agonist GSK1016790A resulted in significant increases in cartilaginous matrix production. An improved understanding of the role of TRPV4 in chondrogenesis may provide new insights into the development of new therapeutic approaches for diseases of cartilage, such as osteoarthritis, or channelopathies and hereditary disorders that affect cartilage during development. Harnessing the role of TRPV4 in chondrogenesis may also provide a novel approach for accelerating stem cell differentiation in functional tissue engineering of cartilage replacements for joint repair.


Recovery following treatment of descending thoracic aortic disease. A comparison between endovascular repair and open surgery.
The aim of this study was to compare the postoperative course in patients treated by endovascular repair (endo) with patients treated by open surgery (open) for descending thoracic aortic disease. Twenty-five patients treated with stent grafting for aneurysmal disease or type B dissection were compared with 35 historical controls treated by open surgery. Stay in the intensive care unit, need for artificial ventilation and to where the patient had been discharged, were noted. Pain medication, use of nasogastric tube, time until total oral nutrition, mobilization and the patients' mental condition in the postoperative period, were studied in the patients charts and the nursing reports. Time on the intensive care unit or intermediate care unit was median 45 h in the endo group compared with 192 h in the open group. Eighty percent of the patients in the endo group were discharged directly to their homes in contrast to 23% after open surgery. In the endo group 67% of the patients started oral nutrition on the 1st postoperative day compared to 10% in the open group. There was a significantly faster mobilization in the endo group. There was a significantly shorter recovery after stent grafting for descending thoracic aortic disease compared to patients operated with open surgical technique.


Diffuse Lamellar Keratitis: Confocal Microscopy Features of Delayed-Onset Disease.
Diffuse lamellar keratitis is a fairly uncommon complication of laser in situ keratomileusis (LASIK) that usually occurs within 1 week of surgery. It is described as an inflammatory reaction in the lamellar interface characterized by a diffuse, white granular lamellar keratitis. Progression of the keratitis can result in scarring and significant visual loss. We report a case of bilateral diffuse lamellar keratitis (DLK) of delayed onset and look at confocal microscopic features of corneal interface. A 35-year-old male patient was referred with visual concerns and red eye. The patient had undergone LASIK procedure for high myopia 3 months previously. A detailed examination revealed a clinical presentation of DLK. A thorough account of the past revealed no pertinent medical history or risk factors for delayed-onset DLK after LASIK. The patient was put on topical antibiotics (ofloxacin, Exocin 3 mg/mL) and topical steroids (prednisolone acetate 1%, Pred Forte). Because of poor response to treatment, an interface washout was carried out and treatment with Pred Forte was continued. This helped in resolution of the condition in both eyes with residual faint, diffuse, corneal haze. Confocal microscopy was carried out before and after interface washout to assess features of DLK at cellular level after a delayed onset. The presence of inflammatory cells along with interface debris was noted in our case, which is unusual in stage 3 DLK with a delayed presentation as reported in literature. Although it is difficult to confirm without histology the type of inflammatory response seen, it is advocated that delayed presentation should also be treated quite intensively with steroids and any progression should be dealt with lifting up of the flaps to carry out interface washout.


An Epidemic Recovery Framework to Jump-start Analysis, Planning, and Action on a Neglected Aspect of Global Health Security.
Epidemic readiness and response command the disproportionate attention of health security decision makers, planners, and practitioners, overshadowing recovery. How patients and their families, health organizations, community sectors, and entire societies recuperate from major outbreaks requires more systematic study and better translation into policy and guidance. To help remedy this neglected aspect of health emergency management, we offer a working definition for epidemic recovery and a preliminary model of postepidemic recovery. Guiding this framework's development are insights gleaned from the more mature study of postdisaster reconstruction and rehabilitation as well as recognition that postoutbreak recovery-which involves infectious disease, a biological hazard-presents challenges and opportunities distinct from events involving geological or meteorological hazards. Future work includes developing a consensus around characteristics of successful epidemic recovery, applying these metrics to support preincident planning for postepidemic recovery, and using such a scheme to track and inform actual recovery from an epidemic.


Clinical peritonitis from allergy to silicone ventriculoperitoneal shunt.
Silicones are inorganic compounds that have been used for the purpose of shunting ventricular fluid since the mid-20th century [1]. Complications of ventriculoperitoneal shunts have rarely been attributed to silicone allergy, with only a handful of cases reported in literature. The classic presentation of allergy to silicone ventriculoperitoneal shunt, i.e., abdominal pain with recurrent skin breakdown along the shunt tract, is nonspecific and difficult to distinguish clinically from other causes of shunt-related symptoms. It can be diagnosed by detection of antisilicone antibodies and is treated with removal of the shunt and replacement, if needed, with a polyurethane shunt system. We report the first case of suspected silicone allergy presenting as clinical peritonitis without overt colonic perforation.


Detection of carcinoembryonic antigen messenger RNA-expressing cells in peripheral blood 7 days after curative surgery is a novel prognostic factor in colorectal cancer.
The significance of detection of circulating cancer cells in blood during surgery in patients with colorectal cancer (CRC) remains controversial. Experimental study revealed that the cancer cells injected from the vein disappeared completely until 7 days. The aim of this study was to clarify that the detection of circulating cancer cells in blood taken later than 7 days after curative surgery may be a prognostic factor. Two hundred consecutive patients with CRC who underwent potentially curative surgery were the subjects. Peripheral blood was collected between 7 and 10 days after resection. Cancer cells were detected using reverse transcriptase-polymerase chain reaction targeting carcinoembryonic antigen (CEA) messenger RNA (mRNA). The median follow-up period was 52 months (range: 34-69 months). The overall positive incidence of CEA mRNA was 22%. Detection of CEA mRNA was not significantly related to conventional clinicopathological findings. Recurrence has been confirmed in 55 patients (28%). The recurrence rate was significantly higher in patients with rectal cancer, deep penetration, lymph node metastasis, preoperative chemoradiotherapy and positive CEA mRNA. The CEA mRNA positive patients showed significantly poorer disease free survival (DFS) and overall survival (OS) than the negative patients (DFS, P = 0.007; OS, P = 0.04). Multivariate analysis revealed that the positive expression of CEA mRNA (P < 0.01) as well as the tumor location and TNM stage classification was identified as the significant risk factors for recurrence. Detection of CEA mRNA expressing cells in peripheral blood 7 days after curative surgery is a novel independent factor predicting recurrence in patients with CRC.


Adipocyte Gq signaling is a regulator of glucose and lipid homeostasis in mice.
Obesity is the major driver of the global epidemic in type 2 diabetes (T2D). In individuals with obesity, impaired insulin action leads to increased lipolysis in adipocytes, resulting in elevated plasma free fatty acid (FFA) levels that promote peripheral insulin resistance, a hallmark of T2D. Here we show, by using a combined genetic/biochemical/pharmacologic approach, that increased adipocyte lipolysis can be prevented by selective activation of adipocyte Gq signaling in vitro and in vivo (in mice). Activation of this pathway by a Gq-coupled designer receptor or by an agonist acting on an endogenous adipocyte Gq-coupled receptor (CysLT2 receptor) greatly improved glucose and lipid homeostasis in obese mice or in mice with adipocyte insulin receptor deficiency. Our findings identify adipocyte Gq signaling as an essential regulator of whole-body glucose and lipid homeostasis and should inform the development of novel classes of GPCR-based antidiabetic drugs.


Life beyond depression: the experience of gays and lesbians who self-identify as depressed.
The purpose of this research was to compare differences in the experiences of gay men and lesbian women who describe experiences of depression or depressed mood. The 2 main research questions were how do descriptions of depression and daily life differ between gay males and lesbian females. To this end, Weblogs containing narratives of 19 gay men and 19 lesbian women were coded, analyzed, and compared using qualitative content analysis methods. Differences in described sources of depression and responses to depression, but not features of depression were found. Women and men also differed with respect to their main priorities; their descriptions of social interactions, social issues, reflections, and emotions; and a number of other daily life experiences. Findings were discussed with respect to implications for treatment and prevention of depression among sexual minorities.


Impact of a Resident-as-Teacher Workshop on Teaching Behavior of Interns and Learning Outcomes of Medical Students.
Residents and interns are recognized as important clinical teachers and mentors. Resident-as-teacher training programs are known to improve resident attitudes and perceptions toward teaching, as well as their theoretical knowledge, skills, and teaching behavior. The effect of resident-as-teacher programs on learning outcomes of medical students, however, remains unknown. An intervention cohort study was conducted to prospectively investigate the effects of a teacher-training workshop on teaching behavior of participating interns and on the clerkship learning outcomes of instructed fourth-year medical students. The House Officer-as-Teacher Training Workshop was implemented in November 2009 over 1.5 days and attended by all 34 interns from one teaching hospital. Subsequently, between February and August 2010, 124 fourth-year medical students rated the observable teaching behavior of interns during 6-week general surgery clerkships at this intervention hospital as well as at 2 comparable hospitals serving as control sites. Ratings were collected using an anonymous 15-item Intern Clinical Teaching Effectiveness Instrument. Student achievement of clerkship learning outcomes during this period was evaluated using a validated and centralized objective structured clinical examination. Medical students completed 101 intern clinical teaching effectiveness instruments. Intern teaching behavior at the intervention hospital was found to be significantly more positive, compared with observed behavior at the control hospitals. Objective structured clinical examination results, however, did not demonstrate any significant intersite differences in student achievement of general surgery clerkship learning outcomes. The House Officer-as-Teacher Training Workshop noticeably improved teaching behavior of surgical interns during general surgery clerkships. This improvement did not, however, translate into improved achievement of clerkship learning outcomes by medical students during the study period.


Why bluefin tuna have warm tummies: temperature effect on trypsin and chymotrypsin.
Giant bluefin tuna warm their viscera during and after a meal. The cecum of a 500-kg bluefin weighs about 9 kg and contains about 20,000 pyloric ceca, each about 10 cm long and 1.5 mm diam. Trypsin was assayed with alpha-benzoyl-DL-arginine-p-nitroanilide HCl and chymotrypsin with glutaryl-L-phenylalanine-p-nitroaniline. The effects of pH on specific activity over the range 7.5-9.5 were negligible relative to temperature effects. Specific activity and maximal reaction velocity extrapolated from a Lineweaver-Burke plot (Vmax) increased with an increase in temperature in a similar fashion (Q10 ca. 2 over temperature range of physiological significance), whereas Km was constant over the same temperature range. The advantage of the warm cecum is that protein is digested in about one-third the time, so that these tuna can process about three times as much food per day.


Effects of biological reactions and modifications on conductance of nanofluidic channels.
Conductance characteristics of nanofluidic channels (nanochannels) fall into two regimes: at low ionic concentrations, conductance is governed by surface charge while at high ionic concentrations it is determined by nanochannel geometry and bulk ionic concentration. We used aminosilane chemistry and streptavidin-biotin binding to study the effects of surface reactions on nanochannel conductance at different ionic concentrations. Immobilization of small molecules such as aminosilane or biotin mainly changes surface charge, affecting conductance only in the low concentration regime. However, streptavidin not only modifies surface charge but also occludes part of the channel, resulting in observable conductance changes in both regimes. Our observations reflect the interplay between the competing effects of charge and size of streptavidin on nanochannel conductance.


Malate and Aspartate Increase L-Arginine and Nitric Oxide and Attenuate Hypertension.
Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. The Dahl salt-sensitive (SS) rat, a model of salt-sensitive hypertension, exhibits fumarase insufficiencies. To investigate the mechanism mediating the effect of fumarase-related metabolites on hypertension, we considered the pathway in which L-malate can be converted to oxaloacetate, aspartate, argininosuccinate, and L-arginine, the substrate of nitric oxide (NO) synthase. The levels of aspartate, citrulline, L-arginine, and NO were significantly decreased in the kidneys of SS rats compared to salt-insensitive consomic SS.13BN rats. Knockdown of fumarase in human kidney cells and vascular endothelial cells resulted in decreased levels of malate, aspartate, L-arginine, and NO. Supplementation of aspartate or malate increased renal levels of L-arginine and NO and attenuated hypertension in SS rats. These findings reveal a multi-step metabolic pathway important for hypertension in which malate and aspartate may modulate blood pressure by altering levels of L-arginine and NO.


[Distribution of antibodies against Encephalitis ixodica viruses among north-east healthy populations of Poland].
We have undertaken the investigations for the detection of the presence of antibodies against Encephalitis ixodica viruses among North-East population of Poland. We have found these antibodies in 6.5% among 676 of tested healthy persons. The highest % of detected antibodies were noted in forest rangers and in physicians acting as hunters. Our data seems to indicate that Encephalitis ixodica is still actual disease in this region. Therefore one can suggest the necessity vaccination against Encephalitis ixodica.


[The hemodynamic effects of various hydroxyethyl starch solutions in heart surgery patients].
Blood conservation is gaining more and more interest because of the increasing risks involved in homologous blood transfusions. Acute normovolemic hemodilution (ANH) is becoming an established technique even in cardiac surgery patients. The "optimal" kind of volume replacement, however, is still controversial. Thus, this study was carried out to investigate the hemodynamic response of 6 different hydroxyethyl starch (HES) solutions as volume replacement. METHODS. In 60 patients undergoing elective aortocoronary bypass surgery, acute, preoperative hemodilution was performed (10 ml/kg) and HES with different concentrations, molecular weight, and substitution was infused according to a randomized sequence: 1. 6% HES 450,000/0.7; 2. 10% HES 200,000/0.5; 3. 3% HES 200,000/0.5%; 4. 6% HES 40,000/0.5; 5. 6% HES 200,000/0.5; 6. 6% HES 200,000/0.62. All patients were monitored using a new pulmonary artery catheter that allows measurement of the right ventricular ejection fraction (RVEF), right ventricular enddiastolic volume (RVEDV), and right ventricular end systolic volume (RVESV) in addition to standard hemodynamic parameters. RESULTS. Immediately after finishing ANH the typical hemodynamic changes of hemodilution (HD) were apparent (decrease in peripheral resistance and increase in cardiac index (CI]. All 6 solutions investigated were effective in hemodynamic stabilization (no changes in mean arterial pressure (MAP), filling pressures (PCP, RAP), or heart rate (HR]. Forty min after ANH, however (before beginning extracorporeal circulation (ECC], there were significant differences between the groups: in groups 3 and 4 the increase in CI had already disappeared, and SVI in group 3 was even lower than the baseline values (-8%). In the other groups, a higher CI level remained even 40 min after ANH, which was most pronounced in groups 2 (+40%) and 5 (+43%). Right ventricular performance was not changed by ANH (RVEF unchanged in all groups). Forty min after hemodilution RVEDVI (-8%) and RVESVI (-16%) decreased significantly only in group 4, whereas in the other groups these parameters were still elevated. The most pronounced positive fluid balance after the end of ECC was found in group 4 (+850 ml); in these patients paO2 decreased significantly (-150 mmHg). CONCLUSIONS. The guarantee of stable hemodynamic conditions is a prerequisite when performing ANH in coronary surgery patients. The different physiochemical attributes of various HES solutions seem to be important, thus influencing their hemodynamic response. In this study, low-concentration (3% HES 200/0.5) and low-molecular (6% HES 40/0.5) HES solutions were less effective in stabilizing hemodynamics until the beginning of ECC. Additionally, their negative influence on fluid balance during ECC, followed by a deterioration in pulmonary function led to the conclusion that other solutions are preferable; in particular, 10% HES seems to be of advantage in these situations.


Anticancer Effects of Valproic Acid via Regulation of Epigenetic Mechanisms in Non-small-cell Lung Cancer A549 Cell Line.
Epigenetic mechanisms are the most important factors contributing to both the development and metastasis of cancer cells. We aimed to scrutinize the role of epigenetic alternations of genes involved in cancer metastasis, including CD44v6 (metastasis indicator) and Nm23-H1 (a novel tumor suppressor), in the A549 lung cancer cell line. The A549 cells were cultured in the DMEM medium. Valproic acid (VPA) was used as a histone deacetylase inhibitor. Caspase-3 activity was assessed by adding DEVD-pNA substrate to the cell lysate. Gene expression was determined by real-time PCR. Finally, protein expression was assessed by western blot. The results showed that VA significantly decreased the expression of the CD44v6 gene and its protein level. This was further accompanied by lower expressions of MMP-2 and MMP-9 genes. On the other hand, the expression of Nm23-H1 and its protein were significantly increased in the cells accompanied by higher activity of caspase-3 (P ˂ 0.05). Our results showed that epigenetic regulation of CD44v6, Nm23-H1, MMP-2, and MMP-9 might be involved in the pathogenesis and metastasis of lung cancer. Therefore, the use of histone deacetylase inhibitors can be effective in the suppression of metastases and the treatment of these tumors.


[Difference of body movements accompanying mandibular movements in standing and sitting positions].
To assess whether body movement accompanying jaw movement exists even in sitting position, and, if so, to investigate differences of body movements in the sitting and standing positions. The subjects were six men (age, 25-29 years, mean, 27.0 years) without stomatognathic problems. During the measurements, their Camper's planes were kept horizontal. One measurement sequence consisted of 20 s of tapping preceded and followed by 10 s of intercuspation. Mandibular movements (lower incisor point) were measured by referring to a coordinate system located on the maxilla, and head movements (upper incisor, condyle, etc) with TRIMETII (Tokyo Sizaisya) and body movements (sternum point) in sagittal plane were measured by referring to a coordinate system located on the floor with Proreflex (Qualisys). Body movements accompanying jaw movements were detected even in sitting position. The ratio of body movements to jaw movements was significantly larger in standing position than in sitting position using Wilcoxon matched-pairs signed-rank test. Peak power of body movement at corresponding frequency to the open-close movement was significantly larger in standing position than in sitting position using Wilcoxon matched-pairs signed-rank test. On the other hand, there was no difference between sitting and standing position in probability of body movement detection by the original wave analysis using Wilcoxon matched-pairs signedrank test. Body movements accompanying jaw movements were detected even in sitting position, and were smaller than in standing position. However, the probability of movements detected in original wave had no difference between the positions. Thus we concluded that we can analyze body movements during mastication in natural sitting position.


Lymphatic system or hydro-oncotic forces. Which is more significant in drainage of pleural fluid?
Artificial pleural fluids, containing plasma protein from 0.1 to 9.0 g per 100 ml, indocyanine green (ICG) and para-aminohippurate (PAH), were injected into the pleural cavity of dogs. The concentration of these two indicators were measured at a regular time interval, and the lymphatic and non-lymphatic flows and PAH clearance were calculated by Stewart's and Takashina's equations. When the protein concentration in the pleural fluid was less than 4 g per 100 ml, the pleural fluid volume decreased at a rate of 0.20 ml/kg/hour. The decrease was due to pleural fluid drainage by the lymphatic flow, because the inward and outward non-lymphatic flows due to hydro-oncotic forces balanced each other and the net non-lymphatic flow was essentially zero. When the protein concentration was 6 g per 100 ml or more, the decrease of pleural fluid was remarkably attenuated, because of an increase of the inward non-lymphatic flow due to an increase of protein concentration in the pleural fluid. Even in these situations, the lymphatic flow was kept at the rate of 0.20 ml/kg/hour, similarly with the former conditions. From these results, it may be concluded that the lymphatic system is a principal factor, and that factors governed by hydro-oncotic elements have additive effect to that of the lymphatic system in the regulation of pleural fluid dynamics.


[Model of nasal cavity and paranasal sinuses created for studying the dynamics of the nasal airflow].
To create a model from an adult cadaver's nasal cavity and verify whether it can be used to study the airflow dynamics in the nasal cavity and paranasal sinuses. (1) The model was made by the material of transparent resin and Bengal gelatin according to a nasal cast of a cadaver. (2) The model was check by Acoustic Rhino-meter, CT scan and nasal endoscope, then compared with the normal. (3) To observe the smoke flow in the model and record it by a digital camera It was succeeded in creating a model of the nasal cavity and paranasal sinus. The model was good at simulation and transparency. The structure of the model, the cross-sectional areas of the nasal passage and the CT scan results of the model were similar to the normal. The airflows in the model could be recorded by a digital camera. It showed that there were two types of airflows in the nose. The majority of airflows were found in the common and middle nasal meatus, the little part of the airflows passed through the upper of the nose like a parabola. There was an increasing proportion of airflows in the olfactory region when elevated the airflow rates. A relatively large vortex formed in the upper part of the nose, just behind the nasal valve, and another one was in the pharynx nasals. (1) The transparent resin and Bengal gelatin are suitable for making the model of the nose. The model can be used to study the airflows dynamics of the nasal cavity and paranasal sinuses. (2) The majority of inspired airflows go straightly to the pharynx nasals through the combined middle and inferior airways, a little part of inspired airflows through the olfactory region like a parabola. (3) The inspired airflows first arrived at the front position of the middle and inferior turbinate. The airflows can go into the maxillary sinus, a vortex can be see in the maxillary sinus during breath.


Diagnosis of Clostridium difficile infection by toxigenic culture and PCR assay.
Clostridium difficile is responsible for 15-25% of nosocomial antibiotic associated diarrhea (AAD) cases and all cases of pseudomembranous colitis. C. difficile has two major virulence factors, toxin A (enterotoxin) and toxin B (cytotoxin). The aim of this study was to determine the frequency of C. difficile strains in patients with diarrhea in Babol' hospitals with toxigenic culture and PCR assay. One hundred stool specimens were taken from diarrheal patients in hospitals of the city of Babol. All patients had a history of antibiotic use. The samples were cultured on CCFA medium. In the next stage, toxigenic culture was performed for isolated C. difficile strains. Then, PCR assay was used to identify gdh, tcdA and tcdB genes among isolated C. difficile strains. From the 100 stool samples, eight (8%) samples were positive in C. difficile culture. In toxigenic culture, two (2%) of these strains had cytopathic effects on Vero cells. All eight strains had the gdh gene. This gene is specific for C. difficile. Two strains that had cytopathic effects on toxigenic culture were positive for toxin genes. The frequency of toxigenic strains in different parts of the world is variable, and needs to be continually investigated. In the present study, the PCR method had a good correlation with toxigenic culture. Thus, it can replace the laborious and costly cell culture method.


Use of CO2 laser in the treatment of periungual fibromas associated with tuberous sclerosis.
Tuberous sclerosis complex is an autosomal dominant disorder with variable clinical expression. In severe forms it may involve almost any organ system. Periungual fibromas are a common cutaneous manifestation and a frequent source of cosmetic and functional concern. Current treatment involves surgical excision of the lesions. To evaluate laser vaporization of periungual fibromas and to compare results to the standard surgical treatment. A patient with tuberous sclerosis and recurrent periungual fibromas was treated with a continuous wave CO2 laser in sequential focused and defocused modes at 10-15 W. Laser treatment required approximately 10 seconds per lesion and produced no intraoperative bleeding. The wounds healed well with good cosmetic results. Though similar to conventional surgery in terms of cosmetic satisfaction, CO2 laser presents a viable alternative to surgery through significantly reduced treatment time and amount of bleeding.


The enigma of the near-symmetry of proteins: Domain swapping.
The majority of proteins form oligomers which have rotational symmetry. Literature has suggested many functional advantages that the symmetric packing offers. Yet, despite these advantages, the vast majority of protein oligomers are only nearly symmetric. A key question in the field of proteins structure is therefore, if symmetry is so advantageous, why do oligomers settle for aggregates that do not maximize that structural property? The answer to that question is apparently multi-parametric, and involves distortions at the interaction zones of the monomer units of the oligomer in order to minimize the free energy, the dynamics of the protein, the effects of surroundings parameters, and the mechanism of oligomerization. The study of this problem is in its infancy: Only the first parameter has been explored so far. Here we focus on the last parameter-the mechanism of formation. To test this effect we have selected to focus on the domain swapping mechanism of oligomerization, by which oligomers form in a mechanism that swaps identical portions of monomeric units, resulting in an interwoven oligomer. We are using continuous symmetry measures to analyze in detail the oligomer formed by this mechanism, and found, that without exception, in all analyzed cases, perfect symmetry is given away, and we are able to identify that the main burden of distortion lies in the hinge regions that connect the swapped portions. We show that the continuous symmetry analysis method clearly identifies the hinge region of swapped domain proteins-considered to be a non-trivial task. We corroborate our conclusion about the central role of the hinge region in affecting the symmetry of the oligomers, by a special probability analysis developed particularly for that purpose.


Visualization of the missing role of hydrothermal interactions in a Japanese megalopolis for a win-win solution.
The urban heat island effect has become a serious environmental problem with the expansion of cities and industrial areas. Prohibition of the use of groundwater has caused a further serious problem such as floating of subways, stations and buildings through an imbalance of the hydrologic cycle in a Japanese megalopolis. Most of the previous research has evaluated separately hydrologic and thermal cycles in atmospheric, land and water areas because of the complexity in this feedback mechanism. In this study, the author used the process-based National Integrated Catchment-based Eco-hydrology (NICE) model, which includes surface-unsaturated-saturated water processes coupled with the urban canopy and regional atmospheric models, to simulate the effect of urban geometry and anthropogenic exhaustion on the hydrothermal changes in the atmospheric/land areas of the Japanese megalopolis. The simulation was conducted with multi-scale in horizontal regional-urban-point levels and in vertical atmosphere-surface-unsaturated-saturated layers, and projected the effect of water resources use to ameliorate the heat island and its impact on the hydrologic change in the catchment. Finally, the author presented the procedure to visualize the missing role of hydrothermal interactions in atmospheric, land and water areas, which would be effective to recover a sound hydrologic cycle and to create thermally pleasing environments in an eco-conscious megalopolis.


Expression profiling of immature thymocytes revealed a novel homeobox gene that regulates double-negative thymocyte development.
Intrathymic development of CD4/CD8 double-negative (DN) thymocytes can be tracked by well-defined chronological subsets of thymocytes, and is an ideal target of gene expression profiling analysis to clarify the genetic basis of mature T cell production, by which differentiation of immature thymocytes is investigated in terms of gene expression profiles. In this study, we show that development of murine DN thymocytes is predominantly regulated by largely repressive rather than inductive activities of transcriptions, where lineage-promiscuous gene expression in immature thymocytes is down-regulated during their differentiation. Functional mapping of genes showing common temporal expression profiles implicates previously uncharacterized gene regulations that may be relevant to early thymocytes development. A small minority of genes is transiently expressed in the CD44(low)CD25(+) subset of DN thymocytes, from which we identified a novel homeobox gene, Duxl, whose expression is up-regulated by Runx1. Duxl promotes the transition from CD44(high)CD25(+) to CD44(low)CD25(+) in DN thymocytes, while constitutive expression of Duxl inhibits expression of TCR beta-chains and leads to impaired beta selection and greatly reduced production of CD4/CD8 double-positive thymocytes, indicating its critical roles in DN thymocyte development.


Long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic tinnitus.
The pathophysiologic mechanisms of idiopathic tinnitus remain unclear. Recent studies demonstrated focal brain activation in the auditory cortex of patients with chronic tinnitus. Low-frequency repetitive transcranial magnetic stimulation (rTMS) is able to reduce cortical hyperexcitability. Fusing of the individual PET-scan with the structural MRI-scan (T1, MPRAGE) allowed us to identify exactly the area of increased metabolic activity in the auditory cortex of patients with chronic tinnitus. With the use of a neuronavigational system, this target area was exactly stimulated by the figure 8-shaped magnetic coil. In a prospective study, rTMS (110% motor threshold; 1 Hz; 2000 stimuli/day over 5 days) was performed using a placebo controlled cross-over design. Patients were blinded regarding the stimulus condition. For the sham stimulation a specific sham-coil system was used. Fourteen patients were followed for 6 months. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller). Tertiary referral medical center. Increased metabolic activation in the auditory cortex was verified in all patients. After 5 days of verum rTMS, a highly significant improvement of the tinnitus score was found whereas the sham treatment did not show any significant changes. The treatment outcome after 6 months still demonstrated significant reduction of tinnitus score. These preliminary results demonstrate that neuronavigated rTMS offers new possibilities in the understanding and treatment of chronic tinnitus.


Relearning of writing skills in Parkinson's disease: a literature review on influential factors and optimal strategies.
Patients with Parkinson's disease (PD) suffer from severe motor symptoms which can only be partly alleviated by means of dopaminergic medication. Motor rehabilitation, i.e. relearning of a known motor skill through intensive practice, can be an effective and lasting therapeutic supplement in chronic neurodegenerative diseases. Recent studies on motor learning in PD provide insights for the development of optimal motor rehabilitation strategies, with a particular focus on achieving consolidated learning and retention. In this review, findings from the last couple of years are discussed with specific interest in the potential benefits from cueing and feedback strategies as means to achieve lasting changes. In addition, current neuroscientific insights on the impact of dopamine and cognitive functioning on learning are summarized. Finally, the knowledge on these topics is combined to propose an optimal strategy for relearning of writing skills in PD, a frequently reported motor deficit also known as micrographia.


Prediction of PM2.5 concentration based on the CEEMDAN-RLMD-BiLSTM-LEC model.
Air quality has emerged as a critical concern in recent years, with the concentration of PM2.5 recognized as a vital index for assessing it. The accuracy of predicting PM2.5 concentrations holds significant value for effective air quality monitoring and management. In response to this, a combined model comprising CEEMDAN-RLMD-BiLSTM-LEC has been introduced, analyzed, and compared against various other models. The combined decomposition method effectively underlines the fundamental characteristics of the data compared to individual decomposition techniques. Additionally, local error correction (LEC) efficiently addresses the issue of prediction errors induced by excessive disturbances. The empirical results of nine steps indicate that the combined CEEMDAN-RLMD-BiLSTM-LEC model outperforms single prediction models such as RLMD and CEEMDAN, reducing MAE, RMSE, and SAMPE by 36.16%, 28.63%, 45.27% and 16.31%, 6.15%, 37.76%, respectively. Moreover, the inclusion of LEC in the model further diminishes MAE, RMSE, and SMAPE by 20.69%, 7.15%, and 44.65%, respectively, exhibiting commendable performance in generalization experiments. These findings demonstrate that the combined CEEMDAN-RLMD-BiLSTM-LEC model offers high predictive accuracy and robustness, effectively handling noisy data predictions and severe local variations. With its wide applicability, this model emerges as a potent tool for addressing various related challenges in the field.


Photons Induce Vesicular Exocytotic Release of Glutamate in a Power-Dependent Way.
Increasing evidence indicates that photobiomodulation, based on tissue irradiation with photons in the red to near-infrared spectrum, may be an effective therapeutic approach to central nervous system disorders. Although nervous system functionality has been shown to be affected by photons in animal models, as well as in preliminary evidence in healthy subjects or in patients with neuropsychiatric disorders, the mechanisms involved in the photobiomodulation effects have not yet been clarified. We previously observed that photobiomodulation could stimulate glutamate release. Here, we investigate mechanisms potentially involved in the glutamate-releasing effect of photons from adult mouse cerebrocortical nerve terminals. We report evidence of photon ability to induce an exocytotic vesicular release of glutamate from the terminals of glutamatergic neurons in a power-dependent way. It can be hypothesized that photobiomodulation, depending on the potency, can release glutamate in a potentially neurotoxic or physiological range.


Prognostic factors of motor recovery after stereotactic evacuation of intracerebral hematoma.
Spontaneous intracerebral hemorrhage represents 20 to 30% of all stroke patients in Japan. However, the treatment strategy of intracerebral hematoma remains controversial. Stereotactic hematoma evacuation is minimally invasive surgery and is beneficial for clot removal with limited tissue damage. The purpose of this study was to investigate the factors affecting motor recovery after stereotactic hematoma evacuation. This retrospective analysis included 30 patients with spontaneous thalamic or putaminal hemorrhage who underwent stereotactic hematoma evacuation. We compared age, presurgical muscle strength, hematoma volume and removal rate between the patients who showed improvement of motor function (improved group) and the patients associated with no motor improvement (unchanged group). Twenty-one patients were classified into the improved group and nine patients into the unchanged group. Statistical analysis revealed that age in the improved group was significantly younger than in the unchanged group (p < 0.01), whereas there was no significant difference in presurgical muscle strength, hematoma volume and removal rate between the two groups. The present results revealed that stereotactic hematoma evacuation is attributable to the improvement of motor function, especially in the younger population, indicating the importance of cortical reorganization during post-surgical rehabilitation. In addition, this procedure could provide functional improvement in severely disabled patients. Proper patient selection to receive this therapy would be beneficial for further advances of this technique. The present result might be useful in elucidating the mechanism of motor recovery and proper patient selection for this technique.


Ionic strength independence of charge distributions in solvation of biomolecules.
Electrostatic forces enormously impact the structure, interactions, and function of biomolecules. We perform all-atom molecular dynamics simulations for 5 proteins and 5 RNAs to determine the dependence on ionic strength of the ion and water charge distributions surrounding the biomolecules, as well as the contributions of ions to the electrostatic free energy of interaction between the biomolecule and the surrounding salt solution (for a total of 40 different biomolecule/solvent combinations). Although water provides the dominant contribution to the charge density distribution and to the electrostatic potential even in 1M NaCl solutions, the contributions of water molecules and of ions to the total electrostatic interaction free energy with the solvated biomolecule are comparable. The electrostatic biomolecule/solvent interaction energies and the total charge distribution exhibit a remarkable insensitivity to salt concentrations over a huge range of salt concentrations (20 mM to 1M NaCl). The electrostatic potentials near the biomolecule's surface obtained from the MD simulations differ markedly, as expected, from the potentials predicted by continuum dielectric models, even though the total electrostatic interaction free energies are within 11% of each other.


Modification of gas-chromatographic method for blood chlorpropamide determination and evaluation of its use for clinical and pharmacological purposes.
A gas-chromatographic method for isolation and determination of blood chlorpropamide, described originally in literature [10], was modified and its usefulness for clinical and pharmacological purposes evaluated by testing fluctuations in blood chlorpropamide concentration with time in healthy subjects (control group) and patients with type II diabetes mellitus, in relation to glycemia and insulinemia (IRI). In this respect the effects of a single dose and of prolonged chlorpropamide therapy were studied. Large individual variability in the time-related concentration curves and no statistically significant correlation between chlorpropamide, insulin and glycemia were noted.


The refeeding syndrome and hypophosphatemia.
The refeeding syndrome is an underappreciated entity characterized by acute electrolyte derangements--notably hypophosphatemia--that occur during nutritional repletion of patients with significant suboptimal caloric intake. Adverse effects of hypophosphatemia include cardiac failure, muscle weakness, immune dysfunction, and death. Hypokalemia and hypomagnesemia commonly complicate refeeding syndrome as well; however, this report briefly reviews the clinical manifestations of refeeding-induced hypophosphatemia.


Do Pertussis Vaccines Protect Against Bordetella parapertussis?
We calculated the effectiveness of pertussis vaccine in preventing parapertussis among Oregon children 2 months to 10 years of age using 2 methods. During 2011-2016, the 2 VE methods found 66% (95% CI, 59-75%) and 82% (95% CI, 69-90%) effectiveness against parapertussis. Pertussis vaccine may induce cross-immunity.


Factor VII deficiency and a copper metabolism disorder in a patient with Klippel-Trenaunay syndrome.
We report on a patient with Klippel-Trenaunay (KT) syndrome, a factor VII deficiency and a copper metabolism disorder. The KT syndrome involved the left leg and, histologically, the liver. Dermatological examination, duplex ultrasonography and a skin and liver biopsy verified the KT syndrome. A long prothrombin time prompted clotting studies revealing a factor VII deficiency while the other factors were in the normal range. Further laboratory examinations showed a copper metabolism disorder similar to Wilson's disease with a low serum ceruloplasmin level, elevated copper concentration in the urine and increased copper deposition in the liver. Neither liver cirrhosis nor a Kayser-Fleischer corneal ring was present. Sequencing analysis of the Wilson's disease gene ATB7B showed no mutations. The occurrence of these three uncommon pathologies in a single patient has not been described to date, which may suggest a mutation in a hypothetical common regulatory gene leading to this unusual phenotype.


Recent Advances in Enzymes for the Bioremediation of Pollutants.
Nowadays, pollution of the environment is a huge problem for humans and other organisms' health. Conventional methods of pollutant removal like membrane filtration or ion exchange are not efficient enough to lower the number of pollutants to standard levels. Biological methods, because of their higher efficiency and biocompatibility, are preferred for the remediation of pollutants. These cost-effective and environment-friendly methods of reducing pollutants are called bioremediation. In bioremediation methods, enzymes play the most crucial role. Enzymes can remedy different types of organic and inorganic pollutants, including PAHs, azo dyes, polymers, organocyanides, lead, chromium, and mercury. Different enzymes isolated from various species have been used for the bioremediation of pollutants. Discovering new enzymes and new subtypes with specific physicochemical characteristics would be a promising way to find more efficient and cost-effective tools for the remediation of pollutants.


Refined crystal structure of porcine class Pi glutathione S-transferase (pGST P1-1) at 2.1 A resolution.
The crystal structure of class Pi glutathione S-transferase from porcine lung (pGST P1-1) in complex with glutathione sulphonate has been refined at 2.11 A resolution, to a crystallographic R-factor of 16.5% for 21, 165 unique reflections. The refined structure includes 3314 protein atoms, 46 inhibitor (glutathione sulphonate) atoms and 254 water molecules. The model shows good stereochemistry, with root-mean-square deviations from ideal bond lengths and bond angles of 0.011 A and 2.8 degrees, respectively. The estimated root-mean-square co-ordinate error is 0.2 A. The protein is a dimer assembled from identical subunits of 207 amino acid residues. The tertiary structure of the pGST P1 subunit is organized as two domains, the N-terminal domain (domain I, residues 1 to 74) and the larger C-terminal domain (domain II, residues 81 to 207). Glutathione sulphonate, a competitive inhibitor, binds to the G-site region (i.e. the glutathione-binding region) of the active site located on each subunit. Each G-site is, however, structurally dependent of the neighbouring subunit as structural elements forming a fully functional G-site are provided by both subunits, with domain I as the major supporting framework. A number of direct and water-mediated polar interactions are involved in sequestering the glutathione analogue at the G-site. The extended conformation assumed by the enzyme-bound inhibitor as well as the strategic interactions between inhibitor and protein, closely resemble those observed for the physiological substrate, reduced glutathione bound at the active site of class Mu glutathione S-transferase 3-3. Hydrogen bonding between the sulphonyl moiety of the inhibitor and the hydroxyl group of an evolutionary conserved tyrosine residue, Tyr7, provides the first direct structural evidence for a catalytic protein group in glutathione S-transferases that is involved in the activation of the substrate glutathione. The catalytic role for Tyr7 has subsequently been confirmed by mutagenesis and kinetic studies. Comparison of the known crystal structures for class Pi, class Mu and class Alpha isoenzymes, indicates that the cytosolic glutathione S-transferases share a common fold and that the structural features for catalysis are similar.


Toward Inexpensive Photocatalytic Hydrogen Evolution: A Nickel Sulfide Catalyst Supported on a High-Stability Metal-Organic Framework.
Few-atom clusters composed of nickel and sulfur have been successfully installed into the Zr(IV)-based metal-organic framework (MOF) NU-1000 via ALD-like chemistry (ALD = atomic layer deposition). X-ray photoelectron spectroscopy and Raman spectroscopy are used to determine that primarily Ni(2+) and S(2-) sites are deposited within the MOF. In a pH 7 buffered aqueous solution, the porous catalyst is able to produce H2 gas at a rate of 3.1 mmol g(-1) h(-1) upon UV irradiation, whereas no H2 is generated by irradiating bare NU-1000. Upon visible light irradiation, little H2 generation was observed; however, with the addition of an organic dye, rose bengal, NiS-AIM can catalyze the production of H2 at an enhanced rate of 4.8 mmol g(-1) h(-1). These results indicate that ALD in MOFs (AIM) can engender reactivity within high surface area supports for applications in the solar fuels field.


Do managed care plans' tiered networks lead to inequities in care for minority patients?
This study examined whether specialists designated as meeting efficiency thresholds in an insurance company's performance network were less likely than non-designated specialists to treat minority patients insured by that company. Claims data were used to identify patients treated by specialists. Claimants' race/ethnicity status was self-reported to the insurer at enrollment. In large part, minority patients appeared to be evenly distributed across the performance network, with the exception of Asian/Pacific Islanders, who appeared to be more likely to be treated by nondesignated physicians than by designated "good-performing" specialists.


Ca2+ Binding and Conformational Switch of the Photoprotein Mnemiopsin.
Bioluminescence in Ca2+-binding photoproteins is an intramolecular reaction triggered by the addition of Ca2+. A comparative study has been done on Ca2+-depleted and Ca2+-loaded apo-mnemiopsin to understand the structural transition of the photoprotein by Ca2+ binding. Ca2+ is removed by TCA (trichloroacetic acid) precipitation to obtain Ca2+-depleted apomnemiopsin. UV-visible, CD and fluorescence spectroscopic studies demonstrate that the addition of Ca2+ is brought about by the overall structure of apo-mnemiopsin becomes more open in a concentration- dependent manner without significantly influencing the secondary structure and indicate that the Ca2+-depleted form of apo-mnemiopsin, in contrast to most other EF-hand calcium binding proteins, adopt a closed conformation when compared to the Ca2+-loaded form. On the other hand, dynamic quenching and limited proteolysis analysis revealed that Ca2+-loaded apo-mnemiopsin became much more flexible than Ca2+ free apo-mnemiopsin. It seems that increased flexibility of the protein, which occurs due to calcium binding, is a critical factor in oxidative decarboxylation reaction on coelenterazine and consequently light emission.


Differing Experiences with Pre-Exposure Prophylaxis in Boston Among Lesbian, Gay, Bisexual, and Transgender Specialists and Generalists in Primary Care: Implications for Scale-Up.
The Centers for Disease Control and Prevention estimates that one in four sexually active men who have sex with men (MSM) could decrease their HIV risk by using HIV pre-exposure prophylaxis (PrEP). Because many MSM access healthcare from primary care providers (PCPs), these clinicians could play an important role in providing access to PrEP. Semistructured qualitative interviews were conducted with 31 PCPs in Boston, MA, to explore how they approach decisions about prescribing PrEP to MSM and their experiences with PrEP provision. Purposive sampling included 12 PCPs from an urban community health center specializing in the care of lesbian, gay, bisexual, and transgender persons ("LGBT specialists") and 19 PCPs from a general academic medical center ("generalists"). Analyses utilized an inductive approach to identify emergent themes. Both groups of PCPs approached prescribing decisions about PrEP as a process of informed decision-making with patients. Providers would defer to patients' preferences if they were unsure about the appropriateness of PrEP. LGBT specialists and generalists were at vastly different stages of adopting PrEP into practice. For LGBT specialists, PrEP was a disruptive innovation that rapidly became normative in practice. Generalists had limited experience with PrEP; however, they desired succinct decision-support tools to help them achieve proficiency, because they considered preventive medicine to be central to their professional role. As generalists vastly outnumber LGBT specialists in the United States, interventions to support PrEP provision by generalists could accelerate the scale-up of PrEP for MSM nationally, which could in turn decrease HIV incidence for this priority population.


An examination of depression through the lens of spinal cord injury. Comparative prevalence rates and severity in women and men.
This study describes the prevalence of probable major depressive disorder (MDD) as well as other depressive disorders (ODD) and severity of depressive symptoms in a national sample of women with spinal cord injury (SCI) and compares them with a case-matched sample of men with SCI. A sample of 585 women was drawn and case-matched with men from the SCI Model System National SCI Database according to level/completeness of injury, follow-up year, and age. The outcome measure of depression was the Patient Health Questionnaire. Prevalence rates for women were 7.9% for probable MDD and 9.7% for ODD; rates for men were 9.9% and 10.3%, respectively. Logistic regression revealed that women who were divorced or at year 1 follow-up had a higher odds of having probable MDD (odds ratio [OR], 3.4 and 2.9, respectively). Employed women and men had significantly lower odds of probable MDD (OR, 0.274 and 0.358, respectively). Statistically significant differences were not found in gender comparisons for either probable MDD or symptom severity, which also were not associated with injury characteristics. The most significant, and unexpected, research finding is the absence of gender differences in probable MDD and symptom severity. Results challenge notions that depression will necessarily follow SCI; that injury characteristics determine the development and severity of depression; and that women experience a greater burden of depression than men. The main clinical implication is that depression screening and referral should be a routine feature of health care for women living with SCI, as well as for their male counterparts. Furthermore, nearly one fourth of women and men reported experiencing some or greater difficulty in daily life and relationships in the absence of probable depressive disorder, warranting monitoring of subsyndromal depression as well.


Multicomponent dynamics of coupled quantum subspaces and field-induced molecular ionizations.
To describe successive ionization steps of a many-electron atom or molecule driven by an ultrashort, intense laser pulse, we introduce a hierarchy of successive two-subspace Feshbach partitions of the N-electron Hilbert space, and solve the partitioned time-dependent Schrödinger equation by a short-time unitary algorithm. The partitioning scheme allows one to use different level of theory to treat the many-electron dynamics in different subspaces. We illustrate the procedure on a simple two-active-electron model molecular system subjected to a few-cycle extreme Ultra-Violet (XUV) pulse to study channel-resolved photoelectron spectra as a function of the pulse's central frequency and duration. We observe how the momentum and kinetic-energy distributions of photoelectrons accompanying the formation of the molecular cation in a given electronic state (channel) change as the XUV few-cycle pulse's width is varied, from a form characteristic of an impulsive ionization regime, corresponding to the limit of a delta-function pulse, to a form characteristic of multiphoton above-threshold ionization, often associated with continuous-wave infinitely long pulse.


Appendiceal neuroendocrine neoplasms: diagnosis and management.
Gastrointestinal neuroendocrine neoplasms (GI-NENs) are increasingly being recognised, while appendiceal NENs (aNENs) currently constitute the third most common GI-NEN. Appendiceal NENs are generally considered to follow an indolent course with the majority being localised at diagnosis. Thus, the initial surgical approach is not that of a planned oncological resection. Due to the localised nature of the disease in the majority of cases, subsequent biochemical and radiological assessment are not routinely recommended. Histopathological criteria (size, mesoappendiceal invasion, Ki-67 proliferation index, neuro- and angio-invasion) are mainly used to identify those patients who are also candidates for a right hemicolectomy. Goblet cell carcinoids are a distinct entity and should be treated as adenocarcinomas. Despite the absence of any substantial prospective data regarding optimal management and follow-up, recent consensus statements and guidelines have been published. The purpose of this review is to overview the published studies on the diagnosis and management of appendiceal NENs and to suggest a possible management protocol.


Spontaneous activity in the perinatal trigeminal nucleus of the rat.
The role of electrical activity in establishing appropriate connections in the trigeminal pathway remains controversial. We report here a novel observation of spontaneous activity in the perinatal trigeminal sensory nucleus between embryonic day (E) 16 to postnatal day (P) 8. Most of these spontaneous bursts had the same polarity and were of comparable amplitude to the trigeminal nerve-evoked response. This synchronized activity was abolished by bicuculline or kynurenic acid. Recording from the teased trigeminal root during the spontaneous bursts also showed a corresponding afferent depolarization. We speculate that the GABAergic depolarization of pre- and postsynaptic cells may contribute to the generation of the spontaneous activity and its propagation throughout the trigeminal sensory pathway, even in the absence of activity initiated from peripheral sensory receptors.


Inferring frail life expectancies in Chicago from daily fluctuations in elderly mortality.
Susceptible sub-populations with existing disease have exhibited stronger relationships between air quality and mortality in time-series studies, but their associated life expectancies have largely been overlooked. Murray and Nelson developed a new time-series model that estimated a small unobserved (frail) sub-population and their resulting life expectancies in Philadelphia, including environment relationships. As a further example in a different geographic area, we used this model with 1987-2000 daily mortality data in Chicago and found a stable frail population at risk of ∼900 persons with a mean life expectancy of ∼11 days; fewer than two daily deaths were associated with air pollution. We considered daily concentrations of CO, NO₂, O₃, PM₁₀ and SO₂, and found PM₁₀ and O₃ to have stronger associations with frail mortality. Our estimates of life expectancy and air pollution and temperature relationships are similar to those found in other studies that used different methods. Temperature was more important than air pollution during the 1995 heat wave, when mortality risks increased dramatically after 2 d exposure and life expectancies decreased to 3-5 d. Modeling this event separately had substantial effects on lagged mortality--air pollution relationships and the population at risk. The premises of the Murray-Nelson model were supported by simultaneously considering an additional subgroup of non-frail individuals; they contributed only ∼1% of total elderly deaths. We conclude that frail life expectancies estimated by the Murray-Nelson model are robust, and that under these conditions non-frail persons have little risk of acute mortality, with or without contributions from air pollution.


Characteristics of Ge-Sb-Te films prepared by cyclic pulsed plasma-enhanced chemical vapor deposition.
Ge-Sb-Te (GST) thin films were deposited on TiN, SiO2, and Si substrates by cyclic-pulsed plasma-enhanced chemical vapor deposition (PECVD) using Ge{N(CH3)(C2H5)}, Sb(C3H7)3, Te(C3H7)3 as precursors in a vertical flow reactor. Plasma activated H2 was used as the reducing agent. The growth behavior was strongly dependent on the type of substrate. GST grew as a continuous film on TiN regardless of the substrate temperature. However, GST formed only small crystalline aggregates on Si and SiO2 substrates, not a continuous film, at substrate temperatures > or = 200 degrees C. The effects of the deposition temperature on the surface morphology, roughness, resistivity, crystallinity, and composition of the GST films were examined.