Rate theory calculation of gramicidin single-channel currents using NMR-derived rate constants.
By means of 23Na NMR, two ion binding sites were observed in phospholipid-packaged gramicidin channels and the four associated rate constants were approximated. Limits also were placed on a fifth rate constant for an intrachannel ion translocation. By using Eyring rate theory to introduce voltage dependence, these rate constants were used in steady-state-current equations for calculation of gramicidin single-channel currents for two- and three-site models. Calculated single-channel currents are compared with previously published experimental single-channel currents obtained by electrical measurements on Na+ transport across gramicidin-doped planar lipid bilayers. The calculated results for the two- and three-site models compare favorably with the experimental results. Accordingly, it is demonstrated that NMR-derived rate constants can be coupled with Eyring rate theory to calculate currents through a transmembrane channel and to do so within levels of variation that compare with the differences obtained on planar lipid bilayers formed with different lipids.


Growing up: perspectives of children, families and service providers regarding the needs of older children with perinatally-acquired HIV.
Children with perinatally-acquired HIV are living into adolescence and adulthood. As this is a relatively new phenomenon, there is a paucity of research highlighting the complex issues that arise for these children. This qualitative case-study examines the needs of a select group of older children (9-16 years old) with perinatally-acquired HIV in the province of British Columbia, Canada through focus groups and interviews conducted with ten HIV-infected children, 11 family members and 11 service providers. The needs of this population are diverse, reflecting its heterogeneity. However, participants consistently highlighted issues of stigma, sexual health and mental health as major areas of current and future concern. Continued support, education and future planning in these areas are necessary for older HIV-infected children as they transition out of childhood.


Metal 3D-printed catalytic jet and flame ionization detection for in situ trace carbon oxides analysis by gas chromatography.
A gas chromatographic approach for the determination and quantification of trace levels of carbon oxides in gas phase matrices for in situ or near-line/at-line analysis has been successfully developed. Catalytic conversion of the target compounds to methane via the methanation process was conducted inside a metal 3D-printed jet that also acted as a hydrogen burner for the flame ionization detector. Modifications made to a field transportable gas chromatograph enabled the leveraging of advantaged microfluidic-enhanced chromatography capability for improved chromatographic performance and serviceability. The compatibility with adsorption chromatography technology was demonstrated with in-house constructed columns. Sustained reliable conversion efficiencies of greater than 99% with respectable peak symmetries were attained at 400°C. Quantification of carbon monoxide and carbon dioxide at a parts-per-million level over a range from 0.2 ppm to 5% v/v for both compounds with a respectable precision of less than 3% relative standard deviation for peak area (n = 10) and a detection limit of 0.1 ppm v/v was achieved. Linearity with correlation coefficients of R2 greater than 0.9995 and measured recoveries of >99% for spike tests were achieved. The 3D-printed steel jet was found to be reliable and resilient against potential contamination from the matrices owing to the in situ backflushing capability.


Silencing of galectin-1 inhibits retinal neovascularization and ameliorates retinal hypoxia in a murine model of oxygen-induced ischemic retinopathy.
Aberrant neovascularization is a consequence of inappropriate angiogenic signaling and contributes to several diseases. Although many regulators of pathogenic angiogenesis have been identified, the understanding of this process remains incomplete. Galectin-1 (Gal-1), as a homodimeric protein with a single carbohydrate-recognition domain, is implicated in several pathologic processes, including angiogenesis; however, its involvement in retinal neovascularization (RNV) remains unknown. Here, we investigated the anti-angiogenic effect of silencing Gal-1 through intravitreal injection in a mouse model of oxygen-induced retinopathy (OIR). Our results revealed that Gal-1 was overexpressed and closely related to retinal neo-vessels in OIR retinas. After silencing Gal-1 via intravitreal injection of adenoviral-Gal-1-RNA interference (Ad-Gal-1-RNAi), RNV and retinal hypoxia were significantly attenuated, indicating the anti-angiogenic effect of Gal-1 inhibition. Western blot analysis and real-time polymerase chain reaction indicated that the expression of both neuropilin-1 (Nrp-1) and B cell lymphoma-2 (Bcl-2) decreased after intravitreal injection of Ad-Gal-1-RNAi, implying the possible involvement of Nrp-1 and Bcl-2 in Gal-1-related angiogenic processes. Additionally, whole-mount fluorescence and hematoxylin and eosin staining showed that intravitreal injection of Ad-Gal-1-RNAi did not significantly disrupt the retinal vasculature and neuronal structure of room air mice. Moreover, Ad-Gal-1-RNAi transfer promoted retinal vascular sprouting and increased retinal vascular perfusion, likely through decreased phosphorylation of myosin phosphatase target protein-1. Collectively, our results demonstrated that Gal-1 functions as an important regulator in RNV and offers a promising strategy for the treatment of RNV diseases, such as proliferative diabetic retinopathy and retinopathy of prematurity.


Imaging of vaccinia virus entry into HeLa cells.
The recently developed technique of live cell imaging has found numerous applications, including the detection of virus movements in living cells. To monitor virus motility, viruses or cellular proteins are fused with fluorescence markers and then detected by time-lapse fluorescence microscopy. These techniques allow kinetic analyses of individual virus particles in motion during the virus entry process as well as monitoring of dynamic interactions between viruses and cellular structures in real time. The methods presented here describe how to construct a fluorescent recombinant vaccinia virus expressing the core protein A4L fused to mCherry, and how to detect the virus movement on actin-EYFP-expressed HeLa cells.


Hemodynamic consequences of PEEP in seated neurological patients--implications for paradoxical air embolism.
In order to better understand the hemodynamic consequences of the use of positive end-expiratory pressure (PEEP) in patients in the seated position, 11 patients undergoing neurosurgical operations were monitored with radial arterial and thermistor-tipped Swan-Ganz catheters both before and during 10-cm H2O PEEP. Significant (P less than 0.05) reductions in cardiac output (15%), stroke volume (15%), and mean arterial pressure (14%) occurred with the introduction of PEEP, while pulmonary vascular resistance increased 47% and right atrial pressure (RAP) increased from 3.6 +/- 0.7 SEM mm Hg to 8.9 +/- 0.9 SEM mm Hg (P less than 0.05). Pulmonary capillary wedge pressure (PCWP) did not increase significantly during PEEP. RAP exceeded PCWP in only two patients before PEEP, but RAP exceeded PCWP in seven patients during PEEP. We conclude that PEEP is potentially detrimental during operations in the seated position because it not only impairs hemodynamic performance, but might predispose patients with a probe-patent foramen ovale to the risk of paradoxical air embolism.


Substitution of asparagine 76 by a tyrosine residue induces domain swapping in Helicobacter pylori phosphopantetheine adenylyltransferase.
Phosphopantetheine adenylyltransferase (PPAT) catalyses the penultimate step in coenzyme A biosynthesis in bacteria and is therefore a candidate target for antibacterial drug development. We randomly mutated the residues in the Helicobacter pylori PPAT sequence to identify those that govern protein folding and ligand binding, and we describe the crystal structure of one of these mutants (I4V/N76Y) that contains the mutations I4 → V and N76 → Y. Unlike other PPATs, which are homohexamers, I4V/N76Y is a domain-swapped homotetramer. The protomer structure of this mutant is an open conformation in which the 65 C-terminal residues are intertwined with those of a neighbouring protomer. Despite structural differences between wild-type PPAT and IV4/N76Y, they had similar ligand-binding properties. ATP binding to these two proteins was enthalpically driven, whereas that for Escherichia coli PPAT is entropically driven. The structural packing of the subunits may affect the thermal denaturation of wild-type PPAT and I4V/N76Y. Mutations in hinge regions often induce domain swapping, i.e. the spatial exchange of portions of adjacent protomers, but residues 4 and 76 of H. pylori PPAT are not located in or near to the hinge region. However, one or both of these residues is responsible for the large conformational change in the C-terminal region of each protomer. To identify the residue(s) responsible, we constructed the single-site mutant, N76Y, and found a large displacement of α-helix 4, which indicated that its flexibility allowed the domain swap to occur.


[The role of the bacterial inflammation in subglottic laryngitis in children].
The aim of this study is to assess the impact of some selected bacteriological factors on the occurrence of subglottic laryngitis in children. The research covered 72 children hospitalized in the Children's Hospital in Warsaw with the following symptoms: dry barking cough, stridor, inspiratory dyspnoea with the participation of auxiliary respiratory muscles, agitation and change of colour of skin. Subglottic laryngitis is one of the acute children's diseases, directly caused by a violently growing odema of the subglottic area. The disease constitutes 5-8% of all severe airways inflammations and states that subglottic laryngitis is responsible for 6.5% off all lower airways inflammation cases. Based on preliminary examinations, the patients were divided into two groups--one of them composed of 41 patients with simultaneous atopy, the other--of 31 patients with no atopy symptoms. The examination of each patient included subjective, objective (pediatric and laryngological) and auxiliary (primary-blood cell count, OB and specialized-bacteriological tests) examinations. Own research showed that out of 72 patients with subglottic laryngitis 56.95% had bacterial symptoms. 90.32% in non atopic group have higher NBT test, in atopic children it was 39.02%. We observed that 50.51% of the patients suffering from subglottic laryngitis had an inflammation of upper airways (otitis media, rhinitis, pharyngitis) and 13.89% of lower respiratory tract (bronchitis, pneumonitis). Many authors incline to say that bacteria may be a conductive factor for subglottic laryngitis to develop. However, many factors seem to suggest that the occurrence and symptoms of subglottic laryngitis are primarily caused by the reaction to an infection. The impact of bacteria onto the etiopathogenesis of subglottic laryngitis has been discussed for many years. Some experts are of the opinion that the disease develops on the bacteriologic background.


[Oculomotor control by cerebellar flocculus studied in the monkey].
137 unitary activities were recorded from cerebellar flocculus of two pig-tail monkeys; 40 being Purkinje neurons and 81 being mossy fiber activities. Discharge patterns of these unitary activities were modulated accompanying to saccade in the dark. 11 Purkinje neurons stopped the discharge and 3 neurons and 26 mossy fibers showed burst discharges. The monkey was trained to fixate a target; 19 mossy fibers responded to the whole background sinusoidal movement, and 18 mossy fibers responded to passive head rotation. 15 mossy fibers responded to smooth target pursuit movement. 2 Purkinje neurons responded to eye position, 4 neurons responded to eye movement velocity. Responses of 3 Purkinje neurons correspond to sum of the velocity of the eye and head movements. 10 neurons respond to both position and velocity of the eye movement; response phase of 9 out of the 10 neurons changed according to the phase of the sinusoidal pursuit eye movement. The experimental results suggest that the Purkinje neurons in cerebellar flocculus of the monkey send informations concerning eye position, eye movement velocity and head movement velocity to the brain stem, thus functioning as a part of the oculomotor control system.


Synthesis and Coordination Chemistry of a Phosphine-Decorated Fluorescein: "Double Turn-On" Sensing of Gold(III) Ions in Water.
Although phosphine ligands are ubiquitous in transition metal chemistry, few reports of fluorescent phosphines exist that explore the effect of metal coordination on the photophysical properties of a phosphine-bound fluorescent group. The coordination chemistry of a derivative of fluorescein decorated with an o-phenylene-linked phosphine group has been studied with late transition metals. An Au(I) complex of the phosphine-decorated fluorescein has been structurally characterized, showing that the metal center is held closely over the plane of the fluorophore. Despite the presence of the heavy metal center, however, the phosphine-gold complex displays greatly increased fluorescence compared to the free ligand, in which photoelectron transfer from the lone-pair-bearing phosphine causes low emission. The phosphine-decorated fluorescein ligand was tested in a simple sensing system for metal ions in aqueous solution and shows a "turn-on" response to Au, Ag, and Hg, with an especially dramatic response to Au(III) species. The selectivity for Au(III) was determined to be the result of a "double turn-on" response that is both reaction- and coordination-based.


The net benefit for time-to-event outcome in oncology clinical trials with treatment switching.
The net benefit is an effect measure for any type of endpoint, including the time-to-event outcome, and can provide intuitive and clinically meaningful interpretation. It is defined as the probability of a randomly selected subject from the experimental arm surviving by at least a clinically relevant time longer than a randomly selected subject from the control arm. In oncology clinical trials, an intercurrent event such as treatment switching is common, which potentially causes informative censoring; nevertheless, conventional methods for the net benefit are not able to deal with it. In this study, we proposed a new estimator using the inverse probability of censoring weighting (IPCW) method and illustrated an oncology clinical trial with treatment switching (the SHIVA study) to apply the proposed method under the estimand framework. The net benefit can be estimated using the survival functions of each treatment group. The proposed estimator was based on the survival functions estimated by the inverse probability of the censoring weighting method that can handle covariate-dependent censoring. The simulation study was undertaken to evaluate the operating characteristics of the proposed estimator under several scenarios; we varied the shapes of the survival curves, treatment effect, covariates effect on censoring, proportion of the censoring, threshold of the net benefit, and sample size. We also applied conventional methods (the scoring rules by Péron or Gehan) and the proposed method to the SHIVA study. Our simulation study showed that the proposed estimator provided less biased results under the covariate-dependent censoring than existing estimators. When applying the proposed method to the SHIVA study, we were able to estimate the net benefit by incorporating the information of the covariates with different estimand strategies to address the intercurrent event of the treatment switching. However, the estimates of the proposed method and those of the aforementioned conventional methods were similar under the hypothetical strategy. We proposed a new estimator of the net benefit that can include covariates to account for the possibly informative censoring. We also provided an illustrative analysis of the proposed method for the oncology clinical trial with treatment switching using the estimand framework. Our proposed new estimator is suitable for handling the intercurrent events that can potentially cause covariate-dependent censoring.


Rapid in-focus corrections on quantitative amplitude and phase imaging using transport of intensity equation method.
Transport of intensity equation (TIE) method can acquire sample phase distributions with high speed and accuracy, offering another perspective for cellular observations and measurements. However, caused by incorrect focal plane determination, blurs and halos are induced, decreasing resolution and accuracy in both retrieved amplitude and phase information. In order to obtain high-accurate sample details, we propose TIE based in-focus correction technique for quantitative amplitude and phase imaging, which can locate focal plane and then retrieve both in-focus intensity and phase distributions combining with numerical wavefront extraction and propagation as well as physical image recorder translation. Certified by both numerical simulations and practical measurements, it is believed the proposed method not only captures high-accurate in-focus sample information, but also provides a potential way for fast autofocusing in microscopic system.


Real-Time Neuroimaging and Cognitive Monitoring Using Wearable Dry EEG.
We present and evaluate a wearable high-density dry-electrode EEG system and an open-source software framework for online neuroimaging and state classification. The system integrates a 64-channel dry EEG form factor with wireless data streaming for online analysis. A real-time software framework is applied, including adaptive artifact rejection, cortical source localization, multivariate effective connectivity inference, data visualization, and cognitive state classification from connectivity features using a constrained logistic regression approach (ProxConn). We evaluate the system identification methods on simulated 64-channel EEG data. Then, we evaluate system performance, using ProxConn and a benchmark ERP method, in classifying response errors in nine subjects using the dry EEG system. Simulations yielded high accuracy (AUC = 0.97 ± 0.021) for real-time cortical connectivity estimation. Response error classification using cortical effective connectivity [short-time direct-directed transfer function (sdDTF)] was significantly above chance with similar performance (AUC) for cLORETA (0.74 ±0.09) and LCMV (0.72 ±0.08) source localization. Cortical ERP-based classification was equivalent to ProxConn for cLORETA (0.74 ±0.16) but significantly better for LCMV (0.82 ±0.12) . We demonstrated the feasibility for real-time cortical connectivity analysis and cognitive state classification from high-density wearable dry EEG. This paper is the first validated application of these methods to 64-channel dry EEG. This study addresses a need for robust real-time measurement and interpretation of complex brain activity in the dynamic environment of the wearable setting. Such advances can have broad impact in research, medicine, and brain-computer interfaces. The pipelines are made freely available in the open-source SIFT and BCILAB toolboxes.


Structural and Theoretical Study of Copper(II)-5-fluoro Uracil Acetate Coordination Compounds: Single-Crystal to Single-Crystal Transformation as Possible Humidity Sensor.
This paper describes the synthesis and characterization of seven different copper(II) coordination compounds, as well as the formation of a protonated ligand involving all compounds from the same reaction. Their synthesis required hydrothermal conditions, causing the partial in situ transformation of 5-fluoro uracil-1-acetic acid (5-FUA) into an oxalate ion (ox), as well as the protonation of the 4,4'-bipyridine (bipy) ligand through a catalytic process resulting from the presence of Cu(II) within the reaction. These initial conditions allowed obtaining the new coordination compounds [Cu2(5-FUA)2(ox)(bipy)]n·2n H2O (CP2), [Cu(5-FUA)2(H2O)(bipy)]n·2n H2O (CP3), as well as the ionic pair [(H2bipy)+2 2NO3-] (1). The mother liquor evolved rapidly at room temperature and atmospheric pressure, due to the change in concentration of the initial reagents and the presence of the new chemical species generated in the reaction process, yielding CPs [Cu(5-FUA)2(bipy)]n·3.5n H2O, [Cu3(ox)3(bipy)4]n and [Cu(ox)(bipy)]n. The molecular compound [Cu(5-FUA)2(H2O)4]·4H2O (more thermodynamically stable) ended up in the mother liquor after filtration at longer reaction times at 25 °C and 1 atm., cohabiting in the medium with the other crystalline solids in different proportions. In addition, the evaporation of H2O caused the single-crystal to single-crystal transformation (SCSC) of [Cu(5-FUA)2(H2O)(bipy)]n·2n H2O (CP3) into [Cu(5-FUA)2(bipy)]n·2n H2O (CP4). A theoretical study was performed to analyze the thermodynamic stability of the phases. The observed SCSC transformation also involved a perceptible color change, highlighting this compound as a possible water sensor.


Live-Cell Imaging of Endogenous RNA with a Genetically Encoded Fluorogenic Allosteric Aptamer.
Imaging and tracking tools for natural cellular RNA with improved biocompatibility, specificity, and sensitivity are critical to understanding RNA function and providing insights into disease therapeutics. We developed a new genetically encoded sensor using fluorogenic allosteric aptamer (FaApt) for the sensitive imaging of the localization and dynamics of RNA targets in live cells. Target RNAs can be specifically recognized with our sensor by forming perfectly complementary duplexes, which in turn can induce allosteric structural changes of the sensor to refold the native conformation of fluorogenic RNA aptamers. We demonstrated the ability of the sensor to monitor the effect of tumor necrosis factor and small-molecule inhibitor on the expression abundance of CXCL1 and survivin mRNA in human cancer cells, respectively. The asymmetrical distribution of endogenous Squint mRNA was confirmed in developing zebrafish embryos through microinjection of FaApt probes. This study provides an effective molecular tool for sensitive imaging and tracking endogenous RNA in living cells. Due to the high specificity and small size of our sensor system, it is expected to be applied to early diagnosis of RNA marker-related diseases and real-time evaluation of the treatment process.


Atrio-oesophageal fistula: dismal outcome of a rare complication with no common solution.
Atrio-oesophageal fistula caused by diffusion of ablative energy through the left atrial wall to the oesophagus is a lethal complication. A high level of suspicion, rapid diagnosis and early correction are of crucial importance. In this review, we highlight the key points that will aid in the thought processes and provide guidance in the prevention, early diagnosis and management to reduce complications and improve outcome when atrio-oesophageal fistula is suspected.


What do people want to know about "Growing Up with Migraine"? Results of a preference survey of people with lived experience to guide future research.
In recent years, emphasis has been placed on conducting headache research that is patient-centered to more explicitly incorporate the input of people who live with headache diseases. The Growing Up with Migraine Study was developed with this intention using a two-step process: 1. develop and administer a survey to identify research areas that matter most to people with adolescent migraine and/or their caregivers and 2. use the survey results to guide future secondary data analyses. This brief report summarizes the survey results from 373 individuals impacted by adolescent migraine. Findings suggested that people with history of adolescent migraine and/or their caregivers are most interested in research about migraine comorbidities and effects on psychological/social/emotional health, along with health-related outcomes and family-related topics. Future quantitative studies are planned that will explore these patient-identified priorities through secondary data analysis of an existing dataset.


Lower cutaneous microvascular reactivity in adult cancer patients receiving chemotherapy.
Cancer patients with a history of anticancer chemotherapy are at an increased cardiovascular disease risk compared with cancer-free populations. Therefore, we tested the hypothesis that cancer patients receiving adjuvant chemotherapy would have a lower cutaneous microvascular reactivity and lower endothelium-dependent flow-mediated dilation (FMD) of the brachial artery compared with matched cancer-free control subjects. To test this hypothesis, we performed a case control study with seven cancer patients receiving adjuvant chemotherapy and seven matched healthy reference control subjects. Red blood cell flux was measured as an index of cutaneous blood flow via laser Doppler flowmetry. Acetylcholine (ACh)-mediated vasodilation was determined by iontophoresis. Data were expressed as percent increase in cutaneous vascular conductance. Endothelium-dependent FMD of the brachial artery via ultrasonography was determined as an index of macrovessel endothelial function. Cutaneous microvascular reactivity was attenuated in cancer patients compared with control subjects [cancer: 959.9 ± 187.3%, control: 1,556.8 ± 222.2%; P = 0.03, effect size (ES) = 1.1]. Additionally, cancer patients demonstrated a significantly lower area under the curve response to ACh iontophoresis compared with healthy control subjects. Brachial artery FMD was also significantly lower in cancer patients compared with control subjects (cancer: 2.2 ± 0.6%, control: 6.6 ± 1.4%; P = 0.006, ES = 1.6), which was significantly associated with measurements of microvascular reactivity. These findings suggest that decreases in vascular reactivity can occur during cancer chemotherapy, which may have implications for the long-term risk of cardiovascular disease morbidity and mortality. NEW & NOTEWORTHY Cancer survivors treated with chemotherapy experience an increased risk of cardiovascular events, linked to both cardiac and vascular toxicity. The major finding of this study is that microvascular reactivity and macrovascular endothelium-dependent flow-mediated dilation are lower in cancer patients currently receiving adjuvant chemotherapy compared with healthy counterparts.


A case report of acute inferior myocardial infarction in a patient with severe hemophilia A after recombinant factor VIII infusion.
The extent of protective effects of hemophilia against thrombotic events such as myocardial infarction (MI) and other acute coronary syndromes remains to be determined, as major risk factors for cardiovascular disease exist despite factor VIII (FVIII) deficiency. We present a case report of a 41-year-old male with severe hemophilia A and several cardiovascular risk factors. This morbidly obese patient developed chest pressure, followed by chest pain and difficulty in breathing shortly after receiving on-demand treatment with intravenous recombinant FVIII (rFVIII) (turoctocog alfa) dosed per body weight. An electrocardiogram revealed a diagnosis of inferior ST-segment elevation MI. The patient underwent an urgent coronary angiography using a radial artery approach. During the next 12 months, he received dual antiplatelet treatment, acetylsalicylic acid 100 mg, and clopidogrel 75 mg daily. His treatment for severe hemophilia A was changed to plasma-derived FVIII replacement therapy. During this 12-month period, he experienced several small bleeds in his elbows. The temporal relationship between rFVIII infusion and onset of the MI suggests a possible association; however, apart from obesity, the patient also had other major risk factors for arterial thrombosis, such as hypertension and smoking. Furthermore, atherosclerotic disease and underlying atherosclerotic changes could not be excluded with certainty. This case highlights the importance of studies assessing the impact of excess body weight on rFVIII dosing.


[A theoretical analysis of the binding of methyl derivatives of uracil at the contact portion of the active center of ribonuclease S].
In terms of the mechanical model of molecules, a calculation has been carried out of possible positions and binding energies of 1-methyl uracyl in the contact region of the ribonuclease S active site. In the most preferential orientation, 1-methyl uracyl forms hydrogen bonds C(2)=O(uracyl)...H-N(Thr-45), N-H...Ogamma (Thr-45), C(4)=O... ...H-Ogamma (Ser-123). The base position found (atom coordinates are given) is in complete qualitative agreement with the position of the uracyl in UpcA bound to ribonuclease S as revealed by X-ray analysis. The influence studied of methyl substitution in positions 3 and 5 of the pyrimidine cycle on the base orientation within the protein field. It has been shown that the formation of hydrogen bonds with Thr-45 and Ser-123 is not prerequisite for productive fixation of the phosphoribosyl nucleotide moiety in the catalytic region of the enzyme active site.


Determination of isocyanates in air using 1-(2-methoxyphenyl)piperazine-impregnated filters: long-term sampling performance and field comparison with impingers with dibutylamine.
Isocyanates may be harmful to workers and methods for monitoring air exposure in the field are necessary. The main aim of this study was to study the field performance of a method using 1-(2-methoxyphenyl)piperazine (2MP)-impregnated filters, by side-by-side comparison of long-term sampling with consecutive short-term samplings and also by short-term comparisons with other methods. Apart from using 2MP-impregnated filters, air monitoring was also performed by a modified 2MP method (FINMP) and by an impinger method using dibutylamine (DBA), which was the reference method. For short-term sampling the compared methods performed equally well for 2,6-toluenediisocyanate (2,6-TDI) and for isocyanic acid. For 2,4-toluenediisocyanate (2,4-TDI), the DBA method gave approximately 10% higher results according to linear regression than the 2MP method and for phenyl isocyanate, the DBA method gave significantly higher results than both the 2MP and FINMP methods. During long-term sampling (2-4 h) of TDI with the 2MP method, significantly lower levels were found compared with parallel sampling with consecutive short-term samplings. A time-dependent correction factor for long-term sampling was calculated to be 1.7 for 2,4-TDI and 1.5 for 2,6-TDI for 4 h sampling. The long-term sampling performance for other isocyanates was not studied. In conclusion, short-term monitoring shows that the 2MP method slightly underestimates the true air concentration for some of the isocyanates studied, but the error is relatively small considering the variation in exposure. For long-term monitoring the 2MP method can be applied for TDI but, since the method underestimates the concentrations, a correction factor is needed which needs to be corroborated further.


Magnetic resonance active lesions as individual-level surrogate for relapses in multiple sclerosis.
Use of quantitative magnetic resonance imaging (MRI) metrics as surrogates for clinical outcomes in multiple sclerosis (MS) trials is controversial. We sought to validate, at the individual-patient level, the number of MRI active lesions, as a surrogate marker for relapses in MS. Individual-patient data from two large, placebo-controlled clinical trials of subcutaneous interferon β-1a in patients with relapsing-remitting or secondary progressive (SP) MS were analysed separately and as pooled data. The four Prentice criteria were applied to assess surrogacy for the number of new T2 MRI lesions. The predictive value of short-term treatment effects on this MRI marker for longer-term clinical relapses was also assessed. All Prentice criteria were satisfied. The number of new T2 MRI lesions correlated with the number of relapses over the follow-up period. The proportion of treatment effect on relapses accounted for by the effect of treatment on new T2 MRI lesions over 2 years was 53% in patients with relapsing-remitting MS, 67% in patients with secondary progressive MS, and 62% in pooled data. In the pooled data, treatment effects on new lesions over 1 year mediated a good proportion (70%) of effects on relapses over the subsequent year. This study provides evidence that new T2 MRI lesion count is a surrogate for relapses in patients with MS treated with interferon or drugs with a similar mechanism of action. Short-term treatment effects on this MRI measure can predict longer-term effects on relapses.


Preliminary Study on Physicochemical and Biochemical Stress Markers at Poultry Slaughterhouse.
Pre-slaughter stress can result in variations in the glycogen storage and metabolic changes of muscle, responsible for quality poultry meat. Aim of this study was to investigate, as pre-slaughter stress markers and quality meat, physicochemical (pH), biochemical (muscle glycogen content), and chemical (super oxides free radicals) parameters. The carcass quality, as incidence of individual carcass defects, was also evaluated. Twenty broilers were processed with two different electrical stunning: high (250 Hz; 640 mA; 60V) (Lot C or control) and low (150 Hz; 360 mA; 60 V) (Lot A) frequency and intensity, using sinusoidal alternating current. As preliminary results, the use of low frequency and intensity induced faster pH decline post mortem and adequate acidification of pH at 3 hours (6.49 Lot C; 6.37 Lot A), better muscle glycogen reserve (0.770 μL/50 mL Lot C; 1.497 μL/50mL Lot A), and lightly more rapid muscle oxidation (IDF: 0.109 Lot C; 0.122 Lot A), (FOX: 0.131 MeqO2/kg Lot C; 0.140 MeqO2/kg Lot A). The incidence of individual carcass defects sufficient to cause downgrading or rejection, both in Lot C and Lot A, was generally low. In a multidisciplinary approach, to assess animal welfare and quality poultry meat, additional and feasible parameters should be implemented. Monitoring of pH, muscle glycogen reserve and superoxide free radical production measurements might be markers easier to use, routinely, in practice at abattoir. Further studies are needed to evaluate the usefulness of these parameters.


Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks.
A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons ([Formula: see text]) in proton-proton collisions collected by the CMS experiment at the LHC at [Formula: see text]. The data correspond to an integrated luminosity of 19.7[Formula: see text]. The search considers [Formula: see text] resonances with masses between 1 and 3[Formula: see text], having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and [Formula: see text] events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 % confidence level for the product of the production cross section and branching fraction [Formula: see text] range from 10 to 1.5[Formula: see text] for the mass of X from 1.15 to 2.0[Formula: see text], significantly extending previous searches. For a warped extra dimension theory with a mass scale [Formula: see text] [Formula: see text], the data exclude radion scalar masses between 1.15 and 1.55[Formula: see text].


TNF-alpha reduces PGC-1alpha expression through NF-kappaB and p38 MAPK leading to increased glucose oxidation in a human cardiac cell model.
Inflammatory responses in the heart that are driven by sustained increases in cytokines have been associated with several pathological processes, including cardiac hypertrophy and heart failure. Emerging data suggest a link between cardiomyopathy and myocardial metabolism dysregulation. To further elucidate the relationship between a pro-inflammatory profile and cardiac metabolism dysregulation, a human cell line of cardiac origin, AC16, was treated with tumour necrosis factor-alpha (TNF-alpha). Exposure of AC16 cells to TNF-alpha inhibited the expression of peroxisome proliferator-activated receptor coactivator 1alpha (PGC-1alpha), an upstream regulator of lipid and glucose oxidative metabolism. Studies performed with cardiac-specific transgenic mice (Mus musculus) overexpressing TNF-alpha, which have been well characterized as a model of cytokine-induced cardiomyopathy, also displayed reduced PGC-1alpha expression in the heart compared with that of control mice. The mechanism by which TNF-alpha reduced PGC-1alpha expression in vitro appeared to be largely mediated via both p38 mitogen-activated protein kinase and nuclear factor-kappaB pathways. PGC-1alpha downregulation resulted in an increase in glucose oxidation rate, which involved a reduction in pyruvate dehydrogenase kinase 4 expression and depended on the DNA-binding activity of both peroxisome proliferator-activated receptor beta/delta and estrogen-related receptor alpha transcription factors. These results point to PGC-1alpha downregulation as a potential contributor to cardiac dysfunction and heart failure in metabolic disorders with an inflammatory background.


Pedometer accuracy during walking over different surfaces.
This study examined the effect of surface (concrete, grass, dry beach sand, wet beach sand) and gender on pedometer accuracy during walking. Fifty-two healthy university students volunteered for this study and completed six 150-m walking trials for each of the four different surfaces while wearing a YAMAX SW-700 Digiwalker pedometer. For each trial, time, number of steps taken and number of steps registered by the pedometer were recorded. These variables and pedometer accuracy for each walking surface and gender were analyzed by two-way repeated-measures ANOVA and Tukey's post hoc tests. Walking over dry beach sand significantly reduced walking speed (concrete, 5.6 +/- 0.5 km.h(-1); grass, 5.6 +/- 0.5 km.h(-1); dry beach sand, 5.0 +/- 0.5 km.h(-1): wet beach sand, 5.4 +/- 0.4 km.h(-1)) and increased the number of steps taken (concrete, 190 +/- 13; grass, 186 +/- 12; dry beach sand, 207 +/- 12; wet beach sand, 194 +/- 11) and registered (concrete, 195 +/- 14; grass, 191 +/- 14; dry beach sand, 213 +/- 15; wet beach sand, 201 +/- 16) by the pedometer compared with concrete and grass. Compared with males, females registered a greater number of pedometer steps (204 +/- 18 vs 197 +/- 15) and a greater absolute (9 +/- 12 vs 3 +/- 7 steps) and relative (4.46 +/- 5.72 vs 1.63 +/- 3.57%) pedometer error during walking over dry beach sand. Walking on a soft surface such as dry beach sand significantly reduced walking speed and increased pedometer error for females compared with males, possibly by exacerbating hip and walking movements. Identification of gender and softer surfaces should be considered when documenting physical activity levels in field studies.


Advanced microscopic imaging methods to investigate cortical development and the etiology of mental retardation.
Studies on human patients and animal models of disease have shown that disruptions in prenatal and early postnatal brain development are a root cause of mental retardation. Since proper brain development is achieved by a strict spatiotemporal control of neurogenesis, cell migration, and patterning of synapses, abnormalities in one or more of these events during prenatal development can lead to cognitive dysfunction after birth. Many of underlying causes of mental retardation must therefore be studied in developing brains. To aid in this research, live imaging using laser scanning microscopy (LSM) has recently allowed neuroscientists to delve deeply into the complex three-dimensional environment of the living brain to record dynamic cellular events over time. This review will highlight recent examples of how LSM is being applied to elucidate both normal and abnormal cortical development.


The Ionescu-Shiley pericardial bioprostheses in the aortic position. A 5-year perspective.
From August 1977 to August 1982, aortic valve replacement (AVR) with the Ionescu-Shiley pericardial valve was carried out on 172 patients. Hospital mortality was 4.3% for solitary AVR and 15% for patients with additional surgery. The expected 5 year survival rate was 96.7% for patients with isolated AVR and 81.8% for associated AVR. Cumulative duration of follow-up was 3,892 patient-months (mean 26.8 months per patient). The actuarial projection of freedom from thromboembolic episodes was 98.6% for isolated AVR and 91.6% for associated AVR. Seven patients underwent reoperation: 4 for infective endocarditis, 1 for massive perivalvular leak, 2 for primary tissue failure. Although the actuarial rate of freedom from valve failure for isolated AVR with Ionescu-Shiley valve was 93.7% at 5 years after surgery, the next few years of follow-up will be critical in determining the superiority of this valve over the porcine bioprostheses.


The Use of Vasoconstrictors in Acute Variceal Bleeding: How Long Is Enough?
Vasoconstrictors are often used as the first line therapy for acute esophageal variceal hemorrhage. They might also be used for a few days after endoscopic therapy to prevent early rebleeding. International guidelines recommend the use of vasoconstrictor therapy when acute esophageal variceal hemorrhage is suspected and continuation of the therapy until 3 to 5 days after endoscopic treatment. However, the duration of use of vasoconstrictors after endoscopic therapy is not clear. This review shows that if variceal bleeding is successfully controlled by endoscopic variceal ligation, the combination of vasoconstrictors can be reduced to less than 1 day.


Molecularly imprinted bacterial cellulose for sustained-release delivery of quercetin.
Bacterial cellulose (BC) has been used in the combination with molecularly imprinted polymer (MIP) for controlled-release drug delivery. In the present study, the molecular imprinting was directly performed on BC to avoid the use of synthetic materials for sustained-release of quercetin, which was used as the template molecule. The phase inversion method was successfully used to prepare molecularly imprinted BC (MI-BC). The molecular recognition ability and controlled drug release behavior of MI-BC were then evaluated. MI-BC was found to have approximately 1.6 times higher ability to bind quercetin than the non-imprinted BC (NI-BC) did. The composite membrane containing MI-BC and quercetin (MI-BC-com) delayed and sustained drug release more effectively than the composite membrane containing NI-BC and quercetin (NI-BC-com). MI-BC-com released quercetin approximately two times more slowly than NI-BC-com did at the final hour of the drug release study. The mechanism of quercetin release followed the Higuchi model. Due to the relatively simple method of preparing the drug delivery system without using synthetic MIP, the application of MI-BC may be of great interest in medicine and pharmaceutics.


Efficacy of glycoprotein inhibitors alone and in combination with trifluridine in the treatment of murine herpetic keratitis.
The present study examined the anti-herpetic effect of the glycoprotein inhibitors, hydroxynorvaline and 2-deoxyglucose, alone and in combination with trifluridine on murine ocular herpes. Following ocular inoculation with a large dose of HSV-1 RE strain (10(6) pfu), ICR mice were treated during the acute infection with different therapeutic regimens, and their efficacy was evaluated by ocular virus titers, clinical grading of blepharo-conjunctivitis and histological evaluation of stromal keratitis and iridocyclitis. The results following a large dose HSV-1 inoculum demonstrated that trifluridine was the best single therapeutic agent. Hydroxynorvaline and 2-deoxyglucose had no effect at all. Combination therapy of the glycoprotein inhibitors with trifluridine was no better than trifluridine alone. The mouse HSV-1 keratitis model proved to be an effective, economical alternative to the rabbit model for the evaluation of new antiviral agents.


Differential modulation of behavioral responses by [D-Ala2, NMePhe4, Gly-ol]enkephalin, [D-Ala2] deltorphin II and [D-Pen2, L-Pen5]enkephalin in the mouse.
The effects of [D-Ala2, NMePhe4, Gly-ol]enkephalin (DAMGO), a mu-selective opioid receptor agonist, [D-Ala2]deltorphin II (DELT) and [D-Pen2, L-Pen5]enkephalin (DPLPE), delta-selective opioid receptor agonists, on different behavioral responses were investigated in mice by multidimensional behavioral analyses. DAMGO (0.1 and/or 0.3 microgram) produced a marked increase in circling, rearing and grooming within 15-30 min after the start of behavioral measurements. DELT (0.3, 1.0 and/or 3.0 micrograms) produced a significant increase in linear locomotion and circling within 15-30 min after the start of behavioral measurements, whereas DPLPE (10.0 micrograms) increased only circling. The behavioral effects of DAMGO, DELT or DPLPE were almost completely antagonized by beta-funaltrexamine (2.5 and 5.0 micrograms) or naltrindole (3.0 and 10.0 mg/kg). These results suggest that opioid peptides selective for receptor types elicit different behavioral responses in mice. Moreover, the different behavioral effects between DPLPE and DELT may be due to the delta opioid receptor subtypes such as delta-1 and delta-2.


Measurement of the W-boson mass in pp collisions at s = 7 TeV with the ATLAS detector.
A measurement of the mass of the W boson is presented based on proton-proton collision data recorded in 2011 at a centre-of-mass energy of 7 TeV with the ATLAS detector at the LHC, and corresponding to 4.6 fb - 1 of integrated luminosity. The selected data sample consists of 7.8 × 10 6 candidates in the W → μ ν channel and 5.9 × 10 6 candidates in the W → e ν channel. The W-boson mass is obtained from template fits to the reconstructed distributions of the charged lepton transverse momentum and of the W boson transverse mass in the electron and muon decay channels, yielding m W = 80370 ± 7 ( stat. ) ± 11 ( exp. syst. ) ± 14 ( mod. syst. ) MeV = 80370 ± 19 MeV , where the first uncertainty is statistical, the second corresponds to the experimental systematic uncertainty, and the third to the physics-modelling systematic uncertainty. A measurement of the mass difference between the W + and W - bosons yields m W + - m W - = - 29 ± 28 MeV.


Thermodynamics of quasideterministic digital computers.
A central result of stochastic thermodynamics is that irreversible state transitions of Markovian systems entail a cost in terms of an infinite entropy production. A corollary of this is that strictly deterministic computation is not possible. Using a thermodynamically consistent model, we show that quasideterministic computation can be achieved at finite, and indeed modest cost with accuracies that are indistinguishable from deterministic behavior for all practical purposes. Concretely, we consider the entropy production of stochastic (Markovian) systems that behave like and and a not gates. Combinations of these gates can implement any logical function. We require that these gates return the correct result with a probability that is very close to 1, and additionally, that they do so within finite time. The central component of the model is a machine that can read and write binary tapes. We find that the error probability of the computation of these gates falls with the power of the system size, whereas the cost only increases linearly with the system size.


Psychomotor effects of ketorolac in comparison with buprenorphine and diclofenac.
1. Ketorolac is an investigational non-opioid analgesic. Buprenorphine, an opioid compound and diclofenac, a non-steroidal anti-inflammatory, are analgesics used in clinical practise. 2. The psychomotor effects of ketorolac (30 mg), buprenorphine (0.3 mg), diclofenac (50 mg) and placebo all administered i.m., were examined in 12 healthy male volunteers (age 19-38 years), up to 8 h post-dose. 3. Creatine phosphokinase (CPK) was measured up to 24 h post-dose, providing an indication of local tissue damage following injection. 4. Buprenorphine caused significant psychomotor impairment in seven out of eight psychomotor tests. The effects consistently peaked 4 h post-dose and were still apparent in many cases 8 h post-dose. These psychomotor effects were supported by marked symptoms in all volunteers. 5. Ketorolac and diclofenac had no clinically significant effects on psychomotor tests and only minimal symptoms were reported. 6. Diclofenac caused a marked increased in CPK (mean Cmax 298 iu l-1) compared with ketorolac (mean Cmax 70 iu l-1) and buprenorphine (mean Cmax 68 iu l-1). 7. These results suggest that ketorolac and diclofenac are suitable for administration following day case surgery.


The Relationship Between Internal Employer Branding and Talent Retention: A Theoretical Investigation for the Development of a Conceptual Framework.
The focus of this paper is to develop a comprehensive conceptual framework for the relationship between internal employer brand image and talent retention. An extensive and semi-systematic literature review identified a number of antecedents and consequences that have been empirically tested in various cutting-edge research studies that were conducted around the world. The existing literature is reviewed using a topical approach, and 66 research studies, most recent from various repositories, were carefully chosen and reviewed based on the criteria. Such studies have been discerned and synthesized in order to establish a complete and accurate understanding of the phenomenon. Finally, a comprehensive and relatively rich conceptual framework has been proposed for future empirical explanations in various social settings via prospective research.


Prevention of venous thrombosis after total knee arthroplasty. Comparison of antithrombin III and low-dose heparin with dextran.
In a prospective, randomized trial, we compared the efficacy of a combination of antithrombin III and heparin with that of dextran 40 as prophylaxis against venous thrombosis after total knee arthroplasty. Ascending venography identified thrombosis in about one-third of the patients who received the combination of antithrombin III and heparin, compared with about four-fifths of those who received dextran (p less than 0.001). In both groups, the patients who had venous thrombosis had a significantly lower concentration of antithrombin III postoperatively than those who did not have thrombosis. Venous thrombosis occurred in all patients in whom the concentration of antithrombin III was less than 65 per cent postoperatively. These findings demonstrated that, after total knee replacement, the combination of antithrombin III and heparin effectively reduces the incidence of postoperative venous thrombosis and is significantly better than dextran. Furthermore, the findings suggested a relationship between postoperative deficiency of antithrombin III and the occurrence of thrombotic complications.


Separation of active and inactive forms of recombinant human plasminogen activator inhibitor type 1 (PAI-1) expressed in Chinese hamster ovary cells: comparison with native human PAI-1.
Human plasminogen activator inhibitor type 1, PAI-1, was expressed in Chinese hamster ovary cells. A production level of 10-15 mg latent PAI-1 per liter of media was achieved after methotrexate amplification. Latent recombinant PAI-1 was purified by two chromatographic steps, cation exchange chromatography on CM-Sepharose and affinity chromatography on heparin-Sepharose. The obtained latent PAI-1 was approximately 90-95% pure showing one homogenous peak upon size-exclusion chromatography. However, four different isoforms due to different degrees of sialylation could be seen upon isoelectric focusing. Purified latent PAI-1 was activated by incubation in 6 M guanidine-HCl. By this method, 40-60% of PAI-1 was converted to an active form after removing the denaturant. The active fraction of PAI-1 was separated from inactive material by size exclusion chromatography on Superdex 200. Active PAI-1 migrated as expected for a 43-kDa large protein, while inactive PAI-1 migrated as larger protein complexes, suggesting that the remaining inactive PAI-1 was in the form of aggregates. This method for the separation of active and inactive PAI-1 could also be used for activated native PAI-1 prepared from human endothelial cells. Active recombinant PAI-1 was remarkably stable at pH 5.5, both when stored on ice and when stored at room temperature.


Dominance of Metric Correlations in Two-Dimensional Neuronal Cultures Described through a Random Field Ising Model.
We introduce a novel random field Ising model, grounded on experimental observations, to assess the importance of metric correlations in cortical circuits in vitro. Metric correlations arise from both the finite axonal length and the heterogeneity in the spatial arrangement of neurons. The experiments consider the response of neuronal cultures to an external electric stimulation for a gradually weaker connectivity strength between neurons, and in cultures with different spatial configurations. The model can be analytically solved in the metric-free, mean-field scenario. The presence of metric correlations precipitates a strong deviation from the mean field. Null models of the same networks that preserve the distribution of connections recover the mean field. Our results show that metric-inherited correlations in spatial networks dominate the connectivity blueprint, mask the actual distribution of connections, and may emerge as the asset that shapes network dynamics.


The National Oncology Working Group (NOW) initiative: payer and provider collaborations in oncology benefits management.
Payers recognize the need to expand benefits management for oncology but struggle to find effective solutions amid the complexity of available therapies and skepticism from oncologists, who are facing their own set of economic pressures. An effort called the National Oncology Working Group (NOW) Initiative is trying to change the sometimes adversarial relationship between payers and oncologists through a collaborative model. The group, which is supported by pharmaceutical manufacturer sanofi-aventis, is developing patient-centered strategies for successful and sustainable oncology benefits management. The focus includes finding consensus between payers and providers and devising solutions for oncology management such as decreasing variability of cancer care and improving end-of-life care for patients with terminal illness. NOW is designing tools that will be tested in small-scale regional demonstration projects, which NOW participants anticipate will set an example for successful oncology benefits management that can be replicated and expanded.


SAHA attenuates sevoflurane-induced learning and memory impairments in fetal mice.
Previous studies have found that children with multiple exposures to anesthesia at an early age are at increased risk of learning and memory impairment. Sevoflurane is the most commonly used inhalational anesthetic for general anesthesia in children. Multiple exposures to sevoflurane have been shown to induce neuroinflammation, inhibit neurogenesis, and cause subsequent learning and memory impairments in fetal mice. Histone-tail acetylation has been implicated in memory formation. In this study, we employed suberanilohydroxamic acid (SAHA), an inhibitor of histone deacetylases, to treat sevoflurane-induced learning and memory impairments. Six-day-old C57BL/6 mice were exposed to sevoflurane for 2 h daily for 3 days. Morris water maze test performed to evaluate learning and memory impairments and the expression of genes related in to synaptic remodeling/plasticity, or regulated by neuronal activity or the cell cycle were detected by real-time PCR. We found that SAHA attenuated sevoflurane-induced learning and memory impairments in fetal mice. Our findings suggest that SAHA may have potential as a therapeutic agent for preventing or treating the neurotoxicity associated with anesthesia.


Skin reaction as a biologic parameter for control of different dose schedules and gap correction.
In patients with mammary carcinoma, irradiated postoperatively on the parasternal regions, prospective dose calculations for different fractionation schedules have been performed with the CRE formula. The biologic radiation effect on normal tissue was recorded by reflectance spectrophotometry of skin erythema and pigmentation. The right side received 4 050 R in 25 days, the left side 4 390 R in 47 days with a gap of 3 weeks. A compensation for the gap with 8 per cent of the total exposure was found to be adequate. The smallest exposure difference that could be clearly discriminated visually and with spectrophotometry was recorded in a special series and was found to be 6 to 7 per cent.


Hepatobiliary phase MRI: impact on planning image-guided liver tumor ablations.
To assess the impact of hepatobiliary phase images obtained during intravenous gadoxetate disodium-enhanced liver MRI in the planning of image-guided liver tumor ablations. This institutional review board-approved retrospective study included 34 patients (21 men, 13 women, ages 25-80) who underwent 36 liver MRI examinations with gadoxetate disodium within 12 weeks prior to image-guided thermal ablation of 62 liver tumors during 36 procedures. Visibility of bile ducts, subdivided by branch order, on hepatobiliary phase images was compared to standard MRI sequence images by an attending abdominal radiologist and fellow. Interventional decision making (whether or not to ablate and technical plan) using hepatobiliary phase images was compared with standard MRI sequences by the ablationists. The technical success and adverse events of ablation procedures were noted. Bile duct visibility was significantly increased by at least one branch order in 18/36 (50%) examinations (p < 0.0001). Interventional decisions were significantly impacted in 15 (41.7%) of 36 ablation procedures (p < 0.0001), including changes to the technical plan in six (16.7%) of these procedures (p = 0.005). Technical success was achieved for 60/62 (97%) of tumors. Mild (grade 1) adverse events occurred in 4/36 (11%) procedures; no biliary complications occurred. Use of hepatobiliary phase images obtained during gadoxetate disodium-enhanced liver MRI impacted both when and how to perform image-guided liver tumor ablations in our practice.


[Establishment of nude mouse models of patient-derived lung cancer xenograft].
The aim of this study was to establish patient-derived lung cancer xenograft models in nude mice by subcutaneous and subrenal capsule transplantation, and to analyze the differences in biological characteristics of the xenografts. Surgically resected lung cancer specimens from 11 patients were implanted subcutaneously and under the renal capsule in nude mice. The tumor growth and histopathological features were observed and human origin of the blood vessels in the first-generation xenograft tumors was evaluated by SP immunohistochemistry using anti-human CD31 antibody. The patient-derived lung cancer tissues were successfully implanted subcutaneously and under the renal capsule in 11 nude mice. The operation time of subcutaneous implantation was 13 min, and the tumor formation rate was 36.4% (4/11). The operation time of implantation under the renal capsule was 45 min, and the tumor formation rate was 45.5% (5/11). Histopathological examination of the xenografts using HE staining showed the same morphology of the human lung cancers, and immunohistochemical observation with CD31staining showed that 83.3% (5/6) blood vessels in the xenograft tumors was of human origin. Both methods of subcutaneous and subrenal capsule transplantation can be used to successfully establish patient-derived lung cancer xenograft models in nude mice. The subcutaneous implantation is simple to operate, less time-comsuming, and easy to observe the tumor growth, but with a lower success rate of tumor formation. Transplantation under the renal capsule has a higher tumor formation rate, but is more difficult to operate, taking more time, and difficult to observe the growth of the tumor. The xenograft tumors formed by both methods in the first generation display biological characteristics of human lung cancer, the xenograft tumor models are close to human lung cancer, and therefore may provide a stable, reliable, and useful animal model in human lung cancer research.


Impact of rapid urine antigen tests to determine the etiology of community-acquired pneumonia in adults.
To evaluate the rapid urine antigen tests, including a new rapid immunochromatographic test (ICT) for the detection of the Streptococcus pneumoniae antigen and an enzyme immunoassay (EIA) for the detection of the Legionella antigen, in order to improve the diagnosis of community-acquired pneumonia (CAP) in adults. Prospective study. A tertiary hospital in Spain. We consecutively recruited 107 adults with CAP evaluated at our hospital. The analyses included blood and sputum cultures, pleural fluid culture (if present) and serologic studies. The detection of the Legionella pneumophila urinary antigen was performed by EIA, and the detection of S. pneumoniae antigen in urine samples was performed by counterimmunoelectrophoresis (CIE) and a rapid ICT. Using conventional microbiologic tests we succeeded in performing the etiologic diagnosis of 39 out of the 107 cases (36.4%). The inclusion of rapid antigen detection techniques increased the percentage of diagnosis to 54.2%, which represents a total increase of 17.8% (P=0.034). The data obtained in this study indicate that rapid urine antigen tests are very useful to determine CAP etiology in adults and, consequently, to quickly identify a group of patients in whom narrow spectrum antibiotics may be used.


Communicative Pathways Predicting Adherence in Type II Diabetic Patients: A Mediation Analysis.
Type II diabetes is a chronic health condition and its successful management requires effective patient-provider communication. Responding to a call to model pathways between provider communication and patient health outcomes, this study tested four models of type II diabetic patient adherence with four mediators. Given the complex nature of type II diabetic care, patient adherence was conceptualized as wellness, screening, medication, and treatment adherence. Mediators included patient understanding, agreement, trust, and motivation. A sample of U.S. patients with type II diabetes patients who were both under the care of a medical provider and taking medication for their type II diabetes completed online surveys (n = 793). Findings indicated that the relationships between patient-centered communication and adherence outcomes were mediated by proximal outcomes. The results contribute to the understanding of patient-centered communication, adherence behaviors, and proximal outcomes of patient understanding, agreement, trust, and motivation. Findings indicate that relationships between patient-centered communication and wellness adherence is mediated by patient motivation, patient-centered communication and screening adherence is mediated by patient agreement, trust, and motivation, and patient-centered communication and treatment adherence is mediated by patient agreement, trust, and motivation. The discussion addresses theoretical and practical implications and directions for future research.


Criteria for drop generation in multiphase microfluidic devices.
A theory is presented for the transition between the coflowing and the drop-generation regimes observed in microfluidic channels with a rectangular cross section. This transition is characterized by a critical ratio of the dispersed- to continuous-phase volume flow rates. At flow-rate ratios higher than this critical value, drop generation is suppressed. The critical ratio corresponds to the fluid cross section where the dispersed-phase fluid is just tangent to the channel walls. The transition criterion is a function of the ratio of the fluid viscosities, the three-phase contact angle formed between the fluid phases and the channel walls, and the aspect ratio of the channel cross section; the transition is independent of interfacial tension. Hysteretic behavior of drop generation with respect to the flow-rate ratio is predicted for partially wetting dispersed-phase fluids. Experimental data are consistent with this theory.


Cullin1 binds and promotes NLRP3 ubiquitination to repress systematic inflammasome activation.
Activation of the NACHT, leucine-rich repeat, and pyrin domains-containing protein 3 (collectively known as NLRP3) inflammasome plays a key role in host immune response, which is the first line of defense against cellular stresses and pathogen infections. However, excessive inflammasome activation damages host cells, and therefore it must be precisely controlled. Here, we discover that Cullin1 (CUL1), a key component of the Skp1-Cullin1-F-box E3 ligase, plays a critical role in controlling the NLRP3 inflammasome. CUL1 represses inflammasome assembly in cultured cells, suppresses NLRP3 function in human monocytic cell line macrophages, and attenuates inflammatory responses in mouse model. Detailed studies demonstrate that CUL1 interacts with NLRP3 and promotes NLRP3 ubiquitination, but not protein degradation, to repress the NLRP3 inflammasome activation. Moreover, upon inflammatory stimuli, including ATP and nigericin treatments, CUL1 disassociates from NLRP3 to release the repression of the NLRP3 inflammasome. Thus, this study reveals a distinct and unique mechanism underlying the control of systematic activation of the NLRP3 inflammasome.-Wan, P., Zhang, Q., Liu, W., Jia, Y., Ai, S., Wang, T., Wang, W., Pan, P., Yang, G., Xiang, Q., Huang, S., Yang, Q., Zhang, W., Liu, F., Tan, Q., Zhang, W., Wu, K., Liu, Y., Wu, J. Cullin1 binds and promotes NLRP3 ubiquitination to repress systematic inflammasome activation.


The effect of sexual activity on androgen metabolism, androgen-receptor translocation, and glandular weight of ventral prostates of rats.
The present study was conducted to determine whether sexual activity exerts an effect on the action of androgen in the rat prostate. Eight-week-old Sprague-Dawley male rats were divided into two groups. Rats were grouped with female rats (sexualactive), or male (sexual-inactive) rats, and sacrificed 6 months later, The ventral prostates were dissected, homogenized and processed into cytosol and nuclei fractions. Testosterone and dihydrotestosterone were quantified by radioimmunoassay, and androgen receptor was determined by 'exchange assay' with radioactive methyltrienolone incubated for 18 h at 15 degrees C. The main result were: 1) The steroid levels of testosterone and dihydrotestosterone in plasma and in the cytosolic fraction of prostate showed no significant difference between the two group of rats. 2) The prostatic nuclear dihydrotestosterone concentration of the sexual-active group (4.3 +/- 0.83 pmol/mg DNA, N = 6) was significantly higher (P less than 0.01) than that of the sexual-inactive group (1.68 +/- 0.43, N = 6). 3) The androgen receptor was significantly higher (P less than 0.05) in nuclear extract (0.64 +/- 0.11 pmol/mg DNA, N = 6) and significantly lower (P less than 0.01) in cytosol (53.4 +/- 5.7 fmol/mg protein, N = 6) of the sexual-active group than those of the sexual inactive group (0.42 +/- 0.13, N = 6 and 74.6 +/- 11.8, N = 6, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Saccade impairments in patients with fronto-temporal dementia.
Early diagnosis of fronto-temporal dementia (FTD) is often difficult because of the non-specific presentation. Saccadic eye movements, which are mainly controlled by the frontal areas, may provide a powerful tool for the analysis of frontal lobe dysfunction. The pattern of saccadic abnormalities has not previously been investigated in patients with FTD. To study saccade tasks in a group of 23 patients with FTD and compare the results with aged matched healthy controls. Triggering and inhibition of reflexive prosaccades were evaluated in a prosaccade and an antisaccade task, respectively, while the ability to withhold an antisaccade during a delay was explored in a delayed antisaccade task. Patients with progressive supranuclear palsy (PSP), in whom the pattern of eye movement deficit is well documented, were studied with the same protocol. To characterise the frontal lobe dysfunction in FTD more precisely, a battery of neuropsychological tests was carried out in these patients. Patients with FTD showed impaired reflexive saccade inhibition, similar to that observed in patients with PSP, and a decreased ability to withhold an antisaccade. Inhibition of reflexive and voluntary saccades appears to be independently processed. A delayed antisaccade task could be useful for the early diagnosis of FTD.


Development and validation of an instrument to measure physicians' attitudes toward the clinical pharmacist's role.
A scale to measure physicians' attitudes toward clinical pharmacy was developed and validated. Based on physician-clinical pharmacist interactions, statements were written and edited into tentative subscales. A preliminary test resulted in a reduction in the number of items and subscales. The final field test, based on responses from 166 physicians, after factor analysis, yielded 23 items in 5 subscales, with a scale reliability of 0.94. As additional measures of validity, physicians' responses showed significant differences in attitudes between subscales and differences by specialty. Differences also were demonstrated by physician status and age. No differences were shown by amount of exposure to clinical pharmacists. Reliability and validity of the scale have been supported and additional research into the concurrent validity of the scale is suggested.


Improved Screening Test for Idiopathic Infantile Hypercalcemia Confirms Residual Levels of Serum 24,25-(OH)2 D3 in Affected Patients.
CYP24A1 mutations are now accepted as a cause of idiopathic infantile hypercalcemia (IIH). A rapid liquid-chromatography tandem mass spectrometry (LC-MS/MS)-based blood test enabling measurement of the 25-OH-D3 :24,25-(OH)2 D3 ratio (R) can identify IIH patients on the basis of reduced C24-hydroxylation of 25-OH-D3 by CYP24A1 in vivo. Although values of this ratio are significantly elevated in IIH, somewhat surprisingly, serum 24,25-(OH)2 D3 remains detectable. The current study explores possible explanations for this including: residual CYP24A1 enzyme activity in individuals with certain CYP24A1 genotypes, expression of alternative C24-hydroxylases, and the possibility of isobaric contamination of the 24,25-(OH)2 D3 peak on LC-MS/MS. We employed an extended 20-min run time on LC-MS/MS to study serum vitamin D metabolites in patients with IIH due to mutations of CYP24A1 or SLC34A1; in unaffected heterozygotes and dialysis patients; in patients with vitamin D deficiency; as well as in normal subjects exhibiting a broad range of 25-OH-D levels. We identified 25,26-(OH)2 D3 as a contaminant of the 24,25-(OH)2 D3 peak. In normals, the concentration of 24,25-(OH)2 D3 greatly exceeds 25,26-(OH)2 D3 ; however, 25,26-(OH)2 D3 becomes more significant in IIH with CYP24A1 mutations and in dialysis patients, where 24,25-(OH)2 D3 levels are low when CYP24A1 function is compromised. Mean R in 30 IIH-CYP24A1 patients was 700 (range, 166 to 2168; cutoff = 140) as compared with 31 in 163 controls. Furthermore, patients possessing CYP24A1 L409S alleles exhibited higher 24,25-(OH)2 D3 levels and lower R (mean R = 268; n = 8) than patients with other mutations. We conclude that a chromatographic approach which resolves 24,25-(OH)2 D3 from 25,26-(OH)2 D3 produces a more accurate R that can be used to differentiate pathological states where CYP24A1 activity is altered. The origin of the residual serum 24,25-(OH)2 D3 in IIH patients appears to be multifactorial. © 2017 American Society for Bone and Mineral Research.


κ-opioid receptor is involved in the cardioprotection induced by exercise training.
The present study was designed to test the hypothesis that exercise training elicited a cardioprotective effect against ischemia and reperfusion (I/R) via the κ-opioid receptor (κ-OR)-mediated signaling pathway. Rats were randomly divided into four groups: the control group, the moderate intensity exercise (ME) group, the high intensity exercise (HE) group, and the acute exercise (AE) group. For the exercise training protocols, the rats were subjected to one week of adaptive treadmill training, while from the second week, the ME and HE groups were subjected to eight weeks of exercise training, and the AE group was subjected to three days of adaptive treadmill training and one day of vigorous exercise. After these protocols, the three exercise training groups were divided into different treatment groups, and the rats were subjected to 30 min of ischemia and 120 min of reperfusion. Changes in infarct size and serum cTnT (cardiac troponin T) caused by I/R were reduced by exercise training. Moreover, cardiac dysfunction caused by I/R was also alleviated by exercise training. These effects of exercise training were reversed by nor-BNI (a selective κ-OR antagonist), Compound C (a selective AMPK inhibitor), Akt inhibitor and L-NAME (a non-selective eNOS inhibitor). Expression of κ-OR and phosphorylation of AMPK, Akt and eNOS were significantly increased in the ME, HE and AE groups. These findings demonstrated that the cardioprotective effect of exercise training is possibly mediated by the κ-OR-AMPK-Akt-eNOS signaling pathway.


In-Home Cardiovascular Monitoring System for Heart Failure: Comparative Study.
There is a pressing need to reduce the hospitalization rate of heart failure patients to limit rising health care costs and improve outcomes. Tracking physiologic changes to detect early deterioration in the home has the potential to reduce hospitalization rates through early intervention. However, classical approaches to in-home monitoring have had limited success, with patient adherence cited as a major barrier. This work presents a toilet seat-based cardiovascular monitoring system that has the potential to address low patient adherence as it does not require any change in habit or behavior. The objective of this work was to demonstrate that a toilet seat-based cardiovascular monitoring system with an integrated electrocardiogram, ballistocardiogram, and photoplethysmogram is capable of clinical-grade measurements of systolic and diastolic blood pressure, stroke volume, and peripheral blood oxygenation. The toilet seat-based estimates of blood pressure and peripheral blood oxygenation were compared to a hospital-grade vital signs monitor for 18 subjects over an 8-week period. The estimated stroke volume was validated on 38 normative subjects and 111 subjects undergoing a standard echocardiogram at a hospital clinic for any underlying condition, including heart failure. Clinical grade accuracy was achieved for all of the seat measurements when compared to their respective gold standards. The accuracy of diastolic blood pressure and systolic blood pressure is 1.2 (SD 6.0) mm Hg (N=112) and -2.7 (SD 6.6) mm Hg (N=89), respectively. Stroke volume has an accuracy of -2.5 (SD 15.5) mL (N=149) compared to an echocardiogram gold standard. Peripheral blood oxygenation had an RMS error of 2.3% (N=91). A toilet seat-based cardiovascular monitoring system has been successfully demonstrated with blood pressure, stroke volume, and blood oxygenation accuracy consistent with gold standard measures. This system will be uniquely positioned to capture trend data in the home that has been previously unattainable. Demonstration of the clinical benefit of the technology requires additional algorithm development and future clinical trials, including those targeting a reduction in heart failure hospitalizations.


Characterization of symptomatic hip impingement in butterfly ice hockey goalies.
This study aimed to characterize the radiographic deformity observed in a consecutive series of butterfly goalies with symptomatic mechanical hip pain and to use computer-based software analysis to identify the location of impingement and terminal range of motion. We also compared these analyses to a matched group of positional hockey players with symptomatic femoroacetabular impingement (FAI). A consecutive series of 68 hips in 44 butterfly-style hockey goalies and a matched group of 34 hips in 26 positional hockey players who underwent arthroscopic correction for symptomatic FAI were retrospectively analyzed. Each patient underwent preoperative anteroposterior (AP) and modified Dunn lateral radiographs and computed tomography (CT) of the affected hips. Common FAI measurements were assessed on plain radiographs. Patient-specific, CT-based 3-dimensional (3D) models of the hip joint were developed, and the femoral version, alpha angles at each radial clock face position, and femoral head coverage were calculated. Maximum hip flexion, abduction, internal rotation in 90° flexion (IRF), flexion/adduction/internal rotation (FADIR), and butterfly position were determined, and the areas of bony collision were defined. Butterfly goalies had an elevated mean alpha angle on both AP (61.3°) and lateral radiographs (63.4°) and a diminished beta angle (26.0°). The mean lateral center-edge angle (LCEA) measured 27.3° and acetabular inclination was 6.1°. A crossover sign was present in 59% of the hips. The maximum alpha angle on the radial reformatted computed tomographic scan was significantly higher among the butterfly goalies (80.9° v 68.6°; P < .0001) and was located in a more lateral position (1:00 o'clock v. 1:45 o'clock; P < .0001) compared with positional players. Symptomatic butterfly hockey goalies have a high prevalence of FAI, characterized by a unique femoral cam-type deformity and noted by an elevated alpha angle and loss of offset, which is greater in magnitude and more lateral when compared with that in positional hockey players. Associated acetabular dysplasia is also common among hockey goalies. Level IV, prognostic case series.


Midwives, labour induction and the Wooden Spoon award Part 2.
Rates of labour induction without clear medical indication have risen exponentially. This trend has not been without consequence of increased perinatal mortality and morbidity. Midwives must understand the importance of educating pregnant women and other obstetrical providers, about the risks associated with labour induction. Maternal-child health policy that minimises unnecessary interventions is urgently needed and prevention strategies are described in the second part of this article. Midwives are challenged to consider their role in reducing unnecessary labour inductions in a rapidly changing birth culture reflecting high intervention.


OTX2 represses sister cell fate choices in the developing retina to promote photoreceptor specification.
During vertebrate retinal development, subsets of progenitor cells generate progeny in a non-stochastic manner, suggesting that these decisions are tightly regulated. However, the gene-regulatory network components that are functionally important in these progenitor cells are largely unknown. Here we identify a functional role for the OTX2 transcription factor in this process. CRISPR/Cas9 gene editing was used to produce somatic mutations of OTX2 in the chick retina and identified similar phenotypes to those observed in human patients. Single cell RNA sequencing was used to determine the functional consequences OTX2 gene editing on the population of cells derived from OTX2-expressing retinal progenitor cells. This confirmed that OTX2 is required for the generation of photoreceptors, but also for repression of specific retinal fates and alternative gene regulatory networks. These include specific subtypes of retinal ganglion and horizontal cells, suggesting that in this context, OTX2 functions to repress sister cell fate choices.


Personalising nutritional guidance for more effective behaviour change.
Improving diet and other lifestyle behaviours has considerable potential for reducing the global burden of non-communicable diseases, promoting better health across the life-course and increasing wellbeing. However, realising this potential will require the development, testing and implementation of much more effective behaviour change interventions than are used conventionally. Evidence-based, personalised (or stratified) interventions which incorporate effective behaviour change techniques (BCT) and which are delivered digitally are likely to be an important route to scalable and sustainable interventions. Progress in developing such interventions will depend on the outcomes of research on: (i) the best bases for personalisation of dietary advice; (ii) identification of BCT which are proven to enhance intervention efficacy; (iii) suitable platforms (digital-based tools) for collection of relevant participant characteristics (e.g. socioeconomic information, current diet and lifestyle and dietary preferences) linked with intelligent systems which use those characteristics to offer tailored feedback and advice in a cost-effective and acceptable manner. Future research should focus on such interventions aiming to reduce health inequalities and to improve overall public health.


Model of fluorescence intermittency of single colloidal semiconductor quantum dots using multiple recombination centers.
We present a new physical model resolving a long-standing mystery of the power-law distributions of the blinking times in single colloidal quantum dot fluorescence. The model considers the nonradiative relaxation of the exciton through multiple recombination centers. Each center is allowed to switch between two quasistationary states. We point out that the conventional threshold analysis method used to extract the exponents of the distributions for the on times and off times has a serious flaw: the qualitative properties of the distributions strongly depend on the threshold value chosen for separating the on and off states. Our new model explains naturally this threshold dependence, as well as other key experimental features of the single quantum dot fluorescence trajectories, such as the power-law power spectrum (1/f noise).


Hierarchical Status Predicts Behavioral Vulnerability and Nucleus Accumbens Metabolic Profile Following Chronic Social Defeat Stress.
Extensive data highlight the existence of major differences in individuals' susceptibility to stress [1-4]. While genetic factors [5, 6] and exposure to early life stress [7, 8] are key components for such neurobehavioral diversity, intriguing observations revealed individual differences in response to stress in inbred mice [9-12]. This raised the possibility that other factors might be critical in stress vulnerability. A key challenge in the field is to identify non-invasively risk factors for vulnerability to stress. Here, we investigated whether behavioral factors, emerging from preexisting dominance hierarchies, could predict vulnerability to chronic stress [9, 13-16]. We applied a chronic social defeat stress (CSDS) model of depression in C57BL/6J mice to investigate the predictive power of hierarchical status to pinpoint which individuals will exhibit susceptibility to CSDS. Given that the high social status of dominant mice would be the one particularly challenged by CSDS, we predicted and found that dominant individuals were the ones showing a strong susceptibility profile as indicated by strong social avoidance following CSDS, while subordinate mice were not affected. Data from 1H-NMR spectroscopy revealed that the metabolic profile in the nucleus accumbens (NAc) relates to social status and vulnerability to stress. Under basal conditions, subordinates show lower levels of energy-related metabolites compared to dominants. In subordinates, but not dominants, levels of these metabolites were increased after exposure to CSDS. To the best of our knowledge, this is the first study that identifies non-invasively the origin of behavioral risk factors predictive of stress-induced depression-like behaviors associated with metabolic changes.


Emergence delirium in children: many questions, few answers.
The introduction of a new generation of inhaled anesthetics into pediatric clinical practice has been associated with a greater incidence of ED, a short-lived, but troublesome clinical phenomenon of uncertain etiology. A variety of anesthesia-, surgery-, patient-, and adjunct medication-related factors have been suggested to play a potential role in the development of such an event. Restless behavior upon emergence causes not only discomfort to the child, but also makes the caregivers and parents feel unhappy with the quality of recovery from anesthesia. Although the severity of agitation varies, it often requires additional nursing care, as well as treatment with analgesics or sedatives, which may delay discharge from hospital. To reduce the incidence of this adverse event, it is advisable to identify children at risk and take preventive measures, such as reducing preoperative anxiety, removing postoperative pain, and providing a quiet, stress-free environment for postanesthesia recovery. More clinical trials are needed to elucidate the cause as well as provide effective treatment.


Optical response of CdSe quantum dots to cesium-137 gamma-ray radiation.
The optical response of colloidal photoluminescent (PL) semiconductor nanocrystals to 137Cs gamma radiation was investigated. The quantum dots (QDs) used were CdSe dispersed in hexane, exhibiting bandgap absorption and emission peaking at 556 nm and 563 nm, respectively. The doses of the 137Cs gamma radiations were 0.1, 1.0, 10 and 100 Gy with a dose rate of 0.805 Gy/min. Each radiation was performed on two identical samples; right after the radiation, absorption and emission measurements were performed. The change of the optical properties after the radiation was presented together with those of a control sample without radiation exposure. The prompt absorption measurements showed that there is little change with the 0.1 Gy up to 100 Gy radiations, while the prompt emission measurements showed that with the 0.1 Gy and 1 Gy radiation, there is a negligible change in the PL intensity; with the 10 Gy and 100 Gy radiation, there is a noticeable decrease in the PL intensity. Therefore, it seems that the radiation does not destroy the QDs themselves but leads to some loss of their surface passivation. Furthermore, the optical properties of the eight irradiated samples and the control sample were monitored periodically up to days. Interestingly, after the storage of days in dark, there is significant recovery in the PL intensity of the large-dose irradiated samples; such a rebound tendency provides the potential for the colloidal QDs to be novel and promising candidates in radiation dosimeter with multi-detection capability.


[Risk factors of cerebral embolism in patients with atrial fibrillation].
Cerebral embolism is one of the major complications of atrial fibrillation (Af). We studied patients with Af, retrospectively, as to the factors related to cerebral embolism. We examined 82 cases with transthoracic echocardiography (TTE) and trans-esophageal echocardiography (TEE) as well as ambulatory (Holter) ECG and 12 leads ECG. Thirty-three patients had cerebral ischemic attack (CIA), including 14 patients with mitral stenosis (MS) and 19 patients with other heart disease or lone Af (NonMS). The CIA group of NonMS were older than other groups. Both the CIA and NonCIA groups had the same frequency of paroxysmal and chronic Af. In the CIA group, there was a tendency of small amplitude of f wave and longer RR interval than the NonCIA group with ambulatory ECG. The CIA group also had larger left atrial cavity size and aortic diameter with TTE. TEE revealed thrombus formation in 29 cases, and the CIA group had a higher occurrence rate of thrombus than NonCIA group. TEE also detected a fuzzy echo in the left atrium in 88% of the CIA group and 42% of the NonCIA group. The risk factors of cerebral embolism could not be made clear in this study, but a fuzzy echo and thrombus in the left atrium with TEE are specific findings of cerebral embolism. Therefore, older patients with paroxysmal Af, large LAD, AOD, small f wave or long RR interval need to be examined by TEE to detect LA thrombus or a fuzzy echo, which are probably major risk factors of cerebral embolism.


Neural representation of motion-in-depth in area MT.
Neural processing of 2D visual motion has been studied extensively, but relatively little is known about how visual cortical neurons represent visual motion trajectories that include a component toward or away from the observer (motion in depth). Psychophysical studies have demonstrated that humans perceive motion in depth based on both changes in binocular disparity over time (CD cue) and interocular velocity differences (IOVD cue). However, evidence for neurons that represent motion in depth has been limited, especially in primates, and it is unknown whether such neurons make use of CD or IOVD cues. We show that approximately one-half of neurons in macaque area MT are selective for the direction of motion in depth, and that this selectivity is driven primarily by IOVD cues, with a small contribution from the CD cue. Our results establish that area MT, a central hub of the primate visual motion processing system, contains a 3D representation of visual motion.


Perspectives on the drug court model across systems: a process evaluation.
Drug courts have been in existence since 1989, yet few process evaluations have appeared in the literature to help inform the discussion about their effectiveness. This article reports findings from a process evaluation of a drug court program in San Mateo, California. The evaluation was designed to document the history of the program, to examine program strengths and areas of improvement, to assess the roles and relationships among the various agencies involved and to describe the impact of the drug court on the justice and drug treatment systems. Methods included review of available drug court program documents, interviews with key stakeholders, and focus groups with drug court participants. The main findings were: support for the continuation of drug court, enhanced collaboration among all agencies, and an increased awareness of the needs of substance-using clients in the criminal justice system. Potential lessons for other drug courts include the importance of building strong collaborations and maintaining good communication, recognizing competing interests in developing procedures for drug court, and considering changes in eligibility criteria as experience with the drug court model expands.


Reduced expression of metabotropic glutamate receptor 2mRNA in T cells of ALS patients.
Metabotropic glutamate receptors alter the vulnerability of neurons to excitotoxic damage and are reported to display abnormal expression in the central nervous system of ALS patients. Using reverse transcriptase polymerase chain reaction, we investigated the mRNA expression of specific metabotropic glutamate receptor subtypes in T lymphocytes of 20 patients with sporadic ALS, compared with healthy age-matched control subjects and patients with other neurological disorders. The levels of metabotropic glutamate receptor 2 mRNA were markedly reduced, whereas the expression of other subtypes (1b, 3, 8) was similar to control levels. Our findings may provide a reliable peripheral marker of the glutamatergic dysfunction that characterizes ALS.


Immediate hypersensitivity in the guinea pig conjunctiva intravitreal and topical sensitization.
The right eyes of guinea pigs were injected with 1.5 mg sterile ovalbumin. Two months later, one drop of ovalbumin (approximately 0.6 mg) was applied to the conjunctiva of both eyes. All challenged eyes developed an immediate hypersensitivity reaction within 5 min. The reaction subsided within 2 hrs. Prechallenge antibody titers, as determined by passive hemagglutination, passive cutaneous anaphylaxis, and by an ELISA test were low. Titers rose rapidly after two conjunctival applications at weekly intervals. The hypersensitivity reaction was elicited each time antigen was applied to the conjunctiva of the intravitreally sensitized guinea pigs. Control guinea pigs received weekly conjunctival application of ovalbumin, without prior intravitreal sensitization. Most animals developed an immediate hypersensitivity reaction following the fourth application of the antigen. There was no detectable hemagglutinating or ELISA (IgG1, IgG2) antibody at the time the conjunctival reaction was first elicited. These experiments demonstrated that high circulating IgG1 or IgG2 antibody is apparently not necessary to initiate an immediate hypersensitivity reaction in the guinea pig conjunctiva. The authors also demonstrated that weekly topical application of ovalbumin sensitized guinea pigs for immediate hypersensitivity.


Insurers reign.
Double-digit premium increases, an easing of runaway cost growth and less competition have led to record profits and climbing stock prices for the nation's insurance companies. While the immediate outlook is rosy, there are hints that a backlash may be developing among providers and consumers disgruntled over the high premiums, and among policy-makers alarmed at the climb in the number of uninsured Americans, which is estimated at 41 million now and is expected by all forecasters to continue to surge.


Statin escape phenomenon: Fact or fiction?
To evaluate the presence of the so called "statin escape" phenomenon among hyperlipidemic subjects attending a lipid clinic. This was a retrospective analysis of 1240 hyperlipidemic individuals followed-up for ≥ 3 years. We excluded those individuals meeting one of the following criteria: Use of statin therapy at baseline visit, discontinuation of statin treatment at most recent visit, change in statin treatment during follow-up and poor compliance to treatment. Statin escape phenomenon was defined as an increase in low-density lipoprotein cholesterol (LDL-C) levels at the most recent visit by > 10% compared with the value at 6 mo following initiation of statin treatment. Of 181 eligible subjects, 31% exhibited the statin escape phenomenon. No major differences regarding baseline characteristics were found between statin escapers and non-statin escapers. Both escapers and non-escapers had similar baseline LDL-C levels [174 (152-189) and 177 (152-205) mg/dL, respectively]. In comparison with non-escapers, statin escapers demonstrated lower LDL-C levels at 6 mo after treatment initiation [88 (78-97) mg/dL vs 109 (91-129) mg/dL, P < 0.05], but higher levels at the most recent visit [103 (96-118) mg/dL vs 94 (79-114) mg/dL, P < 0.05]. These data confirm the existence of an escape phenomenon among statin-treated individuals. The clinical significance of this phenomenon remains uncertain.


Impact of terlipressin infusion during and after live donor liver transplantation on incidence of acute kidney injury and neutrophil gelatinase-associated lipocalin serum levels: A randomized controlled trial.
Acute kidney injury (AKI) with liver transplantation (LT) is not uncommon. Impact of terlipressin infusion on AKI, hemodynamics, and plasma concentration of neutrophil gelatinase-associated lipocalin (NGAL) was studied. Patients (n=50) were randomized (NCT02059460, USA) into two equal groups: terlipressin vs Controls. Terlipressin (1-4 μg/kg/h) was administrated for 5 days. Intraoperative transesophageal Doppler for hemodynamic management. Renal functions, peak portal vein blood flow velocity (PPV), and hepatic artery resistive index (HARI) were recorded. Plasma NGAL (pNGAL) was measured baseline, 2 and 24 hours postreperfusion. Hepatitis C virus (HCV) was the main etiology. Age, sex, model of end-stage liver disease (MELD), and renal functions were comparable. Postoperative AKI incidence and NGAL concentrations were comparable (P>.05) between terlipressin and controls groups (44% vs 48% and 112.5±9 vs 93.1±8 ng/mL), respectively, but intraoperative NGAL in both groups increased significantly 2 hours postreperfusion (P<.05). The three NGAL readings were comparable (P>.05) between AKI (n=23) and non-AKI developers (n=27). Mean arterial blood pressure (MAP) was maintained in both groups with less systemic vascular resistance (SVR) fluctuations with terlipressin. Median norepinephrine consumption was lower in terlipressin vs controls (8 vs 12 mg; P=.04). The PPV and HARI were not affected by terlipressin at any stage (P>.05). Postliver transplant AKI was not prevented by terlipressin use nor predicted by NGAL levels.


Retrospective analysis of newly recorded certifications of visual impairment due to diabetic retinopathy in Wales during 2007-2015.
The aim of this study was to analyse the changes in new certifications for both sight impairment (SI) and severe sight impairment (SSI, blindness) in Wales due to diabetic retinopathy (DR)/maculopathy between 2007 and 2015. This is a retrospective analysis of annual data of new certifications for visual impairment and blindness (Certificate of Vision Impairment) for England and Wales derived from the national database provided by the Certifications Office, Moorfields Eye Hospital, over a period of 8 years from 2007. In Wales there were 339 less new certifications for both SI and severe SSI from any cause combined from 2007-2008 to 2014-2015. The number SI and SSI combined specifically due to DR was reduced by 22 in people with known diabetes. This was a reduction in new certifications over the observation period from 82.4 to 46.9 per 100 000 (-43.1%) with a fall in SSI from 31.3 to 15.8 per 100 000 (-49.4%), respectively. During this observation period however, there was a parallel increase in 52 229 (39.8%) persons with diabetes in Wales. While acknowledging the limitations of the certification process and the increasing numbers of persons with diabetes, the incidence of SI and SSI per 100 000 population of persons with diabetes in Wales has almost halved over an 8-year period up to 2015. This may reflect the earlier diagnosis of DR and sight-threatening DR since the introduction of screening and/or improved diabetes management with timely onward referral and newer treatments.