Risk factors for mortality after primary combined valvular and coronary artery surgery.
Risk factors for death after combined valvular and coronary artery bypass graft surgery (CABG) were examined in 141 patients undergoing isolated mitral valve (MV) surgery and CABG (n = 47) or isolated aortic valve (AV) surgery and CABG (n = 94) between January 1, 1986, and January 1, 1988. Actuarial survival was 92% at 1 month and 79% at 1 year. The hazard function for death was highest immediately after operation, had a single phase of decline, and reached a low level only after about 4 months. Risk factors for death included older age at operation, preoperative hemodynamic instability, left main coronary artery disease, ischemic mitral valve disease, important tricuspid valve incompetence, and longer ischemic time. The adverse effect of hemodynamic instability at time of surgery was most pronounced in the elderly (age 70 years or more, 20% 30-day mortality). A favorable risk group includes patients under 70 years of age without left main stenosis, hemodynamic instability, or ischemic mitral valve disease; the 30-day mortality for this subset undergoing isolated valve surgery and CABG is less than 5%. A proper comparison of surgical therapy in differing patient subsets with combined valvular and coronary artery disease should include multivariate analysis in which nondichotomous variables are examined in a continuous manner rather than establishing arbitrary stratifications.


[Limits of ultrasonics in the study of urinary tract malformations].
Ultrasound is limited by the fact it gives no direct information about kidney function. Ultrasound does not allow fine structural analysis of minor calyces. It shows only secondary signs of important vesico-ureteric reflux. Normal ureters are not usually pictured by ultrasound. Bowel gas can impede good visualization of ectopic kidneys. Nevertheless ultrasound is the first test to do when searching for kidney malformations and it is important as a follow-up examination.


High-performance iterative electron tomography reconstruction with long-object compensation using graphics processing units (GPUs).
Iterative reconstruction algorithms pose tremendous computational challenges for 3D Electron Tomography (ET). Similar to X-ray Computed Tomography (CT), graphics processing units (GPUs) offer an affordable platform to meet these demands. In this paper, we outline a CT reconstruction approach for ET that is optimized for the special demands and application setting of ET. It exploits the fact that ET is typically cast as a parallel-beam configuration, which allows the design of an efficient data management scheme, using a holistic sinogram-based representation. Our method produces speedups of about an order of magnitude over a previously proposed GPU-based ET implementation, on similar hardware, and completes an iterative 3D reconstruction of practical problem size within minutes. We also describe a novel GPU-amenable approach that effectively compensates for reconstruction errors resulting from the TEM data acquisition on (long) samples which extend the width of the parallel TEM beam. We show that the vignetting artifacts typically arising at the periphery of non-compensated ET reconstructions are completely eliminated when our method is employed.


The Effects of Number and Separation of Support Lines on the Size, Velocity, and Smoothness of Handwriting.
We examined the effects of number of and separation between support lines on handwriting characteristics of primary school students with satisfactory and unsatisfactory handwriting. Students (mean age 7.9 years) copied a text on paper with a baseline and with two or four support lines with a separation of 3 or 4 mm between the central lines. Handwriting size, velocity, and smoothness were determined for the four conditions relative to baseline. Children with unsatisfactory handwriting wrote larger and had more lifts during baseline condition. Writing between support lines, especially with small separation, immediately reduced the size of handwriting, but also adversely affected velocity and smoothness. Future research is needed to assess long-term effects.


RXR agonists inhibit high glucose-induced upregulation of inflammation by suppressing activation of the NADPH oxidase-nuclear factor-κB pathway in human endothelial cells.
An inflammatory response induced by high glucose is a cause of endothelial dysfunction in diabetes and is an important contributing link to atherosclerosis. Diabetes is an independent risk factor of atherosclerosis and activation of retinoid X receptor (RXR) has been shown to exert anti-atherogenic effects. In the present study, we examined the effects of the RXR ligands 9-cis-retinoic acid (9-cis-RA) and SR11237 on high glucose-induced inflammation in human umbilical endothelial vein endothelial cells (HUVECs) and explored the potential mechanism. Our results showed that the inflammation induced by high-glucose in HUVECs was mainly mediated by the activation of nuclear factor-B (NF- κB). High glucose-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were in comparison, significantly decreased by treatment with RXR. The effect of RXR agonists was mainly due to the inhibition of NF-κB activation. Using pharmacological inhibitors and siRNA, we confirmed that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was an upstream activator of NF-κB. Furthermore, RXR agonists significantly inhibited high glucose-induced activation of NADPH oxidase and significantly decreased the production of reactive oxygen species (ROS). To explore whether the rapid inhibitory effects of RXR agonists were in fact mediated by RXR, we examined the effect of RXR downregulation by RXR siRNA. Our results showed that RXR siRNA largely abrogated the effects of RXR agonists, suggesting the requirement of RXR expression. Therefore, we have shown that RXR is involved in the regulation of NADPH oxidase- NF-κB signal pathway, as the RXR ligands antagonized the inflammatory response in HUVECs induced by high glucose.


Electrophoresis of end-labeled DNA: theory and experiment.
The dynamic behavior of end-labeled DNA during free-solution electrophoresis is investigated using a simple dumbbell model for the labeled DNA. We study the effect of the applied field, label size, and chain stiffness on DNA conformation and electrophoretic mobility. High applied fields are predicted to magnify the size-dependence of mobility and to yield a nonmonotonic dependence of electrophoretic mobility on applied field. The effectiveness of leveraging label size and DNA chain stiffness for improving resolution is also discussed in the context of DNA deformation. To evaluate the most salient model predictions, we use capillary electrophoresis experiments to characterize the size- and field-dependent mobility of dsDNA fragments (300 bp-2 kbp) end-functionalized with streptavidin. Our experimental results are found to be in generally good accord with expectations based on the dumb-bell model. We discuss implications of these findings for fast, size-based separation of DNA in free solution.


CD8 T cell memory development: CD4 T cell help is appreciated.
An important goal of vaccination strategies is to elicit long term, effective immunity. Therefore it is imperative to define the parameters that regulate the development and preservation of the numbers and functional quality of cells that confer this property to the host. CD8 T cells are a key component of the host adaptive immune response that helps eradicate invading viruses and other cell-associated pathogens. Once the primary infection is controlled, the CD8 T cells transition from being effector cells into memory cells that act as sentinels of the immune system capable of rapidly purging the host of recurrent infections by the same pathogen. The factors that regulate and orchestrate this transition from effector CD8 T cells into functionally robust memory CD8 T cells are poorly understood. In recent years it has been determined that CD4 T cells play a vital role in the survival and functional responsiveness of memory CD8 T cells. However, the mechanism(s) of this interaction are still unclear.


Tonometry by Ocular Response Analyzer in Keratoconic and Warpage Eyes in Comparison with Normal Eyes.
To compare intraocular pressure (IOP) values measured by ocular response analyzer (ORA) in contact lens-induced corneal warpage, normal, and keratoconic eyes. In a prospective, observational case-control study, 94 eyes of 47 warpage-suspected cases and 46 eyes of 23 keratoconic patients were enrolled. Warpage-suspected cases were followed until a definite diagnosis was made (warpage, nonwarpage normal, or keratoconus). ORA tonometry and corneal biomechanics testing were performed for all cases in each visit. We had 2-3 measured corneal-compensated IOP (IOPcc) and Goldmann-correlated IOP (IOPg) for each patient (based on group) with at least 2-week interval. After following up of warpage-suspected patients, finally 44 eyes of 22 patients had confirmed soft contact lens-related corneal warpage. Forty-six eyes of 23 people were finally diagnosed as nonwarpage normal eyes. Forty-six eyes of 23 known keratoconus patients were also included for comparison. The demographic and refractive data were not different between the warpage and nonwarpage normal groups but were different in the keratoconus group. Both IOPcc and IOPg were statistically different with the highest value in the warpage group followed by normal and keratoconus groups; the same trend was observed in central corneal thickness (CCT). The mean of IOPg was 14.94 ± 2.65, 13.7 ± 2.33, and 10.86 ± 3 and IOPcc was 15.73 ± 2.4, 15.28 ± 2.43, and 14.08 ± 2.55 in the warpage, normal, and keratoconus groups, respectively. IOPg and IOPcc in the warpage group (based on baseline diagnosis) did not regress to become closer to IOP of normal eyes after discontinuation of contact lens in their follow-up visits (P value for IOPg and IOPcc trends in the warpage group was 0.07 and 0.09 controlling for CCT, respectively). Both IOPcc and IOPg were significantly lower in keratoconic eyes in comparison with normal eyes. After correction for the confounding effect of CCT, a lower IOPcc in keratoconus versus warpage remained significant (P = 0.02). Both IOPcc and IOPg were statistically different with the highest value in the warpage group followed by normal and keratoconus groups, just like their CCT. After correction for the confounding effect of CCT, there was no statistically significant difference between the three groups in their measured IOPcc and IOPg except for IOPcc in keratoconus versus warpage (P = 0.02).


Association of adaptor protein TRIP8b with clathrin.
TPR-containing Rab8b-interacting protein (TRIP8b) is a brain-specific hydrophilic cytosolic protein that contains tetratricopeptide repeats (TPRs). Previous studies revealed interaction of this protein via its TPR-containing domain with Rab8b small GTPase, hyperpolarization-activated cyclic nucleotide-regulated channel (HCN) channels and G protein-coupled receptor calcium-independent receptor of α-latrotoxin. We identified clathrin as a major component of eluates from the TRIP8b affinity matrix. In the present study, by in vitro-binding analysis we demonstrate a direct interaction between clathrin and TRIP8b. The clathrin-binding site was localized in the N-terminal (non-TPR containing) part of the TRIP8b molecule that contains two short motifs involved in the clathrin binding. In transfected HEK293 cells, co-expression of HCN1 with TRIP8b resulted in translocation of the channels from the cell surface to large intracellular puncta where both TRIP8b and clathrin were concentrated. These puncta co-localized partially with an early endosome marker and strongly overlapped with lysosome staining reagent. When HCN1 was co-expressed with a clathrin-non-binding mutant of TRIP8b, clathrin did not translocate to HCN1 and TRIP8b-containing puncta, suggesting that TRIP8b interacts with HCN and clathrin independently. We found TRIP8b present in the fraction of clathrin-coated vesicles purified from brain tissues. Stripping the clathrin coat proteins from the vesicles with Tris alkaline buffer resulted in concomitant release of TRIP8b. Our data suggest complex regulatory functions of TRIP8b in neuronal endocytosis through independent interaction with membrane proteins and components of the clathrin coat.


Use of beta-funaltrexamine to determine mu opioid receptor involvement in the analgesic activity of various opioid ligands.
Systemic administration of beta-funaltrexamine (beta-FNA) 24 hr before analgesic testing produced approximately a 10-fold parallel shift in the dose-response curves of the prototypic mu agonists morphine, I-methadone, fentanyl and etorphine in the mouse abdominal constriction test. In contrast, prior administration of beta-FNA produced no appreciable shift in the analgesic dose-response curve of the selective kappa agonist, U-50, 488H. These results suggest that beta-FNA is selective for mu over kappa receptors under the conditions used in this study. The dose-response curves for ethylketazocine and proxorphan were affected only to a small extent by beta-FNA pretreatment, suggesting that these compounds have analgesic actions mediated primarily through nonmu, probably kappa receptors. The dose-response curves for cyclazocine, buprenorphine, butorphanol, nalorphine and nalbuphine were shifted markedly to the right and frequently not in a parallel fashion by the prior administration of beta-FNA. These results seem to indicate a major role for the mu receptor in the analgesic actions of these compounds.


Prolactin and delayed pseudopregnancy in the rat.
In (RXU)F1 hybrid rats delayed pseudopregnancy was induced in three different ways: 1) by removal of all recent corporl lutea on day 2 of pseudopregnancy, 2) by removal of the in situ ovaries from ovarian graft-bearing animals on day 0 of pseudopregnancy, 3) by administration of 1 mg of ergocornine hydrogenmaleinate (ECO) on day 1 of pseudopregnancy. These procedures ended pseudopregnancy and in 50-60% of the animals a delayed pseudopregnancy with a duration of 6-15 days was observed after the experimental cycle. After sterile copulation two daily prolactin peaks were observed. Removal of the ovaries in situ (from ovarian graft-bearing animals) or of recently formed corpora lutea (from non-grafted animals) caused the disappearance of the prolactin peak at 19.00 h, without affecting the occurrence of the 03.00 h peak. The administration of ECO caused the disappearance of both prolactin peaks. Until the day of estrus prior to delayed pseudopregnancy there were no differences in prolactin concentrations at 03.00 or 19.00 h between animals which became delayed pseudopregnant and those which remained cyclic. In the latter animals the 03.00 h surges decreased slowly in the luteectomized and the ovariectomized animals and were no longer present 7-9 days after copulation. In animals becoming delayed pseudopregnant both prolactin peaks were present from day 0 of delayed pseudopregnancy onwards. Progesterone cencentrations during delayed pseudopregnancy were relatively low when delayed pseudopregnancy had a duration of 6-9 days. When delayed pseudopregnancy lasted 10 days or more normal progesterone values were found.


Oral cancer risk factors in New Zealand.
Oral cancer constitutes the majority of head and neck cancers, which are the fifth most common malignancy worldwide, accounting for an estimated 984,430 cases in 2012. Between 2000 and 2010, there were 1,916 cases of OSCC in New Zealand with a male to female ratio of 1.85:1, and an age-standardised incidence rate of 42 persons per 1,000,000 population. This article presents an overview of the main risk factors for oral and oropharyngeal cancers and their prevalence in New Zealand. Alcohol consumption is the most prevalent risk factor in New Zealand, followed by tobacco. Given the high prevalence of these two risk factors and their synergistic effect, it is important for doctors and dentists to encourage smoking cessation in smokers and to recommend judicious alcohol intake. Research is needed to determine the prevalence of use of oral preparations of tobacco and water-pipe smoking in New Zealand, especially due to changing demography and increases in migrant populations. UV radiation is also an important risk factor. Further investigations are also needed to determine the prevalence of oral and oropharyngeal cancers attributable to oncogenic HPV infection.


First synthesis and anticancer activity of phosmidosine and its related compounds.
This paper describes the first synthesis of phosmidosine and phosmidosine B, i.e., nucleotide antibiotics composed of 8-oxoadenosine and L-proline which are connected via a unique N-acyl phosphoramidate linkage. Phosmidosine has a yet-undetermined chiral center at the phosphorus atom of the N-acyl phosphoramidate linkage. Phosmidosine B is a demethylated phosmidosine derivative with no chirality on the phosphorus. Phosmidosine B was successfully synthesized by the reaction of an N-acetyl-8-oxoadenosine 5'-O-phosphoramidite derivative with an N-protected prolinamide in the presence of 5-(3,5-dinitrophenyl)-1H-tetrazole. The successful synthesis of phosmidosine was achieved by use of a tert-butoxycarbonyl (Boc) group, which was found to be selectively introduced into the 7-NH function of 8-oxoadenosine and to serve as a pseudo-protecting group due to its steric effect in such manner that the unmasked 6-amino group was not phosphitylated. Final coupling reaction of the 8-oxoadenosine 5'-phosphoramidite derivative with N-tritylprolinamide followed by full deprotection gave a mixture of phosmidosine and its diastereoisomer. The (13)C NMR spectra of the diastereomers suggest that the slow-eluted diastereomer 1b is the naturally occurring phosmidosine. The growth inhibitory activity of phosmidosine 1b, its diastereomer 1a, and phosmidosine B in various tumor cell lines was evaluated by the MTT assay. As the result, phosmidosine B showed high anticancer activities and both the diastereomers 1a and 1b of phosmidosine isolated were found to have similar but approximately 10 times higher anticancer activities than phosmidosine B. Moreover, it turned out that these phosmidosine derivatives showed characteristic inhibitory activities against cancer cells independent of their p53 phenotypes. These results suggest that phosmidosine and its related compounds would be promising as a new type of anticancer agents having a wide range of inhibitory activities against tumor cells.


Beyond classical derivatization: analyte 'derivatives' in the bioanalysis of endogenous and exogenous compounds.
The analysis of endogenous and exogenous analytes in biological matrices presents several challenges to the bioanalyst. These analytes are often present at low concentrations, typically in complex matrices, and may have physicochemical properties that are not amenable to LC-MS analysis. The bioanalyst thus relies heavily on the formation of analyte derivatives for the efficient quantification of these compounds. These derivatives are also critically employed to derive information on the biology of living systems, potential drug or disease targets, and biomarkers of drug efficacy, safety, or disease progression. In this perspective, we demonstrate how analyte derivatives are applied in modern bioanalytical workflows and we discuss the potential use of these derivatives in the future.


Analysis of load distribution in tooth-implant supported fixed partial dentures by the use of resilient abutment.
Differences between the tooth and implant response to load can lead to many biological and technical implications in the conditions of occlusal forces. The objective of this study was to analyze load distribution in tooth/implant-supported fixed partial dentures with the use of resilient TSA (Titan Shock Absorber, BoneCare GmbH, Augsburg, Germany) abutment and conventional non-resilient abutment using finite element method. This study presents two basic 3D models. For one model a standard non-resilient abutment is used, and on the implant of the second model a resilient TSA abutment is applied. The virtual model contains drawn contours of tooth, mucous membranes, implant, cortical bones and spongiosa, abutment and suprastructure. The experiment used 500 N of vertical force, applied in three different cases of axial load. Calculations of von Mises equivalent stresses of the tooth root and periodontium, implants and peri-implant tissue were made. For the model to which a non-resilient abutment is applied, maximum stress values in all three cases are observed in the cortical part of the bone (maximum stress value of 49.7 MPa). Measurements of stress and deformation in the bone tissue in the model with application of the resilientTSA abutment demonstrated similar distribution; however, these values are many times lower than in the model with non-resilient TSA abutment (maximum stress value of 28.9 MPa). Application of the resilient TSA abutment results in more equal distribution of stress and deformations in the bone tissue under vertical forces. These values are many times lower than in the model with the non-resilient abutment.


Burnout among healthcare providers: Its prevalence and association with anxiety and depression during the COVID-19 pandemic in Macao, China.
Burnout in healthcare providers (HPs) might lead to negative consequences at personal, patient-care and healthcare system levels especially during the COVID-19 pandemic. This study aimed to investigate the prevalence of burnout and the contributing variables, and to explore how, from health workforce management perspective, HPs' experiences related to carrying out COVID-19 duties would be associated with their burnout. A cross-sectional, open online survey, informed by physical and psychological attributes reportedly related to burnout, the Copenhagen Burnout Inventory (CBI) and the Hospital Anxiety and Depression Scale (HADS), was completed by HPs in Macau, China during October and December 2021. Factors associated with burnout were analysed using multiple logistic regressions. Among the 498 valid responses, the participants included doctors (37.5%), nurses (27.1%), medical laboratory technologist (11.4%) and pharmacy professionals (10.8%), with the majority being female (66.1%), aged between 25-44years (66.0%), and participated in the COVID-19 duties (82.9%). High levels of burnout (personal (60.4%), work-related (50.6%) and client-related (31.5%)), anxiety (60.6%), and depression (63.4%) were identified. Anxiety and depression remained significantly and positively associated with all types of burnout after controlling for the strong effects of demographic and work factors (e.g. working in the public sector or hospital, or having COVID-19 duties). HPs participated in COVID-19 duties were more vulnerable to burnout than their counterparts and were mostly dissatisfied with the accessibility of psychological support at workplace (62.6%), workforce distribution for COVID-19 duties (50.0%), ability to rest and recover (46.2%), and remuneration (44.7%), all of which were associated with the occurrence of burnout. Personal, professional and health management factors were found attributable to the burnout experienced by HPs during the COVID-19 pandemic, requiring actions from individual and organizational level. Longitudinal studies are needed to monitor the trend of burnout and to inform effective strategies of this occupational phenomenon.


[Analysis of Nucleotide Changes in RT-PCR Primer/Probe Binding Regions in SARS-CoV-2 Isolates Reported from Turkey].
The SARS-CoV-2 virus, which caused the COVID-19 epidemic, caused more than 55 million cases and nearly 1.5 million deaths worldwide. For the microbiological diagnosis of the disease, the most valid method is detecting the presence of the viral genome by real-time reverse transcription polymerase chain reaction (rRT-PCR). However, due to the nature of the RNA viruses, frequent mutations may affect the sensitivity of the analyses made on the genetic material of the virus, such as PCR. In this study, we aimed to investigate the mutations in the primer-probe binding regions of the rRT-PCR panels used in COVID-19 diagnosis. SARS-CoV-2 whole genome sequence data (n= 194) isolated from COVID-19 cases in Turkey and uploaded on GISAID database from the centers in İstanbul (n= 78), Ankara (n= 58), Kars (n= 47), Bursa (n= 2), Adıyaman (n= 2), Erciyes (n= 1) and Kocaeli (n= 1) between March 17-September 14, 2020 were analyzed. In order to determine the nucleotide changes, SARS-CoV-2 sequences from Turkey were compared to the reference genome sequence (NC_045512.1) present in "GenBank" website. The constructed data set was aligned using the MAFFT program and was checked manually if the sequences were in the same frame by using the AliView program. Primer-probe binding sites of the thirteen SARS-CoV-2 rRT-PCR panels from seven different institutes (US CDC, China CDC, Charite CDC, Pasteur, HKU, Thailand, NIID) that are being used in COVID-19 diagnosis were evaluated in terms of nucleotide changes within the corresponding regions compared to the reference genome. Sequence diversities in the viral genomes were determined via positional nucleotide numerical calculator and entropy calculator modules and nucleotide and entropy changes in primer-probe binding regions for each rRT-PCR panel were examined. Among thirteen different primer-probe panels, nucleotide changes in the target regions of the seven primer-probe panels were determined. When viral sequences with nucleotide changes in the primer-probe binding regions were examined, the most common changes were observed in the "China CDC" N-forward primer and "US CDC" N3-forward primer binding regions. It is important that the kits to be used as diagnostic tests are designed specific to the regions with less nucleotide changes. Nucleotide changes may not be critical for DNA amplification for most PCR panels, but should be carefully monitored as they may affect the sensitivity of the assay. If the risk of alteration of the designed region is high, the primer - probe binding sites should be checked frequently and updated when necessary.


Inhibition of soluble epoxide hydrolase activity by compounds isolated from the aerial parts of Glycosmis stenocarpa.
The aim of this study is to search for soluble epoxide hydrolase (sEH) inhibitors from natural plants, bioassay-guided fractionation of lipophilic n-hexane and chloroform layers of an extract of the aerial parts of Glycosmis stenocarpa led to the isolation of 12 compounds (1-12) including murrayafoline-A (1), isomahanine (2), bisisomahanine (3), saropeptate (4), (24 S)-ergost-4-en-3,6-dione (5), stigmasta-4-en-3,6-dion (6), stigmast-4-en-3-one (7), β-sitosterol (8), 24-methylpollinastanol (9), trans-phytol (10), neosarmentol III (11) and (+)-epiloliolide (12). Their structures were elucidated on the basis of spectroscopic data. Among them, neosarmentol III (11) was isolated from nature for the first time. All the isolated compounds were evaluated for their inhibitory activity against sEH. Among isolated carbazole-type compounds, isomahanine (2) and bisisomahanine (3) were identified as a potent inhibitor of sEH, with IC50 values of 22.5 ± 1.7 and 7.7 ± 1.2 µM, respectively. Moreover, the inhibitory action of 2 and 3 represented mixed-type enzyme inhibition.


Spectrum of adrenal lesions on fine needle aspiration cytology.
Fine needle aspiration (FNA) cytology of adrenal gland is not a commonly performed technique and is limited primarily to tertiary care centers. However, it is a sensitive and specific procedure in the workup of patients with adrenal gland's mass lesions. Though cytomorphological features for various lesions have been described, there are a limited number of studies in cytologic literature. We report our 7 years of experience in FNAC of adrenal lesions. We have not only described the cytomorphological details of different lesions, but also tried to discuss the various diagnostic difficulties encountered during reporting of adrenal fine needle aspirations. All ultrasound-guided percutaneous aspirations of adrenal gland received in the department between the years 2002 and 2009 were reviewed. There were a total of 52 FNA samples of adrenal masses from 35 patients in 7 years. The lesions were categorized as non-neoplastic and neoplastic categories. Neoplastic lesions were further divided into benign and malignant lesions. In our study, FNA proved to be 100% specific for diagnosing malignant lesions. The overall inadequacy rate was 11.4% with no major complications of the procedure. A wide variety of non-neoplastic as well as neoplastic lesions were identified.


Synthesis, Structure, and Physicochemical Characteristics of Zn1-xRexCr2Se4 Single Crystals.
This study aimed to obtain and investigate ZnCr2Se4 single crystals doped with rhenium. The single crystals were obtained by applying chemical vapour transport. An X-ray study confirmed the cubic (Fd3¯m) structure of the tested crystals. Thermal, magnetic, electrical, and specific heat measurements accurately determined the physicochemical characteristics, which revealed that the obtained single crystals are p-type semiconductors with antiferromagnetic order below the Néel temperature TN = 21.7 K. The Debye temperature had a value of 295 K. The substitution of Re-paramagnetic ions, possessing a screened 5d-shell, in place of Zn-diamagnetic ions, caused an increase in the activation energy, Fermi energy, and Fermi temperature compared to the pure ZnCr2Se4. The boost of the dc magnetic field induced a shift of TN towards lower temperatures and a spin fluctuation peak visible at Hdc = 40 and 50 kOe. The obtained single crystals are thermally stable up to 1100 °C.


Analyzing cell mechanics in hematologic diseases with microfluidic biophysical flow cytometry.
Pathological processes in hematologic diseases originate at the single-cell level, often making measurements on individual cells more clinically relevant than population averages from bulk analysis. For this reason, flow cytometry has been an effective tool for single-cell analysis of properties using light scattering and fluorescence labeling. However, conventional flow cytometry cannot measure cell mechanical properties, alterations of which contribute to the pathophysiology of hematologic diseases such as sepsis, diabetic retinopathy, and sickle cell anemia. Here we present a high-throughput microfluidics-based 'biophysical' flow cytometry technique that measures single-cell transit times of blood cell populations passing through in vitro capillary networks. To demonstrate clinical relevance, we use this technique to characterize biophysical changes in two model disease states in which mechanical properties of cells are thought to lead to microvascular obstruction: (i) sepsis, a process in which inflammatory mediators in the bloodstream activate neutrophils and (ii) leukostasis, an often fatal and poorly understood complication of acute leukemia. Using patient samples, we show that cell transit time through and occlusion of microfluidic channels is increased for both disease states compared to control samples, and we find that mechanical heterogeneity of blood cell populations is a better predictor of microvascular obstruction than average properties. Inflammatory mediators involved in sepsis were observed to significantly affect the shape and magnitude of the neutrophil transit time population distribution. Altered properties of leukemia cell subpopulations, rather than of the population as a whole, were found to correlate with symptoms of leukostasis in patients-a new result that may be useful for guiding leukemia therapy. By treating cells with drugs that affect the cytoskeleton, we also demonstrate that their transit times could be significantly reduced. Biophysical flow cytometry offers a low-cost and high-throughput diagnostic and drug discovery platform for hematologic diseases that affect microcirculatory flow.


[A new allele variant of ssa and its participation in regulating the proliferation of the stem elements of the leg and antenna imaginal disks in Drosophila melanogaster].
Using a highly mutable FM/w oc system, we have established a new allele of ssa40aSc mutation whose phenotype is identical to ssa40aNs compound described in the literature. The following features are characteristic of the ssa40aSc flies phenotype: (1) the increased number of sex comb teeth, (2) complete fusion of tarsal segments, and (3) the decreased bristle size corresponding to that of ss flies. The first two features are evidence for the impaired stem cell proliferation in the antennal and leg imaginal discs which are determined to form distal structures. This assumption was experimentally confirmed when we transplanted leg imaginal discs from III instar larvae of different age into prepupae. The observed phenomenon is probably due to the defects of the Antp and Pc translation products binding site in the ss locus.


Bayesian Phylogeography and Pathogenic Characterization of Smallpox Based on HA, ATI, and CrmB Genes.
Variola virus is at risk of re-emergence either through accidental release, bioterrorism, or synthetic biology. The use of phylogenetics and phylogeography to support epidemic field response is expected to grow as sequencing technology becomes miniaturized, cheap, and ubiquitous. In this study, we aimed to explore the use of common VARV diagnostic targets hemagglutinin (HA), cytokine response modifier B (CrmB), and A-type inclusion protein (ATI) for phylogenetic characterization as well as the representativeness of modelling strategies in phylogeography to support epidemic response should smallpox re-emerge. We used Bayesian discrete-trait phylogeography using the most complete data set currently available of whole genome (n = 51) and partially sequenced (n = 20) VARV isolates. We show that multilocus models combining HA, ATI, and CrmB genes may represent a useful heuristic to differentiate between VARV Major and subclades of VARV Minor which have been associated with variable case-fatality rates. Where whole genome sequencing is unavailable, phylogeography models of HA, ATI, and CrmB may provide preliminary but uncertain estimates of transmission, while supplementing whole genome models with additional isolates sequenced only for HA can improve sample representativeness, maintaining similar support for transmission relative to whole genome models. We have also provided empirical evidence delineating historic international VARV transmission using phylogeography. Due to the persistent threat of re-emergence, our results provide important research for smallpox epidemic preparedness in the posteradication era as recommended by the World Health Organisation.


Efficacy and safety of a readjustable midurethral sling (Remeex system) for stress urinary incontinence with female voiding dysfunction.
We investigated the efficacy and safety of a readjustable midurethral sling (Remeex system) for stress urinary incontinence with female voiding dysfunction. From May 2007 to December 2015, 151 women received the Remeex system. We excluded patients who presented with pelvic organ prolapse and/or who missed the regular follow-up. Finally, 102 patients were included in the study, and we divided them into 2 groups: group A (n=74), who did not present with female voiding dysfunction and group B (n=28), who presented with female voiding dysfunction. Female voiding dysfunction was defined as a maximal flow rate≤12 mL/s when the voided volume was ≥150 mL on preoperative uroflowmetry. We retrospectively reviewed the patients' medical records and compared surgical outcomes between groups A and B. There were no significant differences in subjective surgical outcomes and patient satisfaction between the 2 groups. Postoperative uroflowmetry showed that the maximal flow rate and voided volume decreased and the postvoid residual urine volume increased in both groups, and these changes were not significantly different between groups. The overall complication rate was 21.6% (22 of 102), and the complication rate was not significantly different between the 2 groups according to the modified Clavien-Dindo classification. The Remeex system is efficacious and safe for stress urinary incontinence with female voiding dysfunction.


Active Tuberculosis Case Finding in Haiti.
In 2010, Haiti suffered from a devastating earthquake; data on the impact on the tuberculosis (TB) epidemic are limited. From January to June 2013, we conducted active case finding at the household level in a slum in Port-au-Prince. Community health workers identified individuals with cough ≥ 2 weeks, and referred them for evaluation. Contact tracing was conducted for patients with active TB. Of an estimated 7,500 residents screened, 394 (5%) had cough and were tested for TB. One hundred (25%) were diagnosed with active TB; 53 (53%) were smear positive. Ninety of these TB index cases provided 317 contacts, and 44 (14%) were diagnosed with active TB; 17 (39%) were smear positive. Overall, 144 TB cases were detected in 6 months (1,920/100,000; national estimate 200/100,000). We found a high burden of undiagnosed TB in Port-au-Prince 3 years after the earthquake. Further assessment of the burden of TB is indicated.


Immunohistochemical localization of the metalloproteinase meprin in salivary glands of male and female mice.
Meprin is a membrane-bound metalloproteinase which is expressed at high levels in the brush border membrane of proximal tubules of kidneys of some mouse strains (referred to as high meprin-activity mice). The mature active proteinase is not present in kidneys of many inbred strains of mice; however, these low meprin-activity mice possess a kidney protein that crossreacts with polyclonal antibodies prepared against meprin. In the present studies, immunohistochemical methods were used to determine the presence of meprin in liver, pancreas, spleen, testis, thymus, kidney, salivary glands, stomach, duodenum, and skin. Meprin crossreactivity was observed only in kidney and salivary glands. In salivary glands, the enzyme was found on the luminal surface of intercalated and striated ducts of submandibular and parotid glands and on interlobular ducts of the latter. In both kidney and salivary glands, the intensity of immunochemical staining was greater in males compared with females. For both sexes, immunoreactivity was markedly greater in the high meprin-activity mice compared to the low meprin-activity mice. These studies indicate that meprin has a limited tissue distribution, and that genetic and hormonal factors that regulate the proteinase are similar in kidney and salivary glands. The localization of the proteinase implies that the enzyme functions in modifying proteins and peptides that are secreted or re-absorbed in the ducts of these tissues.


Self-management for bipolar disorder and the construction of the ethical self.
The promotion of the self-managing capacities of people has become a marker of contemporary mental health practice, yet self-management remains a largely uncontested construct in mental health settings. This discourse analysis based upon the work of Foucault investigates self-management practices for bipolar disorder and their action upon how a person with bipolar disorder comes to think of who they are and how they should live. Using Foucault's framework for exploring the ethical self and transcripts of interviews with people living with bipolar disorder, this discourse analysis finds that the discursive practices of self-management for bipolar disorder are prescribing a restricted regime for living based upon the quintessential neo-liberal subject using practices that are focused upon managing an unreliable and problematic self. The article concludes with the proposition that the problem of bipolar disorder (for which self-management is an answer) is less about the object itself and more about how we construct the nature of the self. A Māori indigenous ontology is used here as an example of an alternative discursive resource through which people make sense of the self and which allows ways of thinking about self-management that engage with ambivalence and ambiguity rather than restriction and regulation.


The public hospital mission at Seattle's Harborview Medical Center: high-quality care for the underserved and excellence in medical education.
United States public hospitals and medical schools commonly enter into partnerships that serve the patient care, education, and research missions of both institutions. Harborview Medical Center, the county hospital in Seattle, Washington, and the University of Washington School of Medicine (UWSOM) have enjoyed a long affiliation that began at the medical school's founding 60 years ago. A formal agreement in 1967 turned over responsibility for all Harborview operations to UWSOM at a time when Harborview's facilities had fallen into serious disrepair and public hospitals were closing across the United States. All faculty and staff based at Harborview are employed by the University of Washington. By the mid-1970s a revitalization was underway at Harborview. The Medic One paramedic program drew national acclaim for pioneering prehospital emergency cardiac care, and the trauma and burn centers grew rapidly to meet specialized intensive care needs of the Pacific Northwest. Today, the success of the trauma, specialty surgery, and rehabilitation services have allowed Harborview to consistently maintain a positive operating margin while caring for the county's uninsured and indigent patients ($98 million in charity care in 2005). The hospital also offers nationally recognized residency programs and supports nationally and internationally acclaimed research. Harborview faces significant challenges for the future, including rapid growth of the indigent patient load, continually changing expectations for physician training, and growing cost pressures.


Assessing radiation exposure during endoscopic-guided percutaneous nephrolithotomy.
Percutaneous nephrolithotomy (PCNL) may be associated with significant ionizing radiation exposure for patients and operating room staff. Endoscopic-guided PCNL (ePCNL) is a technique that may be associated with less radiation exposure. This study examines ePCNL-related radiation exposure (fluoroscopy time, effective dose) and investigates variables that may predict increased exposure. A retrospective review of all consecutive ePCNLs performed at our institution, by a single surgeon, was conducted between November 2011 and November 2013. Patient demographics, stone characteristics and perioperative details were recorded, including radiation exposure. Pearson and Spearman correlation were used to assess variables correlated with radiation exposure. In total, 55 ePCNL cases were included in the study. The mean age was 60 ± 15 years, mean body mass index (BMI) 30.0 ± 6.4 kg/m(2) and mean stone size 3.2 × 2.1 cm. Seven cases (13%) involved complete staghorn stones, and 69% involved supracostal punctures. The mean fluoroscopy time was 3.4 ± 2.3 minutes, mean ED 2.4 ± 1.9 mSv. The treatment success rate, assessed 1-week postoperatively, was 87.3% and 7.3% of cases required ancillary procedures. The overall complication rate was 29%, but only 3 cases (5.5%) were Clavien ≥3. Longer fluoroscopy time correlated with increased stone size (p < 0.01), longer operative time (p < 0.01) and lower treatment success rates (p < 0.01); higher effective dose correlated with longer fluoroscopy time (p < 0.01) and increased skin-to-stone distance (p < 0.01). BMI did not correlate with fluoroscopy time or effective dose. Outcomes of ePCNL are comparable to traditional PCNL techniques and may be associated with lower radiation exposure, particularly beneficial for patients with higher BMI.


Metabolic enzyme PDK3 forms a positive feedback loop with transcription factor HSF1 to drive chemoresistance.
Background & Aims: Dysregulation of metabolism plays an important role in the development and progression of cancers, while the underlying mechanisms remain largely unknown. This study aims to explore the regulation and relevance of glycolysis in chemoresistance of gastric cancer. Methods: Biochemical differences between chemoresistant and chemosensitive cancer cells were determined by metabolism profiling, microarray gene expression, PCR or western blotting. Cancer cell growth in vitro or in vivo were analyzed by viability, apoptosis and nude mice assay. Immunoprecipation was used to explore the interaction of proteins with other proteins or DNAs. Results: By metabolic and gene expression profiling, we found that pyruvate dehydrogenase kinase 3 (PDK3) was highly expressed to promote glycolysis in chemoresistant cancer cells. Its genetic or chemical inhibition reverted chemoresistance in vitro and in vivo. It was transcriptionally regulated by transcription factor HSF1 (Heat shock factor 1). Interestingly, PDK3 can localize in the nucleus and interact with HSF1 to disrupt its phosphorylation by GSK3β. Since HSF1 was subjected to FBXW7-catalyzed polyubiquitination in a phosphorylation-dependent manner, PDK3 prevented HSF1 from proteasomal degradation. Thus, metabolic enzyme PDK3 and transcription factor HSF1 forms a positive feedback loop to promote glycolysis. As a result, inhibition of HSF1 impaired enhanced glycolysis and reverted chemoresistance both in vitro and in vivo. Conclusions: PDK3 forms a positive feedback loop with HSF1 to drive glycolysis in chemoresistance. Targeting this mitonuclear communication may represent a novel approach to overcome chemoresistance.


Lactobacilli, a Weapon to Counteract Pathogens through the Inhibition of Their Virulence Factors.
To date, several studies have reported an alarming increase in pathogen resistance to current antibiotic therapies and treatments. Therefore, the search for effective alternatives to counter their spread and the onset of infections is becoming increasingly important. In this regard, microorganisms of the former Lactobacillus genus have demonstrated the ability to reduce the virulence of pathogens. In addition to the production of bioactive substances, self- and coaggregation, and substrate competition, lactobacilli influence gene expression by downregulating genes associated with the virulence of pathogens. As demonstrated in many in vivo and in vitro trials, lactobacilli counteract and inhibit various virulence factors that favor pathogens, including the production of toxins, biofilm formation, host cell adhesion and invasion, and downregulation of virulence genes linked to quorum sensing. The aim of this review is to summarize current studies on the inhibition of pathogen virulence by lactobacilli, an important microbial group well known in the industrial and medical fields for their technological and probiotic properties that benefit human hosts with the potential to provide an important aid in the fight against pathogens besides use of the current therapies. Further research could lead to the identification of new strains that, in addition to alleviating adverse effects, could improve the efficacy of antibiotic therapies or play an important preventive role by reducing the onset of pathogen infections if regularly taken.


Quality appraisal of existing guidelines for the management of headache disorders by the AGREE II's method.
To evaluate the quality of existing clinical practice guidelines for headache management and their main recommendations. Evidence-based clinical practice guidelines have been developed to support the clinical decision-making. However, to achieve this goal, the quality of these guidelines must be ensured. A systematic search for clinical practice guidelines for headache management was conducted in the PubMed database, in websites of known guideline developers and in websites of known headache associations. The quality appraisal was performed through the Appraisal of Guidelines for Research and Evaluation II method. Twelve guidelines were evaluated. The domains of rigor of development, applicability, and editorial independence, which most influence the overall quality of guidelines, had the lowest average scores and the highest standard deviation rates (61% ± 23; 37% ± 20; 53% ± 31). The main recommendations regarding medication use for acute treatment of episodic tension-type headache and migraine in adult patients consisted of paracetamol, acetylsalicylic acid, and other nonsteroidal anti-inflammatory drugs in all guidelines. The statistical results indicate that the appraised guidelines have room for both individual and collective improvement. In addition, there is a well-established medication recommendation pattern among all guidelines evaluated.


Interventions combining motivational interviewing and cognitive behaviour to promote medication adherence: a literature review.
This article presents an integrative review of the evidence for combined motivational interviewing and cognitive behavioural interventions that promote medication adherence. We undertook this review to establish a scientific foundation for development of interventions to promote medication adherence and to guide clinical practice. The World Health Organization has designated medication adherence as a global problem. Motivational interviewing and cognitive behaviour interventions have been found to individually promote medication adherence. However, there is a gap in the literature on the effect of combined motivational interviewing and cognitive behavioural approaches to promote medication adherence. Integrative review. COCHRANE, PubMed and CINAHL were searched to access relevant studies between 2004-2014. Inclusion criteria were interventions combining motivational interviewing and cognitive behavioural therapy with medication adherence as the outcome. Articles were assessed for measures of adherence and methodological rigour. Analysis was performed using an integrative review process. Six articles met the inclusion criteria. A randomised controlled trial reported pretreatment missed doses of 5·58 and post-treatment of 0·92 and trended towards significance. Four cohort studies had effect sizes of 0·19-0·35 (p < 0·05). A case study had a pretreatment adherence rate of 25% and post-treatment 77% (p < 0·01). Although there were a limited number of studies on combined motivational interviewing and cognitive behavioural interventions, five out of six were effective at improving medication adherence. Future studies with large rigorous randomised trials are needed. This review provides clinicians with the state of the science in relation to combined motivational interviewing and cognitive behavioural therapy interventions that promote medication adherence. A summary of intervention components and talking points are provided to aid nurses in informing decision-making and translating evidence into practice.


The effect of reducing the fine-particle mass of salmeterol from metered-dose inhalers on bronchodilatation and bronchoprotection against methacholine challenge: a randomized, placebo-controlled, double-blind, crossover study.
This study examined the clinical relevance of fine-particle mass (FPM) delivered from metered dose inhalers (MDIs) to bronchodilatation and bronchoprotection against methacholine challenge by comparing a marketed chlorofluorocarbon (CFC) formulation of salmeterol with an investigational hydrofluoroalkane (HFA)formulation. This was a randomized, double-blind, placebo-controlled, 3-way crossover study in patients with mild to moderate asthma who had a forced expiratory volume in 1 second (FEV (1)) of > or =60% predicted and a base-line provocation dose of inhaled methacholine required to produce a 20% decrease in FEV(1) (PD (20) [methacholine]) of < or =3.2 mg. On separate occasions, patients received 2 inhalations of salmeterol 25 microg from either the CFC MDI (FPM 14 microg), the investigational HFA MDI (FPM 7 microg), or placebo via CFC MDI. Serial measurements of FEV(1) were made over 90 minutes after dosing, followed by methacholine challenge. Efficacy end points were PD(20) (methacholine) and FEV(1) AUC (inc) (incremental area under the FEV(1) curve) over 15 to 90 minutes. The study was designed to demonstrate non-inferiority of the investigational HFA formulation to the CFC formulation in terms of protection against methacholine-induced bronchial hyperresponsiveness; for PD(20) (methacholine), noninferiority was predefined as 1.0 doubling dose of methacholine. The study enrolled 40 patients (65% men; mean age, 36.9 years). Both active treatments were significantly better than placebo in terms of PD(20) (methacholine) (P < 0.001). In the per-protocol population, the mean (SE) difference in bronchoprotection between the CFC MDI and placebo was 2.7888 (0.3432) doubling doses of methacholine (n = 32), and the difference between the investigational HFA MDI and placebo was 1.8268 (0.3418) doubling doses(n = 33). The adjusted mean (SE) treatment difference between the CFC MDI and HFA MDI was 0.9621 (0.3454) doubling doses. The upperlimit of the 95% CI (0.2714-1.6527) was greater than the predefined limit for noninferiority. There was no significant difference in FEV(1) AUC(inc) between formulations (mean treatment difference, 1.895 L . min; 95% CI, -4.893 to 8.684); however, both active treatments were significantly different from placebo (P < 0.001). FPM from different MDI formulations may affect the bronchoprotective properties of salmeterol. In this study, the formulation with the smaller FPM was associated with less-effective bronchoprotection, although there was no difference in bronchodilatation. This study did not demonstrate noninferiority of the investigational HFA formulation to the CFC formulation in terms of protection against methacholine-induced bronchial hyperresponsiveness.


Psoriasis of the dorsal surface of the tongue.
Psoriasis is primarily an inherited inflammatory skin disease, it is characterized by erythemato-squamous lesions that usually involve elbows, knees and the scalp. Oral manifestations are rare in psoriasis, infact, oral psoriasis involves 2% of psoriatic patients and usually it is observed with the onset of cutaneous lesions and progresses with them. Differential diagnosis should be done for Reiter's syndrome, leukoplakia and geographic tongue. The authors describe a case of tongue psoriasis without cutaneous lesions.


The correlation between HER-2 expression and the CEUS and ARFI characteristics of breast cancer.
The purpose of the present study was to explore the correlation between the contrast-enhanced ultrasound (CEUS) and acoustic radiation force impulse (ARFI) characteristics of breast cancers and the expression of human epidermal growth factor receptor 2 (HER-2). HER-2 expression levels in the tumor masses of 167 clearly diagnosed cases of breast cancer were measured and analyzed. The enhancement features and time intensity curve (TIC) of CEUS and virtual touch tissue imaging (VTI) and virtual touch tissue quantification (VTQ) technology of ARFI were employed to analyze the relationship between HER-2 expression and the CEUS and ARFI characteristics of breast cancer. (1) Statistically significant differences in the distribution of the contrast agent, perforator blood flow, the overranging phenomenon and perfusion defects between the study groups with different HER-2 expression levels (P < 0.05) were observed on CEUS. In addition, statistically significant differences in the TIC peak time (PT), slope of the ascending branch (K) and area under the curve (AUC) were found in the groups expressing different levels of HER-2 (P < 0.05). In contrast, the degree of contrast agent enhancement and TIC peak intensity (PI) were found to be independent of the expression status of HER-2, as they were not statistically significant (P > 0.05). (2) Statistically significant differences in the VTQ results between the groups with different HER-2 expression levels were found (P < 0.05). However, no statistically significant differences in VTI image characteristics were detected between the groups expressing different levels of HER-2 (P > 0.05). A correlation was found between the CEUS and ARFI characteristics of breast cancer and HER-2 expression levels. This correlation was principally reflected in perfusion defects, perforator blood flow, PI, PT, K and VTQ.


Aerobic and Resistance Training Attenuate Differently Knee Joint Damage Caused by a High-Fat-High-Sucrose Diet in a Rat Model.
Obesity and associated low-level local systemic inflammation have been linked to an increased rate of developing knee osteoarthritis (OA). Aerobic exercise has been shown to protect the knee from obesity-induced joint damage. The aims of this study were to determine (1) if resistance training provides beneficial metabolic effects similar to those previously observed with aerobic training in rats consuming a high-fat/high-sucrose (HFS) diet and (2) if these metabolic effects mitigate knee OA in a diet-induced obesity model in rats. Twelve-week-old Sprague-Dawley rats were randomized into 4 groups: (1) a group fed an HFS diet subjected to aerobic exercise (HFS+Aer), (2) a group fed an HFS diet subjected to resistance exercise (HFS+Res), (3) a group fed an HFS diet with no exercise (HFS+Sed), and (4) a chow-fed sedentary control group (Chow+Sed). HFS+Sed animals were heavier and had greater body fat, higher levels of triglycerides and total cholesterol, and more joint damage than Chow+Sed animals. The HFS+Res group had higher body mass and body fat than Chow+Sed animals and higher OA scores than animals from the HFS+Aer group. Severe bone lesions were observed in the HFS+Sed and Chow+Sed animals at age 24 weeks, but not in the HFS+Res and HFS+Aer group animals. In summary, aerobic training provided better protection against knee joint OA than resistance training in this rat model of HFS-diet-induced obesity. Exposing rats to exercise, either aerobic or resistance training, had a protective effect against the severe bone lesions observed in the nonexercised rats.


Insulin resistance and pancreatic beta-cell function in patients with hypertensive kidney disease.
Insulin resistance and hyperinsulinaemia have been reported among patients with chronic renal failure. However, little is known concerning insulin sensitivity among patients with hypertensive kidney disease (HKD), especially in those with moderate or severe renal dysfunction. We examined and compared 30 patients with HKD, 30 normotensive patients with chronic kidney disease (CKD-NT), 30 normal controls and 30 patients with hypertension and normal renal function (HTN). Moderate and severe renal dysfunction were defined according to the K/DOQI definitions (estimated glomerular filtration rates between 15 and 59 ml/min per 1.73 m(2)). The homeostasis model assessment of insulin resistance (HOMA-R) and three surrogate indexes based on 75 g oral glucose tolerance test results were used to determine insulin sensitivity. A trend to higher HOMA-R values in the HTN and HKD groups than in the other groups was noted, but the difference was not statistically significant. The insulin sensitivity index (ISI) proposed by Stumvoll et al. was significantly lower in the HTN, HKD and CKD-NT groups than in controls and was significantly lower in HKD than in the HTN and CKD-NT groups. The insulin sensitivity index proposed by Gutt et al. was significantly lower in HKD than in the control and HTN groups and showed a trend to being lower in HKD than in CKD-NT. The same patterns prevailed in the oral glucose ISI. We assumed that subjects whose ISI values decreased below the mean value minus 2-SD in the control group manifest apparent insulin resistance. According to this criterion, approximately 40% of HKD subjects were in an insulin-resistant state: only <10% of HTN subjects and approximately 10-30% of CKD-NT subjects were insulin resistant. HKD with moderate to severe renal dysfunction is associated with insulin resistance.


Asynchronous GABA release generates long-lasting inhibition at a hippocampal interneuron-principal neuron synapse.
Hippocampal GABAergic interneurons show diverse molecular and morphological properties. The functional significance of this diversity for information processing is poorly understood. Here we show that cholecystokinin (CCK)-expressing interneurons in rat dentate gyrus release GABA in a highly asynchronous manner, in contrast to parvalbumin (PV) interneurons. With a gamma-frequency burst of ten action potentials, the ratio of asynchronous to synchronous release is 3:1 in CCK interneurons but is 1:5 in parvalbumin interneurons. N-type channels trigger synchronous and asynchronous release in CCK interneuron synapses, whereas P/Q-type Ca(2+) channels mediate release at PV interneuron synapses. Effects of Ca(2+) chelators suggest that both a long-lasting presynaptic Ca(2+) transient and a large distance between Ca(2+) source and sensor of exocytosis contribute to the higher ratio of asynchronous to synchronous release in CCK interneuron synapses. Asynchronous release occurs at physiological temperature and with behaviorally relevant stimulation patterns, thus generating long-lasting inhibition in the brain.


Extracellular pH dynamically controls cell surface delivery of functional TRPV5 channels.
Extracellular pH has long been known to affect the rate and magnitude of ion transport processes among others via regulation of ion channel activity. The Ca(2+)-selective transient receptor potential vanilloid 5 (TRPV5) channel constitutes the apical entry gate in Ca(2+)-transporting cells, contributing significantly to the overall Ca(2+) balance. Here, we demonstrate that extracellular pH determines the cell surface expression of TRPV5 via a unique mechanism. By a comprehensive approach using total internal reflection fluorescence microscopy, cell surface protein labeling, electrophysiology, (45)Ca(2+) uptake assays, and functional channel recovery after chemobleaching, this study shows that upon extracellular alkalinization, a pool of TRPV5-containing vesicles is rapidly recruited to the cell surface without collapsing into the plasma membrane. These vesicles contain functional TRPV5 channels since extracellular alkalinization is accompanied by increased TRPV5 activity. Conversely, upon subsequent extracellular acidification, vesicles are retrieved from the plasma membrane, simultaneously resulting in decreased TRPV5 activity. Thus, TRPV5 accesses the extracellular compartment via transient openings of vesicles, suggesting that rapid responses of constitutive active TRP channels to physiological stimuli rely on vesicular "kiss and linger" interactions with the plasma membrane.


Unusual cause of upper gastrointestinal bleed, when OGD could be fatal.
A 57-year-old man presented with chest pain, dyspnoea and coffee grounds emesis. He was haemodynamically stable without significant drop in haemoglobin. He suddenly developed cardiac arrest with wide complex tachycardia and became comatose. CT scan of the head revealed pneumocephalus and multiple infarcts. Given the recent history of radiofrequency ablation for atrial fibrillation, atrio-oesophageal fistula (AOF) was suspected. CT angiography of the thorax showed a 5 mm diverticulum on the posterior wall of the left atrium, also raising suspicion for AOF. The patient was taken to the operating room. An AOF was found and repaired. He did not have any further gastrointestinal bleeding. There was no neurological recovery at day 11 and life support was withdrawn per his family's request. This case highlights the importance of obtaining history of recent cardiac procedures in patients presenting with an upper gastrointestinal bleed. An oesophagogastroduodenoscopy in this patient could have been instantaneously deadly.


Relative cerebral flow from dynamic PIB scans as an alternative for FDG scans in Alzheimer's disease PET studies.
In Alzheimer's Disease (AD) dual-tracer positron emission tomography (PET) studies with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and 11C-labelled Pittsburgh Compound B (PIB) are used to assess metabolism and cerebral amyloid-β deposition, respectively. Regional cerebral metabolism and blood flow (rCBF) are closely coupled, both providing an index for neuronal function. The present study compared PIB-derived rCBF, estimated by the ratio of tracer influx in target regions relative to reference region (R1) and early-stage PIB uptake (ePIB), to FDG scans. Fifteen PIB positive (+) patients and fifteen PIB negative (-) subjects underwent both FDG and PIB PET scans to assess the use of R1 and ePIB as a surrogate for FDG. First, subjects were classified based on visual inspection of the PIB PET images. Then, discriminative performance (PIB+ versus PIB-) of rCBF methods were compared to normalized regional FDG uptake. Strong positive correlations were found between analyses, suggesting that PIB-derived rCBF provides information that is closely related to what can be seen on FDG scans. Yet group related differences between method's distributions were seen as well. Also, a better correlation with FDG was found for R1 than for ePIB. Further studies are needed to validate the use of R1 as an alternative for FDG studies in clinical applications.


Tonus of Extrinsic Laryngeal Muscles during Sleep and Dreaming.
The tonus of extrinsic laryngeal muscles was studied in sleeping humans by means of electromyograms. A striking decrease in the muscle tonus was observed at the onset of each phase of electroencephalographic light sleep, rapid eye movements, and dreaming.


Experience of Point-of-Care Devices in Obstetrical Care.
During pregnancy and puerperium, there are pronounced hemostatic changes characterized by increased coagulability and decreased fibrinolysis. In addition, hemostasis can change dramatically during obstetric complications. Several reports have described substandard management of hemostatic defects in this setting and state the need for guidelines and better care. Point-of-care devices can assess hemostatic status and are especially suitable in perioperative settings. Using point-of-care devices, no time is required for transportation, allowing faster availability of results and providing potential for better care of the patient. This article will demonstrate the use of a viscoelastic method in six different patients; five with impaired hemostasis, and where the use of viscoelastic method contributes or should have contributed to better care. The cases represent patients with normal delivery; postpartum hemorrhage (PPH); PPH with low fibrinogen; placental abruption; preeclampsia with hemolysis, elevated liver enzymes, low platelet count syndrome; and finally, one patient with sepsis. This article also shows the need for good practices and good supervision to implement the devices in patient care.


Lysophospholipid receptor-dependent and -independent calcium signaling.
Changes in cellular Ca(2+) concentrations form a ubiquitous signal regulating numerous processes such as fertilization, differentiation, proliferation, contraction, and secretion. The Ca(2+) signal, highly organized in space and time, is generated by the cellular Ca(2+) signaling toolkit. Lysophospholipids, such as sphingosine-1-phosphate (S1P), sphingosylphosphorylcholine (SPC), or lysophosphatidic acid (LPA) use this toolkit in a specific manner to initiate their cellular responses. Acting as agonists at G protein-coupled receptors, S1P, SPC, and LPA increase the intracellular free Ca(2+) concentration ([Ca(2+)](i)) by using the classical, phospholipase C (PLC)-dependent pathway as well as PLC-independent pathways such as sphingosine kinase (SphK)/S1P. The S1P(1) receptor, via protein kinase C, inhibits the [Ca(2+)](i) transients caused by other receptors. Both S1P and SPC also act intracellularly to regulate [Ca(2+)](i). Intracellular S1P mobilizes Ca(2+) in intact cells independently of G protein-coupled S1P receptors, and Ca(2+) signaling by many agonists requires SphK-mediated S1P production. As shown for the FcepsilonRI receptor, PLC and SphK may contribute specific components to the overall [Ca(2+)](i) transient. Of the many open questions, identification of the intracellular S1P target site(s) appears to be of particular importance.


Light-Driven, Caterpillar-Inspired Miniature Inching Robot.
Liquid crystal elastomers are among the best candidates for artificial muscles, and the materials of choice when constructing microscale robotic systems. Recently, significant efforts are dedicated to designing stimuli-responsive actuators that can reproduce the shape-change of soft bodies of animals by means of proper external energy source. However, transferring material deformation efficiently into autonomous robotic locomotion remains a challenge. This paper reports on a miniature inching robot fabricated from a monolithic liquid crystal elastomer film, which upon visible-light excitation is capable of mimicking caterpillar locomotion on different substrates like a blazed grating and a paper surface. The motion is driven by spatially uniform visible light with relatively low intensity, rendering the robot "human-friendly," i.e., operational also on human skin. The design paves the way toward light-driven, soft, mobile microdevices capable of operating in various environments, including the close proximity of humans.


Light induced spiking of proteinoids.
Proteinoids, or thermal proteins, are produced by heating amino acids to their melting point and initiating polymerisation to produce polymeric chains. In aqueous solutions proteinoids swell into hollow microspheres. These microspheres produce endogenous burst of electrical potential spikes and change patterns of their electrical activity in response to illumination. We report results on a detailed investigation on the effects of white cold light on the spiking of proteinoids. We study how different types and intensities of light determine proteinoids' spiking amplitude, period, and pattern. The results of this study will be utilised to evaluate proteinoids for their potential as optical sensors and their application in unconventional computing.


Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers.
The transport activity of human mitochondrial aspartate/glutamate carriers is central to the malate-aspartate shuttle, urea cycle, gluconeogenesis and myelin synthesis. They have a unique three-domain structure, comprising a calcium-regulated N-terminal domain with eight EF-hands, a mitochondrial carrier domain, and a C-terminal domain. Here we present the calcium-bound and calcium-free structures of the N- and C-terminal domains, elucidating the mechanism of calcium regulation. Unexpectedly, EF-hands 4-8 are involved in dimerization of the carrier and form a static unit, whereas EF-hands 1-3 form a calcium-responsive mobile unit. On calcium binding, an amphipathic helix of the C-terminal domain binds to the N-terminal domain, opening a vestibule. In the absence of calcium, the mobile unit closes the vestibule. Opening and closing of the vestibule might regulate access of substrates to the carrier domain, which is involved in their transport. These structures provide a framework for understanding cases of the mitochondrial disease citrin deficiency.


A cross sectional survey of knowledge, attitude and practices related to the use of insecticides among farmers in industrial triangle of Punjab, Pakistan.
Pesticides in Pakistan are abundantly utilized for pest control in agriculture sector. The over and unsafe use of insecticides plus poor handling leads to the development of resistance, outbreak of secondary pests and hazardous impact on environment. The present study was aimed to access the current knowledge, attitude and common practices of farmers about the use of insecticides against pest in industrial triangle of Province Punjab, Pakistan. This study was conducted during October 2019 to February 2020. In this study farmers (n = 300) took part from three localities of Province Punjab (Gujrat, Gujranwala and Sialkot). Farmers were interviewed using a questionnaire to collect data about the knowledge of pest control by use of chemical method, biological method and combination of both to eradicate the pests. The result shows almost all (93%) farmers were male and they did not know about the insecticides mode of action and its chemical composition. They do not have any knowledge about the biological control of pests and did not get any assistance or help from Agriculture Extension Officer. They even did not properly dispose off the empty containers of insecticides. Statistical analysis reveals that lack of education and awareness about biological control of pest depicts development of resistance and outbreak of secondary pest including health hazards and environmental pollution. Poor understanding about pests, abundant use of insecticides, incorrect perception about application of insecticides and negligence regarding biological control shows that there is need to initiate public awareness programs to ensure the application of integrated pest management (IPM) and sustainable agriculture.


Headache after lumbar puncture: review of the epidural blood patch.
The incidence of accidental dural puncture during epidural block is 2.9%; headache follows in as many as 76.5% of these patients. Treatment by injection of autologous blood into the epidural space has gained wide acceptance since its introduction in 1960, though it is contraindicated by blood dyscrasias, anticoagulant therapy, bleeding, and localized infection. The procedure is done by slowly injecting 15 to 20 ml of blood into the same interspace, no sooner than 24 hours after the original puncture. Serious complications are rare.


Cutaneous Langerhans cell histiocytosis with subsequent development of haematological malignancies. Report of two cases.
Adult cutaneous Langerhans cell histiocytosis (LCH) is a rare disease. We report two cases illustrating the variability of the clinical presentation and the response to treatment. In both cases a remission was achieved: in one case a partial remission with psoralen plus UVA irradiation (PUVA) and methotrexate plus topical corticosteroid ointment; in the other case by treatment with thalidomide. Despite a therapeutic response, both patients later developed haematological malignancies: a chronic myelo-monocytic leukaemia and an acute lymphatic leukaemia. In conclusion, patients with adult cutaneous LCH should be monitored carefully so that a secondary malignancy is not overlooked.


Ongoing outbreak of tuberculosis in a low-incidence community: a molecular-epidemiological evaluation.
Federal State of Hamburg, Germany, 1997-2002. To identify the pathways of tuberculosis (TB) transmission and to evaluate possible risk factors for recent transmission in Hamburg. A prospective, molecular-epidemiological study was performed. Conventional contact tracing and an indepth epidemiological analysis were conducted. A predominant cluster of Mycobacterium tuberculosis strains was identified by IS6110 DNA fingerprinting of 828 TB cases notified during the study period. The cluster expanded from seven cases in 1997 to 38 in June 2002. A single source case could not be identified. Transmission links were confirmed in 20 cases. Twenty-five patients were regular customers at a bar close to the red-light district. Seven patients, including one regular customer in the bar, were staying at a nearby hostel for homeless men, and four were living in a far-away hostel for alcoholic men. Of the 421 close contact persons investigated, 169 (40.1%) had positive tuberculin skin tests, and eight became ill (1.9%). Twelve of 20 cases with confirmed recent transmission could only be determined a posteriori by fingerprinting. An ongoing outbreak at a local bar indicates chronic alcoholism as a high-risk factor for the dissemination of TB in a large metropolitan area. The fact that conventional contact tracing is insufficient for the detection of chains of transmission in this milieu indicates the need for an improved, location-based approach, e.g., the implementation of an outreach strategy.


Antioxidative enzymes and biochemical changes in paclobutrazol induced flowering in mango (M. indica) cultivars.
A study was conducted to examine the level of nonstructural carbohydrate, protein concentration and the activity of antioxidative enzymes viz. catalase and peroxidase in buds of different stages (Stages: I-before flower bud differentiation, II-flower bud differentiation, III-bud burst, IV-panicle elongation) and their adjacent leaves of biennial (Chausa, Dashehari, Langra) and the regular (Amrapali) cultivars. In the present study, Amrapali being the regular cultivar, contained higher levels of total and reducing sugar (4.49 to 12.67 mg g(-1) f.wt.) and protein content (1.90 to 6.78 mg g(-1)) in all the developmental stages of flowering as compared to biennial cultivars. However, in leaves gradual reduction in sugar and protein content was noticed in the advance stages of flowering. Paclobutrazol (2-8 g.a.i.), a flower inducing chemical, enhanced the catalase and peroxidase activities over the untreated control and maximum enhancement was recorded at 8 g.a.i. On the other hand, decreasing trend of protein with paclobutrazol treatment was recorded in adjacent leaves of flower buds. The results implicated the possible role of catalase and peroxidase and other associated biochemical changes in paclobutrazol induced flowering in mango.


Genome-scale cloning and expression of individual open reading frames using topoisomerase I-mediated ligation.
The in vitro cloning of DNA molecules traditionally uses PCR amplification or site-specific restriction endonucleases to generate linear DNA inserts with defined termini and requires DNA ligase to covalently join those inserts to vectors with the corresponding ends. We have used the properties of Vaccinia DNA topoisomerase I to develop a ligase-free technology for the covalent joining of DNA fragments to suitable plasmid vectors. This system is much more efficient than cloning methods that require ligase because the rapid DNA rejoining activity of Vaccinia topoisomerase I allows ligation in only 5 min at room temperature, whereas the enzyme's high substrate specificity ensures a low rate of vector-alone transformants. We have used this topoisomerase I-mediated cloning technology to develop a process for accelerated cloning and expression of individual ORFs. Its suitability for genome-scale molecular cloning and expression is demonstrated in this report.


The BioRef Infrastructure, a Framework for Real-Time, Federated, Privacy-Preserving, and Personalized Reference Intervals: Design, Development, and Application.
Reference intervals (RIs) for patient test results are in standard use across many medical disciplines, allowing physicians to identify measurements indicating potentially pathological states with relative ease. The process of inferring cohort-specific RIs is, however, often ignored because of the high costs and cumbersome efforts associated with it. Sophisticated analysis tools are required to automatically infer relevant and locally specific RIs directly from routine laboratory data. These tools would effectively connect clinical laboratory databases to physicians and provide personalized target ranges for the respective cohort population. This study aims to describe the BioRef infrastructure, a multicentric governance and IT framework for the estimation and assessment of patient group-specific RIs from routine clinical laboratory data using an innovative decentralized data-sharing approach and a sophisticated, clinically oriented graphical user interface for data analysis. A common governance agreement and interoperability standards have been established, allowing the harmonization of multidimensional laboratory measurements from multiple clinical databases into a unified "big data" resource. International coding systems, such as the International Classification of Diseases, Tenth Revision (ICD-10); unique identifiers for medical devices from the Global Unique Device Identification Database; type identifiers from the Global Medical Device Nomenclature; and a universal transfer logic, such as the Resource Description Framework (RDF), are used to align the routine laboratory data of each data provider for use within the BioRef framework. With a decentralized data-sharing approach, the BioRef data can be evaluated by end users from each cohort site following a strict "no copy, no move" principle, that is, only data aggregates for the intercohort analysis of target ranges are exchanged. The TI4Health distributed and secure analytics system was used to implement the proposed federated and privacy-preserving approach and comply with the limitations applied to sensitive patient data. Under the BioRef interoperability consensus, clinical partners enable the computation of RIs via the TI4Health graphical user interface for query without exposing the underlying raw data. The interface was developed for use by physicians and clinical laboratory specialists and allows intuitive and interactive data stratification by patient factors (age, sex, and personal medical history) as well as laboratory analysis determinants (device, analyzer, and test kit identifier). This consolidated effort enables the creation of extremely detailed and patient group-specific queries, allowing the generation of individualized, covariate-adjusted RIs on the fly. With the BioRef-TI4Health infrastructure, a framework for clinical physicians and researchers to define precise RIs immediately in a convenient, privacy-preserving, and reproducible manner has been implemented, promoting a vital part of practicing precision medicine while streamlining compliance and avoiding transfers of raw patient data. This new approach can provide a crucial update on RIs and improve patient care for personalized medicine.


Enhanced preconcentration of selected chlorofluorocarbons on multiwalled carbon nanotubes with polar functionalities.
Chromatographic monitoring of chlorofluorocarbons in air requires the preconcentration of these highly volatile species. In this paper, we present functionalized multiwalled carbon nanotubes as effective sorbents for a microtrap designed for chlorofluorocarbons preconcentration. Among the commercial carbons and carbon nanotubes studied, functionalization via carboxylation and propyl amine was most effective for dichlorofluoromethane and trichlorofluoromethane (Freon 11), which were selected as representative chlorofluorocarbons. The results show that carbon nanotubes functionalized with a polar groups led to as much as a 300% increase in breakthrough volume and the desorption bandwidth was reduced by 2.5 times.


Extracellular polyvalent cation block of slow Na+ channels in Xenopus laevis oocytes.
Sustained depolarization of the Xenopus oocyte membrane elicits a slowly activating Na+ current, thought to be due to the opening of sodium selective channels. These channels are induced to become voltage gated by the depolarization. They show unconventional gating properties and are insensitive to tetrodotoxin (TTX). The present study was undertaken to evaluate the effect of extracellular multivalent cations (Ca2+, Co2+, Cd2+, La3+, Mg2+, Mn2+, Ni2+, Sr2+ and Zn2+) on these TTX-resistant channels, either on membrane potential responses or on current responses. Our data show that all the polyvalent cations used blocked Na+ channels in a concentration-dependent manner. The order of potency of the most efficient cations was Co2+ < Ni2+ < Cd2+ < Zn2+, the respective concentration required to cause a 50% decrease of Na+ current was 0.9+/-0.29; 0.47+/-0.15; 0.36+/-0.09 and 0.06+/-0.02 mmol/l. The comparison of the activation curves from controls and after treatment with the cations indicated a shift towards more positive voltages. These results can be interpreted as due to the screening effect of divalent cations together with an alteration of the Na+ channel gating properties. We also show that divalent cations blocked Na+ channels in an open state without interfering with the induction mechanism of the channels. The possibility that cation block was due to a possible interaction between cations and SH-groups was investigated, but a sulphydryl alkylating reagent failed to abolish Zn2+ block.


Porous carbon powders prepared by ultrasonic spray pyrolysis.
New, thermally robust meso- and macroporous carbon powders were prepared by ultrasonic spray pyrolysis (USP) of aqueous solutions using an inexpensive high-frequency ultrasound generator from a household humidifier. We choose our molecular precursors rationally, so that the expected decomposition pathways produce only remnant carbon atoms. Specifically, our rational design criterion led to halo-organic carboxylate salts, whose pyrolysis yields well-defined carbon solids with a temporary template being generated in situ, simply an inorganic salt, which is easily dissolved during aqueous workup. The materials have been characterized by SEM, TEM, XRD, 13C NMR MAS, XPS, FTIR spectroscopy, and BET surface area measurements. Changing the alkali metal alters the morphology and pore structure of the final material, which can be explained in terms of the observed differences in the DSC and TGA of the various precursors. This preparatory method provides an extremely facile and versatile method for the generation of meso- and macroporous carbons.


The effects of improved child survival on family planning practice and fertility.
The relationship between improvements in child survival, family planning, and fertility is viewed here as the outcome of a process of family building that evolves through distinct phases as the mortality transition progresses. The speed with which family building strategies evolve from "family building by fate" to "family building by design" and from "insurance" to "replacement" as child survival improves depends on the pattern (by age and causes of death) of mortality decline and the sociocultural context. While child survival improvements will not lead to compensatory declines in fertility when fate or replacement behavior govern family building, more than compensatory fertility declines can result when families shift to family building by design, which, in its initial phases, is manifested by so-called insurance behavior. A literature review supports these hypotheses and identifies family planning availability as a critical additional factor. These results provide strong support for an integrated approach to the delivery of health and family planning services.


On the content and purview of Christian bioethics.
The author argues that to explore what is distinctly Christian about Christian bioethics requires clarity about what is Christian. He distinguishes between the Christian (that which can be identified as authentically Christian), Christianity (the sum of that which is authentically Christian), and ecclesiastical traditions (the historical communities of faith and practice that are predicated upon both Christian and extra-Christian tradition) to critically assess what it is to be declared Christian. In addition to exploring the role of New Testament scripture in identifying the Christian, the author emphasizes the need to recognize the extent to which the content of Christianity is Hebraic and Jewish.


Universal dispersing agent for electrophoretic deposition of inorganic materials with improved adsorption, triggered by chelating monomers.
Poly[1-[4-(3-carboxy-4-hydroxyphenylazo)benzenesulfonamido]-1,2-ethanediyl, sodium salt] (PAZO) is a polymeric functional material with a number of unique physical properties, which attracted significant interest of different scientific communities. Films of PAZO were deposited by anodic electrophoretic deposition (EPD) under constant current and constant voltage conditions. The deposition kinetics was analyzed under different conditions and the deposition mechanism was discussed. New strategy was developed for the EPD of different inorganic materials and composites using PAZO as a dispersing, charging, binding and film forming agent. It was found that PAZO exhibits remarkable adsorption on various inorganic materials due to the presence of chelating salicylate ligands in its molecular structure. The salicylate ligands of PAZO monomers provide multiple adsorption sites by complexation of metal atoms on particle surfaces and allow for efficient electrosteric stabilization of particle suspensions. The remarkable performance of PAZO in its application in EPD have been exemplified by deposition of a wide variety of inorganic materials including the single element oxides (NiO, ZnO, Fe2O3) the complex oxides (Al2TiO5, BaTiO3, ZrSiO4, CoFe2O4) different nitrides (TiN, Si3N4, BN) as well as pure Ni metal and hydrotalcite clay. The use of PAZO can avoid limitation of other dispersing agents in deposition and co-deposition of different materials. Composite films were obtained using PAZO as a co-dispersant for different inorganic materials. The deposit composition, microstructure and deposition yield can be varied. The EPD method offers the advantages of simplicity, high deposition rate, and ability to deposit thin or thick films.


The Glutathione Peroxidase Gene Family in Gossypium hirsutum: Genome-Wide Identification, Classification, Gene Expression and Functional Analysis.
The plant glutathione peroxidase (GPX) family consists of multiple isoenzymes with distinct subcellular locations, tissue-specific expression patterns and environmental stress responses. In this study, 13 putative GPXs from the genome of Gossypium hirsutum (GhGPXs) were identified and a conserved pattern among plant GPXs were exhibited, besides this they also responded to multiple environmental stresses and we predicted that they had hormone responsive cis-elements in their promoter regions. Most of the GhGPXs on expression in yeast can scavenge H2O2. Our results showed that different members of the GhGPX gene family were co-ordinately regulated under specific environmental stress conditions, and suggested the importance of GhGPXs in hormone treatments and abiotic stress responses.


Transmission, attenuation and reflection of shear waves in the human brain.
Traumatic brain injuries (TBIs) are caused by acceleration of the skull or exposure to explosive blast, but the processes by which mechanical loads lead to neurological injury remain poorly understood. We adapted motion-sensitive magnetic resonance imaging methods to measure the motion of the human brain in vivo as the skull was exposed to harmonic pressure excitation (45, 60 and 80 Hz). We analysed displacement fields to quantify the transmission, attenuation and reflection of distortional (shear) waves as well as viscoelastic material properties. Results suggest that internal membranes, such as the falx cerebri and the tentorium cerebelli, play a key role in reflecting and focusing shear waves within the brain. The skull acts as a low-pass filter over the range of frequencies studied. Transmissibility of pressure waves through the skull decreases and shear wave attenuation increases with increasing frequency. The skull and brain function mechanically as an integral structure that insulates internal anatomic features; these results are valuable for building and validating mathematical models of this complex and important structural system.


Computer-assisted simulation of high-voltage electron microscopy using serial images recorded by conventional transmission electron microscopy.
Here we describe a computer-assisted method which, based on conventional transmission electron microscopy, renders simulated high-voltage electron micrographs. We perform arithmetic minimum filtering on stacks of aligned serial transmission electron microscopic images. In this way, the structural information of the separate images is fused into one compound image that highlights organization patterns otherwise easily overlooked or impossible to comprehend. Our method, like high-voltage electron microscopy, offers the possibility to build stereo-pairs for high-resolution three-dimensional analysis of tissue layers 1-2 microm thick. The use of background elimination and the development of a depth enhancement routine improved the three-dimensional effect and facilitated the analysis of the interior of objects. As an example, we use the method to display the distribution of axonal organelles at nodes of Ranvier and the shape and contents of a highly branched hippocampal dendritic spine.


Clinical onset of atopic eczema: Results from 2 nationally representative British birth cohorts followed through midlife.
Atopic eczema onset is described primarily in early childhood, and the frequency and characteristics of adult-onset disease remain controversial. We sought to determine the proportion of subjects who report atopic eczema symptoms between birth and midadulthood and to examine demographic, immunologic, and genetic factors associated with period of symptom onset. We conducted a longitudinal study using data from 2 nationally representative community-based birth cohorts from the United Kingdom: the British Cohort Studies 1958 and 1970. Subjects were followed from birth through age 42 to 50 years. The primary outcome was the age period of self-reported atopic eczema symptom onset based on repeated measures of self-reported atopic eczema at each survey wave. The annual period prevalence of atopic eczema ranged from 5% to 15% in 2 cohorts of more than 17,000 participants each followed from birth through middle age. There was no clear trend in prevalence by age, and among adults reporting active atopic eczema during a given year, only 38% had symptom onset reported in childhood. When compared with subjects whose eczema started in childhood, those with adult-onset disease were more likely to be women, from Scotland or Northern England, of lower childhood socioeconomic group, smokers in adulthood, and less likely to have a history of asthma. In a subanalysis using data from the 1958 cohort only, genetic mutations previously associated with atopic eczema, including filaggrin-null mutations, and allergen-specific IgE were more common among those with childhood-onset disease. Rates of self-reported atopic eczema remain high after childhood, and adult-onset atopic eczema has different risk factor associations than childhood-onset eczema.


Impact of a program aimed at reducing catheter-related infections implemented in nine pediatric intensive care units in Argentina.
Catheter-related infections (CRIs) cause a high level of morbidity and mortality with the increasing use of hospital resources. To describe the outcomes of a program implemented to reduce the rate of CRIs in pediatric intensive care units in Argentina. Collaborative, multi center, clinical-epidemiological, quasiexperimental, before-and-after intervention study. Children who had a central venous catheter during hospitalization in 9 pediatric intensive care units in the Autonomous City of Buenos Aires, Greater Buenos Aires, and other provinces between June 2011 and April 2012 were included. A bundle of measures based on health care staff training on catheter insertion, hand hygiene, and checklists was put into practice and implemented measures were monitored. The number and annual rate of CRIs and the rate of central venous catheter use before and after the program implementation were compared (Stata 8.0). The total number of CRIs was 117 and 74 before and after the intervention, respectively. The rate of CRIs was 8.6/1000 days of central venous catheter use and 5.8/1000 days before and after the intervention, respectively; RR: 0.82 (95% confidence interval: 0.68-0.98), p= 0.015. The rate of central venous catheter use decreased from 54% to 49%, a non-significant difference. The program achieved a significant reduction in CRI rates. Based on the program, CRI surveillance was implemented in all participating pediatric intensive care units. Training and continuous surveillance are necessary to maintain and improve the outcomes accomplished with the program.


TPA inhibits the tyrosine kinase activity of the neu protein in vivo and in vitro.
P185 is a receptor-like protein encoded by the neu/erbB-2 proto-oncogene. A point mutation in the transmembrane domain renders this protein oncogenic. We report here that incubation of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulates the phosphorylation of the normal neu protein (p185) and the oncogenic neu protein (p185*). The increased phosphorylation occurs mainly on serine and threonine residues. Phosphate labeling experiments showed that TPA causes a reduction of basal phosphotyrosine in p185 but not p185*. Immunoblotting with antiphosphotyrosine antibody yielded similar results. TPA also inhibited tyrosine phosphorylation of p185* in an in vitro immune complex kinase assay. These data suggest that protein kinase C, the receptor for TPA, regulates p185 function through serine or threonine phosphorylation.


AANEM - IFCN glossary of terms in neuromuscular electrodiagnostic medicine and ultrasound.
Modern neuromuscular electrodiagnosis (EDX) and neuromuscular ultrasound (NMUS) require a universal language for effective communication in clinical practice and research and, in particular, for teaching young colleagues. Therefore, the AANEM and the IFCN have decided to publish a joint glossary as they feel the need for an updated terminology to support educational activities in neuromuscular EDX and NMUS in all parts of the world. In addition NMUS has been rapidly progressing over the last years and is now widely used in the diagnosis of disorders of nerve and muscle in conjunction with EDX. This glossary has been developed by experts in the field of neuromuscular EDX and NMUS on behalf of the AANEM and the IFCN and has been agreed upon by electronic communication between January and November 2019. It is based on the glossaries of the AANEM from 2015 and of the IFCN from 1999. The EDX and NMUS terms and the explanatory illustrations have been updated and supplemented where necessary. The result is a comprehensive glossary of terms covering all fields of neuromuscular EDX and NMUS. It serves as a standard reference for clinical practice, education and research worldwide.