Residue analysis evidence for wine enriched with vanilla consumed in Jerusalem on the eve of the Babylonian destruction in 586 BCE.
The article presents results of residue analysis, based on Gas Chromatograph Mass Spectrometer (GC-MS) measurements, conducted on 13 ceramic storage jars unearthed in the Babylonian destruction layer (586 BCE) in Jerusalem. Five of the jars bear rosette stamp impressions on their handles, indicating that their content was related to the kingdom of Judah's royal economy. The identification of the original contents remains is significant for the understanding of many aspects related to the nutrition, economy and international trade in the ancient Levant. The study shed light on the contents of the jars and the destruction process of the buildings in which they were found. The jars were used alternatively for storing wine and olive oil. The wine was flavored with vanilla. These results attest to the wine consumption habits of the Judahite elite and echo Jerusalem's involvement in the trans-regional South Arabian trade of spices and other lucrative commodities on the eve of its destruction by Nebuchadnezzar.


Hypo- or conventionally fractionated radiotherapy combined with chemotherapy in patients with limited stage small cell lung cancer.
Previous data from our institution showed that hypofractionated thoracic radiotherapy (HypoTRT) with concurrent etoposide/platinum chemotherapy yielded favorable survival in patients with limited-stage small cell lung cancer (LS-SCLC). The present study retrospectively compared the survival outcomes, failure patterns and toxicities between groups of LS-SCLC patients treated with conventionally fractionated thoracic radiotherapy (ConvTRT) or HypoTRT combined with chemotherapy. Medical records of LS-SCLC patients between January 2010 and December 2013 at Fudan University Shanghai Cancer Center were retrospectively reviewed. All patients treated with chemotherapy and ConvTRT (2 Gy per fraction daily, DT ≥ 56 Gy) or HypoTRT (2.5 Gy per fraction daily, DT = 55 Gy) were eligible for analysis. Progression-free survival (PFS) and overall survival (OS) were generated for different populations using the Kaplan-Meier method and compared using the log-rank test. Comparisons of failure patterns and toxicity were analyzed using the χ 2 test. A total of 170 patients treated with HypoTRT (n = 69) or ConvTRT (n = 101) were eligible for analysis. The median PFS and OS were 13.7 and 25.3 months, respectively, in the ConvTRT cohort, which was similar to the HypoTRT cohort (PFS 18.2 months, p = 0.991, and OS 27.2 months, p = 0.698), with a median follow-up of 30 months. Multivariate analysis revealed that PCI and TNM stage were prognostic factors for PFS and that PCI was prognostic for OS. The patterns of failure (stratified by local-regional recurrence, distant metastasis or both as first relapse) were similar between the dose cohorts (p = 0.693, p = 0.330, p = 0.572). Distant metastasis remained the main failure pattern. The brain was the most frequent remote failure site, followed by bone, liver and adrenal gland. PCI improved the 2-year survival rate from 46.1% to 70.0% and the 2-year PFS rate from 20.9% to 45.3%, respectively (p < 0.001). Grade ≥3 esophagitis and pneumonitis occurred in 9.9% and 11.9%, respectively, of the patients in the ConvTRT cohort and in 11.6% and 10.0%, respectively, of those in the HypoTRT cohort (p = 0.815). This retrospective analysis demonstrated that HypoTRT or ConvTRT combined with etoposide/platinum chemotherapy yielded statistically similar survival, treatment failure outcomes, and toxicity profiles. PCI correlated with improved PFS and OS.


Electrochemical and nonenzymatic glucose biosensor based on MDPA/MWNT/PGE nanocomposite.
The nonenzymatic detection of glucose has been widely investigated in a variety of fields ranging from biomedical applications to ecological approaches. Among these fields, electrochemical methods have great advantages such as high electrocatalytic ability, high sensitivity, good selectivity and low-cost for the electrooxidation of glucose. Future trends on glucose sensing are nanostructured electrodes depending upon the development of nanotechnology. In this study, an electrochemical and nonenzymatic glucose sensor based on (E)-4-((5-methylthiazole-2-yl)diazenyl)-N-phenylaniline (MDPA)/multi-walled carbon nanotube (MWNT)/pencil graphite electrode (PGE) was performed. Electrochemical measurements were obtained using cyclic voltammetry and square wave voltammetry techniques, and characterization of surfaces was carried out using scanning electron microscope and electrochemical impedance spectroscopy techniques. The modification of PGE was made using MDPA and MWNT, and 10 cycles coating was used to prepare the proposed electrode. The effects of scan rate and pH on the peak potential and the peak current were determined. The limit of detection and linear range were calculated using various concentrations of glucose. The interference study was made using coexisting substances including metal ions such as Al3+, Cu2+, Fe3+ and ascorbic acid.


Reduction of Cr, Mo, Se and U by Desulfovibrio desulfuricans immobilized in polyacrylamide gels.
Intact cells of Desulfovibrio desulfuricans, immobilized in polyacrylamide gel, removed Cr, Mo, Se and U from solution by enzymatic-mediated reduction reactions. Lactate or H2 served as the electron donor and the oxidized Cr(VI), Mo(VI), Se(VI) and U(VI) served as electron acceptors. Reduction of the oxidized metal species resulted in the precipitation of solid phases of the metals. Metal removal efficiencies of 86-96% were achieved for initial concentrations of 1 mM Mo, Se, and U and 0.5 mM Cr. Insoluble metal phases accumulated on both the surface and the interior of the polyacrylamide gel. In column tests conducted for U removal, effluent concentrations less than 20 micrograms L(-1) were achieved with initial concentrations of 5 mg L(-1) and 20 mg L(-1) U and residence times from 25-37 h. The enzymatic reduction of Cr, Mo, Se, and U by immobilized cells of D. desulfuricans may be a practical method for removing these metals from solution in a biological reactor.


Current perspectives in the recognition and management of psoriatic arthritis: implications for integrated patient care.
Psoriatic arthritis (PsA), a chronic and debilitating spondyloarthropathy, is believed to affect as many as 30% of those with psoriasis. The use of tumor necrosis factor (TNF) inhibitors shows promise in the treatment of PsA and psoriasis. Etanercept, the first TNF inhibitor to be approved for use in PsA, inhibits the proinflammatory cytokine TNF in both conditions, making it possible for the clinician to prescribe a single agent to manage both the joint manifestations of PsA and the cutaneous manifestations of psoriasis. Etanercept has been shown to be well tolerated, even for long-term use, and is potentially superior to disease-modifying antirheumatic drugs.


Deregulated BCL2 expression enhances growth of a human B cell line.
The BCL2 (B cell lymphoma/leukemia -2) and C-MYC oncogenes become activated by chromosomal translocations involving the immunoglobulin heavy chain locus in human follicular lymphomas and Burkitt lymphomas, respectively. Though much is known about the biological actions of C-MYC, little information is available concerning the functions of BCL2, particularly in human B cells. Using a gene transfer approach we contrasted the effects of deregulated BCL2 and C-MYC expression in a human EBV-immortalized B cell line GM607B. Both BCL2 and C-MYC enhanced the ability of GM607B cells to grow in reduced serum and in limiting dilution cultures. These findings provide direct evidence that BCL2 can alter the growth characteristics of human B lymphocytes, thus strengthening arguments for its role in the pathogenesis of human lymphomas.


Mechanism of N-acetyl-cysteine inhibition on the cytotoxicity induced by titanium dioxide nanoparticles in JB6 cells transfected with activator protein-1.
The present study investigated the mechanism of N-acetyl-cysteine (NAC) inhibition on the cytotoxicity induced by titanium dioxide (TiO2) nanoparticles (NPs) using murine epidermal JB6 cells transfected with activator protein-1 (AP-1), JB6-AP-1 cells. Confocal microscopy was performed to localize TiO2 NPs in cultured cells. The level of reactive oxygen species (ROS) present in cells was evaluated by staining with 2',7'-dichlorodihydrofluorescein diacetate and dihydroethidium. AP-1 gene expression levels in the cells were detected using the luciferase assay. Confocal microscopy indicated that TiO2 NPs passed through the cell membrane into the cytoplasm; however, they did not penetrate the nuclear membrane. The present findings indicated that NAC markedly inhibited ROS generation and significantly inhibited cytotoxicity (P<0.05) induced by TiO2 NPs. Furthermore, alternative studies have demonstrated that AP-1 luciferase activity induced by TiO2 NPs may be significantly inhibited by NAC. In conclusion, the ability for NAC to inhibit the cytotoxicity induced by TiO2 NPs may primarily occur by blocking ROS generation in the cultured cells.


Anatomical localization of the binding and functional characterization of responses to dopexamine hydrochloride in the rat mesenteric vasculature.
Dopamine receptors of the DA1 subtype have been identified in mesenteric blood vessels, stimulation of which leads to vasodilation. In this study, we have determined the anatomical localization of dopexamine-hydrochloride-binding sites and carried out functional characterization of responses to this DA1-receptor and beta 2-adrenoceptor agonist in rat mesenteric vasculature. Autoradiographic studies showed the presence of [3H]-dopexamine-binding sites in all the different layers of the mesenteric artery. The DA1 receptor antagonist, SCH 23390 (IC50 = 4.9 mumol/l), and the beta-adrenoceptor antagonist, propranolol (IC50 = 6.0 mumol/l), inhibited the binding of dopexamine. The inhibitory effect of these compounds on dopexamine binding was selective for different regions of the mesenteric artery. Also, dopexamine produced concentration-related increases in cAMP formation in membrane particles from superior mesenteric artery and its main branches. The presence of both SCH 23390 and propranolol was required to completely abolish dopexamine-induced increases in cAMP formation. In functional studies, dopexamine (1 and 3 micrograms/kg/min) produced dose-related increases in mesenteric blood flow (23 and 38%, respectively) which were accompanied by concomitant decreases in the calculated mesenteric vascular resistance. As seen with increases in cAMP, the vascular responses to dopexamine could be completely abolished only by prior treatment with both SCH 23390 and propranolol. These results suggest that in mesenteric vasculature of rat dopexamine binds primarily to DA1 receptors and beta 2-adrenoceptors. The activation of these receptors by dopexamine leads to vasodilation which is mediated by an increase in the intracellular levels of cAMP.


Recognition of reversible and irreversible myocardial injury by technetium pyrophosphate extraction kinetics.
The need for a more accurate method of detecting episodes of myocardial ischemia during cardiac operations, particularly during the ischemic arrest interval, prompted us to investigate the usefulness of measuring the active extraction of technetium pyrophosphate in identifying and quantitating ischemic injury. Twenty-four adult mongrel dogs were subjected to cardiopulmonary bypass, and normothermic global ischemia was induced by cross-clamping the proximal aorta. Technetium pyrophosphate (1 mCi) was injected through a standard cardioplegia line with normal saline, simulating administration of cardioplegic solution, upon placement of the aortic cross-clamp (time 0), at 15, 30, 45, and 60 minutes of global ischemia, and with the onset and completion of ischemic contracture. Radioactive counts were recorded over the heart at 1 second intervals, and the extraction fraction and half-time of clearance were calculated. The extraction fraction increased from 0.22 at time 0 to 0.58 at 15 minutes, 0.82 at 30 minutes, 0.85 at 45 minutes, and 0.91 at 60 minutes. The halftime increased from a baseline of 114 seconds (time 0) to a maximum of 321 seconds at 60 minutes of ischemia. The onset and completion of ischemic contracture showed a return toward baseline of both the extraction fraction and halftime of clearance, with an extraction fraction of 0.44 and 0.46 and a halftime of 135 and 133 seconds, respectively. These data clearly show that reversible myocardial injury increased the extraction and reduced the clearance of technetium pyrophosphate and that the magnitude of change related to the extent of injury. The progression to irreversible myocardial injury decreased the active extraction of technetium pyrophosphate. This simple procedure for real-time documentation of myocardial injury promises to provide easily obtainable endpoints of injury for use during cardiac operations in humans.


[Clinical outcome evaluation of midpalatal mini-implant anchorage system in orthodontic treatment].
To evaluate the effect of midpalatal mini-implant anchorage system in fixed appliance treatment. In this study, 14 adolescents who had skeletal class I or II malocclusions were involved. Maximal anchorage was required during orthodontic treatment. Maxillary first premolars of the selected individuals were extracted and the individuals were treated by fixed appliance. One mini-implant was inserted in the midpalatal suture region and a transpalatal arch (TPA) made of 0.019 inch×0.022 inch(1 inch=2.54 cm) stainless steel was adhered to the mini-implant and upper first molars. Cephalometric radiographs taken after mini-implants inserted (T0) and before mini-implants removing (T1) were traced and measured. SN-7 plane and PP plane were used as reference planes. Student's t-test was used. The successful rate of midpalatal mini-implant was 73.9%. All the items measured were found with no significant difference between the two groups. This mini-implant system as orthodontic anchorage in midpalatal region can be an alternative method of maximal anchorage during orthodontic treatment.


Elucidation of CuWO4 Surface States During Photoelectrochemical Water Oxidation.
Electrochemical, photoelectrochemical, and impedance spectroscopy measurements were performed to investigate the role of CuWO4 surface states during water oxidation. We found that a capacitive feature related to a surface state is clearly observable under water oxidation conditions. The magnitude of the surface state capacitance is light intensity-dependent, with a peak potential that coincides with the water oxidation onset potential region. The surface state is not observed in the dark nor in contact with nonaqueous solvents. These results strongly support our assignment of this surface state as the buildup of water oxidation intermediate species at the surface of CuWO4 photoanodes, not a permanent or intrinsic state as previously reported. We suggest this is a general feature that controls the behavior and efficiency of solar water splitting reactions.


Determining behavioural and physiological responses to pain in infants at risk for neurological impairment.
Multiple researchers have validated indicators and measures of infant pain. However, infants at risk for neurologic impairment (NI) have been under studied. Therefore, whether their pain responses are similar to those of other infants is unknown. Pain responses to heel lance from 149 neonates (GA>25-40 weeks) from 3 Canadian Neonatal Intensive Care units at high (Cohort A, n=54), moderate (Cohort B, n=45) and low (Cohort C, n=50) risk for NI were compared in a prospective observational cohort study. A significant Cohort by Phase interaction for total facial action (F(6,409)=3.50, p=0.0022) and 4 individual facial actions existed; with Cohort C demonstrating the most facial action. A significant Phase effect existed for increased maximum Heart Rate (F(3,431)=58.1, p=0.001), minimum Heart Rate (F(3,431)=78.7, p=0.001), maximum Oxygen saturation (F(3,425)=47.6, p=0.001), and minimum oxygen saturation (F(3,425)=12.2, p=0.001) with no Cohort differences. Cohort B had significantly higher minimum (F(2,79)=3.71, p=0.029), and mean (F(2,79)=4.04, p=0.021) fundamental cry frequencies. A significant Phase effect for low/high frequency Heart Rate Variability (HRV) ratio (F(2,216)=4.97, p=0.008) was found with the greatest decrease in Cohort A. Significant Cohort by Phase interactions existed for low and high frequency HRV. All infants responded to the most painful phase of the heel lance; however, infants at moderate and highest risk for NI exhibited decreased responses in some indicators.


A Greener, Quick and Comprehensive Extraction Approach for LC-MS of Multiple Mycotoxins.
In food/feed control, mycotoxin analysis is often still performed "one analyte at a time". Here a method is presented which aims at making mycotoxin analysis environmentally friendlier through replacing acetonitrile by ethyl acetate and reducing chemical waste production by analyzing four mycotoxins together, forgoing sample extract clean-up, and minimizing solvent consumption. For this, 2 g of test material were suspended in 8 mL water and 16 mL ethyl acetate were added. Extraction was accelerated through sonication for 30 min and subsequent addition of 8 g sodium sulfate. After centrifugation, 500 µL supernatant were spiked with isotopologues, dried down, reconstituted in mobile phase, and measured with LC-MS. The method was validated in-house and through a collaborative study and the performance was fit-for-purpose. Repeatability relative standard deviation (RSDs) between 16% at low and 4% at higher contaminations were obtained. The reproducibility RSDs were mostly between 12% and 32%. The trueness of results for T-2 toxin and Zearalenone were not different from 100%, for Deoxynivalenol and HT-2 toxin they were larger than 89%. The extraction was also adapted to a quick screening of Aflatoxin B1 in maize by flow-injection-mass spectrometry. Semi-quantitative results were obtained through standard addition and scan-based ion ratio calculations. The method proved to be a viable greener and quicker alternative to existing methods.


The role of tissue transglutaminase in cell-matrix interactions.
Numerous studies over the last two decades revealed a complexity and multiple functions of tissue transglutaminase (tTG or TG2, EC 220.127.116.11). Besides the ability to catalyze Ca2+-dependent transamidation of proteins and formation of protein polymers via protease-resistant covalent isopeptide bonds, tTG also possesses GTPase enzymatic activity which links this protein to certain intracellular signaling pathways. Moreover, in addition to cytoplasmic and nuclear localization, a significant part of the protein pool is present on the cell surface. A number of recent findings indicate that surface tTG is involved in the interactions of cells with the surrounding extracellular matrix (ECM). In this review we will focus on the newly defined non-enzymatic adhesive function of tTG in cell-matrix interactions and discuss contributions of previously characterized enzymatic activities of tTG to cell-matrix adhesion and adhesion-dependent processes. Understanding molecular interactions and enzymatic activities of tTG will gain further insights into the role of this protein in normal human physiology and various pathological conditions.


Emergency Patient Handoffs: Identifying Essential Elements and Developing an Evidence-Based Training Tool.
Patient handoffs between care teams have been recognized as a major patient safety risk due to inadequate exchange or loss of critical information, especially during emergent patient transfers. The purpose of this literature review was to identify the essential elements of effective patient handoffs in emergency situations to develop a standardized tool to support a structured patient handoff procedure capable of guiding education and training. A literature search of handoff procedures and patient transfers was conducted using the Cumulative Index to Nursing and Allied Health Literature and PubMed between 2008 and 2015. Two global themes were identified-Crew Interactions, and Essential Data Elements-resulting in a tool containing 30 objective and five subjective items. Through the literature review, synthesis, and workgroup consensus, we developed a standardized tool to guide standardized education, training, and future inquiry in prehospital and emergent patient handoffs. J Contin Educ Nurs. 2018;49(1):34-41.


Density functional study of the antioxidant activity of some recently synthesized resveratrol analogues.
In this paper we have investigated the two main working mechanisms (H atom and single-electron transfer) of five new potential antioxidant analogues of cis-resveratrol. The O-H bond dissociation energy (BDE) and ionization potential (IP) key parameters were computed in methanol. Results obtained indicate that all the examined compounds are more efficient antioxidants than the molecule from which they derive, mainly due to their higher degree of conjugation and the capability to delocalize the π-electrons which contribute to the stabilization of the radical species. The enhancement of these stabilizing effects is in part a result of the introduction of a single bond between the C2' and C6 carbon atoms of cis-resveratrol that generates a new central aromatic ring. However, the number of hydroxyl groups and in particular the presence of the catechol moiety remains the most significant features in determining the order of radical scavenging potentiality. Spectroscopic UV-Vis characterization is also reported and discussed.


Sound focusing by a broadband acoustic Luneburg lens.
The high-performance and aberration-free broadband acoustic lens holds promise for extensive applications, yet remains challenged. In this work, a scheme is proposed, and the experimental demonstration of a planar acoustic Luneburg lens capable of focusing broadband sound ranging from 1 to 3 kHz (relative bandwidth approaching to 100%) in an aberration-free manner is presented. Concretely, plane sound within the frequency range incident from one side can be concentrated on a same point on the opposite edge of the Luneburg lens. The demanded refractive indexes of the lens are obtained from the component space coil acoustic metamaterials, which can easily manipulate the refractive index by adjusting a structural parameter. The prototype of the proposed Luneburg lens is fabricated by three-dimensional printing technology and experimentally characterized in a two-dimensional acoustic measuring platform. The measured results are consistently in good agreement with those from the numerical simulations. Finally, the proposed Luneburg lens is employed to construct a wide-angle acoustic reflector, which can produce a strong echo propagating in the direction exactly opposite to the incident wave. These results facilitate potential possibilities for developing more acoustic functional devices capable of manipulating broadband sound.


Malignant cauda equina paraganglioma in a cat.
An 11-year-old spayed female domestic long-haired cat presented for surgical removal of a slowly growing and deeply invasive 2.5 x 3.5-cm mass cranial to the base of the tail. Light microscopic examination of surgical biopsy specimens revealed an encapsulated mass composed of packets of polygonal cells of various sizes separated by a delicate fibrovascular stroma. Gömöri's reticulum stain revealed a characteristic endocrine or "Zellballen" pattern. Tumor cells contained diffuse positive reactivity to synaptophysin and neuron-specific enolase, reactions consistent with a neuroendocrine neoplasm. S-100 protein-positive cells reminiscent of sustentacular (support) cells occurred singly or in small clusters within tumor packets. At postmortem examination 3 months later, a 9- x 5- x 4-cm multinodular raised tan mass involving the caudal pelvis, sacrum, and tail-head regions was found. The base of this neoplastic mass originated within the cauda equina region and involved approximately five caudal nerve roots. Numerous 1-3-mm metastatic nodules were identified disseminated throughout the pulmonary parenchyma. The tumor was diagnosed as a malignant paraganglioma of the cauda equina region with pulmonary metastasis.


Popliteal artery pseudoaneurysm due to femur exostosis.
Vascular complications of femur exostoses are rare, with popliteal pseudoaneurysm being the most common. After establishing the diagnosis, surgical treatment is mandatory. A 35-year-old woman presented with a painful pulsatile swelling in the lower medial aspect of the left thigh. Investigations revealed a pseudoaneurysm arising from the left popliteal artery adjacent to femur exostoses. Skeletal survey revealed multiple exostoses involving the upper and lower limbs. Surgical excision of the pseudoaneurysm was followed by ePTFE patch repair of the defect and excision of the exostoses. The patient was discharged after 5 days and followed up for 6 months with excellent results.


A unifying approach to non-inferiority, equivalence and superiority tests via multiple decision processes.
Two approaches of multiple decision processes are proposed for unifying the non-inferiority, equivalence and superiority tests in a comparative clinical trial for a new drug against an active control. One is a method of confidence set with confidence coefficient 0.95 improving the conventional 0.95 confidence interval in the producer's risk and also the consumer's risk in some cases. It requires to include 0 within the region as well as to clear the non-inferiority margin so that a trial with somewhat large number of subjects and inappropriately large non-inferiority margin for proving non-inferiority of a drug that is actually inferior should be unsuccessful. The other is the closed testing procedure which combines the one- and two-sided tests by applying the partitioning principle and justifies the switching procedure by unifying the non-inferiority, equivalence and superiority tests. In particular regarding the non-inferiority, the proposed method justifies simultaneously the old Japanese Statistical Guideline (one-sided 0.05 test) and the International Guideline ICH E9 (one-sided 0.025 test). The method is particularly attractive, changing the strength of the evidence of relative efficacy of the test drug against a control at five levels according to the achievement of the clinical trial. The meaning of the non-inferiority test and also the rationale of switching from it to superiority test will be discussed.


Removal of foreign bodies from esophagus and stomach with flexible fiberoptic panendoscopes.
Accidentally swallowed foreign bodies were removed from the esophagus or stomach in six children using flexible panendoscopes. Complications did not occur. The increased flexibility of these new instruments allows removal of objects from the stomach that would previously have required gastrotomy. Our experience suggests that fiberoptic endoscopy should be used for removal of foreign bodies.


Sediminihaliea albiluteola gen. nov., sp. nov., a new member of the family Halieaceae, isolated from marine sediment.
A Gram-stain-negative, rod-shaped and facultatively aerobic bacterial strain, designated F7430T, was isolated from coastal sediment collected at Jingzi Wharf in Weihai, PR China. Cells of strain F7430T were 0.3-0.4 µm wide, 2.0-2.6 µm long, non-flagellated, non-motile and formed pale-beige colonies. Growth was observed at 4-40 °C (optimum, 30 °C), pH 6.0-9.0 (optimum, pH 7.5-8.0) and at NaCl concentrations of 1.0-10.0 % (w/v; optimum, 1.0 %). The sole respiratory quinone of strain F7430T was ubiquinone 8 and the predominant cellular fatty acids were summed feature 8 (C18 : 1 ω7c / C18 : 1 ω6c; 60.7 %), summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c; 30.2 %) and C15 : 0 iso (13.9 %). The polar lipids of strain F7430T consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one unidentified phospholipid and three unidentified lipids. Results of 16S rRNA gene sequences analyses indicated that this strain belonged to the family Halieaceae and had high sequence similarities to Parahaliea aestuarii JCM 51547T (95.3 %) and Halioglobus pacificus DSM 27932T (95.2 %) followed by 92.9-95.0 % sequence similarities to other type species within the aforementioned family. The rpoB gene sequences analyses indicated that the novel strain had the highest sequence similarities to Parahaliea aestuarii JCM 51547T (82.2 %) and Parahaliea mediterranea DSM 21924T (82.2 %) followed by 75.2-80.5 % sequence similarities to other type species within this family. Phylogenetic analyses showed that strain F7430T constituted a monophyletic branch clearly separated from the other genera of family Halieaceae. Whole-genome sequencing of strain F7430T revealed a 3.3 Mbp genome size with a DNA G+C content of 52.6 mol%. The genome encoded diverse metabolic pathways including the Entner-Doudoroff pathway, assimilatory sulphate reduction and biosynthesis of dTDP-l-rhamnose. Based on results from the current polyphasic study, strain F7430T is proposed to represent a novel species of a new genus within the family Halieaceae, for which the name Sediminihaliea albiluteola gen. nov., sp. nov. is proposed. The type strain of the type species is F7430T (=KCTC 72873T=MCCC 1H00420T).


Bayesian hierarchical modeling of joint spatiotemporal risk patterns for Human Immunodeficiency Virus (HIV) and Tuberculosis (TB) in Kenya.
The simultaneous spatiotemporal modeling of multiple related diseases strengthens inferences by borrowing information between related diseases. Numerous research contributions to spatiotemporal modeling approaches exhibit their strengths differently with increasing complexity. However, contributions that combine spatiotemporal approaches to modeling of multiple diseases simultaneously are not so common. We present a full Bayesian hierarchical spatio-temporal approach to the joint modeling of Human Immunodeficiency Virus and Tuberculosis incidences in Kenya. Using case notification data for the period 2012-2017, we estimated the model parameters and determined the joint spatial patterns and temporal variations. Our model included specific and shared spatial and temporal effects. The specific random effects allowed for departures from the shared patterns for the different diseases. The space-time interaction term characterized the underlying spatial patterns with every temporal fluctuation. We assumed the shared random effects to be the structured effects and the disease-specific random effects to be unstructured effects. We detected the spatial similarity in the distribution of Tuberculosis and Human Immunodeficiency Virus in approximately 29 counties around the western, central and southern regions of Kenya. The distribution of the shared relative risks had minimal difference with the Human Immunodeficiency Virus disease-specific relative risk whereas that of Tuberculosis presented many more counties as high-risk areas. The flexibility and informative outputs of Bayesian Hierarchical Models enabled us to identify the similarities and differences in the distribution of the relative risks associated with each disease. Estimating the Human Immunodeficiency Virus and Tuberculosis shared relative risks provide additional insights towards collaborative monitoring of the diseases and control efforts.


Novel Xanthate Complexes for the Size-Controlled Synthesis of Copper Sulfide Nanorods.
We present a simple, easily scalable route to monodisperse copper sulfide nanocrystals by the hot injection of a series of novel copper(I) xanthate single-source precursors [(PPh3)2Cu(S2COR)] (R = isobutyl, 2-methoxyethyl, 2-ethoxyethyl, 1-methoxy-2-propyl, 3-methoxy-1-butyl, and 3-methoxy-3-methyl-1-butyl), whose crystal structures are also reported. We show that the width of the obtained rods is dependent on the length of the xanthate chain, which we rationalize through a computational study, where we show that there is a relationship between the ground-state energy of the precursor and the copper sulfide rod width.


Leishmanial dactylitis: an unusual clinical presentation.
Cutaneous leishmaniasis (CL) is one of the most common endemic diseases in Iran. It has a diverse spectrum of clinical manifestations. Herein we present a woman with leishmanial dactylitis, which is a very rare clinical form of CL. Successful treatment consisted of parenteral pentavalent antimonials for two months. Leishmanial dactylitis can be easily misdiagnosed as bacterial or fungal infections, psoriasis, or even malignancies. Accordingly, it should be considered in the differential diagnosis of dactylitis in endemic areas and in travelers from endemic countries.


Specific anti-viral effects of RNA interference on replication and expression of hepatitis B virus in mice.
RNA interference (RNAi) is a powerful tool to silence gene expression post-transcriptionally. Our previous study has demonstrated that small interfering RNAs (siRNAs) have sufficiently inhibited hepatitis B virus (HBV) replication and expression in vitro. In this study we observed the RNAi-mediated inhibitory effects on HBV replication in mice models and accessed the specificity of these effects. A mutant RNAi vector (pSI-C mut) with two base pairs different from the original target gene sequence at the RNAi vector (pSI-C) was constructed according to the method described in this study. A mouse model of acute hepatitis B virus infection was established by injecting naked plasmid pHBV1.3 via the tail vein with acute circulatory overload. pSI-C, pSI-C mut and the irrelevant RNAi control plasmid for green fluorescent protein (GFP) gene, pSIGFP were respectively delivered with pHBV1.3 by tail vein injection method. Six days post injection, enzyme-linked immunosorbent assay (ELISA) assay was used to measure the concentration of HBV surface antigen (HBsAg) in mouse serum, immunohistochemical straining method was used to visualize the expression of HBV core protein (HBcAg) in liver tissues, and the transcriptional level of HBV C mRNA in liver tissues was detected by reverse transcriptase PCR (RT-PCR) analysis. Injection of pSI-C exerted magnificent and specific inhibitory effects on the replication and expression of HBV in the murine model. After 6-day post-injection (p.i.), the OD values were shown to be 5.07 +/- 1.07 in infecting group and 0.62 +/- 0.59 in pSI-C group. The concentration of HBsAg in pSI-C group was significantly lower than that in infecting group (P < 0.01). Liver intracellular synthesis of viral core protein was sharply reduced to 0.9% +/- 0.1%, compared with 5.4% +/- 1.2% of positive hepatocytes in infecting group (P < 0.01), and the transcriptional level of HBV C mRNA was greatly reduced by 84.7%. However, the irrelevant RNAi control plasmid (pSIGFP), and the pSI-C mut did not show the same robust inhibitory effects as pSI-C. pSI-C exert efficient and specific inhibitory effects on HBV replication and expression in mice models.


CaMKII locally encodes L-type channel activity to signal to nuclear CREB in excitation-transcription coupling.
Communication between cell surface proteins and the nucleus is integral to many cellular adaptations. In the case of ion channels in excitable cells, the dynamics of signaling to the nucleus are particularly important because the natural stimulus, surface membrane depolarization, is rapidly pulsatile. To better understand excitation-transcription coupling we characterized the dependence of cAMP response element-binding protein phosphorylation, a critical step in neuronal plasticity, on the level and duration of membrane depolarization. We find that signaling strength is steeply dependent on depolarization, with sensitivity far greater than hitherto recognized. In contrast, graded blockade of the Ca(2+) channel pore has a remarkably mild effect, although some Ca(2+) entry is absolutely required. Our data indicate that Ca(2+)/CaM-dependent protein kinase II acting near the channel couples local Ca(2+) rises to signal transduction, encoding the frequency of Ca(2+) channel openings rather than integrated Ca(2+) flux-a form of digital logic.


Serum osteocalcin levels and bone alkaline phosphatase isoenzyme after oophorectomy and in primary hyperparathyroidism.
Serum osteocalcin levels peaked 1 yr after oophorectomy in a prospective study of 12 women. Estrogen treatment restored serum osteocalcin to the normal range within 4 months of therapy. The changes in serum osteocalcin preceded those in bone alkaline phosphatase activity by 1-2 months, in these oophorectomized patients and during estrogen treatment. The changes in these two markers of bone formation over time were significantly different from those in urinary hydroxyproline excretion. A significant positive correlation was found between bone alkaline phosphatase and serum osteocalcin levels in patients after oophorectomy and in 18 patients with primary hyperparathyroidism. Significant positive correlations also were found between the biochemical indices of osteoblastic function and urinary hydroxyproline excretion and/or nephrogenous cAMP in primary hyperparathyroidism. In most of the patients with primary hyperparathyroidism, however, the elevation in bone alkaline phosphatase was more marked than that in osteocalcin. These data indicate that the clinical utility of serum osteocalcin as a marker of bone formation is similar but not identical to that of bone alkaline phosphatase.


Screening for BRCA1 large genomic rearrangements in female Egyptian hereditary breast cancer patients.
Approximately 5%-10% of all breast cancers are inherited as the result of germline mutations in the BRCAl gene. Large genomic rearrangements (LGRs) in BRCA1 have not been well-researched in the Egyptian population. Using multiplex ligation-dependent probe amplification, we showed BRCA1 rearrangements in 4/22 cases (18.2%) of familial breast cancer. No influence of having multiple breast cancer cases within the family was observed in patients diagnosed at <or>or=45 years and having BRCAl-positive LGRs. However, focusing on cases with first- and second-degree relatives affected, we observed a significant difference between the percentage of patients with BRCA1-positive versus BRCAl-negative LGRs. Our results provide the first evidence that LGRs in BRCA1 exist in the Egyptian population. Screening for these alterations may be desirable when breast cancer patients are diagnosed at an early age, especially if these cases have first- and second-degree of relatives with breast cancer.


Scintigraphic variations of normal biliary physiology.
We studied 115 healthy adult volunteers, fasting overnight, to establish the normal scintigraphic variability. Five Tc-99m IDA agents with liver excretion half-times ranging from 18 to 108 min were used. The time of appearance of the common bile duct correlated directly with the liver's excretion half-time. The appearance of the gallbladder and the small intestine were independent of the excretion half-time and showed a reciprocal relationship suggesting a major role for the sphincter of Oddi. In 22% of the subjects, the sphincter tonus was tight enough to divert all of the hepatic bile into the gallbladder, allowing none into the intestine. All of such subjects showed normal dynamic response to intravenous cholecystokinin. The pattern of the bile drainage from the two lobes differed, resulting in asymmetry of the right and left hepatic ducts. It is concluded that the selection of a Tc-99m IDA agent should be based on the clinical problem at hand and that a clinician's understanding of the scintigraphic variability in normal subjects is critical before attempting diagnosis.


Laser Therapy for Onychomycosis: Fact or Fiction?
Onychomycosis is a common fungal infection, afflicting some 10% of the adult population in industrialized countries. Aside from cosmetic concerns, onychomycosis can be the cause of toe and foot pain, as well as the underlying etiology for serious secondary bacterial infections and traumatic ulcerations. In select populations, such as diabetics, the latter conditions may even result in loss of all or part of the lower extremity. Thus, a simple, cost-effective and safe treatment for onychomycosis is highly desirable. Although both topical and oral systemic antifungal agents are available for this purpose, they are not always effective, carry some medical risks, are associated with potentially significant drug-drug interactions, and may be unacceptable to patient and healthcare provider alike. Physical modalities, such as laser therapy, therefore appear appealing. The question is whether laser treatment is sufficiently efficacious and safe to warrant the current high cost per treatment. The readily available literature on this controversy will be reviewed herein.


Pressure injuries and skin tone diversity in undergraduate nurse education: Qualitative perspectives from a mixed methods study.
To, firstly, explore student and academic nurse perceptions of classroom content about the assessment and identification of pressure injuries across skin tone diversity and, secondly, to describe the impact of classroom content on student nurse understanding of pressure injury in people with dark skin tones. Qualitative case study employing focus groups and semi-structured interviews. Five higher education institutions in the United Kingdom were purposively chosen. At each of the five-case sites, one focus group with student nurses and one semi-structured interview with a nurse academic were conducted between May 2018 and April 2019. The participants' narratives were transcribed verbatim and analysed via thematic analysis. Classroom learning was predominately framed through a white lens with white normativity being strongly reinforced through teaching and learning activities. This reinforcement of white normativity was evidenced through two main themes: (i) dominance of whiteness in the teaching and learning of pressure injuries in undergraduate nurse education and (ii) the impact and implications for student nurses of whiteness as the norm in pressure injury teaching. Nurses responsible for the design and delivery of teaching and learning experiences for nursing students need to ensure meaningful teaching and learning experiences. This learning should assist future nurses to interrogate their complicity in a system of white dominance. Nurse education delivered today influences and shapes nurses of the future. Nurses are the cornerstone of healthcare and play a significant role in the delivery of equitable healthcare. Nurse academics have a duty of care to inform and highlight health inequities in nursing and ultimately to enhance equity in care.


Impact of obesity on vascular calcification in patients with chronic kidney disease.
The aim of this study was to compare vascular calcification (VC) in obese and non-obese chronic kidney disease (CKD) patients, using three methods for measuring VC. The study included 168 consecutive patients with CKD. Patients were divided into two groups by body mass index (BMI) - group 1 (BMI ≥ 30 kg/m2) and group 2 (BMI < 30 kg/m2), and according to estimated glomerular filtration rate (eGFR) - subgroup A (eGFR < 45 mL/min/1.73m2) and subgroup B (eGFR < 45 mL/min/1.73m2). VC was assessed by measuring abdominal aortic calcification (AAC), ankle-brachial index (ABI) and echocardiography. Group 1 patients were older (p = 0.03). There was a relatively low number of diabetics in our study cohort: 41 patients, (24%). The number of diabetics was similar in both groups. The presence of AAC was more common in 1B and 2B than in 1A and 2A groups (p = 0.005 and p = 0.02) and in 1B group compared to 2B group (p = 0.05). In both groups, ABI ≥ 1.3 and ABI < 0.9 were more common in B subgroups. The presence of heart valvular lesions was very high in both groups. Spearman rank-order analysis of every cohort demonstrated significant correlation between AAC and heart valve lesions (Spearman R = 0.3; p = 0.01) and also between AAC and LVH (Spearman R = 0.3; p = 0.004). Analysis of variance of every cohort showed that in patients with ABI ≥ 1.3 and heart valve lesions, Kauppila score was significantly higher than in those with normal heart valves. Our study shows that obesity is not an independent predictor of VC in CKD patients. VC, assessed by three different methods, was more pronounced in obese patients with lower kidney function.


Dual roles of protein tyrosine phosphatase kappa in coordinating angiogenesis induced by pro-angiogenic factors.
A potential role may be played by receptor-type protein tyrosine phosphatase kappa (PTPRK) in angiogenesis due to its critical function in coordinating intracellular signal transduction from various receptors reliant on tyrosine phosphorylation. In the present study, we investigated the involvement of PTPRK in the cellular functions of vascular endothelial cells (HECV) and its role in angiogenesis using in vitro assays and a PTPRK knockdown vascular endothelial cell model. PTPRK knockdown in HECV cells (HECVPTPRKkd) resulted in a decrease of cell proliferation and cell-matrix adhesion; however, increased cell spreading and motility were seen. Reduced focal adhesion kinase (FAK) and paxillin protein levels were seen in the PTPRK knockdown cells which may contribute to the inhibitory effect on adhesion. HECVPTPRKkd cells were more responsive to the treatment of fibroblast growth factor (FGF) in their migration compared with the untreated control and cells treated with VEGF. Moreover, elevated c-Src and Akt1 were seen in the PTPRK knockdown cells. The FGF-promoted cell migration was remarkably suppressed by an addition of PLCγ inhibitor compared with other small inhibitors. Knockdown of PTPRK suppressed the ability of HECV cells to form tubules and also impaired the tubule formation that was induced by FGF and conditioned medium of cancer cells. Taken together, it suggests that PTPRK plays dual roles in coordinating angiogenesis. It plays a positive role in cell proliferation, adhesion and tubule formation, but suppresses cell migration, in particular, the FGF-promoted migration. PTPRK bears potential to be targeted for the prevention of tumour associated angiogenesis.


Characterization of Antimicrobial-Producing Beneficial Bacteria Isolated from Huanglongbing Escape Citrus Trees.
The microbiome associated with crop plants has a strong impact on their health and productivity. Candidatus Liberibacter asiaticus (Las), the bacterial pathogen responsible for Huanglongbing (HLB) disease, lives inside the phloem of citrus plants including the root system. It has been suggested that Las negatively affects citrus microbiome. On the other hand, members of citrus microbiome also influence the interaction between Las and citrus. Here, we report the isolation and characterization of multiple putative beneficial bacteria from healthy citrus rhizosphere. Firstly, six bacterial strains showing antibacterial activity against two bacteria closely related to Las: Agrobacterium tumefaciens and Sinorhizobium meliloti were selected. Among them, Burkholderia metallica strain A53 and Burkholderia territorii strain A63 are within the β-proteobacteria class, whereas Pseudomonas granadensis strain 100 and Pseudomonas geniculata strain 95 are within the γ-proteobacteria class. Additionally, two gram-positive bacteria Rhodococcus jialingiae strain 108 and Bacillus pumilus strain 104 were also identified. Secondly, antimicrobial activity against three fungal pathogens: Alternaria alternata, Colletotrichum acutatum, Phyllosticta citricarpa, and two oomycetes: Phytophthora nicotianae and Phytophthora palmivora. Four bacterial strains Burkholderia territorii A63, Burkholderia metallica A53, Pseudomonas geniculata 95, and Bacillus pumilus 104 were shown to have antagonistic activity against the citrus root pathogen Phytophthora nicotianae based on dual culture antagonist assays and compartmentalized petri dish assays. The four selected bacteria were sequenced. Genes involved in phosphate solubilization, siderophore production and iron acquisition, volatile organic compound production, osmoprotection and osmotic tolerance, phytohormone production, antagonism, and nutrient competition were predicted and discussed related to the beneficial traits.


Expression patterns of members of the ethylene signaling-related gene families in response to dehydration stresses in cassava.
Drought is the one of the most important environment stresses that restricts crop yield worldwide. Cassava (Manihot esculenta Crantz) is an important food and energy crop that has many desirable traits such as drought, heat and low nutrients tolerance. However, the mechanisms underlying drought tolerance in cassava are unclear. Ethylene signaling pathway, from the upstream receptors to the downstream transcription factors, plays important roles in environmental stress responses during plant growth and development. In this study, we used bioinformatics approaches to identify and characterize candidate Manihot esculenta ethylene receptor genes and transcription factor genes. Using computational methods, we localized these genes on cassava chromosomes, constructed phylogenetic trees and identified stress-responsive cis-elements within their 5' upstream regions. Additionally, we measured the trehalose and proline contents in cassava fresh leaves after drought, osmotic, and salt stress treatments, and then it was found that the regulation patterns of contents of proline and trehalose in response to various dehydration stresses were differential, or even the opposite, which shows that plant may take different coping strategies to deal with different stresses, when stresses come. Furthermore, expression profiles of these genes in different organs and tissues under non-stress and abiotic stress were investigated through quantitative real-time PCR (qRT-PCR) analyses in cassava. Expression profiles exhibited clear differences among different tissues under non-stress and various dehydration stress conditions. We found that the leaf and tuberous root tissues had the greatest and least responses, respectively, to drought stress through the ethylene signaling pathway in cassava. Moreover, tuber and root tissues had the greatest and least reponses to osmotic and salt stresses through ethylene signaling in cassava, respectively. These results show that these plant tissues had differential expression levels of genes involved in ethylene signaling in response to the stresses tested. Moreover, after several gene duplication events, the spatiotemporally differential expression pattern of homologous genes in response to abiotic and biotic stresses may imply their functional diversity as a mechanism for adapting to the environment. Our data provide a framework for further research on the molecular mechanisms of cassava resistance to drought stress and provide a foundation for breeding drought-resistant new cultivars.


The interaction between a charged wall and its counterions: a condensation theory.
We use the theory of counterion condensation to calculate the potential of mean force between a charged planar wall and an oppositely charged ion of unsigned valence Z. We find two solutions to this problem, an outer potential when the Z-ion is relatively far from the wall and an inner one when it is relatively close. There is a discontinuous upward jump from one to the other branch, as the Z-ion approaches the wall. The jump must occur at the wall itself, and we attribute it to interaction with the condensed layer of counterions which resides on the wall. At an infinitesimal distance from the wall, the Z-ion encounters a repulsive force resisting penetration of the condensed layer. Then, when the Z-ion penetrates the condensed layer, Z univalent counterions are released from the condensed layer into the bulk solution, maintaining the effective charge on the wall at an invariant critical value. We discuss the possible connections of the theory with published data from molecular dynamics simulations on lipid bilayers.


Osteoblasts migration, attachment and human bone marrow-mesenchymal stem cells osteogenic differentiation towards surface engineered and growth factors conjugated poly(lactic acid) microspheres.
Recently, surface engineered biomaterials through surface modification are extensively investigated due to its potential to enhance cellular homing and migration which contributes to a successful drug delivery process. This study is focused on osteoblasts response towards surface engineered using a simple sodium hydroxide (NaOH) hydrolysis and growth factors conjugated poly(lactic acid) (PLA) microspheres. In this study, evaluation of the relationship of NaOH concentration with the molecular weight changes and surface morphology of PLA microspheres specifically wall thickness and porosity prior to in vitro studies was investigated. NaOH hydrolysis of 0.1 M, 0.3 M and 0.5 M were done to introduce hydrophilicity on the PLA prior to conjugation with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Morphology changes showed that higher concentration of NaOH could accelerate the hydrolysis process as the highest wall thickness was observed at 0.5 M NaOH with ~3.52 µm. All surface modified and growth factors conjugated PLA microspheres wells enhanced the migration of the cells during wound healing process as wound closure was 100% after 3 days of treatment. Increase in hydrophilicity of the surface engineered and growth factors conjugated PLA microspheres provides favorable surface for cellular attachment of osteoblast, which was reflected by positive DAPI staining of the cells' nucleus. Surface modified and growth factors conjugated PLA microspheres were also able to enhance the capability of the PLA in facilitating the differentiation process of mesenchymal stem cells (MSCs) into osteogenic lineage since only positive stain was observed on surface engineered and growth factors conjugated PLA microspheres. These results indicated that the surface engineered and growth factors conjugated PLA microspheres were non-toxic for biological environments and the improved hydrophilicity made them a potential candidate as a drug delivery vehicle as the cells can adhere, attach and proliferate inside it.


The spectrum of aeroallergen sensitization in children diagnosed with asthma during first 2 years of life.
Aeroallergens may trigger symptoms in sensitized children with asthma. Documentation of sensitization is crucial to enable effective implementation of measures to prevent asthma exacerbations. To document the sensitization patterns of very young children (≤2 years) with asthma, we retrospectively analyzed the skin-prick test (SPT) results of the largest referral center in the country. During a 4-year period, 432 children (median age, 1.21 years; male/female, 2.35) were referred. All patients had recurrent wheezing attacks and good response to inhaled bronchodilators and were diagnosed with asthma by their referring physician. SPT with eight aeroallergens (grass mix, weed mix, tree mix, mold mix, house-dust mite, cockroach, cat, and dog) was performed in 209 patients (full panel group) and the remaining 223 were tested only with a mixture of two house-dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae; house-dust mite group). The sensitization rates in house-dust mite and full panel groups were 3.2% (7/223) and 3.3% (7/209), respectively. Univariate and multivariate modeling was unable to identify a predictor for the presence of aeroallergen sensitization. During first 2 years of life, low rates of aeroallergen sensitization and lack of predictors of sensitization in children with asthma suggest that skin testing for aeroallergens may not be a routine procedure. When there is a high index of suspicion, testing only for indoor aeroallergens including house-dust mites, molds, and pets may identify the majority of sensitized children.


The effects of hypoventilation disorder on physiological and biochemical properties of the hindlimb muscles.
The purpose of this study was to determine the physiological and biochemical properties of hindlimb muscles after hypoventilation (HPO) induced by bilateral phrenic nerve denervation. Male Wistar rats (10 weeks-old) underwent HPO by the phrenic nerve denervation at the cervical level or sham surgery. Analyses were performed 4, 8, and 12 weeks after the surgery. The myosin heavy chain (MHC) isoform profile and in vitro isometric contractile properties of the soleus (SOL) and extensor digitrum longus muscles (EDL) were analyzed. From the postoperative period, HPO induced characteristic changes in SpO2 such as hypoventilation disorder. After 12 weeks, significant increases in MHC1 and significant decreases in MHC2a were observed in the MHC isoform composition in SOL. Moreover, significant increases in MHC2a and significant decreases in MHC2b were also observed in the MHC isoform composition in EDL muscles in the HPO compared with sham (SHM) group. In our study, the tidal volume after unilateral phrenic nerve denervation decreased by approximately 12%, and that after bilateral phrenic nerve denervation decreased by approximately 35%. We concluded that the reduction in behavioral activity levels in the HPO group may have resulted in changes of the peripheral skeletal muscles as a result of disuse atrophy.


[Current state of wavefront guided corneal surgery to correct refraction disorders].
The present review describes the current status of wavefront-guided corneal surgery and up-to-date results. Wavefront-guided LASIK procedures performed to date achieved uncorrected vision of i.o or better in a larger number of patients than with conventional LASIK surgery, but the "eagle eye" has remained the exception. In part of the patients reductions of higher order aberrations could be obtained, but in the majority of ca-ses an increase was observed. This increase was however less than with conventional LASIK surgery. Correction of higher order aberrations has not yet been perfected since the predictability of corrections appears to be deserving of improvement on the one hand and aberrations are still induced by the technique on the other hand.


Colloidal transport in twisted lattices of optical tweezers.
We simulate the transport of colloidal particles driven by a static and homogeneous drift force, and subject to the optical potential created by two lattices of optical tweezers. The lattices of optical tweezers are parallel to each other, shifted, and rotated by a twist angle. Due to a negative interference between the potential of the two lattices, flat channels appear in the total optical potential. At specific twist angles, known as magic angles, the flat channels percolate the entire system and the colloidal particles can then be transported using a weak external drift force. We characterize the transport in both square and hexagonal lattices of twisted optical tweezers.


Recovery time of independent poststroke life habits: Part II.
The purposes of this study were to determine the time of the recovery of poststroke life habits and to identify prognostic indicators associated with recovery time among stroke patients in a rehabilitation program. A sample of 421 stroke patients who were admitted to a rehabilitation center was recruited from medical records available from January 1987 to December 1992. The relation between the achievement of independent life habits including bed mobility, transfers and ambulation, bathing activities, dressing activities, eating activities, home activities, sphincter control, and sleep with the potential covariates associated with recovery time was assessed through the analysis of survival data using the Cox maximum-likelihood proportional hazard models. The poststroke life habits obtained generated mean recovery times ranging from 5.51 to 57.60 days from admission to rehabilitation. The survival analysis revealed that the recovery time of the selected poststroke abilities was significantly influenced (p <.05) by one or several indicators; these included physical ability and neuropsychological and life habit characteristics. With this precious information, stroke rehabilitation specialists may be able to reduce the length of time required to recover independent poststroke life habits by treating the specific neuropsychological, physical, and life habit characteristics identified in this study. A faster poststroke recovery would reduce the socioeconomic impact generated by stroke disability and would also ensure a better quality of life to the stroke survivor.


Characterization of the binding of plasminogen to fibrin surfaces: the role of carboxy-terminal lysines.
In the present study we have quantitatively characterized the interaction of purified human Glu- and Lys-plasminogen with intact and degraded fibrin by ligand-binding experiments using a radioisotopic dilution method and antibodies against human plasminogen. A fibrinogen monolayer was covalently linked to a solid support with polyglutaraldehyde and was treated with thrombin or with thrombin and then plasmin to respectively obtain intact and degraded fibrin surfaces. Under these conditions, a well-defined surface of fibrin is obtained (410 +/- 4 fmol/cm2) and, except for a 39-kDa fragment, most of the fibrin degradation products remain bound to the support. New binding sites for plasminogen were detected on the degraded surface of fibrin. These sites were identified as carboxy-terminal lysine residues both by inhibition of the binding by the lysine analogue 6-aminohexanoic acid and by carboxy-terminal end-group digestion with carboxypeptidase B. The binding curves exhibited a characteristic Langmuir adsorption isotherm saturation profile. The data were therefore analyzed accordingly, assuming a single-site binding model to simplify the analysis. Equilibrium dissociation constants (Kd) and the maximum number of binding sites (Bmax) were derived from linearized expression of the Langmuir isotherm equation. The Kd for the binding of Glu-plasminogen to intact fibrin was 0.99 +/- 0.17 microM and for degraded fibrin was 0.66 +/- 0.22 microM. The Kd for the binding of Lys-plasminogen to intact fibrin was 0.41 +/- 0.22 microM and for degraded fibrin was 0.51 +/- 0.12 microM.(ABSTRACT TRUNCATED AT 250 WORDS)


Energetics and dynamics in MbCN: CN--vibrational relaxation from molecular dynamics simulations.
The dynamics of the cyanide anion bound to sperm-whale myoglobin is investigated using atomistic simulations. With density-functional theory, a 2D potential energy surface for the cyanide-heme complex is calculated. Two deep minima with a stabilization energy of approximately 50 kcal/mol corresponding to two different binding orientations (Fe-CN and Fe-NC) of the ligand are found. The Fe-CN conformation is favored over Fe-NC by several kcal/mol. Mixed quantum mechanics/molecular mechanics calculations show that the binding orientation affects the bond strength of the ligand, with a significantly different bond length and a 25 cm-1 shift in the fundamental CN-frequency. For the molecular dynamics (MD) simulations, a 3-center fluctuating charge model for the Fe-CN unit is developed that captures polarization and ligand-metal charge transfer. Stability arguments based on the energetics around the active site and the CN- frequency shifts suggest that the Fe-CN conformation with epsilon-protonation of His epsilon 64 are most likely, which is in agreement with experiment. Both equilibrium and nonequilibrium MD simulations are carried out to investigate the relaxation time scale and possible relaxation pathways in bound MbCN. The nonequilibrium MD simulations with a vibrationally excited ligand reveal that vibrational relaxation takes place on a time scale of hundreds of picoseconds within the active site. This finding supports the hypothesis that the experimentally observed relaxation rate (3.6 ps) reflects the repopulation of the electronic ground state.


National assessment of early hospitalization after liver transplantation: Risk factors and association with patient survival.
Hospitalization is known to occur frequently in the first 6 months following liver transplantation (LT). Using a novel data linkage between the Scientific Registry of Transplant Recipients and Centers for Medicare and Medicaid Services, our study has 2 objectives: (1) to determine risk factors for "early" hospitalization (ie, within 6 months of LT); and (2) to quantify the importance of hospitalization history in the first 6 months with respect to subsequent patient survival (ie, survival, conditional on surviving 6 months post-LT). The study population consisted of patients aged ≥18 years who underwent deceased donor LT between January 1, 2003 and December 31, 2010, with Medicare as primary or secondary insurance and were discharged alive from the index LT hospitalization (n = 7220). The early hospitalization rate was 2.76 per patient-year and was significantly associated with many recipient factors (eg, recipient age, hepatitis C, diabetes, poor renal function including dialysis, and recipient of transjugular intrahepatic portosystemic shunt procedure before LT), as well as donor race and donation after cardiac death. Conditional on surviving 6 months after LT, the covariate-adjusted death rate increased by 22% for each additional hospitalization occurring in the first 6 months (hazard ratio, 1.22; P < 0.001). In conclusion, several LT recipient factors are significantly associated with early hospitalization. Moreover, a patient's hospitalization profile during follow-up months 0-6 is a very strong predictor of survival thereafter. Efforts and resources should be devoted toward identifying LT recipients at risk for early hospitalization and modifying the actionable risk factors such as hepatitis C, diabetes, and body mass index to improve resource utilization and overall outcomes. Liver Transplantation 23 1143-1152 2017 AASLD.


Langerhans cell histiocytosis: a 10-year review.
Hospital records of seventeen patients (11 males & 6 females) with Langerhans cell histiocytosis, confirmed by electron microscopic demonstration of Birbeck granules, were studied retrospectively from October 1982 to October 1992 at Taichung Veterans General Hospital. The ages at presentation ranged from 5 months to 17 years (a median of 6 years). The clinical features were protean and included fever, pain, bony lesions, lung lesions, abnormal dentition, diabetes insipidus, oral ulcer, otorrhea, dermatitis, anemia, thrombocytopenia, lymphadenopathy, and hepatosplenomegaly. Skull and femur were the most common sites of bony lesions. The main therapeutic modalities were excision, radiotherapy, and chemotherapy with vincristine and prednisolone. The young age at presentation, several involved organ systems, presence of organ dysfunction, and clinical diagnosis with Letterer-Siwe disease were poor prognostic factors. Although Langerhans cell histiocytosis is not a rare disease, the cause is still unknown. It needs further research to disclose the mystery.


Leukocyte-specific protein 1 links TNF receptor-associated factor 1 to survival signaling downstream of 4-1BB in T cells.
4-1BB is a member of the TNFR superfamily, which contributes to the activation of signaling pathways required for the survival of activated and memory T cells. We have shown previously that TRAF1, an adaptor protein recruited to 4-1BB, is required for 4-1BB-mediated CD8 T cell survival in vivo. With the use of a proteomics approach in primary T cells, we have identified LSP1 as a novel protein recruited to the 4-1BB signaling complex in a TRAF1-dependent manner. Further characterization of the interaction between TRAF1 and LSP1 revealed that LSP1 requires the TRAF-N domain of TRAF1 for direct association. Similarly to TRAF1(-/-) T cells, LSP1(-/-) T cells exhibit impaired ERK activation following stimulation through 4-1BB and consequently, are unable to down-modulate expression of the proapoptotic Bcl-2 family member Bim. Moreover, we demonstrate that the absence of LSP1 expression leads to defective expansion and survival of T cells in response to 4-1BB stimulation. Thus, we have identified LSP1 as a new mediator involved in 4-1BB signaling and T cell survival. Collectively, our work shows that TRAF1 and LSP1 cooperate downstream of 4-1BB to activate ERK signaling and down-modulate the levels of Bim leading to enhanced T cell survival.


Review on Current Status of Echinocandins Use.
Fungal infections are rising all over the world every year. There are only five medical compound classes for treatment: triazoles, echinocandins, polyenes, flucytosine and allylamine. Currently, echinocandins are the most important compounds, because of their wide activity spectrum and much lower sides effects that may occur during therapy with other drugs. Echinocandins are secondary metabolites of fungi, which can inhibit the biosynthesis of β-(1,3)-D-glucan. These compounds have fungicidal and fungistatic activity depending on different genera of fungi, against which they are used. Echinocandin resistance is rare-the major cause of resistance is mutations in the gene encoding the β-(1,3)-D-glucan synthase enzyme. In this review of the literature we have summarized the characteristics of echinocandins, the mechanism of their antifungal activity with pharmacokinetics and pharmacodynamics, and the resistance issue.


Electrophilic reactivity and skin sensitization potency of SNAr electrophiles.
We published in 2011 a quantitative mechanistic model (QMM) for skin sensitization potency of SNAr electrophiles in the mouse local lymph node assay (LLNA). In this model, potency was correlated with a combination of σ* for the leaving group and the total σ(-) values of the other substituents in the aromatic ring. Shortly afterward Natsch et al. published a kinetic study in which rate constants were determined for reactions of SNAr electrophiles with the cysteine-based peptide Ac-RFAACAA (Cys-peptide) that is used in the direct peptide reactivity assay (DPRA), and correlations were sought between these rate constants and sensitization potency in the LLNA. These two publications together have enabled the present study, aiming to develop a linear free energy relationship (LFER) correlating Cys-peptide reactivity with a reactivity parameter (RP) based on a combination of σ* and σ(-) substituent constants and, by analyzing differences between the QMM based on RP and the QMM based on Cys-peptide rate constants, to gain further insights into the underlying chemistry of skin sensitization. For the 2,4-dinitro-X-subsituted benzenes (DNXB), the rate constants of Natsch et al. are well correlated with the reactivity parameter used in our earlier work, with two outliers. These are the compounds with X = F and X = SCN, which are both substantially more reactive toward Cys-peptide than predicted from comparison of their RP values with those of the other DNXB compounds. These two compounds are both negative outliers from a correlation of sensitization potency with experimental rate constants, but fit well to the correlation of sensitization potency with RP values. With these two compounds excluded, sensitization potency is well correlated with the experimental rate constants for the DNXB compounds (X = SO3(-), I, Br, Cl) together with 2,4-dichloro-1-nitrobenzene and 1,3,4,5-tetrachloro-2,6-dicyanobenzene. The regression equation is pEC3 = 0.88 log k + 4.03, R(2) = 0.966. The implication of DNFB being an outlier is that the model Cys-peptide nucleophile is substantially more sterically hindered than the cutaneous nucleophile(s) involved in the sensitization process. The pattern seen with 2,4-dinitrothiocyanatobenzene suggests that this compound reacts as an SNAr electrophile in the sensitization process, but by a different pathway, acting as a CN transfer agent, with the model Cys-peptide. For two further compounds, 2,4,6-trinitrochlorobenzene and 2,4,6-trinitrobenzenesulfonate, the Cys-peptide rate constants are well predicted by the reactivity parameter based on displacement of the Cl or SO3(-) substituent, but their sensitization potency is underestimated by both the Cys-peptide rate constant and this reactivity parameter. However, potency of these two compounds is well predicted by a reactivity parameter calculated on the basis of displacement of the 2-nitro group. This is interpreted as a case of sensitization being driven by the thermodynamically favored rather than the kinetically favored reaction product.


Systemic sclerosis and bilateral lung transplantation: a single centre experience.
Lung involvement is the leading cause of death in systemic sclerosis (SSc), but lung transplantation (LT) for systemic disease remains controversial. Our objective was to comprehensively evaluate post-LT outcomes for SSc compared to idiopathic pulmonary fibrosis (IPF). We retrospectively evaluated bilateral LT recipients (LTRs) with SSc or IPF at our centre between January 1, 2003 and December 31, 2007. The primary end-point was all-cause mortality at 1 yr post-LT. Secondary end-points included assessments of acute rejection (AR), pulmonary function, infection and chronic rejection. 14 patients with SSc and 38 patients with IPF underwent LT. Apart from a younger SSc cohort (53.2 versus 58.8 yrs; p = 0.02), the two groups were well matched. 1-yr all-cause mortality was no different between SSc (6.6%) and IPF (13.1%) groups, after adjusting for age (p = 0.62). Rates of (AR) ≥2 were significantly increased for the SSc compared with the IPF group (hazard ratio (HR) 2.91; p = 0.007). Other end-points, including chronic rejection, infection and pulmonary function, showed no differences. SSc LTRs experience similar survival 1 yr post-LT when compared to IPF. AR rates may be significantly higher in the SSc group. Longer follow-up is necessary to determine the effects of gastrointestinal dysfunction and AR on late allograft function in SSc LTR.


[The results of phase III multicenter open randomized controlled study REM-Chol-III-16 in patients with intrahepatic cholestasis syndrome caused by chronic diffuse liver diseases].
To assess the safety and efficacy of Remaxol, solution for infusion, compared with parenteral form of S-adenosyl-L-methionine, in the treatment of patients with intrahepatic cholestasis syndrome accompanying chronic diffuse liver diseases of various etiology. In a multicenter open-label comparative study of the safety and efficacy of Remaxol (inosine + meglumine + methionine + nicotinamide + succinic acid) 317 patients aged 18 to 65 years were randomized into 2 groups: patients of the experimental group (n=168) received intravenous Remaxol, solution for infusion, 400 ml, and patients of the control group (n=149) Heptral (S-adenosyl-L-methionine) 800 mg. The duration of treatment was 10 days. The primary efficacy endpoint was the proportion of patients who responded to therapy, as demonstrated by dynamics of laboratory parameters of liver functional status: decrease in gamma glutamyl transpeptidase level by 40%, and/or alkaline phosphatase level by 30%, and/or decrease total bilirubin level by 30% from baseline by the end of the treatment course. The proportion of responders was 51% in the Remaxol group vs. 44.9% in the Heptral group (p=0.303); the lower limit of the one-sided 95% confidence interval for the difference in the proportions of responders was -4.01%, which exceeds the non-inferiority margin pre-defined by the study protocol, thus, the non-inferiority hypothesis was proven, i.e. Remaxol at a dose of 400 ml/day demonstrates similar efficacy to Heptral at a dose of 800 mg/day in patients with intrahepatic cholestasis syndrome associated with chronic diffuse liver diseases. Similar positive trends in the levels of transaminases, total bilirubin and the severity of pruritus were revealed in both treatment groups. We did not reveal statistically significant between-group differences in the frequency of adverse events definitely related to the study treatment. Administration of Remaxol as a part of the pathogenetic therapy of patients with intrahepatic cholestasis syndrome who need hepatoprotection is justified.


Preliminary data on isolation of an elastase-like proteinase and its inhibitor from ovine neutrophil granulocytes.
Ovine polymorphonuclear leukocytes (PMNs) were purified by counterflow centrifugation of the buffy coat. The resulting cell preparation was gently sonicated and ultracentrifuged for separation of cytosol and cell organelles. The proteolytic activity of the isolated enzyme was determined with the specific substrate MeO-Suc-Ala-Ala-Pro-Val-Nan (methoxysuccinyl-[L-alanyl]2-L-prolyl-L-valine p-nitroanilide). Elastase-like activity was identified in the insoluble (particular) fraction, while an inhibitor of elastase activity was found in the supernatant (cytosolic fraction). Further purification of the elastase-like enzyme was achieved by cation exchange chromatography (SP-Sephadex C-25 and CM-Sephadex C-25) and gel permeation chromatography (Bio-Gel P-30). Purification of the inhibitor from cytosol was accomplished using anion exchange chromatography (DE32 diethylaminoethyl cellulose) and two gel permeation steps (Sephadex G-75 and TSK-G 2000 SW - HPLC column). Degrees of purity in all separation steps were controlled with SDS-polyacrylamide gel electrophoresis. The molecular mass of the elastase-like enzyme is in a range of 25 to 27 kDa. The isoelectric point is between 8.0 and 9.0. Three isoenzymes were found. The optimal activity lies at pH 8.0. The molecular mass of the inhibitor is about 40 kDa.


Unravelling the geometry of data matrices: effects of water stress regimes on winemaking.
A new method is proposed for unravelling the patterns between a set of experiments and the features that characterize those experiments. The aims are to extract these patterns in the form of a coupling between the rows and columns of the corresponding data matrix and to use this geometry as a support for model testing. These aims are reached through two key steps, namely application of an iterative geometric approach to couple the metric spaces associated with the rows and columns, and use of statistical physics to generate matrices that mimic the original data while maintaining their inherent structure, thereby providing the basis for hypothesis testing and statistical inference. The power of this new method is illustrated on the study of the impact of water stress conditions on the attributes of 'Cabernet Sauvignon' Grapes, Juice, Wine and Bottled Wine from two vintages. The first step, named data mechanics, de-convolutes the intrinsic effects of grape berries and wine attributes due to the experimental irrigation conditions from the extrinsic effects of the environment. The second step provides an analysis of the associations of some attributes of the bottled wine with characteristics of either the matured grape berries or the resulting juice, thereby identifying statistically significant associations between the juice pH, yeast assimilable nitrogen, and sugar content and the bottled wine alcohol level.


An aqueous zinc-ion battery based on copper hexacyanoferrate.
A new zinc-ion battery based on copper hexacyanoferrate and zinc foil in a 20 mM solution of zinc sulfate, which is a nontoxic and noncorrosive electrolyte, at pH 6 is reported. The voltage of this novel battery system is as high as 1.73 V. The system shows cyclability, rate capability, and specific energy values near to those of lithium-ion organic batteries based on Li4 Ti5 O12 and LiFePO4 at 10 C. The effects of Zn(2+) intercalation and H2 evolution on the performance of the battery are discussed in detail. In particular, it has been observed that hydrogen evolution can cause a shift in pH near the surface of the zinc electrode, and favor the stabilization of zinc oxide, which decreases the performance of the battery. This mechanism is hindered when the surface of zinc becomes rougher.


Dual Energy CT - a Novel Technique for Diagnostic Testing of Fragility Fractures of the Pelvis.
Background The incidence of fragility fractures of the pelvis is increasing. Established methods to diagnose this condition include X-rays, computed tomography (CT) and magnetic resonance imaging (MRI). Dual energy CT (DECT) is a modern technology for the imaging of bone oedema/bruises and has been used in injuries of the extremities and spine. It is unclear whether this technique can also be used in fragility fractures of the pelvis. The aim of this study was to perform a literature research and survey of the "AG Becken III" members of the German Society of Trauma Surgery (DGU) on the usefulness of DECT in fractures of the pelvis. Material and Methods A PubMed-based literature search on DECT comprised the key words "Dual Energy CT", "Pelvis/Pelvic", "Insufficiency" and "Fractures" and their combinations. Thirty-two publications were reviewed completely (full text). Finally, 15 articles were chosen and included in the current study. The survey of the members of the "AG Becken III" was based on a questionnaire and aimed to determine the popularity and potential benefits of DECT in comparison to established diagnostic options. Results No studies on the use of DECT in fragility fractures of the pelvis were identified; the few articles found referred to fractures of the extremities and spine. The response rate to the questionnaire was 25/83 (30.1 %). The participants had a mean personal experience of 8.4 years/151.6 interventions in pelvic surgery. Although some respondents had heard of DECT, this technique - if available - was only used in other indications. However, the potential benefit of DECT was recognised, especially in the acute diagnostic testing of fragility fractures. There is limited consensus on the optimal diagnostic test (CT vs. MRI) of pelvic fractures. Conclusion Although DECT is already established for other indications and is regarded as a promising method by all respondents of the "AG Becken III", DECT is not yet routinely used for diagnostic testing of fragility fractures of the pelvis. Potential advantages of DECT include its greater sensitivity than CT in detecting bone oedema with equal radiation exposure. Unlike MRI, it is available 24 hours/7 days.


Unsuspected thyrotoxicosis and hyperemesis gravidarum in Asian women.
This report describes three women with hyperemesis gravidarum caused by previously undiagnosed thyrotoxicosis. All three women were eight weeks pregnant and only one woman had typical features of thyrotoxicosis. Hyperemesis could not be controlled by anti-emetics. The patients were successfully treated with antithyroid drugs. Anti-thyroid treatment does not need to be continued once resolution of symptoms and thyrotoxicosis have occurred.


[Idiopathic scoliosis in a student population].
The etiology of idiopathic thoracic scoliosis is a relevant problem in the fields of scholastic medicine and orthopaedics. This disease affects a population of pre-adolescent between ten and fifteen years of age. This study is based on our observations within a population of junior high school students in a suburban town of central Italy. Our data are based on clinical examinations, and the analysis of biophysical and environmental factors evidentiate the genetic and hereditary factors that are of prime importance in the pathogenesis of thoracic idiopathic scoliosis. It's our goal, to inform the scholastic doctor, the orthopaedist, the pediatrician and the internist on the main clinical and evolutionary aspects of thoracic idiopathic scoliosis and other related vertebral pathology. We therefore believe, that a good diagnosis should be based on a thorough genetic and clinical examination; not to mention an examination of vertebral bone morphology in order to exclude other forms of thoracic scoliosis.


Wiskott-Aldrich syndrome iPS cells produce megakaryocytes with defects in cytoskeletal rearrangement and proplatelet formation.
Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterised by microthrombocytopenia, complex immunodeficiency, autoimmunity, and haematologic malignancies. It is caused by mutations in the gene encoding WAS protein (WASP), a regulator of actin cytoskeleton and chromatin structure in various blood cell lineages. The molecular mechanisms underlying microthrombocytopenia caused by WASP mutations remain elusive. Murine models of WASP deficiency exhibited only mild thrombocytopenia with normal-sized platelets. Here we report on the successful generation of induced pluripotent stem cell (iPSC) lines from two patients with different mutations in WASP (c.1507T>A and c.55C>T). When differentiated into early CD34+ haematopoietic and megakaryocyte progenitors, the WAS-iPSC lines were indistinguishable from the wild-type iPSCs. However, all WAS-iPSC lines exhibited defects in platelet productionin vitro. WAS-iPSCs produced platelets with more irregular shapes and smaller sizes. Immunofluorescence and electron micrograph showed defects in cytoskeletal rearrangement, F-actin distribution, and proplatelet formation. Proplatelet defects were more pronounced when using culture systems with stromal feeders comparing to feeder-free culture condition. Overexpression of WASP in the WAS-iPSCs using a lentiviral vector improved proplatelet structures and increased the platelet size. Our findings substantiate the use of iPSC technology to elucidate the disease mechanisms of WAS in thrombopoiesis.


The AD tau core spontaneously self-assembles and recruits full-length tau to filaments.
Tau accumulation is a major pathological hallmark of Alzheimer's disease (AD) and other tauopathies, but the mechanism(s) of tau aggregation remains unclear. Taking advantage of the identification of tau filament cores by cryoelectron microscopy, we demonstrate that the AD tau core possesses the intrinsic ability to spontaneously aggregate in the absence of an inducer, with antibodies generated against AD tau core filaments detecting AD tau pathology. The AD tau core also drives aggregation of full-length wild-type tau, increases seeding potential, and templates abnormal forms of tau present in brain homogenates and antemortem cerebrospinal fluid (CSF) from patients with AD in an ultrasensitive real-time quaking-induced conversion (QuIC) assay. Finally, we show that the filament cores in corticobasal degeneration (CBD) and Pick's disease (PiD) similarly assemble into filaments under physiological conditions. These results document an approach to modeling tau aggregation and have significant implications for in vivo investigation of tau transmission and biomarker development.


BAHA in single-sided deafness: patient compliance and subjective benefit.
Despite most patients with single-sided deafness (SSD) after operation for acoustic neuroma (AN) perceiving a significant hearing handicap, less than 25% are interested in bone-anchored hearing aid (BAHA) implantation. We evaluated the treatment compliance of BAHA in SSD and the effect of BAHA on the subjective handicap. Part 1: It was determined, from our first study, how many of the SDD patients after operation for AN (n = 59) and interested in BAHA (n = 14) had been implanted. Part 2: Of 23 BAHA-implanted patients with SSD due to various causes, including the implanted patients from the previous study, 21 answered a questionnaire on the BAHA treatment compliance and the subjective handicap with and without BAHA. Part 1: Of the 14 patients from our first study who were interested in implantation for BAHA, 11 had been implanted (18.6% of all 59 patients). Part 2: Of the 21 patients with SSD, 95% still used BAHA, and of these, 81% used it more than 8 hours a day. Of the patients, 90% considered BAHA a moderate to significant aid; it reduced the subjective hearing handicap from 7.4 to 2.3 arbitrary units on a visual analog scale. Despite the subjective handicap perception among most patients with SSD after AN surgery, less than 20% chose treatment with BAHA. Conversely, patients with SSD choosing implantation had high treatment compliance and felt that BAHA reduced their handicap. Thus, when selected by the patients after testing, BAHA is effective in SSD and results in a high patient compliance.


Identity of Schizaphis species (Hemiptera: Aphididae) in the United Kingdom: are they a threat to crops?
The greenbug, Schizaphis graminum (Rondani), is a major pest of cereals in some parts of the world and is of particular concern because it can be resistant to some insecticides and overcome the resistance of crops. In the UK, it has never been found on crops, but two rather little-known and closely-related species (Schizaphis holci and Schizaphis agrostis) are associated with the wild grasses, Holcus lanatus and Agrostis stolonifera. Since 1987, winged (alate) aphids morphologically resembling the greenbug have been found in increasing numbers in 12.2 m high suction-trap samples of the Rothamsted Insect Survey (RIS); hence, studies were undertaken to establish their identity. Clones (=asexual lineages) established from populations collected from H. lanatus in southern England showed strong preference for Holcus over Agrostis and Hordeum in laboratory tests and produced sexual morphs when transferred to short-day conditions, the males being apterous, as expected for S. holci. Multivariate morphometric comparisons of alatae caught in UK RIS suction traps in 2007 and 2011 with named specimens from museum collections, including S. graminum from many countries, indicated that the suction-trapped alatae were mostly S. agrostis and S. holci. Cytochrome c oxidase subunit I (COI) mtDNA obtained from 62 UK specimens from suction-traps had 95.4-100% sequence identity with US specimens of S. graminum. Two of the UK specimens had identical COI sequence to the US sorghum-adapted form of S. graminum, and these specimens also had 100% identity with a 640 bp fragment of nDNA CytC, indicating that this form of S. graminum may already be present in the UK. Present and future economic implications of these results are discussed.


Laser diffractometry as a technique for the rapid assessment of aerosol particle size from inhalers.
The rapid assessment of aerosols produced by medicinal inhalers is highly desirable from several standpoints, including the assurance of product quality, the development of new delivery systems, and the need to meet an increasing requirement by regulatory bodies for reliable in vitro performance data. Particle size analysis has traditionally been undertaken by cascade impactor on account of the direct assessment of active pharmaceutical ingredient(s) (APIs) that is possible by this method. However, laser diffractometry is less labor-intensive, more rapid, and can be a less invasive procedure. The technique provides meaningful results; as long as precautions are taken to validate that the measurements are an accurate reflection of the distribution of API mass as a function of particle or droplet size. We begin the review by examining the underlying theory of the laser diffraction method. After a brief description of current laser diffractometers used in inhaler measurements, we continue by examining the range of applications by inhaler class. We then examine the basis upon which inhaler measurements made by laser-diffractometry can be compared with equivalent particle size distribution data from compendial techniques. We conclude the assessment of the technique by developing guidelines for its valid application as a component of the range of in vitro methods that are available for inhaler performance assessment.


Results from transcranial Doppler examination on children and adolescents with sickle cell disease and correlation between the time-averaged maximum mean velocity and hematological characteristics: a cross-sectional analytical study.
Transcranial Doppler (TCD) detects stroke risk among children with sickle cell anemia (SCA). Our aim was to evaluate TCD findings in patients with different sickle cell disease (SCD) genotypes and correlate the time-averaged maximum mean (TAMM) velocity with hematological characteristics. Cross-sectional analytical study in the Pediatric Hematology sector, Universidade Federal de São Paulo. 85 SCD patients of both sexes, aged 2-18 years, were evaluated, divided into: group I (62 patients with SCA/Sß(0) thalassemia); and group II (23 patients with SC hemoglobinopathy/Sß(+) thalassemia). TCD was performed and reviewed by a single investigator using Doppler ultrasonography with a 2 MHz transducer, in accordance with the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol. The hematological parameters evaluated were: hematocrit, hemoglobin, reticulocytes, leukocytes, platelets and fetal hemoglobin. Univariate analysis was performed and Pearson's coefficient was calculated for hematological parameters and TAMM velocities (P < 0.05). TAMM velocities were 137 ± 28 and 103 ± 19 cm/s in groups I and II, respectively, and correlated negatively with hematocrit and hemoglobin in group I. There was one abnormal result (1.6%) and five conditional results (8.1%) in group I. All results were normal in group II. Middle cerebral arteries were the only vessels affected. There was a low prevalence of abnormal Doppler results in patients with sickle-cell disease. Time-average maximum mean velocity was significantly different between the genotypes and correlated with hematological characteristics.


Redescription of the Philippine leafhopper genus Iposcopus Baker (Hemiptera: Cicadellidae: Idiocerinae).
The Philippine leafhopper genus Iposcopus Baker is redescribed. The male and female genitalia of I. breviceps and I. distanti are described and illustrated for the first time. Baker (1915) established the genus Iposcopus and included two new species, I. breviceps and I. distanti (the type species) from the Philippines. Previously, only the external morphology and color have been described, not the genitalia. Here we first give a more complete description of the species, including male and female genitalia.


Staphylococcus aureus VraX specifically inhibits the classical pathway of complement by binding to C1q.
VraX is a protein secreted by Staphylococcus aureus, an important human pathogen. A dramatic over expression of VraX is observed when S. aureus is exposed to several antimicrobial agents; however, its function remains unclear. Here, we aimed to reveal the function of this protein and the mechanism by which it affects the immune system to enhance the pathogenesis of the bacterium. Our results showed that VraX specifically inhibited the classical pathway of the complement system. In particular, VraX could bind to the C1q protein and block the formation of the C1 complex. Deletion of VraX decreased the pathogenesis of S. aureus. Our findings indicate that over expression of VraX might be a protective response for S. aureus survival.


[Study on application of SELDI protein chip technique in diagnosis of systemic lupus erythematosus of yin deficiency caused internal heat syndrome].
To investigate the application of surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI) protein chip in diagnosis and Chinese medicie syndrome type researching of systemic lupus erythematosus (SLE). Eighteen female SLE patients of mild/moderate degree with yin-deficiency caused internal heat syndrome (YDHS) were enrolled in the treatment group, and 15 women healthy volunteers was set up as the control group. Using SELDI method, the pre-, mid- and post-treatment peripheral blood mononuclear cell (PBMC) protein fingerprint of them was created respectively, which was then managed to screen out the markers by using ZUCI-PDAS package for establishing a diagnosis model. Study was completed in 15 cases of the treatment group with 2 cases dropped out and 1 case lost. Before treatment, 44 protein peaks in the treatment group were found significantly different to those in the control group (P<0.01), and the sensitivity and specificity of the created models, 10542 Da m/z and 2554 Da m/z, reached 100%. After a 12-week treatment, 30 peaks were found significantly different between the two groups (P<0.01), and the sensitivity of 3365, 7104, 3882 and 6796 Da m/z created peak models was 100%, its specificity being 93.33%. Comparing the 35 samples (pre-, mid- and post-treatment) got from the treatment group with the 15 samples from the control group, significant difference was found in 55 peaks (P<0.01), the sensitivity and specificity of the 7103, 3882, 7143 Da m/z created peak models was 100% and 91.43% respectively. Significant differences of PBMC protein expression patterns were found between SLE patients of YDHS and healthy persons at times of before, during and after treatment, suggesting that SELDI may be used as a new method to create the diagnosis model, and its application in effecter protein screening, activity scoring and Chinese medicine syndrome type researching are expectable and waiting for further study in depth.


Circulating levels of neuroactive steroids in patients with binge eating disorder: a comparison with nonobese healthy controls and non-binge eating obese subjects.
Increased plasma levels of allopregnenolone (3alpha,5alpha-tetrahydroprogesterone [3alpha,5alpha-THP]), dehydroepiandrosterone (DHEA), and DHEA sulphate (DHEA-S) have been reported in patients with anorexia nervosa or bulimia nervosa. To assess whether those changes are related to malnutrition, we investigated plasma levels of neuroactive steroids in women with binge eating disorder (BED) who compulsively binge as bulimic patients, but do not incur malnutrition. Sixty-eight women participated in the study (31 nonobese healthy controls, 9 nonobese patients with BED, 16 obese patients with BED, and 12 obese non-binge eating women). Blood samples were collected in the morning for determination of plasma levels of 3alpha,5alpha-THP, DHEA, DHEA-S, and cortisol. Nonobese BED women had significantly higher plasma levels of DHEA, DHEA-S, and 3alpha,5alpha-THP than nonobese healthy women. Similarly, obese individuals with BED exhibited significantly higher neurosteroid plasma levels than non-binge eating obese subjects. No significant differences in plasma cortisol levels were observed among the groups. This study shows increased plasma levels of neuroactive steroids in BED patients. These findings could have been influenced by methodologic limitations (e.g., the absence of diurnal sampling). However, they suggest that if malnutrition is involved in the determination of increased plasma levels of neuroactive steroids in people with anorexia or bulimia nervosa, then different factors may induce similar effects in people with BED. Alternatively, common unknown factors could be responsible for neurosteroid changes in anorexia nervosa, bulimia nervosa, and BED.