The Effect of Increasing Autonomy Through Choice on Young Children's Physical Activity Behavior.
Increasing autonomy by manipulating the choice of available physical activity options in a laboratory setting can increase physical activity in older children and adults. However, the effect of manipulating the number of physically active choices has yet to be examined in young children in a gymnasium environment. Twenty children (n = 10 girls, 6.1 ± 1.4 years old) individually participated in 2 [low choice (LC), high choice (HC)] free-choice activity conditions for 30 minutes in a 4360 square foot gymnasium. Children had access to 2 or 8 physical activity options in the LC and HC conditions, respectively. Physical activity behavior was measured via accelerometry. Children's 30-minute accelerometer counts increased (P < .03) from the LC (2675 ± 294 counts·min-1) to the HC (3224 ± 280 counts·min-1) condition. Providing greater autonomy through choice of a greater number of physically active options increased young children's physical activity participation by 20.5%.


Why are ionic liquid ions mainly associated in water? A Car-Parrinello study of 1-ethyl-3-methyl-imidazolium chloride water mixture.
In this study we present the results of a first principles molecular dynamics simulation of a single 1-ethyl-3-methyl-imidazolium chloride [C(2)C(1)im][Cl] ion pair dissolved in 60 water molecules. We observe a preference of the in plane chloride coordination with respect to the cation ring plane as compared to the energetic slightly more demanding on top coordination. Evaluation of the different radial distribution functions demonstrates that the structure of the hydration shell around the ion pair differs significantly from bulk water and that no true ion pair dissociation in terms of completely autonomous solvation shells takes place on the timescale of the simulation. In addition, dipole moment distributions of the solvent in distinct solvation shells around different functional parts of the [C(2)C(1)im][Cl] ion pair are calculated from maximally localized Wannier functions. The analysis of these distributions gives evidence for a depolarization of water molecules close to the hydrophobic parts of the cation as well as close to the anion. Examination of the angular distribution of different OH(H(2)O)-X angles in turn shows a linear coordination of chloride accompanied by a tangential orientation of water molecules around the hydrophobic groups, being a typical feature of hydrophobic hydration. Based on these orientational aspects, a structural model for the obvious preference of ion pair association is developed, which justifies the associating behavior of solvated [C(2)C(1)im][Cl] ions in terms of an energetically favorable interface between the solvation shells of the anion and the hydrophobic parts of the cation.


GSK126 (EZH2 inhibitor) interferes with ultraviolet A radiation-induced photoaging of human skin fibroblast cells.
Polycomb group genes (PcG) encode chromatin modification proteins that are involved in the epigenetic regulation of cell differentiation, proliferation and the aging processes. The key subunit of the PcG complex, enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), has a central role in a variety of mechanisms, such as the formation of chromatin structure, gene expression regulation and DNA damage. In the present study, ultraviolet A (UVA) was used to radiate human dermal fibroblasts in order to construct a photo-aged cell model. Subsequently, the cell viability assay, Hoechst staining, apoptosis detection using flow cytometry, senescence-associated β-galactosidase (SA-β-gal) staining and erythrocyte exclusion experiments were performed. GSK126, a histone methylation enzyme inhibitor of EZH2, was used as an experimental factor. Results suggested that GSK126 downregulated the mRNA expression levels of EZH2 and upregulated the mRNA expression levels of BMI-1. Notably, GSK126 affected the transcription of various photoaging-related genes and thus protected against photoaging induced by UVA radiation.


Mutagenesis and more: umuDC and the Escherichia coli SOS response.
The cellular response to DNA damage that has been most extensively studied is the SOS response of Escherichia coli. Analyses of the SOS response have led to new insights into the transcriptional and post-translational regulation of processes that increase cell survival after DNA damage as well as insights into DNA-damage-induced mutagenesis, i.e., SOS mutagenesis. SOS mutagenesis requires the recA and umuDC gene products and has as its mechanistic basis the alteration of DNA polymerase III such that it becomes capable of replicating DNA containing miscoding and noncoding lesions. Ongoing investigations of the mechanisms underlying SOS mutagenesis, as well as recent observations suggesting that the umuDC operon may have a role in the regulation of the E. coli cell cycle after DNA damage has occurred, are discussed.


The Gordon Memorial Lecture: novel approaches to controlling bacterial infections.
1. There is huge emphasis in veterinary and agricultural science in understanding the basics of processes and exploiting them for benefits to the economy and human and animal welfare. It is always valuable to be able to step back from existing or favourite hypotheses and paradigms to look at an area of work or problem and see whether a different approach might be productive particularly by drawing parallels with other sometimes unrelated problems. 2. This approach has been used to explore (i) the use of live, attenuated Salmonella vaccines to generate a new form of competitive exclusion, (ii) gene expression technology for the design of improved inactivated vaccines (iii) use of cytokine therapy to reduce persistent carriage by Salmonella, (iv) using bacteriophages to reduce carcass contamination by food-borne pathogens and reduce carriage of antibiotic resistance plasmids. 3. The potential for extending virus therapy to parasite infections is also discussed.


Radiative recombination of large polarons in halide perovskites.
In hybrid organic/inorganic perovskites, the majority of charge carriers are large polarons. Slow recombination of the large polarons underlies long carrier lifetime and diffusion length, crucial to optoelectronic applications of the perovskites. However, microscopic mechanisms by which the large polarons recombine remain largely unknown. Here we propose a theoretical model to elucidate radiative recombination of large polarons. Six annihilation pathways are identified which involve the formation of mobile and immobile 'dying pairs', both responsible for charge recombination. The formation probability of the 'dying pair' and the corresponding annihilation rate can be estimated. The product of the formation probability and the annihilate rate gives rise to recombination rate along each pathway and weighted sum of the recombination rates yields an overall rate of radiative recombination in perovskites. The theory sheds light on the physical mechanism by which large polarons recombine via the formation of the dying pairs, assisted by thermal activation and quantum tunneling. The predictions from the theory in general agree well to corresponding experimental measurements on monomolecular and bimolecular recombination rates as well as peak frequency of photoluminescence spectrum.


The association between small tumor size and poor survival in T4 mucinous adenocarcinoma of colon without distant metastasis.
The purpose of this study was to analyze the impact of tumor size on cancer-specific survival (CSS) in patients with mucinous adenocarcinoma (MAC) of the colon, showing heavy intestinal wall invasion without distant metastasis (T4 N0-2 M0). Patients with T4N0-2M0 MAC of colon were analyzed based on data from the US Surveillance, Epidemiology, and End Results (SEER) database. Survival was analyzed using the Kaplan-Meier method, and the log-rank test was used to identify differences. Risk factors were analyzed using the Cox proportional hazard model. A preliminary analysis of T4N0-2M0 adenocarcinoma of colon patients from the SEER database is also presented. A total of 585 patients from the SEER database were included in the analysis. The cutoff value (5.0 cm) was determined using the X-tile program. Kaplan-Meier analysis showed that tumors ≤5.0 cm had a poorer CSS compared to tumors >5.0 cm (p=0.034). Multivariate analysis indicated that tumor size is an independent prognostic factor for these patients, and compared to tumors ≤5.0 cm, tumors >5.0 cm were more likely to have better CSS (HR 0.658, 95% CI 0.506-0.854, p=0.002). Tumor size was also analyzed as a continuous variable in multivariate analysis, and CSS decreased with decreasing tumor size (HR 0.919, 95% CI 0.873-0.968, p<0.001). No significant association between tumor size and CSS was observed in patients with T4N0- 2M0 MAC of the colon. Smaller tumor size is associated with poorer CSS in patients with T4N0-2M0 MAC of the colon.


Quality of life studies of the Australian New Zealand Breast Cancer Trials Group: approaches to missing data.
The purpose of this paper is to describe the degree of compliance with quality of life measures in two clinical trials conducted by the Australian New Zealand Breast Cancer Trials Group comparing different chemotherapy policies for metastatic breast cancer. Quality of life was assessed by the patient using linear analogue scales and by the physician using the Spitzer QLI. Compliance was generally good, ranging from 66 per cent to 79 per cent in the earlier study, and from 63 per cent to 97 per cent in the later study. Compliance with physician rated quality of life was consistently slightly better than for patient self-assessment. The results of physician and patient assessments were generally consistent, but there was a systematic bias toward lower quality of life (as assessed by the physician) in patients who failed to comply with self-assessment. Our conclusions were that quality of life can be assessed in large scale multi-institution clinical trials in metastatic breast cancer. The results are important in assessing treatment comparisons. Missing data cannot be assumed to be similar to those available. Optimal assessment of quality of life therefore requires careful prospective attention to complete data collection.


Cold shock induces the synthesis of stress proteins in human keratinocytes.
Heat shock proteins or stress proteins are synthesized when cells are exposed to a wide variety of physiologic stresses. The stress response is evolutionarily highly conserved, suggestive of an essential function(s) for the survival of organisms, protecting them from harmful trauma. Exposure to cold induces a stress response in organisms such as Drosophila melanogaster and Sarcophaga crassipalpis and this led us to determine whether or not cold shock responses occur in human skin after exposure to cold such as might occur during cryopreservation of tissues or cryosurgery. Biopsies taken from fresh human skin at chest surgery were exposed to 4, 15, 20, and 37 degrees C (control) for 60 min and then allowed to incorporate 35S-methionine at 37 degrees C for up to 3 h. Proteins from the epidermis were extracted and analyzed by sodium dodecyl-sulfate-polyacrylamide gel electrophoresis. At 15 degrees C and below there was increased synthesis of 90 and 72 kD proteins 2 h after shocking. The 72-kD protein was identified as a heat shock protein using a monoclonal antibody to HSP72 and it is proposed from electrophoretic evidence that the 90-kD protein is also a heat shock protein. Clearly, cold shock stimulates a stress response in human epidermis altering the spectrum of proteins expressed and inducing the synthesis of heat shock proteins.


[Dietary intake of some micronutrients in different provinces of China].
Based on the data collected in 1992 China National Nutrition Survey, which covered 100,201 persons of all ages in 29 provinces, the dietary intakes of some micronutrients were calculated. The intake of calcium, retinal equivalent and riboflavin were the most insufficient nutrients; zinc, selenium and thiamin were close to (80%-90%) of Chinese RDAs. The intakes of niacin, ascorbic acid and vitamin E were sufficient. The regions in the northeast, northwestern and the southeastern inland were more at risk of nutrition deficiency. Dietary intervention or food fortification with some micronutrients could be used for improving the situation.


A component of an antigenic rhoptry complex of Plasmodium falciparum is modified after merozoite invasion.
Human antibodies affinity purified on an adsorbent prepared from a cDNA clone (Ag44) expressing a portion of a rhoptry antigen were used to characterize the synthesis and fate of the antigen in the asexual blood stages of Plasmodium falciparum. The rhoptry antigen is synthesized in the mature trophozoite-stage parasites as a 103 kDa polypeptide, is present in the schizonts and merozoites as a 105 kDa polypeptide, is discharged from the rhoptries and found in the newly invaded red cells as a 110 kDa polypeptide. Anti-Ag44 antibodies immunoprecipitate the antigen and two additional polypeptides of 135 and 150 kDa from lysates of infected cells and from culture supernatants. The three polypeptides are associated in a non-covalent complex that persists in the newly invaded red cells. All the components of the high molecular weight rhoptry complex are antigenic and can be precipitated with immune human serum. The 135 kDa polypeptide is identical to a 140 kDa rhoptry antigen previously identified by a monoclonal antibody.


Large outbreak of Jimsonweed (Datura stramonium) poisoning due to consumption of contaminated humanitarian relief food: Uganda, March-April 2019.
Jimsonweed (Datura stramonium) contains toxic alkaloids that cause gastrointestinal and central nervous system symptoms when ingested. This can be lethal at high doses. The plant may grow together with leguminous crops, mixing with them during harvesting. On 13 March 2019, more than 200 case-patients were admitted to multiple health centres for acute gastrointestinal and neurologic symptoms. We investigated to determine the cause and magnitude of the outbreak and recommended evidence-based control and prevention measures. We defined a suspected case as sudden onset of confusion, dizziness, convulsions, hallucinations, diarrhoea, or vomiting with no other medically plausible explanations in a resident of Napak or Amudat District from 1 March-30 April 2019. We reviewed medical records and canvassed all villages of the eight affected subcounties to identify cases. In a retrospective cohort study conducted in 17 villages that reported the earliest cases, we interviewed 211 residents about dietary history during 11-15 March. We used modified Poisson regression to assess suspected food exposures. Food samples underwent chemical (heavy metals, chemical contaminants, and toxins), proteomic, DNA, and microbiological testing in one national and three international laboratories. We identified 293 suspected cases; five (1.7%) died. Symptoms included confusion (62%), dizziness (38%), diarrhoea (22%), nausea/vomiting (18%), convulsions (12%), and hallucinations (8%). The outbreak started on 12 March, 2-12 h after Batch X of fortified corn-soy blend (CSB +) was distributed. In the retrospective cohort study, 66% of 134 persons who ate CSB + , compared with 2.2% of 75 who did not developed illness (RRadj = 22, 95% CI = 6.0-81). Samples of Batch X distributed 11-15 March contained 14 tropane alkaloids, including atropine (25-50 ppm) and scopolamine (1-10 ppm). Proteins of Solanaceae seeds and Jimsonweed DNA were identified. No other significant laboratory findings were observed. This was the largest documented outbreak caused by food contamination with tropane alkaloids. Implicated food was immediately withdrawn. Routine food safety and quality checks could prevent future outbreaks.


Nomogram predicting long-term survival after the diagnosis of intrahepatic recurrence of hepatocellular carcinoma following an initial liver resection.
The aim of this study was to construct and validate a nomogram for predicting survival after the intrahepatic recurrence of hepatocellular carcinoma (HCC) following an initial hepatectomy. A primary cohort of 268 patients who underwent curative hepatectomy for HCC at Shinshu University Hospital between 1990 and 2010 was retrospectively studied. A nomogram was constructed based on independent prognostic factors for overall survival after recurrence. The predictive performance was evaluated using the concordance index (c-index) and a calibration curve. The nomogram was then externally validated in a cohort of patients from Tokyo University Hospital (n = 296). In multivariate analysis, the following 5 variables were identified as independent predictors of overall survival and incorporated into the nomogram-Japan Integrated Stage score at initial liver resection, platelet count at initial liver resection, time until intrahepatic recurrence, vascular invasion at recurrence, and type of treatment used for intrahepatic recurrence. The nomogram had a c-index of 0.75 (95% confidence interval 0.60-0.85) for the Shinshu cohort and 0.71 (0.57-0.81) for the Tokyo cohort. The predicted 3- and 5-year survival probabilities corresponded well with the actual outcomes. The established nomogram might be useful for estimating survival after the intrahepatic recurrence of HCC.


Detecting surgical wound infections.
A review of the literature on detecting wound infection revealed the need for an established definition and a consensus on the way of detecting infection. A unified approach would enable a clearer picture of wound infection in the UK to emerge.


False Data Injection Attack for Cyber-Physical Systems With Resource Constraint.
Cyber-security is of the fundamental importance for cyber-physical systems (CPSs), since CPSs are vulnerable to cyber attack. In order to make the defensive measures better, one needs to understand the behavior from the view of an attacker. In this paper, the problem of false data injection attack on remote state estimation with resource constraints is studied in two cases, where the first case is that the attacker adds a Gaussian noise to the innovation, while the other is that the attacker employs a Gaussian noise to replace the innovation. In addition, the attacker is assumed to has a resource constraint, i.e., he/she cannot attack all the sensors, at the same time should decide which sensors to attack. By using the matrix theory, the optimal attack strategy problem, which aims to maximize the trace of the remote estimation error covariance, is converted into a convex optimization problem that can be solved. Thus, an optimal attack strategy is given to illustrate which sensors should be attacked. An example is given to show the effectiveness of the theoretical results.


Concordant and discordant interleukin-1-mediated signaling in lung fibroblast thy-1 subpopulations.
Following lung injury or inflammation, fibroblasts mediate either restorative repair or disordered remodeling. Interleukin (IL)-1beta is a key mediator in the transition from injury/inflammation to tissue remodeling, in part through its regulation of platelet-derived growth factor alpha receptor (PDGFalphaR). Based on prior demonstration of differential PDGFalphaR expression, we hypothesized that subpopulations of fibroblasts would have heterogeneous responses to IL-1. We report that IL-1beta significantly increases expression of PDGFalphaR in Thy-1-, but not Thy-1+ fibroblasts. Higher baseline expression of PDGFalphaR in Thy-1- fibroblasts is partially abrogated by IL-1 receptor antagonist. There are no differences in IL-1beta binding, as determined by flow cytometry, or in the presence of the type I IL-1 receptor (IL-1RtI) or its associated protein (IL-1RacP) by immunoblotting. IL-1beta induces DNA binding of both nuclear factor kappaB (NF-kappaB) and CAATT-enhancer binding protein (C/EBP), and activation of p38 mitogen-activated protein kinase in both subpopulations. However, IL-1beta-induced proliferation and expression of IL-6 are significantly higher in Thy-1- fibroblasts. Heterogeneous responses to IL-1beta despite equivalent presence of both proximal and distal signaling components indicates that parallel signaling pathways are activated selectively in Thy-1- cells, suggesting a prominent role for this subset in the transition from inflammation to lung remodeling.


[Sodium taurocholate cotransporting polypeptide deficiency manifesting as cholestatic jaundice in early infancy: a complicated case study].
Sodium taurocholate cotransporting polypeptide (NTCP) deficiency is caused by SLC10A1 mutations impairing the NTCP function to uptake plasma bile salts into the hepatocyte. Thus far, patients with NTCP deficiency were rarely reported. The patient in this paper was a 5-month-19-day male infant with the complaint of jaundiced skin and sclera for 5.5 months as well as abnormal liver function revealed over 4 months. His jaundice was noticed on the second day after birth, and remained visible till his age of 1 month and 13 days, when a liver function test unveiled markedly elevated total, direct and indirect bilirubin as well as total bile acids (TBA). Cholestatic liver disease was thus diagnosed. Due to unsatisfactory response to medical treatment, the patient underwent exploratory laparotomy, cholecystostomy and cholangiography when aged 2 months. This revealed inspissated bile but unobstructed bile ducts. Thereafter, his jaundice subsided, but the aminotransferases and TBA levels gradually rose. Of note, his mother also had mildly elevated plasma TBA. Since the etiology was unclear, no specific medication was introduced. The infant has been followed up over 2 years. The aminotransferases recovered gradually, but TBA levels fluctuated within 23.3-277.7 μmol/L (reference range: 0-10 μmol/L). On SLC10A1 genetic analysis at 2 years and 9 months, both the infant and his mother proved to be homozygous for a pathogenic variant c.800C>T(p.S267F), and NTCP deficiency was thus definitely diagnosed. The findings suggest that, although only mildly increased plasma TBA is presented in adults with NTCP deficiency, pediatric patients with this disorder exhibit persistent and remarkable hypercholanemia, and some patients might manifest as cholestatic jaundice in early infancy.


Plasmon excitations by photoelectron emission from rare gas nanobubbles in aluminum.
Aluminum bulk, surface, and multiple plasmons have been observed in the core-level spectra of rare gas (Ne, Ar, and Xe) nanobubbles in Al, whose intensities are even higher than those of Al metal. Both intrinsic and extrinsic bulk plasmons are detected, but they exhibit diametrically opposite intensity variation due to change in the size and implantation depth of the bubbles. Furthermore, the existence of bubble surface plasmon is demonstrated.


Diagnosis of paratuberculosis in sheep.
Paratuberculosis in sheep usually is manifested as emaciation and decreased wool production. Diarrhea occurred in only 18% of affected animals. Significant hematologic changes included decreased RBC count, hemoglobin level and hematocrit. Necropsy revealed pallor, cachexia and serous fluid in body cavities. Staining of intestinal mucosal scrapings and mesenteric lymph node impression smears for acid-fast organisms revealed bright-red clumps of Mycobacterium paratuberculosis bacilli. Fecal examination identified 70% of affected animals, intradermal injection of johnin 60%, and avian tuberculin 39%.


Exhaled human breath measurement method for assessing exposure to halogenated volatile organic compounds.
The organic constituents of exhaled human breath are representative of blood-borne concentrations through gas exchange in the blood/breath interface in the lungs. The presence of specific compounds can be an indicator of recent exposure or represent a biological response of the subject. For volatile organic compounds (VOCs), sampling and analysis of breath is preferred to direct measurement from blood samples because breath collection is noninvasive, potentially infectious waste is avoided, and the measurement of gas-phase analytes is much simpler in a gas matrix rather than in a complex biological tissue such as blood. To exploit these advantages, we have developed the "single breath canister" (SBC) technique, a simple direct collection method for individual alveolar breath samples, and adapted conventional gas chromatography-mass spectrometry analytical methods for trace-concentration VOC analysis. The focus of this paper is to describe briefly the techniques for making VOC measurements in breath, to present some specific applications for which these methods are relevant, and to demonstrate how to estimate exposure to example VOCs on the basis of breath elimination. We present data from three different exposure scenarios: (a) vinyl chloride and cis-1,2-dichloroethene from showering with contaminated water from a private well, (b) chloroform and bromodichloromethane from high-intensity swimming in chlorinated pool water, and (c) trichloroethene from a controlled exposure chamber experiment. In all cases, for all subjects, the experiment is the same: preexposure breath measurement, exposure to halogenated VOC, and a postexposure time-dependent series of breath measurements. Data are presented only to demonstrate the use of the method and how to interpret the analytical results.


Large cavernous hemangioma of the adrenal gland: Laparoscopic treatment. Report of a case.
Cavernous hemangioma of the adrenal gland is a rare benign tumor. The diagnosis is often postoperative on histological exam with the presence of blood-filled, dilated vascular spaces. We report the clinical case of a 49 years-old woman who came to our observation with aspecific abdominal pain. A computed tomography (CT) abdominal scan revealed a 11cm right adrenal mass. This lesion was well circumscribed, round, encapsulated. After iodinated-contrast we observed a progressive, inhomogeneous enhancement without evidence of active bleeding and with pre-operative diagnosis of adrenal hemangioma. Laparoscopic adrenalectomy was performed by a transperitoneal flank approach. Pathological examination revealed a 11cm adrenal mass with extensive central necrotic areas mixed to sinusoidal dilation and fibrotic septa. Postoperative diagnosis was adrenal hemangioma. Adrenal hemangiomas occur infrequently. Generally these adrenal masses are non-functioning and there is no specific symptoms. Recent records demonstrate that laparoscopic adrenalectomy is technically safe and feasible for large adrenal tumors, but controversy exists in cases of suspected malignancy. We choose laparoscopic approach to adrenal gland on the basis of preoperative CT abdominal scan that excludes radiological signs of adrenocortical carcinoma (ACC) such as peri-adrenal infiltration and vascular invasion. Laparoscopic adrenalectomy is considered the standard treatment in case of diagnosis of benign lesions. In this case report we discussed a large adrenal cavernous hemangioma treated with laparoscopic approach. Fundamental is the study of preoperative endocrine disorders and radiologic findings to exclude signs of malignancy.


Functional brain imaging using near-infrared spectroscopy during actual driving on an expressway.
The prefrontal cortex is considered to have a significant effect on driving behavior, but little is known about prefrontal cortex function in actual road driving. Driving simulation experiments are not the same, because the subject is in a stationary state, and the results may be different. Functional near-infrared spectroscopy (fNIRS) is advantageous in that it can measure cerebral hemodynamic responses in a person driving an actual vehicle. We mounted fNIRS equipment in a vehicle to evaluate brain functions related to various actual driving operations while the subjects drove on a section of an expressway that was not yet open to the public. Measurements were recorded while parked, and during acceleration, constant velocity driving (CVD), deceleration, and U-turns, in the daytime and at night. Changes in cerebral oxygen exchange (ΔCOE) and cerebral blood volume were calculated and imaged for each part of the task. Responses from the prefrontal cortex and the parietal cortex were highly reproducible in the daytime and nighttime experiments. Significant increases in ΔCOE were observed in the frontal eye field (FEF), which has not been mentioned much in previous simulation experiments. In particular, significant activation was detected during acceleration in the right FEF, and during deceleration in the left FEF. Weaker responses during CVD suggest that FEF function was increased during changes in vehicle speed. As the FEF contributes to control of eye movement in three-dimensional space, FEF activation may be important in actual road driving. fNIRS is a powerful technique for investigating brain activation outdoors, and it proved to be sufficiently robust for use in an actual highway driving experiment in the field of intelligent transport systems (ITS).


Regio- and Stereoselective Synthesis of Multi-Alkylated Allylic Boronates through Three-Component Coupling Reactions between Allenes, Alkyl Halides, and a Diboron Reagent.
Multisubstituted allylic boronates are attractive and valuable precursors for the rapid and stereoselective construction of densely substituted carbon skeletons. Herein, we report the first synthetic approach for differentially 2,3,3-trialkyl-substituted allylic boronates that contain a stereodefined tetrasubstituted alkene structure. Copper(I)-catalyzed regio- and stereoselective three-component coupling reactions between gem-dialkylallenes, alkyl halides, and a diboron reagent afforded sterically congested allylic boronates. The allylboration of aldehydes diastereoselectively furnished the corresponding homoallylic alcohols that bear a quaternary carbon. A computational study revealed that the selectivity-determining mechanism was correlated to the coordination of a boryl copper(I) species to the allene substrate as well as the borylcupration step.


Gastrointestinal stromal tumors: differential diagnosis.
Availability of KIT tyrosine kinase inhibitors for specific treatment of GISTs has magnified the importance of accurate differential diagnosis of GIST from other tumors occurring in the GI tract and abdomen. The general problems in this distinction include histological mimicry of other mesenchymal tumors with GIST, occasional KIT-negativity of GIST, and KIT-positivity of non-GISTs. Up to 5% to 10% gastric GISTs and <2% of intestinal GISTs can be KIT-negative. The identification of these tumors as GISTs is based on knowledge of the spectrum of GIST morphology, and can be supported by molecular diagnosis of KIT and PDGFRA mutations (the latter pertain to gastric tumors). True smooth muscle tumors (rare in GI tract except in esophagus and colon) can be separated from GISTs by the eosinophilic tinctorial quality of tumor cells, positivity for smooth muscle markers, and negativity for KIT. Desmoids can form large GIST-like masses, but are composed of spindled or stellate-shaped cells in a densely collagenous stroma. Negativity for KIT and nuclear positivity for beta-catenin are differentiating features. GI schwannomas, melanoma, and rare primary clear cell sarcoma are S100-positive, usually with characteristic histology. The latter two can be KIT-positive. KIT-positive non-GISTs include some sarcomas, especially angiosarcoma and Ewing sarcoma, extramedullary myeloid tumor, seminoma, and a few carcinomas, notably small cell carcinoma of lung. Spurious KIT-positivity, seen with some polyclonal KIT antibodies, has been a source of confusion leading to probable false-positive results in fibroblastic tumors and occasional other sarcomas, such as leiomyosarcomas. Integration of histological features with carefully standardized immunohistochemistry, supported by KIT and PDGFRA mutation analysis, is the cornerstone of state-of-the art differential diagnosis of GIST. To comprehensively capture all GISTs, KIT immunostains should be performed on all unclassified epithelioid and mesenchymal tumors of the abdomen. This is a US government work. There are no restrictions on its use.


Diagnostic accuracy of multidetector-row computed tomography for common bile duct calculi: is it necessary to add non-contrast-enhanced images to contrast-enhanced images?
To evaluate the diagnostic accuracy of 16-slice multidetector-row computed tomography (MDCT) for the detection of common bile duct (CBD) stones and to compare the diagnostic values between contrast-enhanced axial with multiplanar reformation (MPR) images and contrast-enhanced combined with non-contrast-enhanced axial images. Fifty-four patients with suspected CBD stones underwent MDCT and endoscopic retrograde cholangiopancreatography (ERCP). Two radiologists independently evaluated contrast-enhanced axial with MPR images for the presence of CBD stones. Two weeks later, they performed a second review of contrast-enhanced and non-contrast-enhanced axial images. The ERCP was used as the criterion standard to confirm the presence of CBD stones. The McNemar test and receiver operating characteristic curve analysis were used to assess the differences in accuracy for detecting CBD stones. The ERCP identified bile duct stones in 27 patients and no stones in the other 27. Contrast-enhanced axial with MPR images had a sensitivity of 88.9%, specificity of 92.6%, and diagnostic accuracy of 90.7%. Contrast-enhanced combined with non-contrast-enhanced axial images had a sensitivity, specificity, and diagnostic accuracy of 88.9%. However, the difference between the 2 groups was not statistically significant. The areas under the receiver operating characteristic curve of the 2 groups were 0.929 and 0.905, respectively. The MDCT provides high accuracy in diagnosis for CBD stones. Adding non-contrast-enhanced images to contrast-enhanced images did not improve diagnostic accuracy, and therefore, additional non-contrast-enhanced images are not necessary.


Women's knowledge and beliefs regarding breast cancer.
Approximately 20-30% of women delay for 12 weeks or more from self-discovery of a breast symptom to presentation to a health care provider, and such delay intervals are associated with poorer survival. Understanding the factors that influence patient delay is important for the development of an effective, targeted health intervention programme to shorten patient delay. The aim of the study was to elicit knowledge and beliefs about breast cancer among a sample of the general female population, and examine age and socio-economic variations in responses. Participants were randomly selected through the Postal Address File, and data were collected through the Office of National Statistics. Geographically distributed throughout the UK, 996 women participated in a short structured interview to elicit their knowledge of breast cancer risk, breast cancer symptoms, and their perceptions of the management and outcomes associated with breast cancer. Women had limited knowledge of their relative risk of developing breast cancer, of associated risk factors and of the diversity of potential breast cancer-related symptoms. Older women were particularly poor at identifying symptoms of breast cancer, risk factors associated with breast cancer and their personal risk of developing the disease. Poorer knowledge of symptoms and risks among older women may help to explain the strong association between older age and delay in help-seeking. If these findings are confirmed they suggest that any intervention programme should target older women in particular, given that advancing age is a risk factor for both developing breast cancer and for subsequent delayed presentation.


The multiple causes of alpha1-antitrypsin deficiency.
Alpha1-antitrypsin deficiency is a genetic model that predisposes to pulmonary emphysema or a form of hepatic cirrhosis in man. The antitrypsin protein protects the tissues from proteolytic digestion by lysosomal proteases from inflammatory cells. The three causes of antitrypsin deficiency demonstrated to date are: 1) A defect in synthesis and release of the Z variant from the liver. 2) Presence of an inactive (null) gene for antitrypsin production, and 3) Increased lability of certain variants associated with the in vivo degradation of antitrypsin.


Rapid palatal expansion: Part 1. Mineralization pattern of the midpalatal suture in cats.
The mineralization pattern of the midpalatal suture after rapid palatal expansion was investigated in 10 treated and 2 control cats, in light of the tendency of RPE to relapse. The rapid palatal expansion treatment consisted of active (25 days), retention (60 days), and relapse (60 days) phases. Standardized occlusal radiographs were taken periodically and analyzed for suture width, suture optical density in anterior vs. posterior regions, and suture area measurements of radiopaque vs. radiolucent zones. Nine cats exhibited suture splitting. During the active phase, the radiolucent zone (nonmineralized tissue) increased 12-fold and the increase in optical density was 50% greater in the anterior over the posterior suture region, demonstrating increased formation of loose connective tissue at the anterior region. During the retention period, the suture's radiopaque zone (mineralized tissue) increased by 62%, the radiolucent zone declined (64%) and the suture width decreased (65%) indicating reorganization of mineralized tissue. The decrease in optical density (increased mineralization) was 2.5 times greater in the posterior over the anterior suture region, indicating that the remineralization (closure) pattern of the expanded suture is analogous to a zipper closed in a posteroanterior direction. During the relapse phase, the reduction in total suture area (41%) and in the radiopaque zone (32%) indicates medial convergence of the maxillary horizontal processes. From our findings we extrapolated that the retention of the suture anterior region should be longer than the posterior region to catch up the lag in rebuilding and maturation of the newly deposited hard tissue.


Diversity-Oriented Synthesis of Substituted Benzo[b]thiophenes and Their Hetero-Fused Analogues through Palladium-Catalyzed Oxidative C-H Functionalization/Intramolecular Arylthiolation.
An efficient, high yielding route to multisubstituted benzo[b]thiophenes has been developed through palladium-catalyzed intramolecular oxidative C-H functionalization-arylthiolation of enethiolate salts of α-aryl-β-(het)aryl/alkyl-β-mercaptoacrylonitriles/acrylates or acrylophenones. The overall strategy involves a one-pot, two-step process in which enethiolate salts [generated in situ through base-mediated condensation of substituted arylacetonitriles, deoxybenzoins, or arylacetates with (het)aryl (or alkyl) dithioates] are subjected to intramolecular C-H functionalization-arylthiolation under the influence of a palladium acetate (or palladium chloride)/cupric acetate catalytic system and tetrabutylammonium bromide as additive in N,N-dimethylformamide (DMF) as solvent. In a few cases, the yields of benzo[b]thiophenes were better in a two-step process by employing the corresponding enethiols as substrates. In a few examples, Pd(OAc)2 (or PdCl2) catalyst in the presence of oxygen was found to be more efficient than cupric acetate as reoxidant, furnishing benzothiophenes in improved yields by avoiding formation of side products. The method is compatible with a diverse range of substituents on the aryl ring as well as on the 2- and 3-positions of the benzothiophene scaffold. The protocol could also be extended to the synthesis of a raloxifene precursor and a tubulin polymerization inhibitor in good yields. The versatility of this newly developed method was further demonstrated by elaborating it for the synthesis of substituted thieno-fused heterocycles such as thieno[2,3-b]thiophenes, thieno[2,3-b]indoles, thieno[3,2-c]pyrazole, and thieno[2,3-b]pyridines in high yields. A probable mechanism involving intramolecular electrophilic arylthiolation via either a Pd-S adduct or palladacycle intermediate has been proposed on the basis of experimental studies.


Preliminary study on the antimicrobial susceptibility pattern related to the genotype of Vibrio vulnificus strains isolated in the north-western Adriatic Sea coastal area.
V. vulnificus is a Gram-negative bacterium, commonly found in estuarine and coastal habitats, that can infect humans through seafood consumption or wound exposure. This study represents the first attempt to correlate the genotype of Vibrio vulnificus strains isolated in the north-western Adriatic Sea coastal area, with their antimicrobial susceptibility patterns. On the whole, 40 V. vulnificus strains, isolated from shellfish (n=20), different coastal water bodies (n=19), and the blood of a Carretta carretta turtle (n=1), were utilized. All strains were positive for the species-specific genes vvhA and hsp, with high variability for other markers: 55% (22 out of 40) resulted of the environmental (E) genotype (vcgE, 16S rRNA type A, CPS2 or CPS0), 10% (4 out of 40) of the clinical (C) genotype (vcgC, 16S rRNA type B, CPS1), and 35% (14 out of 40) of the mixed (M) genotype, possessing both E and C markers. The antimicrobial susceptibility was assayed by the diffusion method on agar, according to the Clinical Laboratory Standards Institute (CLSI), utilizing the following commercial disks (Oxoid): ampicillin (AMP), ampicillin- sulbactam (SAM), piperacillin (PRL), cefazolin (KZ), cefotaxime(CTX), ceftazidime (CAZ), imipenem (IPM), meropenem (MEM), amikacin (AK), gentamicin(CN), tetracycline(TE), ciprofloxacin (CIP), levofloxacin (LEV), trimethoprim-sulfamethoxazole (SXT), and chloramphenicol (C). 75% of the strains, (n=30) including all C strains, was sensitive to all the tested antibiotics, whereas E strains showed intermediate sensitivity to AK (2 strains), CIP and CAZ (1 strain), TE (1 strain) and resistance to KZ (1 strain), and 4 M strains showed I to AK.


Sulforaphane sensitizes tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis through downregulation of ERK and Akt in lung adenocarcinoma A549 cells.
The cytotoxic effect of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is limited in some cancer cells, including A549 lung adenocarcinoma cells. However, treatment with TRAIL in combination with subtoxic concentrations of sulforaphane (SFN) sensitizes TRAIL-resistant A549 cells to TRAIL-mediated apoptosis. Combined treatment with SFN and TRAIL induced chromatin condensation, DNA fragmentation, annexin V staining and sub-G(1) phase DNA content. These indicators of apoptosis correlate with the induction of caspase-3 activity that results in the cleavage of poly(ADP-ribose) polymerase and the release of lactate dehydrogenase. Both the cytotoxic effect and apoptotic characteristics induced by combined treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, demonstrating the important role of caspase-3 in the observed cytotoxic effect. Combined treatment also triggered the activation of p38 MAPK and JNK, and downregulation of ERK and Akt. Inhibitors of ERK (PD98059) or Akt (LY294002), but not p38 MAPK, resulted in significantly decreased cell viability. Although the activation of JNK was increased in response to combined treatment, inhibition of the JNK pathway significantly attenuated cell viability. These results indicate that caspase-3 is a key regulator of apoptosis in response to combined SFN and TRAIL in human lung adenocarcinoma A549 cells through downregulation of ERK and Akt.


Differential activation of dopamine release in the nucleus accumbens core and shell after acute or repeated amphetamine injections: a comparative study in the Roman high- and low-avoidance rat lines.
The selectively bred Roman high- and low-avoidance rats differ in emotionality and responsiveness to the motor effects of acute and repeated psychostimulant administration. These lines also show drastic differences in the neurochemical responses of their mesolimbic dopamine systems to addictive drugs. The nucleus accumbens is critically involved in the locomotor activation produced by psychostimulants and in the augmentation of this effect observed upon repeated drug administration (i.e. behavioral sensitization), although there is not a general consensus as to whether the nucleus accumbens-core or the nucleus accumbens-shell is preferentially involved in such alterations. This study was designed to evaluate the effects of acute amphetamine (0.20 mg/kg, s.c.) on dopamine output in the nucleus accumbens-shell and nucleus accumbens-core of the Roman lines under basal conditions (i.e. naïve rats) and after the repeated administration of amphetamine (1 mg/kg, s.c. x 10 days) or saline. We show that (1) in naïve rats, amphetamine caused a larger increment in dopamine output in the nucleus accumbens-shell vs the nucleus accumbens-core only in the Roman high-avoidance line; (2) repeated amphetamine elicits behavioral sensitization in Roman high-avoidance, but not Roman low-avoidance, rats; (3) in sensitized Roman high-avoidance rats, amphetamine provokes a larger increment in dopamine output in the nucleus accumbens-core, and an attenuated dopaminergic response in the nucleus accumbens-shell, as compared with Roman high-avoidance rats repeatedly treated with saline; and (4) such neurochemical changes are not observed in the mesoaccumbens dopaminergic system of the sensitization-resistant Roman low-avoidance line. We propose that (1) Roman high-avoidance and Roman low-avoidance rats differ in the vulnerability to develop psychostimulant sensitization, (2) the nucleus accumbens-core and nucleus accumbens-shell subserve distinct functional roles in this phenomenon, and (3) comparative studies in the Roman lines may provide insight into the influence of neural substrates and genetic background on the individual vulnerability to addiction.


Disruption of Glutamate Release and Uptake-Related Protein Expression After Noise-Induced Synaptopathy in the Cochlea.
High-intensity noise can cause permanent hearing loss; however, short-duration medium-intensity noise only induces a temporary threshold shift (TTS) and damages synapses formed by inner hair cells (IHCs) and spiral ganglion nerves. Synaptopathy is generally thought to be caused by glutamate excitotoxicity. In this study, we investigated the expression levels of vesicle transporter protein 3 (Vglut3), responsible for the release of glutamate; glutamate/aspartate transporter protein (GLAST), responsible for the uptake of glutamate; and Na+/K+-ATPase α1 coupled with GLAST, in the process of synaptopathy in the cochlea. The results of the auditory brainstem response (ABR) and CtBP2 immunofluorescence revealed that synaptopathy was induced on day 30 after 100 dB SPL noise exposure in C57BL/6J mice. We found that GLAST and Na+/K+-ATPase α1 were co-localized in the cochlea, mainly in the stria vascularis, spiral ligament, and spiral ganglion cells. Furthermore, Vglut3, GLAST, and Na+/K+-ATPase α1 expression were disrupted after noise exposure. These results indicate that disruption of glutamate release and uptake-related protein expression may exacerbate the occurrence of synaptopathy.


Magnetic and structural properties of dinuclear singly bridged-phenoxido metal(II) complexes.
The reaction of a methanolic solution containing the bi-compartmental phenolic ligand 2,6-bis[bis(2-pyridylmethyl)aminomethyl]-4-chlorophenol (L(Cl)-OH) with MCl2·nH2O in the presence of NH4PF6 or NaClO4 afforded the dinuclear bridged-phenoxido dichlorido-metal(ii) complexes [Co2(μ-L(Cl)O)(H2O)2Cl2][Co2(μ-L(Cl)O)(MeOH)2Cl2](PF6)2 (), [Ni2(μ-L(Cl)O)(MeOH)2Cl2]PF6 (), [Ni2(μ-L(Cl)O)(MeOH)(H2O)Cl2]ClO4·1.25H2O (), [Cu2(μ-L(Cl)O)Cl2]PF6·1/2MeOH () and [Zn2(μ-L(Cl)O)Cl2]PF6·MeOH (). The complexes were characterized by elemental microanalyses, conductivity measurements, IR and UV-Vis spectroscopy, mass spectrometry and single crystal X-ray crystallography. Each M(ii) center within the dinuclear complex cations is octahedrally coordinated in complexes , and five-coordinated distorted square pyramidal in and . Magnetic susceptibility measurements at variable temperature of the complexes revealed weak to moderate antiferromagnetic coupling with |J| values = 8.38, 39.0, 30.2 and 0.79 cm(-1), respectively. The results of DFT calculations correlate well with the experimentally determined antiferromagnetic coupling and show that the magnetic exchange coupling occurs mainly through the phenoxido bridge M-O-M. Implications of geometry around the central metal ion, MM distance, M-O-M bond angle and overlapping of magnetic orbitals on the magnetic exchange coupling are discussed.


Application of the random amplified polymorphic DNA technique for the detection of polymorphism among wild and cultivated tetraploid wheats.
Development of a high-density genetic linkage map of cultivated wheats using conventional molecular markers has lagged behind the other major food crops such as rice and tomato because of the large genome size and limited levels of genetic polymorphisms. Recently, random amplified polymorphic DNAs (RAPDs) have been suggested to provide an alternative to visualize more polymorphism. For the construction of a genetic linkage map in tetraploid wheats, one can use a strategy of intersubspecific crosses between the most dissimilar wild and cultivated tetraploid wheats that are easy to hybridize and result in fertile progeny. An assessment of the level of RAPDs among different accessions and varieties of wild and cultivated tetraploid wheats is required to fulfill this objective. We present here the data obtained using RAPD analysis of 40 primers in 20 accessions of wild tetraploid emmer wheats (Triticum turgidum L. ssp. dicoccoides) and 10 genotypes of cultivated tetraploid durum wheats (Triticum turgidum L. ssp. durum) selected from geographically diverse locations. We have observed a higher level of polymorphism among different accessions of wild emmer wheat from Israel. Turkey, and Jordan than the group of cultivated American, Turkish, and Syrian durum wheats. These data have been used to generate a dendrogram suggesting the genetic relationships among these genotypes, and the most dissimilar genotypes are identified for future mapping and gene tagging work.


Quick minds don't blink: electrophysiological correlates of individual differences in attentional selection.
A well-established phenomenon in the study of attention is the attentional blink-a deficit in reporting the second of two targets when it occurs 200-500 msec after the first. Although the effect has been shown to be robust in a variety of task conditions, not every individual participant shows the effect. We measured electroencephalographic activity for "nonblinkers" and "blinkers" during execution of a task in which two letters had to be detected in an sequential stream of digit distractors. Nonblinkers showed an earlier P3 peak, suggesting that they are quicker to consolidate information than are blinkers. Differences in frontal selection positivity were also found, such that nonblinkers showed a larger difference between target and distractor activation than did blinkers. Nonblinkers seem to extract target information better than blinkers do, allowing them to reject distractors more easily and leaving sufficient resources available to report both targets.


Glucose-regulated protein 78 is an antiviral against hepatitis A virus replication.
Infection with hepatitis A virus (HAV) is a major cause of acute hepatitis globally and it is important to identify the mechanisms of HAV replication. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum (ER) chaperone and serves a role in unfolded protein response pathways. Previous studies have demonstrated that GRP78 functions as an endogenous antiviral factor. In the present study, two loss-of-function studies using GRP78 were completed to elucidate the role of GRP78 in HAV infection. HAV replication was observed to be enhanced by deficient GRP78 although GRP78-deficiency also led to lower expression of ER stress molecules downstream of GRP78. Therefore, GRP78 appears to be a potential novel defensive molecule against HAV in hepatocytes.


Jacobson's nerve clues to the round window niche.
The round window niche is used as a primary guide to cochleostomy for cochlear implantation, but sometimes the niche is not visible through the dissected facial recess. In such cases, Jacobson's nerve may be a guide to the niche. The objectives of this study were to depict the distance from Jacobson's nerve to the lip of the round window niche, and how this distance may relate to orientation of the manubrium as viewed through the external ear canal. Also, are these distances related to mastoid pneumatisation size? The study involved post-mortem anatomic dissection of 41 bequeathed adult crania (82 temporal bones). Viewing with an operative microscope, distances were measured with a fenestrometer-type instrument. Mastoid sizes were determined radiographically. Jacobson's nerve was identifiable in 81 of 82 temporal bones. Distances from Jacobson's nerve to the lip of round window niche averaged 2.1 mm, range zero to 3.2 mm. Distances from Jacobson's nerve to the round window niche were not obviously associated with either mastoid size or orientation of the manubrium in the head. If the main trunk of Jacobson's nerve is visible on the promontory (as it is in > or =95% of cases), with 95 per cent certainty it is within 3.3 mm of the lip of the round window niche. Distances from Jacobson's nerve to the lip of the round window niche do not correlate with either manubrium orientation as viewed through the external ear canal, or the extent of mastoid pneumatisation.


Chemical Probes Unravel an Antimicrobial Defense Response Triggered by Binding of the Human Opioid Dynorphin to a Bacterial Sensor Kinase.
Host-microbe communication via small molecule signals is important for both symbiotic and pathogenic relationships, but is often poorly understood at the molecular level. Under conditions of host stress, levels of the human opioid peptide dynorphin are elevated, triggering virulence in the opportunistic pathogenic bacterium Pseudomonas aeruginosa via an unknown pathway. Here we apply a multilayered chemical biology strategy to unravel the mode of action of this putative interkingdom signal. We designed and applied dynorphin-inspired photoaffinity probes to reveal the protein targets of the peptide in live bacteria via chemical proteomics. ParS, a largely uncharacterized membrane sensor of a two-component system, was identified as the most promising hit. Subsequent full proteome studies revealed that dynorphin(1-13) induces an antimicrobial peptide-like response in Pseudomonas, with specific upregulation of membrane defense mechanisms. No such response was observed in a parS mutant, which was more susceptible to dynorphin-induced toxicity. Thus, P. aeruginosa exploits the ParS sensing machinery to defend itself against the host in response to dynorphin as a signal. This study highlights interkingdom communication as a potential essential strategy not only for induction of P. aeruginosa virulence but also for maintaining viability in the hostile environment of the host.


Collective dynamics of complex plasma bilayers.
A classical dusty plasma experiment was performed using two different dust grain sizes to form a strongly coupled asymmetric bilayer (two closely spaced interacting monolayers) of two species of charged dust particles. The observation and analysis of the thermally excited particle oscillations revealed the collective mode structure and dispersion (wave propagation) in this system; in particular, the existence of the theoretically predicted k=0 energy (frequency) gap was verified. Equilibrium molecular-dynamics simulations were performed to emulate the experiment, assuming Yukawa-type interparticle interaction. The simulations and analytic calculations based both on lattice summation and on the quasilocalized charge approximation approach are in good agreement with the experimental findings and help in identifying and characterizing the observed phenomena.


Target trial emulation with multi-state model analysis to assess treatment effectiveness using clinical COVID-19 data.
Real-world observational data are an important source of evidence on the treatment effectiveness for patients hospitalized with coronavirus disease 2019 (COVID-19). However, observational studies evaluating treatment effectiveness based on longitudinal data are often prone to methodological biases such as immortal time bias, confounding bias, and competing risks. For exemplary target trial emulation, we used a cohort of patients hospitalized with COVID-19 (n = 501) in a single centre. We described the methodology for evaluating the effectiveness of a single-dose treatment, emulated a trial using real-world data, and drafted a hypothetical study protocol describing the main components. To avoid immortal time and time-fixed confounding biases, we applied the clone-censor-weight technique. We set a 5-day grace period as a period of time when treatment could be initiated. We used the inverse probability of censoring weights to account for the selection bias introduced by artificial censoring. To estimate the treatment effects, we took the multi-state model approach. We considered a multi-state model with five states. The primary endpoint was defined as clinical severity status, assessed by a 5-point ordinal scale on day 30. Differences between the treatment group and standard of care treatment group were calculated using a proportional odds model and shown as odds ratios. Additionally, the weighted cause-specific hazards and transition probabilities for each treatment arm were presented. Our study demonstrates that trial emulation with a multi-state model analysis is a suitable approach to address observational data limitations, evaluate treatment effects on clinically heterogeneous in-hospital death and discharge alive endpoints, and consider the intermediate state of admission to ICU. The multi-state model analysis allows us to summarize results using stacked probability plots that make it easier to interpret results. Extending the emulated target trial approach to multi-state model analysis complements treatment effectiveness analysis by gaining information on competing events. Combining two methodologies offers an option to address immortal time bias, confounding bias, and competing risk events. This methodological approach can provide additional insight for decision-making, particularly when data from randomized controlled trials (RCTs) are unavailable.


Hydroxyurea as a suppressor of the radioprotective effect of dextran sulfate on bone marrow hemopoietic stem cells in mice.
The changes in hemopoiesis of mice following intraperitoneal administration of dextran sulfate (DS) 24 h before irradiation, as well as the effect of injecting them with hydroxyurea (HU), were analyzed. DS increased the proliferation activity and number of hemopoietic stem cells (CFUs) in the bone marrow. The content of CFUs in the bone marrow and the number of endogenous spleen colonies (ESC) of hemopoietic tissue were higher after irradiation in mice treated with DS than in control groups. The survival rate following a lethal radiation dose was also higher. Injection with HU decreased the number of CFUs in animals injected with DS to the level of controls and suppressed its radioprotective effect.


Moving beyond dwelling in suffering: a situation-specific theory of men's healing from childhood maltreatment.
The authors present an explanation of the development of a situation-specific theory of men's healing from maltreatment during childhood. Development of the theory was guided by Rogers' science of unitary human beings (SUHB). The four multidimensional concepts of the theory are interpreted within the context of the SUHB from themes discovered from the findings of a hermeneutic phenomenological study of men who had been exposed to childhood maltreatment, including neglect and abuse. The concepts are: moving beyond suffering, desiring release from suffering, dwelling in suffering, and experiencing wellbeing. Moving beyond suffering is the process of healing from childhood maltreatment. Desiring release from suffering is the facilitator of men's life experiences that speeds up the rate of evolution from moving beyond suffering to experiencing healing. Dwelling in suffering is the barrier in men's life experiences that slows down the rate of evolution from moving beyond suffering to experiencing wellbeing.


Decoding the puzzle: recent breakthroughs in understanding degradation mechanisms of Li-ion batteries.
Lithium-ion batteries (LIBs) remain at the forefront of energy research due to their capability to deliver high energy density. Understanding their degradation mechanism has been essential due to their rapid engagement in modern electric vehicles (EVs), where battery failure may incur huge losses to human life and property. The literature on this intimidating issue is rapidly growing and often very complex. This review strives to succinctly present current knowledge contributing to a more comprehensible understanding of the degradation mechanism. First, this review explains the fundamentals of LIBs and various degradation mechanisms. Then, the degradation mechanism of novel Li-rich cathodes, advanced characterization techniques for identifying it, and various theoretical models are presented and discussed. We emphasize that the degradation process is not only tied to the charge-discharge cycles; synthesis-induced stress also plays a vital role in catalyzing the degradation. Finally, we propose further studies on advanced battery materials that can potentially replace the layered cathodes.


Effects of Phenolic Respiration Inhibitors on Cytochrome bc1 Complex of Rat-liver Mitochondria.
The respiration inhibitory effects of the inhibitory uncouplers, 2,6-diiodo-4-(2,2-dicyanovinyl)phenol and 2,6-dimethoxy-4-(2,2-dicyanovinyl)phenol, the binding site of which is cytochrome bc1 (cyt. bc1) complex, were studied with rat-liver mitochondria. The inhibitory potency of 2,6-diiodo-4-(2,2-dicyanovinyl)phenol and of 2,6-dimethoxy-4-(2,2-dicyanovinyl)phenol was increased and decreased, respectively, by steep dissipation of the transmembrane electrical potential after adding the potent uncoupler, fluazinam, the uncoupling activity of which disappears with time. Changes in the inhibitory potency may have been due to variation of the binding affinity of these compounds to cyt. bc1 complex. Furthermore, the enhancement to the binding affinity of 2,6-diiodo-4-(2,2-dicyanovinyl)phenol was governed by the degree of reduction in the transmembrane electrical potential. These results suggest that the extent of conformational changes of cyt. bc1 complex, which resulted in an enhanced interaction between 2,6-diiodo-4-(2,2-dicyanovinyl)phenol and its binding niche, increased with decreasing transmembrane electrical potential. From examinations of the reduction of cyt. b, it is suggested that the action site of 2,6-diiodo-4-(2,2-dicyanovinyl)phenol may be close to or partially overlapping that of antimycin A.


Robotic versus Open Level I-II Inferior Vena Cava Thrombectomy: A Matched Group Comparative Analysis.
We compared treatment outcomes of robotic vs open inferior vena cava thrombectomy for renal tumors with level I-II inferior vena cava tumor thrombus. We retrospectively reviewed the medical records of patients who underwent robotic or open inferior vena cava thrombectomy between 2006 and 2016. To reduce the inherent biases of a nonrandomized study the robotic and open groups were matched 1:1 based on key variables. Perioperative data and oncologic outcomes were reviewed. Progression-free and overall survival was analyzed using Kaplan-Meier survival curves and compared between groups using the log rank test. A total of 31 and 37 patients underwent robotic and open inferior vena cava thrombectomy, respectively. After matching there were no significant differences in baseline characteristics between the groups. Of the matched cohorts the robotic cohort had significantly shorter median operative time (150 vs 230 minutes, p <0.001), lower median estimated blood loss (250 vs 1,000 ml, p <0.001), a lower rate of blood transfusion (6.5% vs 54.8%, p <0.001), a lower median transfusion requirement (420 vs 790 ml, p = 0.012) and a shorter median postoperative hospital stay (5 vs 9 days, p <0.001). The postoperative complication rate was lower in the robotic group than in the open group (9.7% vs 29.0%, p = 0.070). However, there were no significant differences in oncologic outcomes between the groups. Robotic inferior vena cava thrombectomy can achieve more favorable perioperative results and similar oncologic outcomes compared with open inferior vena cava thrombectomy. Prospective studies with a larger sample size and longer followup are needed to validate our findings.


[New drinking water reference values for monocyclic nitro compounds].
Nitro compounds are important industrial chemicals with a broad range of applications. During their commercial production or practical use and through leaching from military waste sites they may be released into the environment and thus lead to a contamination of drinking water resources. In the last 15-20 years, the wider public first became aware of nitro compounds as contaminants in groundwater and drinking water resources that originated from manufacturing and processing of secondary explosives during World War II. In 1980, the former Bundesgesundheitsamt (BGA; Federal Health Office) had based its first risk assessment of monocyclic nitro compounds in drinking water on the known carcinogenicity of some aromatic amines in the working environment. On this basis, the BGA recommended for metabolites of aromatic nitro compounds a guide value of 0.1 mug/l for the sum of aromatic amines. From the beginning to the middle of the 1990s, the BGA established a more specific health-related assessment for the individual compounds, but not on the basis of tolerable or acceptable body doses but of dimensionless risk assessment scores ranking their combined toxic and carcinogenic potential on a scale from 1 to 100. In this contribution, we derived new health-based drinking water guide values for 19 nitro(aromatic) compounds and nitramines, including hexogen, octogen, and tetryl as well as the O-nitro compound PETN. All compounds under consideration have been detected within the last 15 years in Germany at contaminated sites close to or directly in groundwater resources for drinking water. For toxicological evaluation and derivation of guideline values for the nitro compounds of interest, the tolerable daily intake (TDI) approach was used for chemicals exhibiting a threshold for toxic effects. This was done by using established tolerable body doses for humans based on an identified NOAEL/LOAEL for the most sensitive toxic endpoint. In the case of non-threshold chemical substances, suitable estimates of excess lifetime cancer risk have been applied.


Lazaroids prevent acute cyclosporine-induced renal vasoconstriction.
Cyclosporine (CsA)-induced nephrotoxicity may be due to intrarenal vasoconstriction and glomerular hypoperfusion. Several factors, including endothelin and prostanoids, are suggested mediators of this response. Recent evidence suggests that CsA leads to increased oxygen-derived free radical (ODFR) production and lipid peroxidation in renal tissue. Whether this leads to alterations in renal vessel reactivity is unclear. Lazaroids, such as U74389G, are radical-quenching antioxidants that inhibit ODFR-induced lipid peroxidation and may improve renal function after ischemia and reperfusion. We hypothesized that ODFRs contribute to CsA-induced alterations of the renal microcirculation. Rat hydronephrotic kidneys were studied by video microscopy. Interlobular arteriolar diameter and flow, afferent and efferent arteriolar diameters, and cardiac output were measured at 15-min intervals for 120 min. U74389G or its vehicle was infused 15 min before topical application of CsA to the kidney. The results were compared with U74389G alone and normal saline. CsA administration caused renal microvascular vasoconstriction (10-25% below baseline) and hypoperfusion (35% below baseline). Both vasoconstriction and hypoperfusion were significantly attenuated by U74389G (5-8% and 20% below baseline, respectively). Inhibition of lipid peroxidation by U74389G maintained renal blood flow during acute CsA administration. These data suggest that ODFRs are involved in the renal microvascular response to CsA. Inhibition of ODFR-induced lipid peroxidation may help prevent CsA-induced glomerular hypoperfusion. Lazaroids may prove an effective adjunct in reducing CsA-induced nephrotoxicity.


[Restless-leg syndrome--possible unrecognized cause for insomnia and irritability in children].
Restless legs syndrome (RLS) has gradually been recognized as a cause for insomnia in adults, but there have been few reports about children with RLS in Japan. Here we described seven pediatric RLS patients. All of the parents of our patients had difficult times to make their children sleep due to irritability, restlessness, and demanding bedtime routines. All patients had asked their parents to rub their feet in bed, and it took more than half an hour to soothe them until they fell asleep. Their mothers had been exhausted from this night-time routine. However, they did not consider the routine abnormal, as it had been their habitual behavior since infancy. Some parents were too distressed or embarrassed to describe the symptoms of their child properly. Five patients had clear family history and none had obvious periodic leg movements during sleep. All patients showed low levels of ferritin and iron supplementation was effective in five cases. In the severest two cases, pramipexole, but not iron, was dramatically effective. Both patients started to show RLS symptoms in the early days of infancy, which may suggest more severe hereditary dopaminergic dysfunction. RLS does occur in childhood and pediatricians should bear it in mind as one of the differential diagnoses when seeing children who are irritated and/or having difficulty in initiating their sleep.


Etiological diagnosis of bloodstream infections through a multiplex real-time polymerase chain reaction test in pediatric patients: a case series from a tertiary Italian hospital.
The outcome of bloodstream infections (BSIs) is strongly related to microbiological diagnosis. Several factors may reduce blood culture (BC) diagnostic yield in pediatric BSIs, making the application of molecular methods quite promising. Multiplex real-time polymerase chain reaction (PCR) tests (the LightCycler Septifast Test MGRADE by Roche Diagnostics--LC-SF) performed in the tertiary centre of Regina Margherita Children's Hospital (Turin, Italy) over a 3-year period were retrospectively evaluated. Results of the LC-SF test were compared with those of BC (Automated Bact/Alert 3D, Biomerieux) collected at a close time point. 545 LC-SF tests were collected from 289 patients (183 males, median age 6.8 years, interquartile range (IQR) = 2.7-13.1); 163 had congenital or acquired immunodeficiency. In 515 cases (94.5%) the LC-SF test was performed with ongoing empirical antimicrobial therapy. Etiological definition was achieved in 111 BSI cases (20.4%). Both LC-SF and BC identified the responsible pathogen in 39 episodes. The LC-SF test alone gave a positive result in 29 septic episodes; BC alone permitted the etiological diagnosis in 43 episodes, but isolates were not included in the LC-SF master list in 10 cases. A 26% increase in bacterial identification chances due to the LC-SF test was documented. Cohen's kappa test indicated a moderate strength of agreement (0.49) between LC-SF tests and BCs closely collected. BC remains the gold standard for the etiological diagnosis of BSIs, but PCR methods proved to be a valuable adjunctive diagnostic tool in pediatric BSIs, especially in children receiving empirical chemotherapy.


Pharmacogenetics in perioperative medicine.
This review will discuss the most recent developments in pharmacogenetics of commonly used perioperative medications, new collaboration networks in the field of personalized medicine, and future clinical implications of pharmacogenetics. Evidence now suggests that pharmacogenetics has a role in the effects of analgesic, sedative, beta-blocker, local anesthetic, antiemetic, and obstetric medications. Variants in the μ opioid receptor gene change the analgesic effects of morphine. Additional opioids recently studied include remifentanil, methadone, tramadol, and codeine. Ibuprofen's clearance varies with CYP2C9*3 genotype. Midazolam is primarily metabolized by the CYP3A4/CYP3A5 enzymes. Enzyme induction was found to be about 50% greater with CYP3A5*3 homozygous genotype. Variations in minimum alveolar concentrations of volatile anesthetics and subcutaneous lidocaine efficacy have been attributed in part to melanocortin-1 receptor variants. Metoprolol achieved different effects in patients with CYP2D6 and beta1-receptor polymorphisms. Genetic background of the beta2-receptor contributes to susceptibility for experiencing preterm labor. The Pharmacogenomics Research Network and the Clinical Pharmacogenetics Implementation Consortium are partnerships of researchers who are dedicated to elucidating how the genome contributes to an individual patient's medication responses. In the near future, pharmacogenetic approaches may facilitate personalized perioperative intervention trials.


Facebook use and its effects on the life of health science students in a private medical college of Nepal.
Facebook, a popular social networking site, has been used by people of different ages and professions for various purposes. Its use in the field of medical education is increasing dramatically. At the same time, the pros and cons of facebook use among the health science students has attracted the attention of educators. The data regarding its use and the effect on the life of Nepalese health science students has not yet been documented. Therefore, this study is carried out to evaluate the effect of facebook use on social interactions, behaviour, academics, and the health of students in a medical college of Nepal. A cross-sectional descriptive study conducted among medical, dental, nursing and allied health science students using self-administered questionnaire. The study showed that 98.2 % of participants were facebook users. Among 452 respondents, 224 and 228 were male and female respectively, with a mean age of 20.2 ± 1.2 years. The main reason for using facebook was to remain in contact with family and friend (32 %), while its use for the academic purpose was only 5 %. However, 80.8 % of students acknowledged ease in acquiring academic materials from others, through facebook. One-fourth of the students acknowledged that they are using facebook late at night on a regular basis, while surprisingly 4.2 % of the students admitted accessing facebook during the classroom lectures. Almost two-third of the users, further admitted that facebook has had a negative impact on their studies. Burning eyes (21 %), disturbed sleep (19 %), and headache (16 %) were the most common adverse health effects reported by the facebook users. Many students (71.4 %) tried and most of them (68.7 %) succeeded, in reducing time spent on facebook, to allow for increased time devoted to their studies. The widespread use of facebook among the health science students, was found to have both positive and negative effects on their academics, social life, and health.


Residual motion on flexion-extension radiographs after simulated lumbar arthrodesis in human cadavers.
Flexion-extension radiographs are commonly used to assess lumbar fusion. Recommended criteria for solid fusion have varied from 1 to 5 degrees of angular motion between vertebrae. Notwithstanding this wide variation, the validity of these criteria have never been biomechanically tested. As a preliminary and initial step, it was the authors' purpose to quantify measurable angular motion after simulating solid lumbar fusion in human cadaver spines. Seven cadaveric spines (L1 to L4) were tested in a radiolucent jig fixed to a servohydraulic testing apparatus. Flexion and extension moments of 10 Nm were applied. Fusion was simulated using metallic implants spanning the L2-L3 motion segment. These included transverse process plates, a spinous process plate, pedicle screw construct, or an anterior vertebral body plate to simulate an intertransverse, interspinous process, facet, and interbody fusions, respectively. Angular movements were measured on lateral radiographs and statistically compared using a repeated measures analysis of variance. Simulated intertransverse fusion resulted in 13+/-4 degrees of motion; interspinous fusion, 9+/-4 degrees; posterior facet fusion, 5+/-3 degrees; and interbody fusion with plate, 3+/-2 degrees. Compared with the intact, only posterior facet fusion and interbody fusion with plate had statistically significantly less motion (P=0.006 and 0.0001, respectively). The amount of radiographically detectable flexion-extension motion with simulated fusions varies widely and seems to be influenced by fusion type. This study documents a range of measurable motion on flexion-extension radiographs after several types of simulated lumbar fusion. However, as the degrees of motion seemed to be high, future studies should use a fusion simulation other than metallic implants that more closely resembles bony arthrodesis.


Reactive Oxygen Species Synergize To Potently and Selectively Induce Cancer Cell Death.
A distinctive feature of cancer cells is their elevated levels of reactive oxygen species (ROS), a trait that can cause cancer cells to be more sensitive to ROS-inducing agents than normal cells. ROS take several forms, each with different reactivity and downstream consequence. Here we show that simultaneous generation of superoxide and hydrogen peroxide within cancer cells results in significant synergy, potently and selectively causing cancer cell death. In these experiments superoxide is generated using the NAD(P)H quinone oxidoreductase 1 (NQO1) substrate deoxynyboquinone (DNQ), and hydrogen peroxide is generated using the lactate dehydrogenase A (LDH-A) inhibitor NHI-Glc-2. This combination reduces tumor burden and prolongs survival in a mouse model of lung cancer. These data suggest that simultaneous induction of superoxide and hydrogen peroxide can be a powerful and selective anticancer strategy.


The acquisition of auxiliaries BE and HAVE: an elicitation study.
Auxiliary syntax is recognized to be one of the more complex aspects of language that children must acquire. However, there is much disagreement among researchers concerning children's early understanding of auxiliaries, with some researchers advocating a relatively abstract grammar as the basis for auxiliary syntax, while others view the acquisition of auxiliary syntax as the gradual accumulation of linguistic knowledge, initially tied to individual lexical items. To investigate the status of children's early knowledge of auxiliary syntax, two studies were carried out. In study 1, 28 children (M= 3;1) were tested for their use of the auxiliaries BE and HAVE in declaratives, while in study 2, 19 children (M=3;3) were tested for their use of these auxiliaries in questions. Although overall error rates were low, there were differences between BE and HAVE in the proportion and types of errors observed in declaratives and questions, and some individual children showed very high error rates. The implications of these findings for different models of auxiliary syntax in children's early utterances are discussed.


[An exploration on the factors of Jiao Xun's compilation and edit of Wu shi ben cao (Wu's Materia Medica)].
Wu shi ben cao (Wu's Materia Medica) written by Wu Pu was long lost. Jiao Xun of the Qing Dynasty was the first to compile and edit this book. The background of Jiao's work included: ① the necessary for revising Mao shi niao shou cao mu chong yu shi (Annotation to the Bird, Beast, Grass, Wood, Insect and Fish in Mao's Book of Songs); ② fond of medicine; ③ the feeling of retaining hometown documents; ④ the influence of the traditional style of compilation and edit; whereas Jiao's intrinsic characteristics included: ① a wealth of books and convenient borrowing environment; ② the habit of reading and transcription; ③ the thought of pu xue (the School of ancient textual criticism), that is "using the Confucian's method to study medical classics" ; ④ the methods of studying classics based on the classical texts; ⑤ high literate level of compilation of losing texts of classics. The original texts of Wu shi ben cao was thus resumed preliminarily by Jiao Xun's work.


What explains nurses' perceptions of staffing adequacy?
Much attention is being paid to the adequacy of nurse staffing in acute care hospitals, and much of the information relies on nurses' perceptions about staffing adequacy. Yet, we know little about what influences these perceptions. We examined the impact of hospital characteristics, nursing unit characteristics, nurse characteristics, and patient characteristics on nurses' perceptions of staffing adequacy. We tested three different models, incorporating different conceptualizations that relate current and past characteristics to these perceptions. This was a secondary analysis of data from the Outcomes Research in Nursing Administration Project, a longitudinal study conducted in 60 hospitals in the Southeastern United States. Perceptions of staffing adequacy were influenced significantly by the hospital's case mix index and growth in hospital admissions, by the number of beds on a unit, and by patient acuity. Further, current perceptions of staffing adequacy were significantly affected by prior perceptions. Based on our results, we present potential interventions for administrators that may ameliorate some of the negative influences on nurses' perceptions of staffing adequacy.


Association of frailty with quality of life in older hypertensive adults: a cross-sectional study.
Hypertension is one of the most common chronic cardiovascular diseases in older adults. Frailty and hypertension often coexist in older people, but few studies have explored frailty in older hypertensive adults. We aimed to explore the association of frailty with quality of life in older hypertensive adults. We collected the data of 291 patients with hypertension aged ≥ 60 years. Blood pressure was measured with a standard aneroid sphygmomanometer and an ambulatory blood pressure monitor. The characteristics of the Fried phenotype were used to assess physical frailty. The Medical Outcomes Study's 36-Item Short Form Health Survey (SF-36) was used to assess the quality of life. Forty-eight (16.5%) patients were frail. Compared with pre-frail or robust older hypertensive patients, those who were frail were older, had higher incidences of living alone, a longer duration of hypertension, lower grip strength, and slower walking speed. Moreover, frail patients had a lower diastolic blood pressure (DBP) and mean arterial pressure (MAP), more chronic diseases, a lower proportion of beta-blocker usage, and worse quality of life. Frailty was positively correlated with pulse pressure and negatively correlated with DBP and MAP, but these associations disappeared after adjustment by age. The SF-36 score was negatively correlated with frailty and positively correlated with grip strength and walking speed. After adjusting for age, the SF-36 total score remained negatively correlated with frailty and positively correlated with walking speed. Frailty states remained significantly associated with the SF-36 score. Frailty was associated with a worse quality of life in older adults with hypertension. Frailty prevention and intervention may help improve the quality of life of older adults with hypertension.


Clinical importance of interleukin-2 receptor alpha-chain expression in acute leukemia. The Japan Cooperative Group of Leukemia/Lymphoma.
To clarify the clinical importance of interleukin-2 (IL-2) receptor (IL-2R) expression in acute leukemia, we examined 517 adult patients with acute leukemia and CML blast crisis (CML-BC). IL-2R alpha was expressed in 42/311 AML, 5/11 acute unclassified leukemia, 24/116 pre-B ALL, 2/32 T-ALL, and 27/47 CML-BC, while IL-2R beta was expressed only in 2 T-ALL. Expression of IL-2R alpha was closely associated with that of different lineage markers, CD11b, CD34, and Ph1+ abnormality. IL-2R alpha(+) non-T leukemic cells did not respond to IL-2. Clinical outcome of IL-2R alpha (+) leukemia showed lower response to conventional chemotherapy and poorer prognosis than IL-2R alpha (-) cases. Serum IL-2R alpha level in IL-2R alpha (+) cases increased at the onset. Our findings indicate the diagnostic importance of IL-2R alpha expression in acute leukemia as a prognostic risk factor with a close relation to the particular cellular characteristics.


Medical management of polymyalgia rheumatica.
Polymyalgia rheumatica (PMR) is a relatively frequent condition in individuals older than 50 who originate from Western countries. Corticosteroids constitute the cornerstone therapy in the management of patients with PMR. This review summarizes the current literature on clinical clues for the diagnosis of PMR, conditions mimicking PMR, relapses in the setting of PMR and the main therapeutic strategies. With this information, the reader receives an overview on the current available data on clinical diagnosis and treatment options in PMR. TAKE-HOME MESSAGES: An initial dose of prednisone of 10-20 mg/day yields clinical improvement in the majority of patients with PMR. This is generally achieved within 7 days of the onset of this therapy. Conditions different from isolated PMR should be considered in atypical cases or when a good response to 20 mg/day of prednisone is not achieved. Relapses of PMR are not uncommon when the dose of prednisone is equal to or below than 5 mg/day. Methotrexate is the most commonly used corticosteroid sparing agent. Osteoporosis prophylaxis is also recommended.


Fractionation of a whey growth factor for Streptococcus agalactiae into two active components containing proteins.
Previously three factors (F-1, F-2, F-3) that stimulated in vitro growth of Streptococcus agalactiae were separated from wheys of milk and colostrum by chromatographic procedures. Now F-1 was separated further into two active components, F-1a and F-1b, when rechromatographed on an anion exchange resin with distilled water as eluent. The stimulatory activity was associated with two protein peaks whereas a third protein peak that was eluted in those fractions containing lactose was not stimulatory. Most of the stimulatory activity (76 to 80%) and protein (90 to 93%) were retained by a filter with retention of greater than 1,000 MW. Two stimulatory factors were confirmed by separation of F-1 fractions by step-gradient elution on a column of octadecylsilica; one protein peak was found for each of the three solvents. Samples with protein eluted with .1 N formic acid and formic acid: methanol (1:1) had stimulatory activity, whereas the sample with protein eluted with 100% methanol was inactive. Results were similar when F-1 fractions were applied to Sep-Pak (muBondapack C18) cartridges and eluted with water, 50% methanol, and 100% methanol. Proteins in the Sep-Pak eluates with stimulatory activity (water and 50% methanol) were heterogeneous and different when separated by high-voltage paper electrophoresis. Proteose-peptone preparations with added lactose were chromatographed on columns of anion exchange resin, with distilled water as eluent, and produced two peaks of protein with elution volumes comparable to peaks 1 and 3. Lactose appeared to be a major factor in eluting the second protein peak.(ABSTRACT TRUNCATED AT 250 WORDS)


Contribution of plasma protease inhibitors to the inactivation of kallikrein in plasma.
Although Cl-inhibitor (Cl-INH) and alpha(2)-macroglobulin (alpha(2)M) have been reported as the major inhibitors of plasma kallikrein in normal plasma, there is little quantitative support for this conclusion. Thus, we studied the inactivation of purified kallikrein in normal plasma, as well as in plasma congenitally deficient in Cl-INH, or artificially depleted of alpha(2)M by chemical modification of the inhibitor with methylamine. Under pseudo-first-order conditions, the inactivation rate constant of kallikrein in normal plasma was 0.60 min(-1). This rate constant was reduced to 0.35, 0.30, and 0.06 min(-1), in plasma deficient respectively in Cl-INH, alpha(2)M, or both inhibitors. Thus Cl-INH (42%) and alpha(2)M (50%) were found to be the major inhibitors of kallikrein in normal plasma. Moreover all the other protease inhibitors present in normal plasma contributed only for 8% to the inactivation of the enzyme. To confirm these kinetic results, (125)I-kallikrein (M(r) 85,000) was completely inactivated by various plasma samples, and the resulting mixtures were analyzed by gel filtration on Sepharose 6B CL for the appearance of (125)I-kallikrein-inhibitor complexes. After inactivation by normal plasma, 52% of the active enzyme were found to form a complex (M(r) 370,000) with Cl-INH, while 48% formed a complex (M(r) 850,000) with alpha(2)M. After inactivation by Cl-INH-deficient plasma, >90% of the active (125)I-kallikrein was associated with alpha(2)M. A similar proportion of the label was associated with Cl-INH in plasma deficient in alpha(2)M. After inactivation by plasma deficient in both Cl-INH and alpha(2)M, (125)I-kallikrein was found to form a complex of M(r) 185,000. This latter complex, which may involve antithrombin III, alpha(1)-protease inhibitor, and/or alpha(1)-plasmin inhibitor, was not detectable in appreciable concentrations in the presence of either Cl-INH or alpha(2)M, even after the addition of heparin (2 U/ml). These observations demonstrate that Cl-INH and alpha(2)M are the only significant inhibitors of kallikrein in normal plasma confirming previous predictions based on experiments in purified systems. Moreover, in the absence of either Cl-INH or alpha(2)M, the inactivation of kallikrein becomes almost entirely dependent on the other major inhibitor.


Synthesis, crystal structure, and magnetic properties of oxynitride perovskites SrMn0.2M0.8O2.6N0.4 (M = Nb, Ta).
Complex perovskites SrMn0.2Nb0.8O2.6N0.4 and SrMn0.2Ta0.8O2.6N0.4 were synthesized; these are rare examples of octahedral Mn2+ in oxynitride perovskites. Joint Rietveld refinement of neutron and X-ray data revealed that SrMn0.2Nb0.8O2.6N0.4 and SrMn0.2Ta0.8O2.6N0.4 had orthorhombic symmetries, in contrast with those of analogous perovskites SrM'0.2M0.8O3-xNx (M' = Li, Na, Mg; M = Nb, Ta), which are all tetragonal. Both SrMn0.2Nb0.8O2.6N0.4 and SrMn0.2Ta0.8O2.6N0.4 exhibited paramagnetic behavior with effective magnetic moments of 5.60μB and 5.94μB, respectively, consistent with a high-spin Mn2+ (d5, S = 5/2) state. The Weiss constants were -24.7 K for SrMn0.2Nb0.8O2.6N0.4 and -15.4 K for SrMn0.2Ta0.8O2.6N0.4, indicating the presence of weak antiferromagnetic spin-spin interactions. The band gaps of SrMn0.2Nb0.8O2.6N0.4 and SrMn0.2Ta0.8O2.6N0.4 were determined to be 1.75 eV and 2.2 eV, respectively, suggesting that the Mn 3d electrons were essentially localized.


Nucleotide sequences of segments 1, 3 and 4 of the genome of Bombyx mori cypovirus 1 encoding putative capsid proteins VP1, VP3 and VP4, respectively.
The complete nucleotide sequences of genomic segments S1, S3 and S4 from Bombyx mori cypovirus 1 (BmCPV-1) have been determined. The segments consisted of 4190, 3846 and 3262 nucleotides encoding putative proteins of 1333, 1239 and 1058 amino acids with molecular masses of approximately 148, 140 and 120 kDa (p148, p140 and p120, respectively). All segments possess a single open reading frame. Homology searches showed that all three proteins have homologies to proteins of Rice ragged stunt virus, a member of the genus Oryzavirus within the family REOVIRIDAE: Partial homologies of p140 to structural proteins in other viruses were also found. The predicted molecular masses and the homologies with structural proteins in other viruses lead us to suggest that S1, S3 and S4 encode the capsid proteins VP1, VP3, and VP4, respectively, of BmCPV-1.


[Neutrophil functions and interactions in the inflammatory reaction].
After 14 days' bone marrow maturation, neutrophil granulocytes reach the tissues where for 1-2 days they form the army whose phagocytic function was described by llya Metchnikoff in 1882. At that time, Paul Ehrlich was developing his neutrophil secretory theory which had less success until it returned with a vengeance in the last decade. Neutrophils are not only phagocytes. Above all they are cells that secrete bactericidal effectors and regulators (amplifiers and modulators) of the inflammatory focus. More and more sophisticated methods are being used to study phagocytosis, from the point of view both of the mechanism of chemotaxis and its role in inflammation and of the mediators of oxygen-dependent bactericidal action (superoxide anion, oxygenated water, hydroxyl radicals, myeloperoxidase, halogen ions and superoxide dismutase). In addition, the importance of oxygen-independent bactericidal mechanisms has been confirmed by the discovery of proteins such as BPI (Bactericidal Permeability Increasing Protein). Study of neutrophil dysfunction throws light on a number of neutrophil regulatory and effector mechanisms; it also proves useful in explaining the recurrent infections observed in some congenital disorders (chronic granulomatous disease, the "lazy leucocyte syndrome", the Chediak-Higashi syndrome, ichthyrosis , Job's syndrome...) or those associated with transitory neutrophil disorders (measles, severe bacterial infection...). Neutropenia induced by some antibiotics is easily demonstrated, but the interactions between these antibiotics and neutrophils are complex: phagocyte concentration of antibiotic, neutrophil inactivation of antibiotic, effect of antibiotic on microbe-leucocyte interaction such as an alteration in phagocytic and chemotactic response. The neutrophil is the first blood cell to arrive at the inflammatory focus; it is also at the centre of the response, next to the humoral mediators which both act upon it and which it itself secretes.


A Qualitative Approach to Understanding the Holistic Experience of Psychotherapy Among Clients.
Background: The study of the experience of clients across multiple service encounters (or touchpoints) is important from the perspective of service research. Despite the availability of effective psychotherapies, there exists a significant gap in the optimal delivery of such interventions in the community. Therefore, the aim of this study was to explore the experience of psychotherapy among clients integrating the before-during-after service encounters using a qualitative approach. Methods: A total of 15 clients of outpatient psychotherapy were interviewed, and data saturation was reached. The topics included pathways and reasons to seeking psychotherapy, aspects of the therapy process that have been helpful or unhelpful, and perceived change after receiving psychotherapy. Information was analyzed using the inductive thematic analysis method. Emergent themes pertaining to pre-psychotherapy encounters were mapped onto major components that were identified in Andersen's Health Service Utilization Model. Results: Mental health stigma and the lack of understanding about psychotherapy were the predisposing factors that impeded service use while the preference for non-pharmacological intervention promoted its use. Enabling factors such as affordability and service availability were also of concern, along with perceived and evaluated needs. The attributes of therapists, application of techniques, and the resistance of the client were found to impact the therapeutic alliance. While the majority of the clients experienced positive change or had engaged in self-help strategies after receiving psychotherapy, some cited limited impact on the recovery of symptoms or problematic self-coping without the therapists. Conclusion: This study proposes to expand on Andersen's Behavioral Model by including therapy-related factors so as to provide a more holistic understanding of the use of psychotherapy among the clients. More importantly, the study identified several barriers to access and negative experiences or outcomes, which should be addressed to promote uptake of the psychotherapy intervention.


Use of Yarrowia lipolytica hexokinase for the quantitative determination of trehalose 6-phosphate.
This paper describes a procedure for the quantitative determination of trehalose 6-phosphate (T6P) based on its ability to inhibit hexokinase from Yarrowia lipolytica. The assay is linear between 1 nmol and at least 8 nmol. The concentration of T6P in wild-type Saccharomyces cerevisiae (0.15 mM) and in ras2 mutants (0.25 mM) remained unchanged in the exponential or stationary phase of growth or after heat shock. A tps1 mutant affected in T6P synthase did not show detectable T6P. Heat shock increased the concentration of T6P in Schizosaccharomyces pombe from 0.43 to 0.75 mM.