A Sensor Fusion Method Based on an Integrated Neural Network and Kalman Filter for Vehicle Roll Angle Estimation.
This article presents a novel estimator based on sensor fusion, which combines the Neural Network (NN) with a Kalman filter in order to estimate the vehicle roll angle. The NN estimates a "pseudo-roll angle" through variables that are easily measured from Inertial Measurement Unit (IMU) sensors. An IMU is a device that is commonly used for vehicle motion detection, and its cost has decreased during recent years. The pseudo-roll angle is introduced in the Kalman filter in order to filter noise and minimize the variance of the norm and maximum errors' estimation. The NN has been trained for J-turn maneuvers, double lane change maneuvers and lane change maneuvers at different speeds and road friction coefficients. The proposed method takes into account the vehicle non-linearities, thus yielding good roll angle estimation. Finally, the proposed estimator has been compared with one that uses the suspension deflections to obtain the pseudo-roll angle. Experimental results show the effectiveness of the proposed NN and Kalman filter-based estimator.


Two new species of Indonemoura (Plecoptera: Nemouridae) from Yunnan Province of southwestern China.
Two new species of the nemourid genus Indonemoura are described, Indonemoura curvispina sp. nov. and I. spirocornua sp. nov., from the Gaoligong Mountains of Yunnan Province of southwestern China. The taxonomic relationships with related species are discussed.


Correlation of cerebral hypoxic-ischemic T2 changes with tissue alterations in water content and protein extravasation.
Age-dependent changes in T2-weighted MR images have been reported in cerebral hypoxia-ischemia. However, the biophysical mechanisms responsible for the image changes remain poorly defined. We investigated whether cerebral hypoxia-ischemia-induced T2 changes correlate with alterations in either water content or protein extravasation. One- and 4-week-old rats were subjected to unilateral carotid artery occlusion plus hypoxia in 8% oxygen. T2 images were acquired before, during, and 1 or 24 hours after hypoxia-ischemia. Blood-brain barrier disruption and brain edema were evaluated by immunohistological detection of IgG extravasation and measurement of water content by dry-wet weight and specific gravity methods. In 1-week-old rats, T2 values, areas of hyperintensity on T2-weighted images, and water content in the ipsilateral hemisphere increased during hypoxia-ischemia, recovered at 1 hour after hypoxia-ischemia, and increased again at 24 hours after hypoxia-ischemia. Extravasation of IgG occurred during hypoxia-ischemia and remained detectable 24 hours after hypoxia-ischemia. In 4-week-old rats, an increase in T2 or extravasation of IgG did not occur until 24 hours after hypoxia-ischemia despite a comparable elevation in water content during and soon after hypoxia-ischemia. T2 imaging appears reliable for detecting edema associated with disruption of the blood-brain barrier but not necessarily an increase in cerebral water or plasma proteins alone. The different hypoxic-ischemic changes in T2 in immature and older brain are associated with differences in alterations in water content plus extravasation of protein, consistent with age-dependent differences in hypoxic-ischemic alterations in vascular permeability.


Sites of action of gamma-hydroxybutyrate (GHB)--a neuroactive drug with abuse potential.
This review highlights the biochemistry, pharmacology, and toxicology of the naturally-occurring fatty acid derivative, gamma-hydroxybutyrate (GHB). GHB is derived from gamma-aminobutyric acid (GABA) and is proposed to function as an inhibitory chemical transmitter in the central nervous system. When administered in pharmacological doses, its powerful central nervous system depressant effects are readily observed. Although some of the neurophysiological actions of GHB could involve alterations in dopaminergic transmission in the basal ganglia, both its physiological and pharmacological actions are probably mediated through specific brain receptors for GHB. In addition, GHB might mediate some of its effects through interaction with the GABA(B) receptor. Experimentally, GHB has been used as a model for petit mal epilepsy; clinically, it has been used as a general anesthetic and as a drug to treat certain sleep disorders and related conditions. Owing to the purported ability of GHB to induce a state of euphoria, recreational use of this substance is popular. Although no deaths or long-term problems have been associated with GHB abuse, symptoms of GHB intoxication can be severe. The continued potential for GHB abuse makes it imperative for clinical toxicologists to be aware of the effects of this agent. Future research on the mechanism of action of GHB is needed to elucidate both its central nervous system depressant properties and its ability to effect a state of well-being.


Safety and feasibility of freehand transperineal prostate biopsy under local anesthesia: Our initial experience.
With the emergence of multidrug-resistant organisms causing urosepsis after transrectal biopsy of prostate, the need for an alternative approach has increased. We assessed the safety and feasibility of transrectal ultrasound (TRUS) guided free-hand transperineal prostate biopsy under local anesthesia (LA) for suspected prostate cancer. This prospective study was conducted from July 2019 to December 2020 in which patients with elevated prostate-specific antigen (PSA) and/or abnormal digital rectal examination underwent magnetic resonance imaging-TRUS cognitive fusion transperineal prostate biopsy (target and systematic) using coaxial needle. Demographic, perioperative, and outcome data of 50 consecutive patients were analyzed. The mean age of the patients was 69.6 ± 7.61 years, median PSA 13.55 ng/mL (4.17-672) and prostate size 45cc (16-520). Prostate Imaging-Reporting and Data System (PIRADS) 2, 3, 4, and 5 lesions were found in 2, 12, 12, and 24 patients, respectively. Average procedure duration was 20 min (15-40 min) and number of cores ranged from 12 to 38 (median 20). Forty out of fifty (40/50) patients experienced only mild pain with visual analog scale ≤2. Histopathological examination showed adenocarcinoma, benign prostatic hyperplasia, and chronic prostatitis in 41, 5, and 4 patients respectively with 82% cancer detection rate (CDR). Over 95% of cases showed clinically significant cancer (International Society of Urological Pathology class ≥ 2) and 91.7% of patients with PIRADS score 4/5 and 66.7% with PIRADS score 3 had malignancy. Three patients developed complications (two hematuria, one urinary retention), both were managed conservatively and none had urosepsis. Free-hand transperineal prostate biopsy by coaxial needle technique under LA is safe and feasible with good tolerability, high CDR, and minimal complications particularly reduced urosepsis.


The invasive phenotype in HMT-3522 cells requires increased EGF receptor signaling through both PI 3-kinase and ERK 1,2 pathways.
We studied the invasion of HMT-3522 breast epithelial cells in response to epidermal growth factor (EGF), and the associated signaling pathways. HMT-3522 T4-2 cells were shown to invade Matrigel-coated Transwell membranes in response to EGF while HMT-3522 S-1 cells failed to invade when treated with EGF. Studies utilizing specific molecular inhibitors showed the importance of beta1 integrin, phosphatidylinositol 3 kinase (PI 3-kinase), p38, extracellular regulated kinase 1, 2 (Erk 1,2) MAP kinases, and metalloproteinases in invasion and motility. T4-2 cell invasion was shown to be time-dependent and also gene transcription-dependent as shown by inhibition with Actinomycin D. T4-2 cells exhibited an increased activation of MAP kinases Erk 1,2 (2-fold), EGF receptor (3-fold), and PI 3-kinase (3- to 4-fold) when compared to the S-1 cells. In response to EGF, T4-2 cells showed a 5-fold greater secretion of matrix metalloproteinase-9 (MMP-9) as compared to S-1 cells, and this increase was largely dependent on the activity of PI 3-kinase. These findings indicate that expression of the invasive phenotype in these breast epithelial cells requires increased EGF receptor signaling, involving both PI 3-kinase and Erk 1,2 activities, which leads to multiple downstream effects, including enhanced secretion of MMP-9 and transcription of invasion-related genes.


[Myocardial protection with pulsatiled retrograde coronary sinus perfusion--using Emax for left ventricular contractility].
Recently retrograde coronary sinus perfusion technique has been frequently used in patients with severe coronary artery disease. However many untoward effects, such as tissue edema and hemorrhage, have also noticed. To evaluate the efficacy of retrograde cardioplegia, 24 mongrel pentobarbital anesthetized dogs were studied. To create hypoperfused area, distal portion of the left anterior descending coronary artery (LAD) was occluded. After cardioplegic arrest under cardiopulmonary bypass, dogs were assigned following 3 experimental groups (8 dogs each). Group I; Glucose-Insulin-Potassium (GIK) solution (K: 20 mEq/l, 20 ml/kg) was given antegradely into the aorta. Group II; GIK was given retrogradely through the coronary sinus. Group III; GIK was given retrogradely with pulsatile device (synchronized retroperfusion pump system). After 30 minutes, same amount of GIK was given again. Then LAD occlusion was released. Sixty minutes after onset of arrest, the aorta was declamped and cardiopulmonary bypass was stopped. The left ventricular contractility (Emax) measured with conductance catheter at the end of experiment was significantly (p < 0.05) better in groups II (13.1 +/- 2.6, mean +/- SD) and III (13.1 +/- 2.9) than in group I (9.6 +/- 2.7). The left ventricular wall-motion measured with ultrasound crystals in hypoperfused area compared to before cardiopulmonary bypass was also significantly better in groups II (76.2 +/- 17.2%) and III (87.9 +/- 16.9%). Regional myocardial temperature suggested that more rapid and homogeneous cooling including right ventricle was achieved in group III than in groups I and II. Retrograde perfusion is more effective method in the setting of coronary stenosis compared to ordinal antegrade technique.(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of risk factors for the development of bronchiolitis obliterans syndrome.
Chronic rejection after lung transplantation, manifesting as bronchiolitis obliterans syndrome (BOS), has become the dominant challenge to long-term patient and graft survival. In order to elucidate risk factors for development of BOS we utilized the 1995 revision of the working formulation for the classification of lung allograft rejection (), and devised a quantitative method to retrospectively study lung transplant biopsies from all patients who survived at least 90 d. All transbronchial biopsies were regraded 0 to 4 for acute perivascular rejection and lymphocytic bronchitis/bronchiolitis (LBB), and the grades were totaled over a period of time to give two scores, respectively, for each patient. Also examined were timing of acute rejection and LBB episodes and decreased immunosuppression defined as two or more cyclosporine A levels < 200 ng/ml. Sixty-six patients with BOS and 68 with no BOS (NBOS) satisfied our criteria for inclusion in the study. Demographics including age, sex, and primary diagnoses were similar. The mean perivascular score for BOS was 6.2 over a mean follow-up of 822 d (range, 113 to 2,146) compared with 3.2 for NBOS over 550 d (range, 97 to 1,734) mean follow-up. Airway scores were 5.3 and 1.7, respectively, for the same follow-up periods. There was no correlation between length of follow-up and rejection or LBB scores, although mean length of follow-up for the two groups was significantly different. Late acute rejection and LBB were significantly associated with BOS as was decreased immunosuppression. In addition to perivascular rejection, LBB, late acute rejection, and decreased immunosuppression are significant risk factors for the development of BOS. Analysis of the current data leads us to believe that LBB, in the absence of infection, is in fact a manifestation of acute rejection, with similar implications for graft function as acute perivascular rejection.


The effects of husbandry training on stereotypic pacing in captive African wild dogs (Lycaon pictus).
To examine the effects of operant conditioning on stereotypic pacing in 3 female African wild dogs located at the Franklin Park Zoo in Boston, this study made recordings of pacing behavior immediately following individual sessions of husbandry training and 2 no-training conditions. The study found significant differences in the percentage of observations spent in stereotypic pacing behaviors for all 3 dogs among the 3 different conditions. The authors discuss the data in terms of the contribution of motivated tasks to the effects and the role of food deprivation in the expression of stereotypic pacing. The study suggests that even short periods of training may improve the African wild dogs' welfare by reducing stereotypic pacing following the conditioning sessions.


NmRF: identification of multispecies RNA 2'-O-methylation modification sites from RNA sequences.
2'-O-methylation (Nm) is a post-transcriptional modification of RNA that is catalyzed by 2'-O-methyltransferase and involves replacing the H on the 2'-hydroxyl group with a methyl group. The 2'-O-methylation modification site is detected in a variety of RNA types (miRNA, tRNA, mRNA, etc.), plays an important role in biological processes and is associated with different diseases. There are few functional mechanisms developed at present, and traditional high-throughput experiments are time-consuming and expensive to explore functional mechanisms. For a deeper understanding of relevant biological mechanisms, it is necessary to develop efficient and accurate recognition tools based on machine learning. Based on this, we constructed a predictor called NmRF based on optimal mixed features and random forest classifier to identify 2'-O-methylation modification sites. The predictor can identify modification sites of multiple species at the same time. To obtain a better prediction model, a two-step strategy is adopted; that is, the optimal hybrid feature set is obtained by combining the light gradient boosting algorithm and incremental feature selection strategy. In 10-fold cross-validation, the accuracies of Homo sapiens and Saccharomyces cerevisiae were 89.069 and 93.885%, and the AUC were 0.9498 and 0.9832, respectively. The rigorous 10-fold cross-validation and independent tests confirm that the proposed method is significantly better than existing tools. A user-friendly web server is accessible at http://lab.malab.cn/∼acy/NmRF.


Lower body mass index potentiates the association between skipping breakfast and prevalence of proteinuria.
Proteinuria is an important predictor of cardiovascular disease and mortality. Several studies reported the association between skipping breakfast and the prevalence of proteinuria. Furthermore, skipping breakfast was associated with an increased risk of obesity. Although proteinuria is highly prevalent in obese individuals, the association between the prevalence of proteinuria and low body mass index (BMI) was reported in a previous cross-sectional study in asymptomatic individuals without known kidney diseases. The aim of this cross-sectional study was to assess the clinical impact of BMI on the association between skipping breakfast and the prevalence of proteinuria in normal renal function subjects. The present study included 26,888 subjects (15,875 males and 11,013 females) with an estimated glomerular filtration rate ≥60 ml/min/1.73 m2 and no history of kidney disease who underwent a health checkup in Sumitomo Hospital. The association between skipping breakfast and the prevalence of proteinuria (defined as dipstick proteinuria of ≥1+) was assessed using logistic regression models adjusted for clinically relevant factors. Skipping breakfast was reported in 3,306 males (20.8%) and 1,514 females (13.8%). Multivariable adjusted logistic regression models showed that skipping breakfast was significantly associated with the prevalence of proteinuria above 1+. This association was evident in lower BMI subjects, even after adjusting for clinically relevant factors (adjusted odds ratios of males and females were 1.67 [1.17-2.38] and 1.92 [1.31-2.82], respectively), whereas this association was not evident in higher BMI subjects. Lower BMI subjects with proteinuria might need to be careful about skipping breakfast.


Osteonecrosis in HIV disease: epidemiology, etiologies, and clinical management.
Osteonecrosis has been increasingly associated with HIV disease throughout the 1990s, and the incidence appears to be rising. The hip is most commonly involved and often bilaterally. Although anecodotal reports suggest an association between osteonecrosis and highly active antiretroviral therapy, controlled epidemiologic studies do not support a direct link. Many patients with osteonecrosis have established risk factors, some of which may be related to HIV disease or its therapy, including corticosteroid use and hyperlipidemia. Alcoholism, hypercoagulability, megesterol acetate use, immune reconstitution, and other factors may also contribute. Plain radiographs and magnetic resonance imaging are the cornerstones of diagnosis. Management is dependent on the stage of bone disease and ranges from observation to total joint arthroplasty. Clinicians may help to prevent HIV-associated osteonecrosis by encouraging patients to limit their exposure to the established risk factors for the disease.


Long-term results of volar ligament reconstruction for symptomatic basal joint laxity.
It has been hypothesized that instability of the thumb trapeziometacarpal joint is a major factor in the etiology of degenerative disease. Theoretically, surgically stabilized joints should be subject to less shear force and, hence, will be less likely to develop degenerative changes. The long-term results of volar ligament reconstruction were assessed in 19 patients (24 thumbs). The average age at surgery was 33 years (range, 18-55 years). Twenty-three thumbs were radiographic stage I; a preoperative x-ray was not available in 1. The follow-up period averaged 15 years (range, 10-23 years). At the final follow-up visit 15 thumbs were stage I, 7 were stage II, and 2 were stage III. Fifteen patients were at least 90% satisfied with the results of the surgery. Only 8% of thumbs advanced to radiographic arthritic disease, which compares favorably with the 17% to 33% reported incidence of stage III/IV basal joint arthritis in the general population.


Mechanisms of immune modulation by mesenchymal stromal cells and clinical translation.
Cell therapy with mesenchymal stromal cells (MSCs) is the focus of intensive investigation. Several clinical trials, including large-scale placebo-controlled phase III clinical trials, are currently underway evaluating the therapeutic potential of autologous and allogeneic MSCs for treatment of catastrophic inflammatory diseases, including steroid-refractory graft-versus-host disease (GvHD), multiple sclerosis (MS) and Crohn's disease. MSCs are also being investigated as carriers of anti-cancer biotherapeutics. We here review recent developments in our understanding of the immunosuppressive properties of MSCs. We firstly discuss the effects of ex vivo culture conditions on the phenotype and functions of MSCs. Secondly, we summarize the immune functions suppressed by MSCs with a focus on T cell, B cell, natural killer cell and dendritic cell functions. Thirdly, we discuss newly identified pathways responsible for the immunosuppressive activity of MSCs, including the expression of heme-oxygenase (HO)-1, the secretion of galectins, CCL2 antagonism, T regulatory cell (Treg) cross-talk and production of TNF-α stimulated gene/protein-6 (TSG-6). Finally, we review the literature on the molecular pathways governing MSC homing and discuss recent clinical data on the use of MSCs for treatment of GvHD, MS and Crohn's disease.


Subcapsular hepatic hematoma after guide wire injury during endoscopic retrograde cholangiopancreatography: management and review.
Complications of endoscopic retrograde cholangiopancreatography (ERCP) that are associated with the guide wire are fortunately rare, but may be more common than is reported. We describe the case of a 43-year-old woman with obstructive jaundice from metastatic pancreatic cancer who underwent an elective ERCP for biliary stent placement. This was complicated by guide wire-associated injury that resulted in the development and eventual rupture of a subcapsular hepatic hematoma and which was successfully treated with nonsurgical management. If identified and treated rapidly, using a multidisciplinary approach (i. e., with medical, interventional radiology, and surgical input), such patients can be conservatively managed.


A parametric model of the brain vascular system for estimation of the arterial input function (AIF) at the tissue level.
In this paper, we introduce a novel model of the brain vascular system, which is developed based on laws of fluid dynamics and vascular morphology. This model is used to address dispersion and delay of the arterial input function (AIF) at different levels of the vascular structure and to estimate the local AIF in DCE images. We developed a method based on the simplex algorithm and Akaike information criterion to estimate the likelihood of the contrast agent concentration signal sampled in DCE images belonging to different layers of the vascular tree or being a combination of different signal levels from different nodes of this structure. To evaluate this method, we tested the method on simulated local AIF signals at different levels of this structure. Even down to a signal to noise ratio of 5.5 our method was able to accurately detect the branching level of the simulated signals. When two signals with the same power level were combined, our method was able to separate the base signals of the composite AIF at the 50% threshold. We applied this method to dynamic contrast enhanced computed tomography (DCE-CT) data, and using the parameters estimated by our method we created an arrival time map of the brain. Our model corrected AIF can be used for solving the pharmacokinetic equations for more accurate estimation of vascular permeability parameters in DCE imaging studies.


Are Multicentre Bond Indices and Related Quantities Reliable Predictors of Excited-State Aromaticity?
Systematic scrutiny is carried out of the ability of multicentre bond indices and the NOEL-based similarity index dAB to serve as excited-state aromaticity criteria. These indices were calculated using state-optimized complete active-space self-consistent field wavefunctions for several low-lying singlet and triplet states of the paradigmatic molecules of benzene and square cyclobutadiene and the inorganic ring S2N2. The comparison of the excited-state indices with aromaticity trends for individual excited states suggested by the values of magnetic aromaticity criteria show that whereas the indices work well for aromaticity reversals between the ground singlet and first triplet electronic states, addressed by Baird's rule, there are no straightforward parallels between the two sets of data for singlet excited states. The problems experienced while applying multicentre bond indices and dAB to singlet excited states are explained by the loss of the information inherently present in wavefunctions and/or pair densities when calculating the first-order density matrix.


sMOOC: A pedagogical model for social inclusion.
In this article, the results of analysing the sMOOC launched by European project E-learning, Communication, Open Data (ECO) are displayed, from the perspective of social inclusion. Firstly, it considers people excluded from the system and, on a second stage, attention is brought towards those agents acting as social mediators. A quantitative methodology of analysis was applied to the interactions occurred in a sample of 1,361 participants at ECO Portal's course "Education Innovation and Professional Development. Possibilities and Limits of the ICTs". Results show that ECO has massively promoted sMOOC-based training and has become present, not only in Europe, but also in a wider geographical spread, particularly in developing countries. Such training offering has been highly valued by participants in aspects related to the knowledge acquired and them feeling active role-players in the education process, which increases their commitment towards sharing that training in diverse social environments and, as a result, makes a significant impact on social inclusion processes.


Serum Neurofilament Light Chain Levels May Be a Marker of Lower Motor Neuron Damage in Amyotrophic Lateral Sclerosis.
Objectives The aims of this study were to investigate whether serum neurofilament light chain (NfL) levels were correlated with the severity of the axonal degeneration of lower motor neurons (LMNs) in the early symptomatic phase of amyotrophic lateral sclerosis (ALS). Methods In this prospective study, the serum samples used for NfL measurement were obtained from 103 sporadic ALS outpatients within 2 years of disease duration. The severity of axonal degeneration was assessed by assessing the decrease in the compound muscle action potentials (CMAPs) within a 1-month interval from serum sampling. Results The NfL levels showed a significant positive correlation with the relative score as a proxy for the axonal damage of LMNs in patients with ALS (coefficient: 0.264, p = 0.009). Furthermore, this correlation became stronger (coefficient: 0.582, p = 0.037) when estimated only among patients with disease subtypes that involve only LMNs, that is, patients with flail arm or leg syndrome (FAS or FLS). The levels of NfL increased with the severity of axonal damage of LMNs (F = 6.694, P = 0.0001). Conclusions Serum NfL levels mirrored the severity of the axonal degeneration of LMNs, particularly in patients with signs of predominant LMN involvement. These results may have a profound effect on the selection of patients and the monitoring of treatment efficacy in future disease-modifying clinical trials.


Naphthalimide gold(I) phosphine complexes as anticancer metallodrugs.
Gold(I) phosphine complexes exhibit promising properties for anticancer drug development. Here we report on a series of gold(I) phosphine complexes containing a naphthalimide ligand. Strong antiproliferative effects were observed in MCF-7 breast cancer cells as well as in HT-29 colon carcinoma cells. The cellular and nuclear gold levels were increased compared to analogues, in which the naphthalimide ligand was replaced by a chloro ligand. Compound 4a was selected for more detailed biochemical and biological studies, which revealed solvent dependent fluorescence emission, uptake of the compound into the organelles of tumor cells as well as antiangiogenic effects concerning angiogenesis and tumor-induced angiogenesis in vivo. Antiangiogenic properties of 4a were observed in two different zebrafish angiogenesis models, including a tumor-cell induced neovascularization assay.


Survey of radiosensitivity in a variety of human cell strains.
gamma-Ray sensitivity for cell killing was assayed in 54 human cell strains, including some derived from individuals suffering from certain heritable diseases. The overall range of Do values in this study was 38 to 180 rads, indicating a considerable range of variability in humans. The normal sensitivity was described by a range of Do values of 97 to 180 rads. All ten ataxia telangiectasia cell strains tested proved radiosensitive and gave a mean Do value of 57 +/- 15 (S.E.) rads, and these represent the most radiosensitive human skin fibroblasts currently available. Representative cell strains from familial retinoblastoma, Fanconi's anemia, and Hutchinson-Gilford progeria occupied positions of intermediate sensitivity, as did one of two ataxia telangiectasia heterozygotes. Six xeroderma pigmentosum cell strains together with two Cockayne's syndrome cell strains (all known to be sensitive to ultraviolet light) fell into the normal range, indicating an absence of cross-sensitivity between ultraviolet light and gamma-irradiation.


Resolution enhancement by extrapolation of coherent diffraction images: a quantitative study on the limits and a numerical study of nonbinary and phase objects.
In coherent diffractive imaging, the resolution of the reconstructed object is limited by the numerical aperture of the experimental setup. We present here a theoretical and numerical study for achieving super-resolution by postextrapolation of coherent diffraction images, such as diffraction patterns or holograms. We demonstrate that a diffraction pattern can unambiguously be extrapolated from only a fraction of the entire pattern and that the ratio of the extrapolated signal to the originally available signal is linearly proportional to the oversampling ratio. Although there could be in principle other methods to achieve extrapolation, we devote our discussion to employing iterative phase retrieval methods and demonstrate their limits. We present two numerical studies; namely, the extrapolation of diffraction patterns of nonbinary and that of phase objects together with a discussion of the optimal extrapolation procedure.


Combined Association Between ADIPOQ, PPARG, and TNF Genes Variants and Obstructive Sleep Apnea in Chinese Han Population.
Obstructive sleep apnea (OSA) is a common chronic polygenic disease. Multiple genetic markers associated with OSA have been identified by genome-wide association studies. Here, we aimed to construct a polygenic risk score (PRS) and examine the association with the presence of OSA in a Chinese Han Population. This study included 1057 individuals who were genotyped for nine susceptibility loci from three genes (ADIPOQ, PPARG, and TNF), from which each individual's PRS was calculated by summing the number of risk alleles. The associations between PRS and OSA were determined by logistic regression analyses. Model discrimination was assessed by a receiver operating characteristic (ROC) curve using bootstrapping with 1000 resamples. The subjects included 874 with OSA and 183 controls. A higher PRS was associated with an increased apnea-hypopnea index (AHI). The PRS was an important risk factor for the development of OSA (OR = 1.237 per SD, P = 0.030). Subjects with higher PRS had a 2.88-fold (95% CI: 1.393-5.955, P = 0.004) and 5.402-fold (95% CI: 2.311-12.624, P<0.001) greater risk for having OSA and moderate-to-severe OSA, respectively, compared with those with lower genetic risk. More importantly, compared with determination of risk based solely on clinical factors, addition of the PRS increased discriminatory accuracy for both OSA (AUC from 0.75 to 0.78, P = 0.02) and moderate-to-severe OSA (AUC from 0.80 to 0.83, P = 0.02). Our study suggests that the PRS is independently associated with AHI and OSA. Combining PRS with conventional risk factors could improve the discrimination of OSA.


Severe diarrhea in renal transplant patients: results of the DIDACT study.
Diarrhea is common in transplant recipients. While the majority of cases are mild and transient, some are severe and prolonged, which can threaten graft survival through dehydration. While it is known that some immunosuppressive agents can elicit diarrhea, there does not appear to be any consensus on the role that other nonimmunosuppressive causes can play in transplant patients. The aim of the present open, nonrandomized, multicenter study was to identify nonimmunosuppressive factors involved in severe diarrhea in renal transplant patients. Patients (n = 108) with severe diarrhea (>/=3 stools/day for >/=7 days) were enrolled from 16 Belgian transplant centers. Patients were diagnosed according to an agreed flowchart that consisted of identification of possible infections, followed by changes in empirical and immunosuppressive treatment. Approximately 50% of patients experienced resolution of severe diarrhea following treatment for infections, dietary problems or diarrhea-causing concomitant medications. In conclusion, a large proportion of the severe diarrhea observed in renal transplant recipients is not associated with immunosuppressive therapy and can be treated through anti-infectives, changes to concomitant medication and other empirical treatments. Correct diagnosis of the cause of severe diarrhea in such patients should help to protect graft survival in transplant recipients.


Polycrystalline diamond based detector for Z-pinch plasma diagnosis.
A detector setup based on polycrystalline chemical-vapor-deposition diamond film is developed with great characteristics: low dark current (lower than 60 pA within 3 V/mum), fast pulsed response time (rise time: 2-3 ns), flat spectral response (3-5 keV), easy acquisition, low cost, and relative large sensitive area. The characterizing data on Qiangguang-I accelerator show that this detector can satisfy the practical requirements in Z-pinch plasma diagnosis very well, which offers a promising prototype for the x-ray detection in Z-pinch diagnosis.


Systematic review of effective strategies for reducing screen time among young children.
Screen-media use among young children is highly prevalent, disproportionately high among children from lower-income families and racial/ethnic minorities, and may have adverse effects on obesity risk. Few systematic reviews have examined early intervention strategies to limit TV or total screen time; none have examined strategies to discourage parents from putting TVs in their children's bedrooms or remove TVs if they are already there. In order to identify strategies to reduce TV viewing or total screen time among children <12 years of age, we conducted a systematic review of seven electronic databases to June 2011, using the terms "intervention" and "television," "media," or "screen time." Peer-reviewed intervention studies that reported frequencies of TV viewing or screen-media use in children under age 12 were eligible for inclusion. We identified 144 studies; 47 met our inclusion criteria. Twenty-nine achieved significant reductions in TV viewing or screen-media use. Studies utilizing electronic TV monitoring devices, contingent feedback systems, and clinic-based counseling were most effective. While studies have reduced screen-media use in children, there are several research gaps, including a relative paucity of studies targeting young children (n = 13) or minorities (n = 14), limited long-term (>6 month) follow-up data (n = 5), and few (n = 4) targeting removing TVs from children's bedrooms. Attention to these issues may help increase the effectiveness of existing strategies for screen time reduction and extend them to different populations.


Be[triple bond, length as m-dash]Be triple bond in Be2X4Y2 clusters (X = Li, Na and Y = Li, Na, K) and a perfect classical Be[triple bond, length as m-dash]Be triple bond presented in Be2Na4K2.
Herein, we presented a series of Be2X4Y2 clusters (X = Li, Na and Y = Li, Na, K) containing Be[triple bond, length as m-dash]Be triple bonds, which were constructed by six alkali metals as electron-donating ligands. By virtue of the electrostatic potential mapping of the precedent Be[double bond, length as m-dash]Be double-π bonded D4h-Be2X4 clusters, the Be2X4Y2trans-bent geometries and the Be[triple bond, length as m-dash]Be triple bonds inside were both well interpreted. More remarkably, we first identified a perfect classical Be[triple bond, length as m-dash]Be triple bond in D4h-Be2Na4K2 and its Wiberg bond index of Be-Be (WBIBe-Be) reached up to 2.43. Meanwhile, our strategy provides a new approach to explain the trans-bent structure caused by terminal coordination.


Injection of poly(beta-L-malate) into the plasmodium of Physarum polycephalum shortens the cell cycle and increases the growth rate.
Poly(beta-L-malate) (PMLA) has been reported as an unconventional, physiologically important biopolymer in plasmodia of myxomycetes, and has been proposed to function in the storage and transport of nuclear proteins by mimicking the phospho(deoxy)ribose backbone of nucleic acids. It is distributed in the cytoplasm and especially in the nuclei of these giant, multinucleate cells. We report here for the first time an increase in growth rate and a shortening of the cell cycle after the injection of purified PMLA. By comparing two strains of Physarum polycephalum that differed in their production levels of PMLA, it was found that growth activation and cell cycle shortening correlated with the relative increases of PMLA levels in the cytoplasm or the nuclei. Growth rates of a low PMLA producer strain (LU897 x LU898) were increased by 40-50% while those of a high producer strain (M(3)CVIII) were increased by only 0-17% in comparison with controls. In both strains, shortening of the cell cycle occurred to a similar extent (7.2-9.5%), and this was associated with similar increases in nuclear PMLA levels. The effects showed saturation dependences with regard to the amount of injected PMLA. A steep rise of intracellular PMLA shortly after injection was followed by the appearance of histone H1 in the cytoplasm. The increase in growth rate, the shortening of the cell cycle duration and the appearance of H1 in the cytoplasm suggest that PMLA competes with nucleic acids in binding to proteins that control translation and/or transcription. Thus, PMLA could play an important role in the coordination of molecular pathways that are responsible for the synchronous functioning of the multinucleate plasmodium.


Development of prototype shielded cervical intracavitary brachytherapy applicators compatible with CT and MR imaging.
Intracavitary brachytherapy (ICBT) is an integral part of the treatment regimen for cervical cancer and, generally, outcome in terms of local disease control and complications is a function of dose to the disease bed and critical structures, respectively. Therefore, it is paramount to accurately determine the dose given via ICBT to the tumor bed as well as critical structures. This is greatly facilitated through the use of advanced three-dimensional imaging modalities, such as CT and MR, to delineate critical and target structures with an ICBT applicator inserted in vivo. These methods are not possible when using a shielded applicator due to the image artifacts generated by interovoid shielding. The authors present two prototype shielded ICBT applicators that can be utilized for artifact-free CT image acquisition. They also investigate the MR amenability and dosimetry of a novel tungsten-alloy shielding material to extend the functionality of these devices. To accomplish artifact-free CT image acquisition, a "step-and-shoot" (S&S) methodology was utilized, which exploits the prototype applicators movable interovoid shielding. Both prototypes were placed in imaging phantoms that positioned the applicators in clinically applicable orientations. CT image sets were acquired of the prototype applicators as well as a shielded Fletcher-Williamson (sFW) ovoid. Artifacts present in each CT image set were qualitatively compared for each prototype applicator following the S&S methodology and the sFW. To test the novel tungsten-alloy shielding material's MR amenability, they constructed a phantom applicator that mimics the basic components of an ICBT ovoid. This phantom applicator positions the MR-compatible shields in orientations equivalent to the sFW bladder and rectal shields. MR images were acquired within a gadopentetate dimeglumine-doped water tank using standard pulse sequences and examined for artifacts. In addition, Monte Carlo simulations were performed to match the attenuation due to the thickness of this new shield type with current, clinically utilized ovoid shields and a 192Ir HDR/PDR source. Artifact-free CT images could be acquired of both generation applicators in a clinically applicable geometry using the S&S method. MR images were acquired of the phantom applicator containing shields, which contained minimal, clinically relevant artifacts. The thickness required to match the dosimetry of the MR-compatible and sFW rectal shields was determined using Monte Carlo simulations. Utilizing a S&S imaging method in conjunction with prototype applicators that feature movable interovoid shields, they were able to acquire artifact-free CT image sets in a clinically applicable geometry. MR images were acquired of a phantom applicator that contained shields composed of a novel tungsten alloy. Artifacts were largely limited to regions within the ovoid cap and are of no clinical interest. The second generation A3 utilizes this material for interovoid shielding.


Coordinated host-pathogen transcriptional dynamics revealed using sorted subpopulations and single macrophages infected with Candida albicans.
The outcome of fungal infections depends on interactions with innate immune cells. Within a population of macrophages encountering Candida albicans, there are distinct host-pathogen trajectories; however, little is known about the molecular heterogeneity that governs these fates. Here we developed an experimental system to separate interaction stages and single macrophage cells infected with C. albicans from uninfected cells and assessed transcriptional variability in the host and fungus. Macrophages displayed an initial up-regulation of pathways involved in phagocytosis and proinflammatory response after C. albicans exposure that declined during later time points. Phagocytosed C. albicans shifted expression programs to survive the nutrient poor phagosome and remodeled the cell wall. The transcriptomes of single infected macrophages and phagocytosed C. albicans displayed a tightly coordinated shift in gene expression co-stages and revealed expression bimodality and differential splicing that may drive infection outcome. This work establishes an approach for studying host-pathogen trajectories to resolve heterogeneity in dynamic populations.


Antihypertensive action of a new angiotensin converting enzyme inhibitor, (R)-3-[(S)-1-carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetr ahy dro-1,5-benzothiazepine-5-acetic acid (CV-5975), in various hypertensive models.
The antihypertensive activity of a new angiotensin converting enzyme (ACE) inhibitor, CV-5975, (R)-3-[(S)-1-carboxy-5-(4-piperidyl)pentyl] amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid, was examined in normotensive rats and various hypertensive animal models. In spontaneously hypertensive rats, CV-5975 (1 to 10 mg/kg, p.o.) had a dose-related, sustained antihypertensive action, which was more potent and longer than that of enalapril. The potency and duration of action of CV-5975 was intensified when it was administered repeatedly or combined with hydrochlorothiazide. CV-5975 (1 mg/kg, p.o.) inhibited the ACE activity of plasma and tissues; inhibition on the ACE activity of the aorta, kidney, and brain was marked when CV-5975 was administered repeatedly. In 2-kidney, 1 clip hypertensive rats (1 to 10 mg/kg, p.o.) and dogs (0.3 and 1 mg/kg, p.o.), CV-5975 had a marked, sustained antihypertensive action, which was more marked than that of enalapril. In normotensive rats (10 mg/kg), 1-kidney, 1 clip hypertensive rats (3 and 10 mg/kg), and hyporeninemic DOCA/salt hypertensive rats (1 to 10 mg/kg/day), CV-5975 administered orally once or repeatedly reduced blood pressure, whereas enalapril did not. These results indicate that CV-5975 is a potent and long-lasting antihypertensive agent, the action of which is mediated primarily by inhibiting ACE activity and partly by some unknown mechanisms.


Glucagon-like peptide-1 receptor agonist reduces di(2-ethylhexyl) phthalate-induced atherosclerotic processes in vascular smooth muscle cells.
Glucagon-like peptide-1 receptor (GLP1R) agonist is an incretin hormone and regulates glucose metabolism. However, phthalates, known as endocrine disruptors, can interfere with hormone homeostasis. In the present study, we aimed to estimate the impact of GLP1R agonist on di(2 ethylhexyl) phthalate (DEHP)-induced atherosclerosis. For this purpose, the effects of GLP1R agonist on various atherogenesis-related cellular processes and pathways were assessed in vascular smooth muscle cells (VSMCs). DEHP-induced cell proliferation and migration were significantly decreased by GLP1R agonist in VSMCs. Protein levels of matrix metalloproteinase (MMP)-2 and MMP-9 were significantly decreased in cells exposed to GLP1R agonist, compared with DEHP-treated cells. Expression levels of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 were also reduced in GLP1R agonist-treated cells. Similarly, DEHP-associated phosphorylation of protein kinase B and extracellular signal-regulated kinase 1/2 was decreased in GLP1R agonist-treated cells, compared with DEHP-treated cells. Our findings suggest that treatment with GLP1R agonist counteracts the activation of pathways related to atherosclerosis.


Insulin-like growth factor-II (IGF-II) and IGF binding proteins in human endometrium.
The insulin-like growth factor autocrine/paracrine system is believed to play a role in steroid-mediated endometrial differentiation. It is constituted of the mitogenic peptides (IGF-I and IGF-II), membrane receptors, and a family of high-affinity binding proteins (IGFBPs) that regulate the actions of the IGFs at their target cells. We have investigated expression of the mRNAs encoding the three major IGFBPs (IGFBP-1, IGFBP-2, and IGFBP-3) in human endometrium and have found, by Northern analysis, differential expression of all three mRNAs in secretory compared to proliferative endometrium, different steroidal milieux. IGF-II mRNAs were also detected in secretory endometrium. Finally, we found that human endometrial stromal cells in culture synthesize and secrete IGFBP-2 and IGFBP-3, and that the synthesis of IGFBP-2 is regulated by steroid hormones.


Pharmacological management of neurobehavioral disorders following traumatic brain injury--a state-of-the-art review.
Pharmacological management of neurobehavioral disorders following traumatic brain injury (TBI) is common practice. However, the evidence available to guide this practice remains sparse. This review summarizes, in brief, the state of knowledge, organized via a time continuum from injury as well as by symptom complex. The areas of neuroprotection, hypo-arousal, attention and memory deficits, aggression, agitation, depression, and mania are reviewed. The literature was searched with PubMed on the terms "traumatic brain injury" or "brain injury" with "pharmacology" (and the symptoms according to which this review is arranged). Additional searches were conducted with the specific symptoms as search terms, crossed with the therapeutic agents or drug classes discussed. Where a paucity of prospective data exists, case reports and retrospective studies are included. Studies to date have yielded minimal positive evidence for enhancing function, memory, and behavior after TBI. No single agent likely will become sentinel in the recovery process, and combination therapy in the acute and postacute settings are required. A need exists to further define the role of psychopharmacology in postacute TBI medicine and the specific characteristics of subpopulations who might benefit.


Effect of Water Temperature and Time during Heating on Mass Loss and Rheology of Cheese Curds.
During the manufacturing of mozzarella, cheese curds are heated to the desired stretching temperature traditionally by immersion in water, which influences the curd characteristics before stretching, and consequently the final cheese properties. In this study, cheese curds were immersed in hot water at 60, 70, 80 and 90 °C up to 16 min and the kinetics of mass loss and changes of rheological properties were investigated. The total mass of cooked curds increased up to 10% during the first minute, independent of the temperature, as a consequence of water retention. Fat was the main component lost into the cooking water (<3.5% w/w), while the concentration of protein increased up to 3.4% (w/w) compared to uncooked curds due to the loss of other components. Curds macrostructure during cooking showed that curds fully fuse at 70 °C/4 min; 80 °C/2 min and 90 °C/1 min, while after intensive cooking (>8 min) they lost the ability to fuse as a consequence of protein contraction and fat loss. Storage modulus, representing the curd strength, was dependent on cooking temperature and positively, and linearly, correlated with curd protein content (21.7-24.9%). This work shows the potential to modify curd composition and structure, which will have consequences for further processing and final product properties.


An integrative module analysis of DNA methylation landscape in aging.
To investigate the molecular mechanism of aging, the combination of module analysis and DNA methylation data was used to detect dynamically controlled modules for aging. Multiple differential expression networks (DENs) were constructed based on the microarray profiles across different aging groups (<70 years, 70-80 years, and >80 years). Next, a module-based approach was utilized to extract the common candidate modules across all age groups. We used Module Connectivity Dynamic Score (MCDS) to quantify the connectivity change of the common modules among the different age groups. Functional analyses were implemented for the genes in the common modules to further identify the significant biological processes. A total of two DENs were constructed. Overall 657 informative genes were screened out. When false discovery rate (FDR) was set as 0.05, we found that 148 modules were significant. Only 1 significant 2-differential modules (DMs) (module 493) with dynamic changes was discovered. Significantly, the genes in the module 493 participated in 7 significant pathways, including pentose phosphate pathway, carbon metabolism, and citrate cycle (TCA cycle). In conclusion, pathway functions [pentose phosphate pathway, carbon metabolism, citrate cycle (TCA cycle), chromosomal instability, ateroid biosynthesis, PPAR signaling pathway, and immune response] may serve as potential therapeutic targets in aging.


The lipid-rich epithelioid glioblastoma.
The authors add to the literature an account of four aggressive glial neoplasms characterized by diffuse cytoplasmic lipidization and a cohesive architectural disposition in epithelioid nests and sheets. These neoplasms arose in the cerebral hemispheres of adults and tended to a circumscribed neuroradiologic presentation that in two instances prompted an unrewarding preoperative search for an extracranial primary. One represented recurrent disease in a patient being followed for a biopsy-proven low-grade astrocytoma. Three cases were collected by way of consultation from pathologists uncertain as to their primary versus metastatic derivation. The apparent expression of cytokeratins and epithelial membrane antigen further conspired to obscure the glial lineage of these peculiar neoplasms, which are best regarded as tumors of the astrocytic series.


Hyaluronan and phospholipid association in biolubrication.
It is becoming increasingly clear that the outstanding lubrication of synovial joints is achieved by a sophisticated hierarchical structure of cartilage combined with synergistic actions of surface-active components present in the synovial fluid. In this work we focus on the association of two components of the synovial fluid, hyaluronan and dipalmitoyl phosphatidyl choline (DPPC), in bulk solution and at interfaces. We demonstrate that hyaluronan associates with DPPC vesicles and adsorbs to supported DPPC bilayers. The association structures formed at the interface are sufficiently stable to allow sequential adsorption of DPPC and hyaluronan, whereby promoting the formation of thick composite layers of these two components. The lubricating ability of such composite layers was probed by the AFM colloidal probe technique and found to be very favorable with low friction coefficients and high load bearing capacity. With DPPC as the last adsorbed component, a friction coefficient of 0.01 was found up to pressures significantly above what is encountered in healthy synovial joints. Hyaluronan as the last added component increases the friction coefficient to 0.03 and decreases the load bearing capacity somewhat (but still above what is needed in the synovial joint). Our data demonstrate that self-assembly structures formed by hyaluronan and phospholipids at interfaces are efficient aqueous lubricants, and it seems plausible that such self-assembly structures contribute to the exceptional lubrication of synovial joints.


Public Law 100-300, International Child Abduction Remedies Act, 29 April 1988.
This Act establishes procedures for the implementation of the 1980 Hague Convention on the Civil Aspects of International Child Abduction. The Convention was ratified by the US in 1986 and its instrument of ratification deposited with the Government of the Netherlands on 30 April 1988. Among other things, the Act grants States and the Federal Government concurrent jurisdiction over most actions, allows courts to take provisional measures to protect the well-being of a child or prevent the child's removal or concealment, and provides for the exchange of information in order to locate children.


Airborne transmission between room occupants during short-term events: Measurement and evaluation.
This study experimentally examines and compares the dynamics and short-term events of airborne cross-infection in a full-scale room ventilated by stratum, mixing and displacement air distributions. Two breathing thermal manikins were employed to simulate a standing infected person and a standing exposed person. Four influential factors were examined, including separation distance between manikins, air change per hour, positioning of the two manikinsand air distribution. Tracer gas technique was used to simulate the exhaled droplet nuclei from the infected person and fast tracer gas concentration meters (FCM41) were used to monitor the concentrations. Real-time and average exposure indices were proposed to evaluate the dynamics of airborne exposure. The time-averaged exposure index depends on the duration of exposure time and can be considerably different during short-term events and under steady-state conditions. The exposure risk during short-term events may not always decrease with increasing separation distance. It changes over time and may not always increase with time. These findings imply that the control measures formulated on the basis of steady-state conditions are not necessarily appropriate for short-term events.


Pulsed suppressive treatment in rheumatoid arthritis: intravenous methylprednisolone and nitrogen mustard.
Persistent polyarticular rheumatoid arthritis (RA) and aggressive disease flares resistant to conventional therapy can effectively be controlled by intravenous pulse methylprednisolone (IVMP) or nitrogen mustard (HN2). The efficacy, toxicity and immunologic effects of each agent are reviewed. Clinical response is evident within days of the start of therapy for both; persisting up to 6 weeks for IVMP and at least 59 days for HN2. Morbidity from both agents is minimal when appropriate precautions are taken. No mortalities directly related to either modality have been reported in RA.


Microhomology-dependent end joining and repair of transposon-induced DNA hairpins by host factors in Saccharomyces cerevisiae.
The maize, cut-and-paste transposon Ac/Ds is mobile in Saccharomyces cerevisiae, and DNA sequences of repair products provide strong genetic evidence that hairpin intermediates form in host DNA during this transposition, similar to those formed for V(D)J coding joints in vertebrates. Both DNA strands must be broken for Ac/Ds to excise, suggesting that double-strand break (DSB) repair pathways should be involved in repair of excision sites. In the absence of homologous template, as expected, Ac excisions are repaired by nonhomologous end joining (NHEJ) that can involve microhomologies close to the broken ends. However, unlike repair of endonuclease-induced DSBs, repair of Ac excisions in the presence of homologous template occurs by gene conversion only about half the time, the remainder being NHEJ events. Analysis of transposition in mutant yeast suggests roles for the Mre11/Rad50 complex, SAE2, NEJ1, and the Ku complex in repair of excision sites. Separation-of-function alleles of MRE11 suggest that its endonuclease function is more important in this repair than either its exonuclease or Rad50-binding properties. In addition, the interstrand cross-link repair gene PSO2 plays a role in end joining hairpin ends that is not seen in repair of linearized plasmids and may be involved in positioning transposase cleavage at the transposon ends.


Molecular characteristics of extended-spectrum-beta-lactamase-producing Escherichia coli isolates causing bacteremia in the Calgary Health Region from 2000 to 2007: emergence of clone ST131 as a cause of community-acquired infections.
A study was designed to characterize extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli isolates causing bacteremia over an 8-year period (2000 to 2007) in a large well-defined geographical region. Molecular characterization was done by using isoelectric focusing; PCR; and sequencing of the bla(CTX-M)-, bla(TEM)-, bla(OXA)-, bla(SHV)-, and plasmid-mediated quinolone resistance determinants. Genetic relatedness was determined by pulsed-field electrophoresis with XbaI and multilocus sequence typing. A total of 67 patients with incident bloodstream infections were identified, and the majority presented with community-acquired infections involving the urinary and biliary tracts. Of the 67 ESBL-producing E. coli isolates recovered, 60 (90%) were positive for bla(CTX-M) genes; 32 (48%) produced CTX-M-15, 25 (37%) produced CTX-M-14, 1 (2%) produced CTX-M-24, 1 (2%) produced CTX-M-2, and 1 (2%) produced CTX-M-3, while 2 (3%) produced TEM-52 and 5 (7%) produced SHV-2. Twenty-four (36%) isolates were positive for aac(6')-Ib-cr. The majority of isolates were resistant to ciprofloxacin (60 [90%] isolates) and gentamicin (40 [60%] isolates). The occurrence of ESBL-producing isolates was stable during the first 5 years, but there was a substantial increase from 2005 to 2007, mostly due to clone ST131, which produces CTX-M-15 and CTX-M-14, in blood cultures submitted from the community. Our results illustrated that E. coli clone ST131, which coproduces CTX-M-15, OXA-1, TEM-1, and aac(6')-Ib-cr, has emerged as an important cause of community-onset bacteremia caused by ESBL-producing E. coli isolates; and this is the first study to identify CTX-M-14 in E. coli clone ST131.


Hydroxyethyl starch 130 kd/0.4 and albumin improve CVVH biocompatibility whereas gelatin and hydroxyethyl starch 200 kd/0.5 lead to adverse side effects of CVVH in anesthetized pigs.
Both fluid management and renal replacement therapies play a fundamental role in the treatment of critically ill patients. In a recent in vitro study, we have shown specific interactions of different colloids and the hemocompatibility of hemofilters. The present study was performed to compare the five most common fluids for volume resuscitation, i.e., normal saline (SAL), hydroxyethyl starch 130 kd/0.4 (HES130), hydroxyethyl starch 200 kd/0.5 (HES200), albumin (ALB), and gelatin (GEL) with respect to their interaction with continuous venovenous hemofiltration (CVVH) in anesthetized domestic pigs. Animals (n = 63) were allocated randomly to the fluid type and the respective subgroups, which were divided into control and CVVH groups (n = 6 ndash; 7 per group). Bolus infusion of group specific fluid was followed by a bolus of heparin and the initiation of hemofiltration in CVVH groups. Thereafter, fluids were infused at constant rates, and heparin application was adjusted to keep the activated clotting time at 200 to 250 s. Hemodynamics, airway pressures, pulmonary gas exchange, diuresis, creatinine clearance, and blood cell counts were investigated during the entire procedure (10 ndash; 12 hours). Basics of in vivo effects of SAL, HES130, and ALB were not altered during CVVH. HES130 and ALB enabled stable hemocompatibility, diuresis, and hemodynamics in the respective groups. In contrast, organ functions were significantly different between control and CVVH groups when animals were treated with GEL or HES200. In particular, during CVVH, HES200 led to reduced platelet counts, deteriorated hemodynamics, and increasing airway pressures during CVVH. GEL led to increasing airway pressures, a decrease in pulmonary gas exchange, deteriorated hemodynamics, altered renal histomorphology, reduced platelet counts, and reduced hemoglobin. Direct in vivo effects of colloids in anaesthetized and ventilated pigs are not predictable for their effects during CVVH. Interaction between CVVH and every volume substitute occur in a highly specific manner. This observation could be helpful to explain contradictory study results and should be considered for future study designs.


Effects of tumour necrosis factor alpha on bone marrow aspirates of patients with acute myelogenous leukemia determined by flow-cytometric cell-cycle analysis.
Tumour necrosis factor alpha (TNF alpha) exerts cytotoxic and antiproliferative effects on neoplastic cells. It has been used as a therapeutic agent for solid tumours and haematological malignancies. We report on the ex vivo determination of the effect of recombinant human rhuTNF alpha on bone marrow aspirates by a bromodeoxyuridine/propidium iodide method. Cell samples were drawn after 0.5, 2, 4, 6, 8, 10, 22, and 25 h from short-term suspension bone marrow cultures from patients with acute myelogenous leukemia (AML). Flow-cytometric cell-cycle analysis was performed after double DNA staining with propidium iodide and anti-BrdU antibodies. By this method the effect of rhuTNF alpha on cell proliferation can be evaluated after only 35 h. In about two-thirds of the bone marrow aspirates of AML an inhibiting effect on rhuTNF alpha can be demonstrated, developing to its full extent after 10 h.


Tailoring cyclic polyamines for inorganic/organic phosphate binding.
In this tutorial review, we will discuss the most significant achievements in the structure-based design of cyclic receptors containing mainly aliphatic amine groups as metal-free hosts for phosphate-based guests in aqueous environment; in particular, inorganic phosphates and mononucleotide anions. The bulk of our attention will be devoted to show how this class of receptors has structurally evolved following the attempts by chemists to optimize all factors indicated by Nature as necessary to achieve the best possible binding of phosphates via non-covalent interactions.


High-Speed Balanced-Detection Visible-Light Optical Coherence Tomography in the Human Retina Using Subpixel Spectrometer Calibration.
Increases in speed and sensitivity enabled rapid clinical adoption of optical coherence tomography (OCT) in ophthalmology. Recently, visible-light OCT (vis-OCT) achieved ultrahigh axial resolution, improved tissue contrast, and provided new functional imaging capabilities, demonstrating the potential to improve clinical care further. However, limited speed and sensitivity caused by the high relative intensity noise (RIN) in supercontinuum lasers impeded the clinical adoption of vis-OCT. To overcome these limitations, we developed balanced-detection vis-OCT (BD-vis-OCT), which uses two calibrated spectrometers to cancel RIN and other noises. We analyzed the RIN to achieve robust subpixel calibration between the two spectrometers and showed that BD-vis-OCT reduced the A-line noise floor by up to 20.5 dB. Metrics comparing signal-to-noise-ratios showed similar image qualities across multiple reference arm powers, a hallmark of operation near the shot-noise limit. We imaged healthy human retinas at an A-line rate of 125 kHz and a field-of-view up to 10 mm ×4 mm. We found that BD-vis-OCT revealed retinal anatomical features previously obscured by the noise floor.


Seed viruses containing novel avian HA and NA antigens for prevention against potential influenza pandemic.
An influenza pandemic could arise unexpectedly with rapid spread across the world. The efficiency of production of a vaccine and the ability to administer it widely will be among the most important factors in the ability to protect public health. The current process for producing inactivated or live attenuated influenza vaccines requires six to nine months. That reduces considerably the likelihood that the vaccine will be available during the first wave of the pandemic. Therefore, a key element of preparedness is to optimize the production process and to reduce the vaccine development time. During the 1997 H5N1 outbreak in Hong Kong, seed viruses were prepared for production of inactivated and live-attenuated vaccines. We used the cold-adapted A/Ann Arbor/6/60 as the donor virus to generate live attenuated vaccines containing genetically modified HA and NA genes from H5N1 influenza viruses. These reassortants were shown to be safe and protective in animal models. This study indicates that production of live attenuated avian influenza vaccines is feasible and that development of a library of reassortants containing different subtype HA and NA genes may reduce the vaccine preparation time for future influenza pandemics.


[Phenotypic analysis of immature T-lineage cells].
The characteristics of very immature T-lineage blasts including co-expression of myeloid properties and the distinctions between the phenotypes of pro-thymic (CD7+ CD5+ CD2+ CD3- CD4- CD8- or more immature) and thymic (CD3- CD4+ CD8+ or more mature) blasts are shown. The lineage-derivation of CD7+ CD5- CD2- and CD7+ CD5+ CD2- lymphoid blasts was investigated based on the gene expression of CD3 epsilon, CD3 delta and myeloperoxidase (MPO). The former group included 4 categories; undifferentiated blasts without commitment to myeloid or T-lineage, T-lineage blasts with mRNA of CD3 epsilon, T/myeloid blasts with mRNA of CD3 epsilon and MPO and blasts with mRNA of MPO. The latter included 2 categories; T-lineage blasts with CD3 epsilon and CD3 delta mRNA and T/myeloid blasts with CD3 epsilon, CD3 delta and MPO mRNA. Thus, CD3 epsilon was expressed at a more immature stage than CD3 delta. The blasts at the pro-thymic stage were different from those at the thymic stage in several respects. The T-cell receptor (TCR) beta-chain gene showed a germ-line configuration in most pro-thymic blasts. The CD13/CD33, CD11b and class II MHC antigens were expressed very frequently in the pro-thymic stage. The CD21 antigen was most selectively expressed at the thymic stage. Pro-thymic blasts were of RA type of CD45 antigen, while thymic blasts were of RO type. Recombination activation gene-1 (RAG-1) was only limitedly expressed at the pro-thymic stage, but was highly expressed at the thymic stage. These findings indicate that there are distinctive differences before and after the initiation of clonal selection which is unique and thymus-specific, and that the neoplastic cells represent each stage of T-lineage differentiation involving the unique thymic function.


Applications of SYPRO orange and SYPRO red protein gel stains.
We have further characterized the sensitivity and specificity of SYPRO Orange protein gel stain and SYPRO Red protein gel stain with native and 2-dimensional polyacrylamide gels and for staining gels prior to Western blot analysis. We found that nucleic acids are not stained by the SYPRO protein gel stains, in contrast to results obtained with commonly used silver staining techniques. Bacterial lipopolysaccharides also stain very weakly with SYPRO dyes in comparison to silver staining. Thus, gels containing whole cell lysates from either bacterial or mammalian cells can be analyzed more easily with the SYPRO stains than by silver staining. In this paper, we demonstrate that SYPRO stains can be used to monitor protein induction in bacterial overproducing strains and are effective stains for 2-dimensional gels. In addition, we developed protocols to detect proteins with these dyes in native gels. Finally, we found that staining proteins in transfer buffer prior to Western blotting does not affect the sensitivity of subsequent immunodetection.


Complete mitochondrial genome and phylogenic analysis of Odontobutis yaluensis, Perciformes, Odontobutidae.
The complete mitochondrial genome of Odontobutis yaluensis was sequenced as to be 16,909 bp in length with (A + T) content of 55.73%, and it contained 13 protein-coding genes, 2 rRNAs, 22 tRNAs and a control region. The gene order and orientation are similar to some typical fish species. The data will provide the useful molecular information for phylogenetic relationships of O. yaluensis with Odontobutis potamophila first clustered into a small branch, and then with Odontobutis platycephala clade, and finally with Odontobutis sinensis clade. Odontobutidae and Rhyacichthyidae formed the sister group, and Eleotridae and Gobiidae formed the sister group.


Role of amygdala in conditioned and unconditioned fear generated in the periaqueductal gray.
The amygdala and ventral portion of the periaqueductal gray (vPAG) are crucial for the expression of the contextual freezing behavior. However, it is still unclear whether the amygdala also plays a role in defensive behaviors induced by electrical stimulation of the dorsal periaqueductal gray (dPAG). In the present study, rats were implanted with electrodes into dPAG for determination of the thresholds for freezing and escape responses before and after sham or electrolytic lesions in the amygdala. Animals were then submitted to a context fear conditioning procedure. Amygdala lesions disrupted contextual freezing but did not affect defensive behaviors induced by dPAG electrical stimulation. These results indicate that contextual and unconditioned freezing behaviors are mediated by independent neural circuits.


Soret effect in molecular mixtures.
A theoretical approach to the description of the Soret effect in binary nonpolar liquids is proposed. The temperature gradient of the partial pressure is determined as the driving force of thermal diffusion. The hard-sphere fluid is chosen as a reference system and an explicit relation for the Soret coefficient is found. Two additive contributions owing to steric repulsions and attractive interactions form the so-called chemical contribution to S_{T} [C. Debuschewitz and W. Köhler, Phys. Rev. Lett. 87, 055901 (2001)]. The parameters of interparticle interactions are defined with the help of the solvation theory. In particular, the van der Waals constant of cross interactions is expressed via the excess volume of mixture. The proposed theory is applied to the benzene-cyclohexane system. A reasonable agreement of theoretical and experimental results is revealed for the Soret coefficient and its temperature dependence.


[Intestinal motility in patients with small bowel diverticulosis].
It has been demonstrated that motility disorders may be responsible for esophageal and colon diverticulosis. Recently anatomic alterations of both small bowel muscular layers and myenteric plexus have been described in patients with small bowel diverticulosis. Such pathological features could be responsible for motility disorders and small bowel diverticulosis formation. The aim of this work was to study the small bowel motility in patients with small bowel diverticulosis. Ten patients (mean age: 69.2 +/- 6 years mean +/- SEM) with more than 3 diverticula in the jejunum or the ileum (excepting duodenal diverticulum) were studied. After an overnight fast, a 4 lumen probe (side holes 10 cm apart) was used to record duodeno-jejunal motility for 4 hours. Esophageal manometry was also performed in 8 patients. The mean number of phase 3 of the migrating motor complex (mean +/- SEM) during 4 hours was significantly lower in patients with small bowel diverticulosis (0.15 +/- 0.05/hours; mean +/- SEM) than in 10 normal volunteers (0.52 +/- 0.07/hours; mean +/- SEM) (P less than 0.01); 5 patients had zero phase 3 during the 4 hours of recording; one patient displayed intestinal hypomotility associated with aberrant phase 3 like activity; 4 patients showed simultaneous minute-rhythm during more than 80 percent of the phase 2 of the migrating motor complex. Esophageal manometry was also disturbed in 6 patients (low amplitude contractions less than 30 cm H2O in the distal esophagus). Bacterial overgrowth was investigated in 8 patients by means of a glucose breath-test and was found in 6 cases. In conclusion, duodeno jejunal motility is altered in patients with small bowel diverticulosis.(ABSTRACT TRUNCATED AT 250 WORDS)


TCR revision generates functional CD4+ T cells.
CD4(+)Vβ5(+) peripheral T cells in C57BL/6 mice respond to encounter with a peripherally expressed endogenous superantigen by undergoing either deletion or TCR revision. In this latter process, cells lose surface Vβ5 expression and undergo RAG-dependent rearrangement of endogenous TCRβ genes, driving surface expression of novel TCRs. Although postrevision CD4(+)Vβ5(-)TCRβ(+) T cells accumulate with age in Vβ5 transgenic mice and bear a diverse TCR Vβ repertoire, it is unknown whether they respond to homeostatic and antigenic stimuli and thus may benefit the host. We demonstrate in this study that postrevision cells are functional. These cells have a high rate of steady-state homeostatic proliferation in situ, and they undergo extensive MHC class II-dependent lymphopenia-induced proliferation. Importantly, postrevision cells do not proliferate in response to the tolerizing superantigen, implicating TCR revision as a mechanism of tolerance induction and demonstrating that TCR-dependent activation of postrevision cells is not driven by the transgene-encoded receptor. Postrevision cells proliferate extensively to commensal bacterial Ags and can generate I-A(b)-restricted responses to Ag by producing IFN-γ following Listeria monocytogenes challenge. These data show that rescued postrevision T cells are responsive to homeostatic signals and recognize self- and foreign peptides in the context of self-MHC and are thus useful to the host.


Effect of reticulocytosis on lactate dehydrogenase isoenzyme distribution in serum: in vivo and in vitro studies.
We investigated the effect of reticulocytosis on the lactate dehydrogenase (LD; EC 22.214.171.124) isoenzyme LD1/LD2 ratio in patients with and without evidence of hemolytic disease. Analysis of sera from patients with reticulocytosis and in vivo hemolysis showed a mean LD1/LD2 ratio of 0.92 compared with a ratio of 0.69 in patients with in vivo hemolysis and normal reticulocyte counts. Determination of LD isoenzymes in erythrocyte lysate revealed significantly increased LD1/LD2 ratios for patients with marked reticulocytosis compared with those for patients with normal-to-minimal increases in reticulocytes. Finally, separation of mature erythrocytes and reticulocytes by flow cytometry revealed marked differences in the LD1/LD2 isoenzyme distribution between these two cell types. The ability of hemolysis to cause a "flipped" LD1/LD2 ratio is dependent on the proportion of the hemolyzed cells that are reticulocytes.


Familial glaucoma iridogoniodysplasia maps to a 6p25 region implicated in primary congenital glaucoma and iridogoniodysgenesis anomaly.
Familial glaucoma iridogoniodysplasia (FGI) is a form of open-angle glaucoma in which developmental anomalies of the iris and irido-corneal angle are associated with a juvenile-onset glaucoma transmitted as an autosomal dominant trait. A single large family with this disorder was examined for genetic linkage to microsatellite markers. A peak LOD score of 11.63 at a recombination fraction of 0 was obtained with marker D6S967 mapping to chromosome 6p25. Haplotype analysis places the disease gene in a 6.4-cM interval between the markers D6S1713 and D6S1600. Two novel clinical appearances extend the phenotypic range and provide evidence of variable expressivity. The chromosome 6p25 region is now implicated in FGI, primary congenital glaucoma, and iridogoniodysgenesis anomaly. This may indicate the presence of a common causative gene or, alternatively, a cluster of genes involved in eye development/function.


Conformational landscape of supersonically expanded 1-(fluorophenyl)ethanols and their monohydrated clusters.
The effects of the presence of the ring fluorine atom on the conformational landscape of supersonically expanded isomeric 1-(fluorophenyl)ethanols and their monohydrated clusters are investigated by resonant two-photon ionization (R2PI) spectroscopy, coupled with time-of-flight (TOF) mass spectrometry. In contrast to the very simple spectrum of 1-phenylethanol, the lack of structural symmetry of the aromatic rings of isomeric 1-(fluorophenyl)ethanols generates more complicated spectra, characterized by several low-frequency progressions of bands. Their interpretation is based on the strict correspondence with theoretical predictions at the D-B3LYP/6-31G** level of theory. Monohydration of the 1-(fluorophenyl)ethanol isomers favours exclusive formation of the corresponding conformers, characterized by the O-H...O(w)-H...pi intracomplex interaction and whose excitation spectrum exhibits features attributed to the C(1)-C(alpha) torsion plus intermolecular water torsion.


Comparative assessment of structural and biological properties of biomimetically coated hydroxyapatite on alumina (alpha-Al2O3) and titanium (Ti-6Al-4V) alloy substrates.
Previous reports have shown the use of hydroxyapatite (HAp) and related calcium phosphate coatings on metal and nonmetal substrates for preparing tissue-engineering scaffolds, especially for osteogenic differentiation. These studies have revealed that the structural properties of coated substrates are dependent significantly on the method and conditions used for coating and also whether the substrates had been modified prior to the coating. In this article, we have done a comparative evaluation of the structural features of the HAp coatings, prepared by using simulated body fluid (SBF) at 25 degrees C for various time periods, on a nonporous metal substrate titanium-aluminium-vanadium (Ti-6Al-4V) alloy and a bioinert ceramic substrate alpha-alumina (alpha-Al(2)O(3)), with and without their prior treatment with the globular protein bovine serum albumin (BSA). Our analysis of these substrates by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared (FTIR) spectrometry showed significant and consistent differences in the quantitative and qualitative properties of the coatings. Interestingly, the bioactivity of these substrates in terms of supporting in vitro cell adhesion and spreading, and in vivo effects of implanted substrates, showed a predictable pattern, thus indicating that some coated substrates prepared under our conditions could be more suitable for biological/biomedical applications.


The effects of acetaldehyde exposure on histone modifications and chromatin structure in human lung bronchial epithelial cells.
As the primary metabolite of alcohol and the most abundant carcinogen in tobacco smoke, acetaldehyde is linked to a number of human diseases associated with chronic alcohol consumption and smoking including cancers. In addition to direct DNA damage as a result of the formation of acetaldehyde-DNA adducts, acetaldehyde may also indirectly impact proper genome function through the formation of protein adducts. Histone proteins are the major component of the chromatin. Post-translational histone modifications (PTMs) are critically important for the maintenance of genetic and epigenetic stability. However, little is known about how acetaldehyde-histone adducts affect histone modifications and chromatin structure. The results of protein carbonyl assays suggest that acetaldehyde forms adducts with histone proteins in human bronchial epithelial BEAS-2B cells. The level of acetylation for N-terminal tails of cytosolic histones H3 and H4, an important modification for histone nuclear import and chromatin assembly, is significantly downregulated following acetaldehyde exposure in BEAS-2B cells, possibly due to the formation of histone adducts and/or the decrease in the expression of histone acetyltransferases. Notably, the level of nucleosomal histones in the chromatin fraction and at most of the genomic loci we tested are low in acetaldehyde-treated cells as compared with the control cells, which is suggestive of inhibition of chromatin assembly. Moreover, acetaldehyde exposure perturbs chromatin structure as evidenced by the increase in general chromatin accessibility and the decrease in nucleosome occupancy at genomic loci following acetaldehyde treatment. Our results indicate that regulation of histone modifications and chromatin accessibility may play important roles in acetaldehyde-induced pathogenesis. Environ. Mol. Mutagen. 59:375-385, 2018. © 2018 Wiley Periodicals, Inc.


Configurational entropy and mechanical properties of cross-linked polymer chains: implications for protein and RNA folding.
We discuss the statistical mechanical properties of a single polymer chain that forms cross links among its monomers. Models of this type have served as prototypes in theories of RNA and protein folding. The chain is allowed to form pseudoknots and its monomers can each participate in multiple cross links. We demonstrate that the conformational free energy of such a chain can be estimated by using an algorithm that scales as a power of the number of cross links N(N1-N3, depending on the problem). Straightforward exact evaluation of the chain partition function via multidimensional integration scales exponentially with N and often is computationally prohibitive. Our approach can also be used to compute the "entropic force" generated by a cross-linked chain when it is stretched at its ends. Such forces can be directly measured by atomic force microscopy or by laser optical trap experiments performed on single RNA, DNA, and protein molecules.


Aphidicolin Inhibition of DNA Synthesis and Germination in Spores of Anemia phyllitidis L. Sw.
Aphidicolin inhibits DNA synthesis and nuclear division in spores of Anemia phyllitidis. In spite of blocked DNA replication, spores germinate under continuous dark conditions, if induced by addition of 5 x 10(-5) grams per milliliter gibberellic acid. Differentiation of aphidicolin-treated prothallia indicate the existence of a prepattern in the dry spore which is realized independent of cell division during early events of spore germination.


Osmotic pressure and polymer size in semidilute polymer solutions under good-solvent conditions.
We consider the lattice Domb-Joyce model at a value of the coupling for which scaling corrections approximately vanish and determine the universal scaling functions associated with the osmotic pressure and the polymer size for semidilute polymer solutions (c/c( *)<or=10, where c is the concentration of the solution and c( *) is the overlap concentration) in good-solvent conditions. Our result for the osmotic pressure agrees with previous renormalization-group calculations (the relative difference is less than 1%) but differs significantly from previous numerical determinations in which polymers were modeled as lattice self-avoiding walks. We show that for c/c( *) greater than or approximately equal 6 simulations of lattice self-avoiding walks give results that are affected by strong scaling corrections even for chain lengths as large as 1000: The self-avoiding walk model is therefore unsuitable for the determination of universal properties of polymer solutions deep in the semidilute regime.


Conformation analysis of glu181 and ser186 in the metarhodopsin I state.
Photoactivation of rhodopsin yields a photointermediate, metarhodopsin I, during the formation of the fully activated photointermediate, metarhodopsin II. It is proposed that Glu181 and Ser186, in the second extracellular loop, play important roles in the stabilization of the protonated Schiff base of metarhodopsin I. Glu181 and Ser186 form a network of hydrogen bonds mediated by a water molecule in the dark-state crystal structure of rhodopsin. On the other hand, the counter-ion of the protonated Schiff base, Glu113, is not involved in the hydrogen-bond network, as it is located further than hydrogen-bond distance from Ser186. Herein, the conformations and proton arrangements of the protonated form of Glu181 and Ser186 in the hydrogen-bond network have been investigated by molecular-dynamics calculations of the rhodopsin crystal structure as well as in the structural model of metarhodopsin I. In the metarhodopsin I model, Ser186 mediated the hydrogen-bond network between Glu113 and Glu181, changing the protein's conformation and creating a space by the outward motion of transmembrane segment 3, while the hydroxyl group of Glu181 was favored in the hydrogen-bond network. The hydrogen bond between Glu113 and Ser186 is thought to reduce the basicity of the carboxylate of Glu113, maintaining the protonated state of the Schiff base in the metarhodopsin I state. In the Glu181Gln mutant, the hydroxyl group of Ser186 favored the water molecule as a proton donor in the metarhodopsin I state, since the carbonyl group of the Gln residue was favored in the hydrogen-bond network. These results indicate that the Gln181 residue interferes with the hydrogen-bond between Glu113 and Ser186 in the metarhodopsin I state, facilitating the neutralization of the protonated Schiff base.


Suicide Gene Therapy By Amphiphilic Copolymer Nanocarrier for Spinal Cord Tumor.
Spinal cord tumors (SCT) are uncommon neoplasms characterized by irregular growth of tissue inside the spinal cord that can result in non-mechanical back pain. Current treatments for SCT include surgery, radiation therapy, and chemotherapy, but these conventional therapies have many limitations. Suicide gene therapy using plasmid encoding herpes simplex virus-thymidine kinase (pHSV-TK) and ganciclovir (GCV) has been an alternative approach to overcome the limitations of current therapies. However, there is a need to develop a carrier that can deliver both pHSV-TK and GCV for improving therapeutic efficacy. Our group developed a cationic, amphiphilic copolymer, poly (lactide-co-glycolide) -graft-polyethylenimine (PgP), and demonstrated its efficacy as a drug and gene carrier in both cell culture studies and animal models. In this study, we evaluated PgP as a gene carrier and demonstrate that PgP can efficiently deliver reporter genes, pGFP in rat glioma (C6) cells in vitro, and pβ-gal in a rat T5 SCT model in vivo. We also show that PgP/pHSV-TK with GCV treatment showed significantly higher anticancer activity in C6 cells compared to PgP/pHSV-TK without GCV treatment. Finally, we demonstrate that PgP/pHSV-TK with GCV treatment increases the suicide effect and apoptosis of tumor cells and reduces tumor size in a rat T5 SCT model.


Adherence to Medication and Physical Activity among People Living with HIV/AIDS.
The aim of this study was to investigate the adherence to medication and Physical Activity (PA) among People Living with HIV (PLHIV). In the present cross-sectional study, 122 PLHIV were selected. The research tools included the Baecke questionnaire and the AIDS Clinical Trials Group questionnaire. Data were analyzed by independent t test and multiple logistic regression. The results of 7- and 30-day recalls showed that 76.21 and 82.23% of patients had proper medication adherence. The mean score of PA in patients was less than the recommended average score in the questionnaire. Furthermore, there was no significant difference observed between the medication adherence and PA. Although the adherence to medication was appropriate, nurses and health care providers should increase the level of PA for PLHIV by dealing with the related barriers to live an active life.


Biodiversity of mosquitoes in Manipur State and their medical significance.
Entomological studies conducted during monsoon and post-monsoon season in Manipur State revealed the presence of fifty-five species of mosquitoes under ten genera. Out of the seventeen Anopheles species recorded, Anopheles aconitus, An. dirus and An. nivipes were recorded for the first time from the state. The present study has confirmed the existence of An. dirus, the major malaria vector in the Northeast from a selected area of the state. Among Culicines, four species viz., Aedes nigrostriatus, Malaya genurostris, Aediomyia catasticta and Toxorhynchites splendens which were not reported earlier from this state have been recorded in the present study. With the addition of these seven species of mosquitoes to the earlier record of mosquitoes so far reported from Manipur, the mosquito fauna swells up to one hundred and eleven including the major vectors of malaria of the Northeast and the potential vectors of Japanese encephalitis and dengue virus transmission in India.


Single cell lineage analysis of mouse embryonic stem cells at the exit from pluripotency.
Understanding how interactions between extracellular signalling pathways and transcription factor networks influence cellular decision making will be crucial for understanding mammalian embryogenesis and for generating specialised cell types in vitro. To this end, pluripotent mouse Embryonic Stem (mES) cells have proven to be a useful model system. However, understanding how transcription factors and signalling pathways affect decisions made by individual cells is confounded by the fact that measurements are generally made on groups of cells, whilst individual mES cells differentiate at different rates and towards different lineages, even in conditions that favour a particular lineage. Here we have used single-cell measurements of transcription factor expression and Wnt/β-catenin signalling activity to investigate their effects on lineage commitment decisions made by individual cells. We find that pluripotent mES cells exhibit differing degrees of heterogeneity in their expression of important regulators from pluripotency, depending on the signalling environment to which they are exposed. As mES cells differentiate, downregulation of Nanog and Oct4 primes cells for neural commitment, whilst loss of Sox2 expression primes cells for primitive streak commitment. Furthermore, we find that Wnt signalling acts through Nanog to direct cells towards a primitive streak fate, but that transcriptionally active β-catenin is associated with both neural and primitive streak commitment. These observations confirm and extend previous suggestions that pluripotency genes influence lineage commitment and demonstrate how their dynamic expression affects the direction of lineage commitment, whilst illustrating two ways in which the Wnt signalling pathway acts on this network during cell fate assignment.


Congenital and acquired conditions of the vulva and vagina on magnetic resonance imaging: a pictorial review.
Magnetic resonance imaging (MRI) has become an established imaging modality for characterizing pelvic pathology, chiefly because of superb contrast resolution and lack of ionizing radiation. In recent years, MRI has been used to stage vulval and vaginal malignancies and assist detection of recurrence. It has also proved useful in the characterization of Müllerian duct anomalies. We review the typical imaging characteristics on MRI of congenital and acquired conditions involving the vulva and vagina.


Subcellular Fractionation for DIGE-Based Proteomics.
Mass spectrometry-based protein methodologies have revolutionized the field of analytical biochemistry and enable the identification of hundreds to thousands of proteins in biological fluids, cell lines, and tissue. This methodology requires the initial separation of a protein constellation and this has been successfully achieved using gel-based techniques, particularly that of two-dimensional difference gel electrophoresis (2D-DIGE). However, given the complexity of the proteome, fractionation techniques may be required to optimize the detection of low-abundance proteins, which are often under-represented, but which may represent important players in health and disease. Such subcellular fractionation protocols typically utilize density-gradient centrifugation and have enabled the enrichment of crude microsomes, the cytosol, the plasmalemma, the nuclei, and the mitochondria. In this chapter, we describe the experimental steps involved in the enrichment of crude microsomes from skeletal muscle using differential centrifugation and subsequent verification of enrichment by gel electrophoresis and immunoblotting, prior to comparative DIGE analysis.


[Research on SCB discharge behavior with atomic emission spectroscopy].
Semiconductor bridge (SCB) was utilized to ignite energetic materials with thin film discharge and characterized of low input energy, high safety and logic control possibility. SCB discharge was diagnosticated with atomic emission spectroscopy. Firstly, discharge temperature was acquired with copper atom spectral lines 510.5 and 521.8 nm, and electron density was calculated with silicon atom spectral line 390.5 nm and corresponding ion line 413.0 nm. As for resistance 1.0 omega of SCB with the discharge voltage of 20 V and capacity of 47 microF, its discharge temperature was about 2 500-4 300 K and electron density 10(16) cm(-3). Meanwhile, the temperature and density V(s) time distributions were acquired simultaneously. And then with the diagnosis results, the discharge behaviors of two sorts of SCB were judged according to plasma space-dimension and time-dimension restrictions. This research set up an efficient technique for the diagnosis of transient small-size discharge behavior and provided instructions for the design of SCB and discharge condition.


A pilot study of combined radiotherapy and chemotherapy for esophageal carcinoma.
Between 9/80 and 9/83, 20 patients with esophageal carcinoma were treated with combined radiotherapy and chemotherapy (5-FU and mitomycin). Thirteen patients with Stages I or II disease received definitive treatment consisting of 6000 rad in 6-7 weeks and 5-FU (1000 mg/m2/24 hours) as a continuous I.V. infusion for 96 hours starting on days 2 and 28. Mitomycin (10 mg/m2) was administered as a bolus injection on day 2. Palliative treatment (5000 rad plus above chemotherapy) was delivered to six patients with Stage III disease (two with extra-esophageal spread, four with distant metastases) and to one patient with an anastomotic recurrence following resection. Two of 13 definitively treated patients were not evaluable due to early death from intercurrent disease. Ten of 11 evaluable patients treated definitively are alive from 4-32 months; the median survival has not been reached at 17 months. Four of 11 evaluable patients treated definitively have relapsed, with only one relapsing within the irradiated field. Among the palliative and definitively treated patients, relief of dysphagia was seen in 16/17, and continued until the time of last follow-up or until death in 13/17. The treatment was well tolerated and no significant hematologic problems were incurred. This combination of radiation therapy with infusional 5-FU and mitomycin appears to be an effective and well-tolerated regimen in the treatment of esophageal carcinoma and is worthy of further study.


[Use of mathematical models for quantitative environmental health risk assessment].
Two groups of mathematical models used in the quantitative assessment of cancer risk resulting from exposure to chemical substances for identifying a dose-response relationship are presented. They are as follows: statistical and stochastic models or those biologically motivated. Among statistical models, the logit, probit and Weibull models were considered. Among those biologically motivated, a one-hit model was analysed with special reference to they way from assumptions of the carcinogenesis theory to obtaining a dose-response curve. The two remaining models--multi-hit and multi-stage are discussed very briefly. An example of the fitting dose-response curves to experimental data is presented.


Baicalin inhibits toll-like receptor 2/4 expression and downstream signaling in rat experimental periodontitis.
Periodontitis is a severe inflammatory response, leading to characteristic periodontal soft tissue destruction and alveolar bone resorption. Baicalin possesses potent anti-inflammatory activity; however, it is still unclear whether baicalin regulates toll-like receptor (TLR) 2/4 expression and downstream signaling during the process of periodontitis. In this study, the cervical area of the maxillary second molars of rats was ligated and inoculated with Porphyromonas gingivalis (P. gingivalis) for 4weeks to induce periodontitis. Some rats with periodontitis were treated intragastrically with baicalin (50, 100 or 200mg/kg/day) or vehicle for 4weeks. Compared with the sham group, the levels of TLR2, TLR4 and MyD88 expression and the p38 MAPK and NF-κB activation were up-regulated in the experimental periodontitis group (EPG), accompanied by marked alveolar bone loss and severe inflammation. Treatment with 100 or 200mg/kg/day baicalin dramatically reduced the alveolar bone loss, the levels of HMGB1, TNF-α, IL-1β, and MPO expression, and the numbers of inflammatory infiltrates in the gingival tissues. Importantly, treatment with 100 or 200mg/kg/day baicalin mitigated the periodontitis-up-regulated TLR2, TLR4 and MyD88 expression, and the p38 MAPK and NF-κB activation. Hence, the blockage of the TLR2 and TLR4/MyD88/p38 MAPK/NF-κB signaling by baicalin may contribute to its anti-inflammatory effects in rat model of periodontitis. In conclusion, these novel findings indicate that baicalin inhibits the TLR2 and TLR4 expression and the downstream signaling and mitigates inflammatory responses and the alveolar bone loss in rat experimental periodontitis. Therefore, baicalin may be a potential therapeutic agent for treatment of periodontitis.