DeepHistReg: Unsupervised Deep Learning Registration Framework for Differently Stained Histology Samples.
The use of several stains during histology sample preparation can be useful for fusing complementary information about different tissue structures. It reveals distinct tissue properties that combined may be useful for grading, classification, or 3-D reconstruction. Nevertheless, since the slide preparation is different for each stain and the procedure uses consecutive slices, the tissue undergoes complex and possibly large deformations. Therefore, a nonrigid registration is required before further processing. The nonrigid registration of differently stained histology images is a challenging task because: (i) the registration must be fully automatic, (ii) the histology images are extremely high-resolution, (iii) the registration should be as fast as possible, (iv) there are significant differences in the tissue appearance, and (v) there are not many unique features due to a repetitive texture. In this article, we propose a deep learning-based solution to the histology registration. We describe a registration framework dedicated to high-resolution histology images that can perform the registration in real-time. The framework consists of an automatic background segmentation, iterative initial rotation search and learning-based affine/nonrigid registration. We evaluate our approach using an open dataset provided for the Automatic Non-rigid Histological Image Registration (ANHIR) challenge organized jointly with the IEEE ISBI 2019 conference. We compare our solution to the challenge participants using a server-side evaluation tool provided by the challenge organizers. Following the challenge evaluation criteria, we use the target registration error (TRE) as the evaluation metric. Our algorithm provides registration accuracy close to the best scoring teams (median rTRE 0.19% of the image diagonal) while being significantly faster (the average registration time is about 2 seconds). The proposed framework provides results, in terms of the TRE, comparable to the best-performing state-of-the-art methods. However, it is significantly faster, thus potentially more useful in clinical practice where a large number of histology images are being processed. The proposed method is of particular interest to researchers requiring an accurate, real-time, nonrigid registration of high-resolution histology images for whom the processing time of traditional, iterative methods in unacceptable. We provide free access to the software implementation of the method, including training and inference code, as well as pretrained models. Since the ANHIR dataset is open, this makes the results fully and easily reproducible.


Magnesium deficiency affects plasma lipoprotein composition in rats.
Weanling rats were pair-fed for 8 d with control and Mg-deficient diets containing 960 and 30 mg of Mg/kg, respectively. The marked reduction in plasma Mg levels indicated that the rats fed the Mg-deficient diet were indeed deficient. In the Mg-deficient rats the percent composition of triglycerides in VLDL, LDL and HDL was elevated and that of protein was reduced. Although the proportion of cholesterol was reduced in LDL and HDL, that of phospholipid was decreased only in HDL. Magnesium deficiency induced a decrease in the percent composition of apolipoprotein (apo) E and a relative increase in the apo C for VLDL. In HDL from Mg-deficient rats, the proportion of apo AI was higher than normal, apo AIV was lower than normal and apo E was virtually absent. The percent composition of oleic and linoleic acids was increased but that of stearic and arachidonic acids was depressed in both VLDL and HDL derived from Mg-deficient rats compared with pair-fed controls. Whether these alterations in lipoprotein profile contribute to hyperlipoproteinemia or are the results of the metabolic changes that produce hyperlipoproteinemia remain to be determined.


Predictors of pre-hospital vs. hospital mortality due to road traffic injuries in an Iranian population: results from Tabriz integrated road traffic injury registry.
Road Traffic Injuries (RTIs) is considered as one of the main health challenges and causes of mortality, worldwide and especially in Iran. Predicting the place where RTIs-related death takes place is vital in decreasing this type of mortality. The purpose of the present study was to identify the predictors of RTI fatalities with respect to the place of death (hospital vs. pre-hospital) during the recent decade in East Azerbaijan Province, Iran. Overall, 7347 RTI fatalities were retrieved from the road traffic injuries registry which is supported by the Forensic Medicine Organization in East Azerbaijan. Among these cases, 2758(37.5%)) were hospital deaths. The registered variables of these cases were analysed using bivariate and multiple logistic regression (STATA version 15). Out of 7347 deaths, 5862 (79.8%) were men and the rest were women 1485 (20.2%).The mean age was 40.3 (SD = 20.8). Of the total number of cases, 2758 (37.5%) died in hospital death and the rest 4589 (62.5) were pre-hospital death. According to the results of the present study, inter-city RTI (OR = 1.7, CI 95% = (1.5-2)) and RTIs inside the city of Tabriz (OR = 1.4, CI 95% = (1.2-1.6)) increases the chance of hospitals death. In addition, having a heavy counterpart vehicle compared to no counterpart vehicle decreased the chances of hospitals death (OR = 0.46, CI 95% = (0.39-0.55)) while motorcycle or bike counterpart vehicle compared to no counterpart vehicle increased the chances of hospital death (OR = 2.26, CI 95% = (1.59-3.22)). Also the users of the motorcycle or bike vehicle compared to the pedestrians increased the chances of hospital death (OR = 1.43, CI 95% = (1.19-1.71)) while any the other vehicle users compared to the pedestrians have significantly lower chances for hospital death. Other factors that increased hospitals death were transferring injured people by ambulance (OR = 1.3, CI 95% = (1.1-1.6)) and being elderly (OR = 1.5, CI 95% = (1.2-1.7)). Moreover, it was found that the annual trend of change in hospital death is strongly affected by the above-identified factors. The effective predictors in hospital death were RTI location, type of counterpart vehicle, used vehicles and lighting condition. The identified factors related to the location of deaths by RTI can be divided into the RTI severity-related factors as well as factors related to the services quality and speed of delivery. According to the present results, through professional training of people in the field and providing immediate assistance in RTIs pre-hospital mortality can be significantly prevented.


Horizontal component of electro-oculogram as a parameter of arousal in dementia: relationship between intellectual improvement and increasing arousal under pharmacotherapy.
Although nootropics and metabolically active compounds sometimes attenuate intellectual deficits of dementia patients, this mechanism has not been discussed or investigated. The authors hypothesized that these compounds act to enhance attention and/or concentration by increasing the arousal level, and then improve intellectual functions. Based on this hypothesis, the authors investigated the arousal level and the improvement of intellectual functions in ten patients with Alzheimer type dementia and ten patients with multi-infarct dementia before and after 3 months pharmacotherapy using bifemelane hydrochloride. They then analyzed whether the increases in arousal level involves or relates to the improvement of intellectual functions. On the 20 patients, psychological tests were carried out, and the arousal level was evaluated using the frequency of rapid eye movements in the electro-oculogram (EOG) before and after 3 months administration of bifemelane hydrochloride. As a result, a significant positive correlation was observed between the improvement on the Hasegawa's dementia scale and the rate of increase in rapid eye movements in the EOG. The EOG monitoring can be a great help in establishing an objective evaluation method on drug efficacy.


Efficacy of percutaneous nephrostomy tube during ureteroscopy for upper ureter stone management.
Preoperative percutaneous nephrostomy (PCN) has been commonly performed for patients with urinary stones complicated with pyelonephritis or obstructive uropathy; in fact, a considerable number of patients undergo ureteroscopic removal of stone (URS) in the presence of a PCN. We assessed the effectiveness of PCN during URS in the management of upper ureteral stones. We retrospectively analyzed 140 patients who underwent URS for upper ureteral stones between January 2008 and December 2011. All URS were performed by a single experienced surgeon. The subjects were divided into two groups depending on the presence of a PCN at the time of the surgery (PCN group: 42 and non-PCN group: 98). The PCN group was subdivided into two groups depending on the performance of external fluid irrigation through PCN during the surgery (irrigation group: 21 and non-irrigation group: 21). To evaluate operative outcomes, we compared operative times, auxiliary procedures required, and success and complication rates. The PCN group showed significantly better outcomes in terms of the operative time (57.4 minute vs. 68.1 minute) and success rate (92.9% vs. 78.6%) without increasing the complication rate. In the PCN group, the irrigation group showed a shorter operative time compared to the non-irrigation group, although statistical significance was not observed. Other perioperative outcomes, such as the success rate, auxiliary procedures, and complication rates, were not significantly different between the two groups. URS for upper ureteral stones in patients with PCN produced superior surgical outcomes in terms of the success rate, operative time, and auxiliary procedure rate without increasing the complication rate. The presence of PCN with/without external irrigation during URS can be a beneficial factor to produce better outcomes of URS for the management of upper ureteral stones.


[Stapes decompression].
Footplate decompression, which has been described in Lyon in 1965, can be easily performed under local anesthesia. The surgical procedure consists of a 8/10 mm diameter stapedotomy followed by an obturation with spongel, gelfoam or a piece of thin fascia. The operation is not a labyrinthectomy or a sacculotomy but aims to decompress endolymphatic hydrops in Ménière's disease. It must be realised only in case of typical unilateral Ménière's disease with disabling vertigo and very poor residual hearing. More than two hundred cases have been operated on. Vertigo has been relieved in 90% of the operated cases, tinnitus less severe in 50% of cases and hearing sometimes worse but often unchanged. In patients suffering from a unilateral Ménière's disease with disabling vertigo and poor residual hearing, footplate decompression appears to be one of the most simple safe and effective surgical procedures.


[3D temperature field reconstruction of Ar plasma jet using CCD cpectrum tomography technology].
For realizing real-time 3D temperature field reconstruction of Ar plasma jet, an orthogonal area array CCD (charge coupled device) spectrum tomography experimental system was proposed according to spectrum relative intensity diagnosis method. The size of tested field was measured using comparison between the tested field image caught through CCD and the plotting paper image when plotting paper was placed in the tested field position with no plasma jet; the emission intensity distribution of tested field was obtained using stepping motor taking fiber probe to scan tested field, and the spectrum analysis instrument was used to show the spectrum intensity information. Based on spectrum selection principle of the spectrum relative intensity method, spectra at 696.5 and 763.5 nm were studied as characteristic spectrum. Novel grad attenuation was designed based on the size and intensity distribution of tested field for not exceeding limen of CCD and avoiding the spectrum information loss at tested field edge. The narrowband filter was set between grad attenuation and CCD, so the whole tested spectrum information can be stored in computer real-time. According to orthogonal two-view spectrum tomography reconstruction algorithm, when tested field is axially symmetric, the reconstruction result is well. So four area array CCDs is placed orthogonally, and the same spectrum narrowband filters are placed in front of two orthogonal CCDs to reconstruct 3D emissivity factor field. Based on the 3D emissivity factor field and spectrum relative intensity theory, 3D temperature field of the tested field was reconstructed satisfactorily. The reconstruction result showed that it agreed with the results from fiber scanning diagnosis system, and the uncertain degreed is 3.3%. The proposed experimental device meets the needs of real-time 3D temperature field reconstruction. It provided a stable base for real-time diagnosis of plasma jet density field, pressure field and velocity field.


Nurses Burnout, Resilience, and Its Association With Socio-Demographic Factors During COVID-19 Pandemic.
In the recent pandemic, nurses have faced workload and being exposed to burnout. Resilience helps address work-related psychological problems such as stressful events and burnout. According to the roles of nurses in the healthcare system, we investigated the relationship between resiliency and burnout in nurses. In this descriptive analytical cross-sectional study, 364 nurses participated from April to June 2021. Census sampling was used to recruit participants. Maslach burnout inventory (MBI), Connor-Davidson Resiliency Scale (CDRISC), and a demographic check-list were utilized to collect data. Data analysis was done using SPSS version 22. Shapiro-Wilk, Kruskal-Wallis test, Mann-Whitney U-test, correlation analysis, and generalized linear model were applied accordingly. Overall, the findings showed that nurses had severe symptoms of burnout and a moderate level of resilience. The two domains of burnout, emotional exhaustion and personal accomplishment had a significantly negative correlation with resilience (r = -0.442, p < 0.001 and r = -0.351, p = 0.03, respectively). Linear regression showed that demographic characteristics (Hospital type, ward type, gender, and overtime) were the major predictors of the 3 sub-categories of burnout. A significant negative correlation was observed between burnout and resilience highlighting the role of resilience in reducing burnout (P < 0.05). In order to help nurses to tackle and endure burnout in pandemic times, there is a need to implement national and local policies to help them accordingly.


[Role of T cells in tumor immunology and immunotherapy].
In the immune defense against cancer, cell-mediated adaptive immune response is considered of primary importance, in which T lymphocytes play a key role. Activation, expansion and function of antigen-specific T cells is a multistep process and its outcome depends on the balance of positive and negative regulatory mechanisms controlling each step. Many factors can hamper the development of an efficient antitumor immune response, such as insufficient expression of tumor antigens or of molecules necessary for their processing, inhibitory molecular interactions (e.g. immune checkpoints), immune suppressive factors or suppressor cells. Various therapeutic strategies have been developed in order to increase the efficiency of antitumor immune defense, of which the application of immune checkpoint inhibitors, antibodies blocking the brakes of immune response, is the most widespread. These immunomodulatory antibodies had more favorable effect than traditional treatment modalities on a widening spectrum of tumor types, still the majority of patients do not or only transiently respond. Therefore, great efforts are made to develop rational combinations of immune and other therapies, and to identify resistance mechanisms and biomarkers predicting therapy outcome.


Attachment of epiphyseal cartilage cells and 17/28 rat osteosarcoma osteoblasts using mussel adhesive protein.
These experiments show that mussel adhesive protein (MAP) enhances the attachment of osteoblasts and epiphyseal cartilage cells to plastic culture dishes and Vitallium. When MAP was applied to culture plate surfaces, there were two- to fivefold increases in the numbers of cells attaching compared to control surfaces (no MAP). Results were confirmed using two different cell attachment assay techniques. Osteoblast replication and culture on MAP is possible, suggesting that MAP is not toxic to cells. MAP also holds applied cells to surfaces as initially attached.


Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function.
New evidence for the regulation of vitamin C homeostasis has emerged from several studies of human genetic variation. Polymorphisms in the genes encoding sodium-dependent vitamin C transport proteins are strongly associated with plasma ascorbate levels and likely impact tissue cellular vitamin C status. Furthermore, genetic variants of proteins that suppress oxidative stress or detoxify oxidatively damaged biomolecules, i.e., haptoglobin, glutathione-S-transferases, and possibly manganese superoxide dismutase, affect ascorbate levels in the human body. There also is limited evidence for a role of glucose transport proteins. In this review, we examine the extent of the variation in these genes, their impact on vitamin C status, and their potential role in altering chronic disease risk. We conclude that future epidemiological studies should take into account genetic variation in order to successfully determine the role of vitamin C nutriture or supplementation in human vitamin C status and chronic disease risk.


Rational design of CPP-based drug delivery systems: considerations from pharmacokinetics.
Therapeutics are restricted from cellular internalization due to the biological barrier formed by the cell membrane. Especially for therapeutics with high molecular weight, strategies are required to enable delivery to intracellular targets. Cell-penetrating peptides (CPPs) represent a powerful tool to mediate the entry of large cargos such as proteins, siRNA and nanoparticles. The high diversity of CPPs is the prerequisite to use this class of carriers for various applications. However, therapies based on CPPs are hampered by their unfavorable pharmacokinetics, mainly dominated by their rapid renal clearance and their lack of specificity. Rational design is required to overcome these disadvantages and thereby exploits the actual potential of CPPs. We summarize and highlight the current state of knowledge with special emphasis on pharmacokinetics. The unclear internalization pathways of CPPs remain one of the main obstacles and therefore have been in the focus of research. In this review, several promising strategies such as the combination with targeting sequences, activatable CPPs and adjustment of the molecular weight are described. In addition, new absorption pathways such as nasal, pulmonary or transdermal uptake expand the applicability of CPPs and may be a promising prospect for clinical application.


Feasibility of a Memory Clinic-Based Physical Activity Prescription Program.
Effective programs for promoting physical activity are needed for those with cognitive impairment. To test the feasibility of mobile Health (mHealth) technology-supported physical activity prescription from a tertiary care memory clinic. This feasibility study was designed as a 16-week randomized, crossover trial of a physical activity prescription: 8 weeks of intervention, 8 weeks of baseline or maintenance phase data collection. We recruited 2 cohorts: 21 individuals with Alzheimer-related cognitive impairment (mean age 72.3 (5.2), 9 females), and 9 individuals with normal cognition (mean age 69.6 (5.8), 8 females). We gave each cohort an mHealth accelerometer-based physical activity prescription to double number of steps taken. Our primary outcomes were feasibility and safety. Our secondary outcomes were change in weekly steps taken, Dementia Quality of Life Scale, Self-efficacy Scale, 6-minute Walk, and mini-Physical Performance Test. Set-up and use of the device was not a barrier to participation. However, only 62% of participants with cognitive impairment completed the intervention. The cohort with cognitive impairment did not change their weekly step count above Week 1. All participants in the cohort with normal cognition were able to set up and use their device and increased their weekly step count above Week 1. There were no differences between Week 1 and Week 8 for any secondary measures in either cohort. Setup and daily use of mHealth technology appears to be feasible for a person with cognitive impairment with the help of a partner, but increasing daily step counts over 8 weeks was not achieved. Future work needs to assess alternative activity prescription goals or additional support for patients and their partners.


Psychiatric disorders and characteristics of abuse in sexually abused children and adolescents with and without intellectual disabilities.
The purpose of this study was to compare sexually abused children and adolescents, with and without intellectual disabilities (ID), in terms of post-abuse psychiatric disorders, features of the sexual abuse, and sociodemographic characteristics. The study included sexually abused children aged 6-16 years, who were sent to three different child mental health units for forensic evaluation; there were 102 cases (69 girls and 33 boys) with ID and 154 cases (126 girls and 28 boys) without ID. Researchers retrospectively examined the files, social examination reports, and the judicial reports of the cases. It was determined that in the group with ID, sexual abuse types including penetration and contact had higher rates, they were exposed to more frequent repeated abuses, the abuses were revealed with their own reports at a later period and lower rates, and post-abuse pregnancies were more frequent. It was also determined that the abuser was a familiar person and a family member at lower rates and more than one abuser was encountered more frequently, compared to the group without ID. While no difference was determined between the two groups in terms of the frequency of post-abuse post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), conduct disorder (CD) was observed more frequently in the group with ID. This study emphasizes that sexual abuse, which is an important problem in individuals with ID, has different features and effects.


Glycerol increases the yield and activity of human phenylalanine hydroxylase mutant enzymes produced in a prokaryotic expression system.
Chemical chaperones are low molecular weight compounds known to stabilize proteins in vitro. Recently it was shown that, in transfected cells, these molecules can also correct the defective folding of some mutant proteins. Hyperphenylalaninemia (HPA) has been proposed to be classified as a "conformational disease," since it has been shown that the majority of the PAH mutations affect protein folding, thereby causing an increasing tendency toward aggregation and proteolytic degradation. Based on these observations, the effect of glycerol as a stabilizer agent of recombinant mutant forms of human phenylalanine hydroxylase enzymes (hPAH) produced in a prokaryotic expression system was investigated. The wild-type and two mutant forms of the hPAH protein (R270K and V388M) were expressed in the presence of glycerol in the culture medium. The yield, specific enzymatic activities, and kinetic properties of the recombinant proteins were determined and compared with the data obtained under normal growth conditions. The results obtained demonstrate that glycerol not only improved the yield of the soluble hPAH proteins (2- to 3-fold depending on the mutant enzyme) produced but also increased the specific activity of the purified recombinant enzymes. We speculate that correction of protein folding abnormalities by chemical chaperones may be a possible therapeutic approach to correct conformational diseases.


Extravasation of paclitaxel into breast tissue from central catheter port.
A 53-year-old woman with advanced-stage ovarian cancer experienced extravasation of paclitaxel into the breast tissue as a result of inappropriate needle insertion and/or dislodgement; it came from a central catheter port (CCP) that was found to be intact under radiological examination with contrast material. The breast became tender and oedematous with erythema, and local warming was observed within a few hours. The patient improved in the next few days during nonsteroidal anti-inflammatory medication and close observation, and the breast healed with thickened and darkened skin and central scarring in the 6th month of follow-up. To the best of our knowledge, extravasation into breast tissue is rare in the literature. Extravasation of vesicant drugs from CCP can cause tissue necrosis; it is therefore essential that ports be carefully assessed and used by experienced staff to lessen the likelihood of such an unpleasant complication.


Evaluation of the efficacy and safety of topical timolol maleate combined with oral propranolol treatment for parotid mixed infantile hemangiomas.
The aim of the present study was to assess the efficacy and safety of topical timolol maleate combined with oral propranolol for parotid infantile hemangiomas. Between October 2012 and April 2014, propranolol was administered orally at a dose of 1.0-1.5 mg/kg/day to 22 infants with proliferating hemangiomas in the Department of Oral and Maxillofacial Surgery (Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China). A small amount of 0.5% timolol maleate eye drop solution was topically applied with medical cotton swabs to the area of the lesion twice a day, every 12 h. The study group consisted of 9 males and 13 females, aged 2-9 months, with a median age of 4.7 months. The lesions were all located in the parotid region, and measured between 3.5×4×0.5 and 7×8×3 cm in volume. The planned duration of therapy was 6-8 months, or the two drugs were stopped when complete regression of the lesions was obtained. The therapeutic outcomes and safety were assessed by the change in the size and color of the tumor, and the presence of adverse effects throughout the course of treatment. The mean duration of therapy was 21.1 weeks and ranged from 3 to 8 months. Of the 22 patients, 16 demonstrated an excellent response, 6 showed a good response and 2 displayed a moderate response. No major collateral effects were observed. Overall, oral propranolol combined with topical timolol maleate may be used as the first-line therapeutic choice in the treatment of infantile parotid mixed hemangioma.


Protective effect of Schisandra chinensis lignans on hypoxia-induced PC12 cells and signal transduction.
It is well-known that hypoxia induces neuronal injury; however, the mechanisms underlying this observed effect remain to be determined. Schisandra chinensis lignans (SCL). The aim of this study was thus to examine the ability of Schisandra chinensis lignans (SCL) to prevent hypoxia-induced neuronal injury using a human adrenal pheochromocytoma cell line (PC12). Exposure to hypoxia significantly reduced cell survival rate in cultured PC12 cells. However, pretreatment with SCL at 10, 20 or 40 μmol/L followed by hypoxia prevented loss of cellular viability. Flow cytometry demonstrated that the apoptotic rate in PC12 cells following hypoxia was significantly increased. Pretreatment with SCL 20 or 40 μmol/L in hypoxia-exposed cells resulted in significantly reduced apoptotic rates compared to hypoxia. Immunocytochemical staining showed that protein expression of p-Akt was significantly diminished by hypoxia. Following pre-treatment with different concentrations of SCL, PC12 cells were markedly stimulated as evidenced by elevated protein expression of p-Akt in a concentration-dependent manner. The expression of p-Akt protein in the presence of PI3K/Akt signaling pathway inhibitor LY294002 and SCL was not markedly changed indicating that signal transduction was affected by this Chinese herb. There were no significant differences in total Akt protein expression following hypoxia or pretreatment with SCL. Western blot demonstrated that expression levels of caspase-3 protein were significantly increased while expression levels of Bcl-2 protein were decreased in hypoxic cells. Pretreatment with SCL followed by hypoxia significantly lowered expression levels of caspase-3 protein accompanied by elevated expression levels of Bcl-2 protein in a concentration-dependent manner. After co-incubation with LY29004 and SCL, down-regulation of expression of caspase-3 protein and up-regulation of the expression of Bcl-2 protein noted with SCL alone were suppressed. Data suggest that the protective effect exerted by SCL in hypoxia-induced PC12 cell injury involves enhanced cell proliferation and inhibition of apoptosis mediated by activation of PI3K/Akt signaling pathway. The increased protein Akt phosphorylation expression levels resulted in consequent reduced downstream caspase-3 expression and enhanced Bcl-2 expression.


Calcium signaling in a narrow somatic submembrane shell during synaptic activity in cerebellar Purkinje neurons.
Temporal and spatial changes in the intracellular Ca2+ concentration ([Ca2+]i) were examined in dendrites and somata of rat cerebellar Purkinje neurons by combining whole-cell patch-clamp recording and fast confocal laser-scanning microscopy. In cells loaded via the patch pipette with the high-affinity Ca2+ indicator Calcium Green-1 (Kd approximately 220 nM), a single synaptic climbing fiber response, a so-called complex spike, resulted in a transient elevation of [Ca2+]i that showed distinct differences among various subcellular compartments. With conventional imaging, the Ca2+ signals were prominent in the dendrites and almost absent in the soma. Confocal recordings from the somatic region, however, revealed steep transient increases in [Ca2+]i that were confined to a submembrane shell of 2- to 3-microns thickness. In the central parts of the soma [Ca2+]i increases were much slower and had smaller amplitudes. The kinetics and amplitudes of the changes in [Ca2+]i were analyzed in more detail by using the fast, low-affinity Ca2+ indicator Calcium Green-5N (Kd approximately 17 microM). We found that brief depolarizing pulses produced [Ca2+]i increases in a narrow somatic submembrane shell that resembled those seen in the dendrites. These results provide direct experimental evidence that the surface-to-volume ratio is a critical determinant of the spatiotemporal pattern of Ca2+ signals evoked by synaptic activity in neurons.


Beta-receptors in resistance to phosphaturic effect of PTH in respiratory alkalosis.
Respiratory alkalosis results in a resistance to the phosphaturic effect of parathyroid hormone (PTH) and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP). The present studies evaluated the role of the beta-adrenergic system in that resistance phenomenon. In clearance experiments on acutely thyroparathyroidectomized male Wistar rats, respiratory alkalosis blunted the PTH-mediated increase in absolute and fractional excretion of phosphate (FEPi). Propranolol infusion restored the phosphaturic response to PTH:FEPi, 0.8 +/- 0.3 vs. 8.1 +/- 2.5% (P less than 0.005). Similarly, the increase of FEPi during cAMP infusion was also diminished by respiratory alkalosis: FEPi, 15.5 +/- 2.2 vs. 5.5 +/- 1.1% (P less than 0.005). This hypophosphaturic effect of respiratory alkalosis in the presence of cAMP was not observed in rats infused with propranolol compared with the period of normal ventilation: FEPi, 21.1 +/- 1.7 vs. 15.3 +/- 1.6 (P less than 0.02). Also, during the infusion of the highly selective beta 2-adrenoceptor antagonist, ICI 118,551, cAMP was phosphaturic in respiratory alkalosis compared with FEPi in the absence of the antagonist: FEPi, 13.0 +/- 2.5 vs. 5.5 +/- 1.1% (P less than 0.02). Finally, the infusion of the beta 2-agonist, fenoterol, to the normally ventilated rats significantly decreased FEPi in cAMP-infused rats in comparison to the absence of the agonist: FEPi, 4.0 +/- 0.7 vs. 22.1 +/- 2.6% (P less than 0.001). We conclude that the resistance to the phosphaturic effect of PTH and cAMP in respiratory alkalosis is mediated by beta-adrenoceptors.


The effect of multilevel anterior cervical fusion on neck motion.
Anterior cervical decompression and fusion (ACDF) procedures are successful in treating multilevel cervical radiculopathy and cervical myelopathy. It was reported that this procedure would result in a loss of cervical range of motion. However, few studies have focused on the exact impact of multilevel (more than 3 levels) ACDF on cervical range of motion. 29 patients underwent a 3-level or 4-level ACDF. In all the patients, preoperative active cervical ROM measurement was performed, and postoperative measurement was performed at 1-year follow-up by a CROM device. The pre- and postoperative data were compared to each other using paired t tests (α = 0.05). The patients had significantly less ROM after the surgery in all planes of motion. Major reduction was observed in flexion (39.5%), left and right lateral flexion (25.7 and 25.9%), with relatively minor impact on extension (18.3%), left and right rotation (14.0 and 14.4%) observed. In the three cardinal planes, major reduction was observed in the sagittal plane (28.2%) and coronal plane (25.8%), while minor impact observed in the horizontal plane (14.1%). The patients of cervical spondylotic myelopathy had an obvious reduction in active cervical ROM following multilevel ACDF. However, patients might not experience great difficulties in performing daily activities with regard to the loss of neck motion after fusion.


Lowering Sample Requirements to Study Tyrosine Kinase Signaling Using Phosphoproteomics with the TMT Calibrator Approach.
Analysis of tyrosine kinase signaling is critical for the development of targeted cancer therapy. Currently, immunoprecipitation of phosphotyrosine (pY) peptides prior to liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used to profile tyrosine kinase substrates. A typical protocol requests 10 mg of total protein from ≈108 cells or 50-100 mg of tissue. Large sample requirements can be cost prohibitive or not feasible for certain experiments. Sample multiplexing using chemical labeling reduces the protein amount required for each sample, and newer approaches use a material-rich reference channel as a calibrator to trigger detection and quantification for smaller samples. Here, it is demonstrated that the tandem mass tag (TMT) calibrator approach reduces the sample input for pY profiling tenfold (to ≈1 mg total protein per sample from 107 cells grown in one plate), while maintaining the depth of pY proteome sampling and the biological content of the experiment. Data are available through PRIDE (PXD019764 for label-free and PXD018952 for TMT). This strategy opens more opportunities for pY profiling of large sample cohorts and samples with limited protein quantity such as immune cells, xenograft models, and human tumors.


A family of cold shock proteins in Bacillus subtilis is essential for cellular growth and for efficient protein synthesis at optimal and low temperatures.
Like other bacteria, Bacillus subtilis possesses a family of homologous small acidic proteins (CspB, CspC and CspD, identity >70%) that are strongly induced in response to cold shock. We show that deletion of cspC or cspD genes did not result in a detectable phenotype; in contrast, csp double mutants exhibited severe reduction in cellular growth at 15 degrees C as well as at 37 degrees C, including impairment of survival during the stationary phase. Two-dimensional gel analysis showed that protein synthesis was deregulated in csp double mutants and that the loss of one or two CSPs led to an increase in the synthesis of the remaining CSP(s) at 37 degrees C and after cold shock, suggesting that CSPs down-regulate production of members from this protein family. A cspB/C/D triple mutant (64BCDbt) could only be generated in the presence of cspB in trans on a plasmid that was not lost, in spite of lack of antibiotic pressure, indicating that a minimum of one csp gene is essential for viability of B. subtilis. After cold shock, synthesis of CspB in 64BCDbt was drastically lower than in wild-type cells accompanied by cessation in growth and strong reduction in general protein synthesis. As CspB, CspC and CspD are shown to bind to RNA in a co-operative and interactive manner, CSPs are suggested to function as RNA chaperones facilitating the initiation of translation under optimal and low temperatures.


Ocuton-S self tonometry vs. Goldmann tonometry; a diurnal comparison study.
To compare 24-hour diurnal intraocular pressure (IOP) measurements obtained using the Ocuton-S applanation self tonometer and the Goldmann tonometer. 24-hour diurnal IOP curves were obtained on 14 eyes of 7 trained patients suffering from medically controlled primary open angle glaucoma. IOP was measured every third hour starting at 9 a.m. with a calibrated Goldmann tonometer; one week later, a similar set of measurements was obtained with Ocuton-S self tonometry by the patients. One week later still, ultrasound corneal pachymetry was performed at the same hours. Overall IOP (24-hour mean) did not differ significantly between the different measuring techniques (ANOVA, p = 0.74), but the IOP differed in a statistically significant manner around the clock (ANOVA, p = 0.00006). The mean Goldmann tonometric readings were up to 2.8 mmHg lower than the Ocuton-S values during the daytime (9 a.m. to 9 p.m.), however, during the night (12 midnight to 6 a.m.) mean IOP measured with Goldmann tonometry was 2.2 to 3.3 mmHg higher than the corresponding average of the self tonometry readings. There was a statistically significant interaction between the type of tonometry and the time of the measurement (p = 0.0007). Central corneal thickness (CCT) showed a significant change during the 24-hour period (p = 0.000001). IOP shows a different diurnal curve when measured with the Goldmann tonometer and with the Ocuton-S applanation self tonometer. The instruments' readings might be influenced in different ways by the diurnal changes of the corneal thickness. Since Ocuton-S self tonometry underestimates the IOP in the early morning period, a careful evaluation is necessary when nocturnal and early morning IOP elevation is investigated with this technique.


Acuity to Changes in Self-Generated Vocal Pitch in Parkinson's Disease.
Purpose Given the role of auditory perception in voice production, studies have investigated whether impairments in auditory perception may underlie the noted disruptions in speech in Parkinson's disease (PD). Studies of loudness perception in PD show impairments in the perception of self-generated speech, but not external tones. Studies of pitch perception in PD have only examined external tones, but these studies differed in terms of the interstimulus intervals (ISIs) that were used, did not examine the impact of cognition, and report conflicting results. To clarify pitch perception in PD, this work investigated perception of self-generated vocal pitch, controlling for cognition and ISI. Method A total of 30 individuals with and without PD completed (a) hearing threshold testing, (b) the Montreal Cognitive Assessment, and (c) an adaptive just-noticeable-difference paradigm under two separate ISIs (100 ms and 1,000 ms) to assess acuity to self-generated vocal pitch. Results There was no significant difference in acuity between individuals with and without PD. Both groups demonstrated significantly worse acuity for longer compared to shorter ISIs. Montreal Cognitive Assessment scores were not a significant predictor of acuity. Conclusions The results suggest that acuity to self-generated vocal pitch does not differ between individuals with and without PD.


Autoimmune pancytopenia following combination chemotherapy for chronic lymphocytic leukaemia.
Autoimmune haemolysis or thrombocytopenia can complicate purine nucleoside monotherapy for chronic lymphocytic leukaemia (CLL), but Evans syndrome is rare. This is a report of the occurrence of pancytopenia secondary to a unique combination of red cell aplasia with autoimmune thrombocytopenia and neutropenia in a patient with CLL following treatment with fludarabine and cyclophosphamide. This case is unusual for the simultaneous targeting of three haemopoietic lineages by immune dysfunction following fludarabine and cyclophosphamide, which is a treatment regimen believed to reduce autoimmune haematological toxicity in CLL.


Glycoarrays--tools for determining protein-carbohydrate interactions and glycoenzyme specificity.
Carbohydrate arrays (glycoarrays) have recently emerged as a high-throughput tool for studying carbohydrate-binding proteins and carbohydrate-processing enzymes. A number of sophisticated array platforms that allow for qualitative and quantitative analysis of carbohydrate binding and modification on the array surface have been developed, including analysis by fluorescence spectroscopy, mass spectrometry and surface plasmon resonance spectroscopy. These platforms, together with examples of biologically-relevant applications are reviewed in this Feature Article.


Treatment of refractory keloids with pulsed dye laser alone and with rotational pulsed dye laser and intralesional corticosteroids: A retrospective case series.
The limited available effective treatments make the management of keloids challenging. Intralesional triamcinolone and pulsed dye laser have been used for the treatment of keloids. We sought to assess the efficacy of a treatment regime using rotational intralesional triamcinolone and pulsed dye laser in the management of keloids. Materials (Subjects) and Methods: Case notes and photographic records of 99 patients with keloids treated with pulsed dye laser (PDL) alone or rotational PDL and intralesional triamcinolone (ILT) at our centre between 2005 and 2010 were reviewed. Patients with raised, erythematous and/or symptomatic keloids unresponsive to ILT alone (usually 6 treatments) are referred for consideration of PDL. Patients are offered repeated rotational treatments of three PDL (4-15 J/cm(2), 7 mm spot, 1.5 msec pulse duration, 595 nm wavelength, DCD, 30 msec spray: 20 msec delay; spaced at 6-8 weeks intervals) followed by one ILT (10 mg or 40 mg/dl). ILT-treated flat but erythematous and/or symptomatic keloids are treated with PDL alone at 6-8 week intervals. Response after each laser treatment is documented as a percentage improvement from baseline. Based on the improvement in redness, thickness and pruritus the operator classified the response to treatment as mild (0-49%), moderate (50-75%) or excellent (>75%). Patients are reviewed at 6 months following last treatment. A patient satisfaction questionnaire was also sent out to all patients who received treatments between 2005 and 2010 and this was compared with the information gathered from the notes. Of the 99 patients, 58 were women and 41 were men and most were Caucasian (n=84). A total of 755 keloids were treated. The average number of PDL treatments to achieve a moderate-excellent result was 14 in male and 12 in females. Moderate-excellent improvement was seen in 76% patients. The average number of ILT required to achieve a moderate-excellent result was 5 in males and 4 in females. All patients were sent a satisfaction questionnaire and 33 responses were received wherein patients reported an average of 70% improvement in the redness and thickness of the keloids. Localised cutaneous atrophy, self-limiting erythema and injection site discomfort were noted in 3 female patients whilst no side-effects noted in the male cohort. Pulsed dye laser with or without intralesional triamcinolone is a moderately effective treatment of keloid scars with a very good side-effect profile and high patient satisfaction.


Optical, Electrical and Thermal Properties of Organic⁻Inorganic Hybrids with Conjugated Polymers Based on POSS Having Heterogeneous Substituents.
Preparation of organic⁻inorganic hybrids with conventional conjugated polymers such as polyfluorene (PF) and poly(3-hexylthiophene) (P3HT) were demonstrated via the facile blending in solution by employing polyhedral oligomeric silsesquioxane (POSS) having heterogeneous alkyl substituents. From the optical measurements, it was shown that the modified POSS derivatives played a critical role in facilitating amorphous state of polymer matrices. Interestingly, although inter-strand interaction decreased after POSS addition in the hybrid films, thermal stability can be enhanced in the presence of the modified POSS with long alkyl chains. Furthermore, it was demonstrated that carrier mobilities through the hybrid film was minimally reduced by POSS. These results suggest that POSS should be a versatile building block to form hybrid with various types of polymers for enhancing durability without loss of electronic properties of organic components.


A one-dimensional ABX3-type coordination polymer: catena-poly[benzyltrimethylammonium [tri-μ-chlorido-cadmium(II)]].
The crystal structure of the title novel one-dimensional ABX3-type organic-inorganic hybrid complex {(C10H16N)[CdCl3]}n, (I), consists of benzyltrimethylammonium (Me3BzN(+)) cations and one-dimensional anionic {[Cd(μ-Cl)3](-)}∞ chains. Each Cd(II) centre is hexacoordinated by bridging chloride ligands, giving a slightly distorted octahedral Cd(μ-Cl)6 arrangement. The octahedra are linked by two opposite shared faces, giving rise to an almost perfectly linear anionic {[Cd(μ-Cl)3](-)}∞ chain in the a-axis direction. Me3BzN(+) cations located in the inter-chain spaces balance the charge. Noncovalent static attracting forces (Coulombic and van der Waals forces) and nonclassical C-H···Cl hydrogen-bond interactions stabilize the crystal structure.


Spatial Navigation and Visuospatial Strategies in Typical and Atypical Aging.
Age-related spatial navigation decline is more pronounced in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia. We used a realistic-looking virtual navigation test suite to analyze different aspects of visuospatial processing in typical and atypical aging. A total of 219 older adults were recruited from the Czech Brain Aging Study cohort. Cognitively normal older adults (CN; n = 78), patients with amnestic MCI (n = 75), and those with mild AD dementia (n = 66) underwent three navigational tasks, cognitive assessment, and brain MRI. Route learning and wayfinding/perspective-taking tasks distinguished the groups as performance and learning declined and specific visuospatial strategies were less utilized with increasing cognitive impairment. Increased perspective shift and utilization of non-specific strategies were associated with worse task performance across the groups. Primacy and recency effects were observed across the groups in the route learning and the wayfinding/perspective-taking task, respectively. In addition, a primacy effect was present in the wayfinding/perspective-taking task in the CN older adults. More effective spatial navigation was associated with better memory and executive functions. The results demonstrate that a realistic and ecologically valid spatial navigation test suite can reveal different aspects of visuospatial processing in typical and atypical aging.


A secure method of nasotracheal tube fixation using an infant feeding tube.
A well secured endotracheal tube is very essential for the safe conduct of anesthesia. In maxillofacial surgeries, providing secure fixation of the nasotracheal tube has always been a problem. We have used an infant feeding tube that goes around the nasal septum for the fixation of the nasal endotracheal tube. This method of securing the nasotracheal tube does not hinder the surgical access, is well tolerated by patients, and is safe.


Separation of cyclic and starlike hierarchical dominance in evolutionary matrix games.
We study antisymmetric components of matrices characterizing pair interactions in multistrategy evolutionary games. Based on the dyadic decomposition of matrices we distinguish cyclic and starlike hierarchical dominance in the appropriate components. In the symmetric matrix games the strengths of these elementary components are determined. The general features and intrinsic symmetries of these interactions are represented by directed graphs. It is found that the variation of a single matrix component modifies simultaneously the strengths of two starlike hierarchical basis games and many other independent rock-paper-scissors type cyclic basis games. The application of the related concepts is illustrated by discussing the three-strategy voluntary prisoner's dilemma.


Cerebellar neurons possess a vesicular compartment structurally and functionally similar to Glut4-storage vesicles from peripheral insulin-sensitive tissues.
The insulin-sensitive isoform of the glucose transporting protein, Glut4, is expressed in fat as well as in skeletal and cardiac muscle and is responsible for the effect of insulin on blood glucose clearance. Recent studies have revealed that Glut4 is also expressed in the brain, although the intracellular compartmentalization and regulation of Glut4 in neurons remains unknown. Using sucrose gradient centrifugation, immunoadsorption and immunofluorescence staining, we have shown that Glut4 in the cerebellum is localized in intracellular vesicles that have the sedimentation coefficient, the buoyant density, and the protein composition similar to the insulin-responsive Glut4-storage vesicles from fat and skeletal muscle cells. In cultured cerebellar neurons, insulin stimulates glucose uptake and causes translocation of Glut4 to the cell surface. Using 18FDG (18fluoro-2-deoxyglucose) positron emission tomography, we found that physical exercise acutely increases glucose uptake in the cerebellum in vivo. Prolonged physical exercise increases expression of the Glut4 protein in the cerebellum. Our results suggest that neurons have a novel type of translocation-competent vesicular compartment which is regulated by insulin and physical exercise similar to Glut4-storage vesicles in peripheral insulin target tissues.


Isolation of the Novel Phage PHB09 and Its Potential Use against the Plant Pathogen Pseudomonas syringae pv. actinidiae.
Bacteriophages are viruses that specifically infect target bacteria. Recently, bacteriophages have been considered potential biological control agents for bacterial pathogens due to their host specificity. Pseudomonas syringae pv. actinidiae (Psa) is a reemerging pathogen that causes bacterial canker of kiwifruit (Actinidia sp.). The economic impact of this pest and the development of resistance to antibiotics and copper sprays in Psa and other pathovars have led to investigation of alternative management strategies. Phage therapy may be a useful alternative to conventional treatments for controlling Psa infections. Although the efficacy of bacteriophage φ6 was evaluated for the control of Psa, the characteristics of other DNA bacteriophages infecting Psa remain unclear. In this study, the PHB09 lytic bacteriophage specific to Psa was isolated from kiwifruit orchard soil. Extensive host range testing using Psa isolated from kiwifruit orchards and other Pseudomonas strains showed PHB09 has a narrow host range. It remained stable over a wide range of temperatures (4-50 °C) and pH values (pH 3-11) and maintained stability for 50 min under ultraviolet irradiation. Complete genome sequence analysis indicated PHB09 might belong to a new myovirus genus in Caudoviricetes. Its genome contains a total of 94,844 bp and 186 predicted genes associated with phage structure, packaging, host lysis, DNA manipulation, transcription, and additional functions. The isolation and identification of PHB09 enrich the research on Pseudomonas phages and provide a promising biocontrol agent against kiwifruit bacterial canker.


New one-pot synthesis of (E)-beta-aryl vinyl halides from styrenes.
A new, efficient protocol for the highly stereoselective one-pot synthesis of (E)-beta-aryl vinyl iodides and (E)-beta-aryl vinyl bromides from styrenes based on sequential ruthenium-catalyzed silylative coupling-N-halosuccinimide-mediated halodesilylation reactions is reported.


Serum paraoxonase 1 (PON1) activity and lipid metabolism parameters changes in different production cycle periods of Holstein-Friesian, Polish Red and Norwegian breeds.
We investigated the measurement of paraoxonase 1 (PON1), as a potential marker of redox state changes in dairy cows, its involvement in lipid metabolism and compared it with superoxide dismutase (SOD) activity changes. We also evaluated lipid metabolism parameters associated with dairy production. PON1 paraoxonase and arylesterase acitvities, SOD activity, beta-hydroxybutyrate (BHB), uric acid (UA), high density lipoprotein (HDL), low density lipoprotein (LDL), cholesterol and triglyceride concentrations were measured in Holstein-Friesian, Polish Red and Norwegian breeds serum in two production cycles. Our data showed a significant postpartum depletion in PON1 activity and lipoprotein and lipid products concentrations, with elevated BHB values. However, there were no significant changes in SOD activity and uric acid concentrations in Holstein-Friesian and Polish Red breeds after calving. At lactation peak there was a significant SOD activity decrease correlated with standardized PON1 activity depletion in all examined breeds. The results suggest that PON1 might be a better parameter for minimal redox state changes in serum, shortly after labour in the examined breeds.


Atomistic origin of lattice strain on stiffness of nanoparticles.
Lattice strain plays a crucial role on the properties of nanoparticles. Although the effect of lattice strain on nanoparticles has been widely studied in experimental measurements and calculations, its physical mechanism from the perfective of bond identities is still poorly understood. Herein we put forward an analytical solution of the size effect and external stimuli such as pressure and temperature dependence of lattice strain and bulk modulus of a nanoparticle from the perspective of atomistic origin. A shell-core configuration has been considered for the nanoparticle structure. It has been found that the lattice strain as well as quantum trapping and energy storage exerted by the compressive stress and thermal stress would be responsible for the mechanical behavior of nanoparticles. The theoretical predictions were well consistent with the experimental data and ab initio calculations, implying that the model could be expected to be a general approach to understand mechanical behavior in nanomaterials.


Effects of Cation Levels of the Nutrient Medium on the Biochemistry of Chlorella: II. Factorial Experiment.
A factorial experiment was designed to study the effects of Mg(2+), K(+), and Na(+) on the growth and biochemistry of Chlorella sorokiniana. Raising Mg(2+) or K(+) concentration in the nutrient medium increased growth rates as well as total N levels and Mg(2+) and K(+) accumulation by the cells. The total N effect was Mg(2+)-dependent-if Mg(2+) was below a certain level in the medium-increasing the K(+) concentration did not raise the total N level of cells. Low nutrient levels of K(+) decreased the levels of unsaturated fatty acids (especially 18:1 and 18:3), while increasing the levels of palmitic acid (16:0), total fatty acids, and total lipid. Increasing nutrient K(+) concentrations were accompanied by increases in levels of some unsaturated fatty acids, with a concomitant reduction in 16:0, total fatty acids and total lipid. Low Mg(2+) levels in the nutrient medium reduced the cellular levels of palmitic acid, total fatty acids, total lipid, and certain unsaturated fatty acids (though this last effect also depended on the nutrient level of K(+)). These relationships indicate that Mg(2+) may be important in the initial steps of fatty acid synthesis, whereas K(+) may be necessary for the formation of certain unsaturated fatty acids. Variations in Na(+) concentration did not have any significant effect on the growth and biochemistry of C. sorokiniana.


Nuclear fallout provides a new link between aPKC and polarized cell trafficking.
Cell polarity, essential for cell physiology and tissue coherence, emerges as a consequence of asymmetric localization of protein complexes and directional trafficking of cellular components. Although molecules required in both processes are well known their relationship is still poorly understood. Here we show a molecular link between Nuclear Fallout (Nuf), an adaptor of Rab11-GTPase to the microtubule motor proteins during Recycling Endosome (RE) trafficking, and aPKC, a pivotal kinase in the regulation of cell polarity. We demonstrate that aPKC phosphorylates Nuf modifying its subcellular distribution. Accordingly, in aPKC mutants Nuf and Rab11 accumulate apically indicating altered RE delivery. We show that aPKC localization in the apico-lateral cortex is dynamic. When we block exocytosis, by means of exocyst-sec mutants, aPKC accumulates inside the cells. Moreover, apical aPKC concentration is reduced in nuf mutants, suggesting aPKC levels are maintained by recycling. We demonstrate that active aPKC interacts with Nuf, phosphorylating it and, as a result, modifying its subcellular distribution. We propose a regulatory loop by which Nuf promotes aPKC apical recycling until sufficient levels of active aPKC are reached. Thus, we provide a novel link between cell polarity regulation and traffic control in epithelia.


The synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces caspase-dependent and -independent apoptosis in acute myelogenous leukemia.
In acute myeloid leukemia (AML), resistance to chemotherapy is associated with defects in both the extrinsic and intrinsic pathways of apoptosis. Novel agents that activate endogenous apoptosis-inducing mechanisms directly may be potentially useful to overcome chemoresistance in AML. We examined the mechanisms of apoptosis induction by the novel synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) in AML cells. CDDO-induced apoptosis was associated with the loss of mitochondrial inner transmembrane potential, caspases activation, the translocation of apoptosis-inducing factor to the nucleus, and DNA fragmentation in AML cells. Apoptosis was equally evident in cells deficient in caspase-9 or caspase-8 after exposure to CDDO, suggesting caspase-independent cell death. The use of small interfering RNA to reduce the expression of apoptosis-inducing factor partially inhibited CDDO-induced apoptosis in AML cells. Cells overexpressing Bcl-2 were markedly resistant to CDDO-induced apoptosis. Moreover, CDDO promoted the release of cytochrome c from isolated mitochondria, suggesting that CDDO targets the mitochondria directly to trigger the intrinsic pathway of cell death in intact cells. Together, these results suggest that CDDO functions by activating the intrinsic pathway of apoptosis and initiates caspase-dependent and independent cell death. The direct modulation of mitochondrial-mediated, caspase-independent apoptosis by CDDO may be advantageous for overcoming chemoresistance in AML.


Increased hepatic iron deposition resulting from treatment of chronic hepatitis C with ribavirin.
Increased levels of hepatic iron may impair the response of patients with chronic hepatitis C to treatment with interferon-alfa, but combination therapy with ribavirin has demonstrated efficacy in the treatment of hepatitis C. When used alone or with interferon-alfa, ribavirin may cause a dose-dependent reversible hemolytic anemia. We compared the extent and cellular localization of iron deposition in liver tissue from biopsy specimens obtained before and after 36 weeks of therapy with ribavirin or placebo for 59 patients with chronic hepatitis C. Paired slides were available for review from 26 ribavirin and 27 placebo recipients. Iron deposition was assessed using coded slides stained with Perls Prussian blue and was semi-quantitated in hepatocytes, Kupffer cells, and areas of fibrosis. The overall iron score fell by 0.96 in the placebo group and increased 1.69 in the ribavirin recipients. Iron was deposited mainly in hepatocytes; the hepatocyte iron score increased from 2.19 to 3.81 in the ribavirin group. The amount of iron staining in Kupffer cells declined in the placebo group and increased slightly in the ribavirin group. Iron changes in areas of fibrosis were minor and did not differ between groups. Increased total hepatic iron deposition occurred during a 9-month course of ribavirin. Ribavirin-associated hemolysis deposits iron preferentially in hepatocytes. This increased deposition of hepatic iron does not seem to affect the biochemical or histologic response to ribavirin therapy but may have implications for hepatocyte susceptibility to future injury.


[Botanicus and phytotox: data base of plant toxicology. Interest in emergency toxicology and in phytovigilance].
The purposes of this project were to summarize more than 279 standard botanical names and their 2294 vernacular ones (French common names, Arabic common names and Moroccan common names) for the first part of database named "Botanicus". The second part of this data base named "Phytotox", concerns relevant toxic data of 120 plants available in Mediterranean region. The database will be useful for emergency physicians, particularly of Maghreb and French- speaking countries. Botanicus and Phytotox permit to assist them in providing fast and appropriate answers to questions concerning adverse effects associated with plant use.


The Effects of Epistemic Trust and Social Trust on Public Acceptance of Genetically Modified Food: An Empirical Study from China.
Most studies exploring the public acceptance of genetically modified food (GMF) are based on social trust and the establishment of a causal model. The underlying premise is that social trust indirectly affects public acceptance of GMF through perceived risks and perceived benefits. The object of social trust is trust in people, organizations, and institutions. Different from the social trust, epistemic trust refers to people's trust in scientific knowledge behind the technology of concern. It has been shown that epistemic trust, like social trust, is also an important factor that affects the public perception of applicable risks and benefits. Therefore, it is necessary to incorporate epistemic trust into the causal model to derive a more complete explanation of public acceptance. However, such work has not been conducted to date. The causal model proposed in this paper integrated epistemic trust and social trust and divided social trust into trust in public organizations and trust in industrial organizations. A representative questionnaire survey (N = 1091) was conducted with Chinese adults. The model was analyzed by the partial least squares structural equation modeling (PLS-SEM) method. Three major findings were obtained: First, epistemic trust is an important antecedent of perceived risks and perceived benefits and exerts a significant indirect effect on the acceptance of GMF. Secondly, trust in industrial organizations negatively impacts perceived risks, while trust in public organizations positively impacts perceived benefits. Thirdly, contrary to the common opinion, trust in industrial organizations did not exert a significant direct effect on perceived benefits, and trust in public organizations did not demonstrate a significant direct effect on perceived risks. Therefore, trust in industrial organizations and trust in public organizations utilize different influence paths on GMF acceptance. This study enriches the understanding of the influence path of trust with regard to the acceptance of emerging technologies and is of great significance to relevant risk-management practices.


Patient education strategies for hospitalized cardiovascular patients: a systematic review.
Although mortality from cardiovascular (CV) disease has fallen in the past decade, the burden of CV disease and related conditions remains high, with rates of hospitalization and disability and cost on the rise. Prevention and treatment of CV conditions often involve a complex regimen of lifestyle modification, medications, and/or symptom monitoring and management. Cardiovascular health professionals spend a great deal of time promoting awareness of and adherence to national guidelines for the prevention and management of CV conditions. In addition, patient education for hospitalized patients is becoming increasingly regulated by national organizations and payors. However, it is unclear which educational intervention elements or strategies are most effective for educating hospitalized CV patients and their families. The purpose of this systematic review of experimental and quasi-experimental studies was to identify and examine the characteristics and outcomes of CV health education interventions for hospitalized CV patients.


Automated extraction and description of dark areas in surface microscopy melanocytic lesion images.
Identification of dark areas inside a melanocytic lesion (ML) is of great importance for melanoma diagnosis, both during clinical examination and employing programs for automated image analysis. The aim of our study was to compare two different methods for the automated identification and description of dark areas in epiluminescence microscopy images of MLs and to evaluate their diagnostic capability. Two methods for the automated extraction of 'absolute' (ADAs) and 'relative' dark areas (RDAs) and a set of parameters for their description were developed and tested on 339 images of MLs acquired by means of a polarized-light videomicroscope. Significant differences in dark area distribution between melanomas and nevi were observed employing both methods, permitting a good discrimination of MLs (diagnostic accuracy = 74.6 and 71.2% for ADAs and RDAs, respectively). Both methods for the automated identification of dark areas are useful for melanoma diagnosis and can be implemented in programs for image analysis.


[Preservation of human corneas in organ culture: technical protocol].
Using organ-culture preservation human corneas were preserved up to 5 weeks in a modified tissue culture medium at 37 degrees C. The endothelial viability was examined after staining with trypan-blue 0.3%, after determination of endothelial cell density and cell loss and by light microscopy after staining with trypan-blue 0.3% and alizarin red 1%. The biochemical analysis of the medium (pH, glucose, lactate) has allowed the evaluation of three kinds of storage. The influence of time preservation on the endothelial viability and the metabolic conditions are determined. At the end of this study a clinical trial is proposed.


Mannose phosphate isomerase regulates fibroblast growth factor receptor family signaling and glioma radiosensitivity.
Asparagine-linked glycosylation is an endoplasmic reticulum co- and post-translational modification that enables the transit and function of receptor tyrosine kinase (RTK) glycoproteins. To gain insight into the regulatory role of glycosylation enzymes on RTK function, we investigated shRNA and siRNA knockdown of mannose phosphate isomerase (MPI), an enzyme required for mature glycan precursor biosynthesis. Loss of MPI activity reduced phosphorylation of FGFR family receptors in U-251 and SKMG-3 malignant glioma cell lines and also resulted in significant decreases in FRS2, Akt, and MAPK signaling. However, MPI knockdown did not affect ligand-induced activation or signaling of EGFR or MET RTKs, suggesting that FGFRs are more susceptible to MPI inhibition. The reductions in FGFR signaling were not caused by loss of FGF ligands or receptors, but instead were caused by interference with receptor dimerization. Investigations into the cellular consequences of MPI knockdown showed that cellular programs driven by FGFR signaling, and integral to the clinical progression of malignant glioma, were impaired. In addition to a blockade of cellular migration, MPI knockdown also significantly reduced glioma cell clonogenic survival following ionizing radiation. Therefore our results suggest that targeted inhibition of enzymes required for cell surface receptor glycosylation can be manipulated to produce discrete and limited consequences for critical client glycoproteins expressed by tumor cells. Furthermore, this work identifies MPI as a potential enzymatic target for disrupting cell surface receptor-dependent survival signaling and as a novel approach for therapeutic radiosensitization.


Regulation of the chloroplast H+-ATPase by light. The involvement of Mg2+ ions.
The involvement of Mg2+ ions in the light-dependent regulation of the chloroplast H+-ATPase was studied in both type C and osmotically shocked type A chloroplasts. The following results were obtained. ATPase activity measured under dark, partially uncoupling conditions, following light activation with dithiothreitol and pyocyanine, was markedly enhanced by the presence of Mg2+ in the activation stage. This Mg2+ effect required concentrations in the millimolar range, was rather slow (time range of minutes), reversible, rather unspecific and did not involve changes in the affinity to dithiothreitol. Dark deactivation of the ATPase in the absence of substrate was accelerated by Mg2+. The dark effect of Mg2+ also required millimolar concentrations, but was fast (time range of seconds), highly specific for Mg2+, and did not involve thiol oxidation. The major effect of the absence of Mg2+ from the light-activation stage or of its presence in the dark interval between activation and assay was the induction of an 'abnormal' sensitivity to uncouplers: after these treatments ATP hydrolysis was not stimulated but rather inhibited by NH4Cl or other uncouplers. The pretreatments in the light without Mg2+ or dark with Mg2+ did not affect the membrane proton permeability, nor the proton pumping coupled to ATPase activity. The results are discussed in terms of Mg2+-dependent regulation of the enzyme complex at the level of subunit interaction and its effect on the affinity to protons.


Cefoperazone concentrations in bile and gall bladder wall after intravenous administration.
Cefoperazone concentrations in the common duct bile, gall bladder bile, and gall bladder wall were determined in four patients with cholelithiasis and one patient with carcinoma of the head of the pancreas, all of whom had normal renal functions. Within 65 min after a 1-g intravenous administration, maximum concentrations ranged from 373.4 to 3,100 micrograms/ml in common duct bile and from 6.8 to 680 micrograms/ml in gall bladder bile. Cefoperazone concentrations per gram of the gall bladder wall ranged from 16.8 to 48.0 micrograms.


Autosomal dominant leukodystrophy presenting as Alzheimer's-type dementia.
Autosomal dominant leukodystrophy is a neurodegenerative disorder caused by either point mutations or duplication of the lamin B1 gene on chromosome 5q23. The typical clinical picture consists of autonomic symptoms as well as cerebellar and pyramidal signs. Here we present the case of a 57-year-old female referred to our clinic due to cognitive decline. Neurological examination was significant for cognitive impairment as well as pyramidal and cerebellar signs. Brain MRI displayed diffuse hyperintense lesions in the subcortical white matter, pontine nuclei, brachium pontis and restiform body. The diagnosis was confirmed via genetic testing. Autosomal dominant leukodystrophy should be included in the differential diagnosis of patients presenting with cognitive impairment, motor signs, and leukodystrophy-like images.


The levels of TNF-alpha in cerebrospinal fluid and serum do not correlate with the counts of the white blood cells in acute phase of ischaemic stroke.
Stroke-induced inflammatory reaction, which leads to invasion of leukocytes into the evolving brain infarct, seems to play a key role in the deterioration of brain ischaemic impairment. We have studied CSF and serum levels of tumour necrosis factor-alpha (TNF-alpha), the potent proinflammatory cytokine, and peripheral white blood cells (WBC) counts in patients within the first 24 hours of ischaemic stroke. TNF-alpha levels in CSF and serum as well as WBC counts were increased. There was no correlation between TNF-alpha levels either in CSF and serum or in WBC counts. The results of our study suggest that increased CSF TNF-alpha levels may represent acute intracerebral inflammation in stroke, whereas elevated levels of TNF-alpha in serum may reflect the peripheral proinflammatory state as well as stroke-induced systemic inflammatory reaction. Increased CSF and serum TNF-alpha levels do not correlate with the elevation of WBC counts, suggesting that TNF-alpha overexpression observed in early phase of stroke is not dependent on increased total number of peripheral leukocytes.


[Quantification of optical coherence tomographic angiography images in type 2 diabetic patients].
Objective: To quantify optical coherence tomographic angiography (OCTA) images and to explore potential clinical values of each parameter in diabetic patients. Methods: A case-control and cross-sectional study of diabetic (129 eyes) and healthy (32 eyes) subjects was conducted. 3-mm OCTA scan, fundus photography and best corrected visual acuity measurement were performed. Image-pro plus was used to calculate microvascular and foveal avascular indices in nonsegmented and segmented OCTA images. Intraclass correlation coefficient and relative standard deviation were used to examine the reliability, reproducibility and accuracy. Correlation of each parameter was calculated, and so was the area under the receiver operating characteristic curve. Results: Vessel density (VD) of diabetic patients measured in the nonsegmented retinal layer (RL) and superficial retinal layer (SRL) was 49.146%±6.097%, 44.038%±5.641%, respectively, significantly lower than healthy subjects 52.212%±6.250%, 46.698%±5.417% (t=2.534, 2.405; P=0.012, 0.017), and vessel length (VL) was (19.905±2.285)mm, (17.596±2.149)mm, (14.479±2.091)mm in the three layers, which was significantly shorter than that in the healthy control group (21.037±2.185)mm, (18.739±1.994)mm, (15.343±2.266)mm (t=2.529, 2.731, 2.059; P=0.012, 0.007, 0.041). Compared with non-diabetes, foveal avascular zone (FAZ) in diabetes was (0.441±0.167)mm(2), larger compared to health eyes 0.352±0.109mm(2) (t=-2.831, P=0.005). FAZ demonstrated a negative correlation with VD and VL in RL or SRL(r=-0.227, -0.338; P<0.05) (r=-0.241, -0.332; P<0.05), while best corrected visual acuity showed a negative correlation with VL in each layer (r=-0.225, -0.201, -0.250; P=0.01, 0.022, 0.004), and VD in DRL (r=-0.197, P=0.026). All parameters showed high reproducibility between graders(intraclass correlation coefficient>0.965), while relative standard deviation was greater than 3.049%. AR had the highest area under the receiver operating characteristic curve (0.737), compared with AI (0.724). Conclusions: Our study demonstrates good reliability, reproducibility and accuracy of quantification of OCTA images and reveals changes of VD, VL and FAZ in diabetes, which may occur earlier than vision impairment. AR and AL may have great values in prompting early diabetic retinopathy in diabetic patients. (Chin J Ophthalmol, 2019, 55:273-279).


Epitope mapping of mitochondrial adenine nucleotide translocase-1 in idiopathic dilated cardiomyopathy.
Mitochondrial adenine nucleotide translocase (ANT) is a specific target for the autoantibody response in idiopathic dilated cardiomyopathy (IDCM). We have undertaken an epitope analysis of ANT in IDCM by immunoblot with recombinant GST-ANT fusion proteins and with cellulose-bound decapeptides of human ANT1. Forty-five patients with IDCM, 17 patients with ischemic left ventricle dysfunction (LVD) and 20 controls were analyzed for circulating antibodies against ANT (AAb-ANT). Sixteen of the 45 (36%) IDCM patients showed AAb-ANT above controls. In immunoblots, AAb-ANT detected purified bovine heart ANT and GST-ANT1 and GST-ANT2 isoforms and, less frequently, the GST-ANT3 isoform. A construct lacking the last 146 amino acids did not react with AAb-ANT, indicating that the main epitopes are in the C-terminal 146 amino acids. Immunodetection of decapeptides covering this region shows that AAb-ANT detects at least three epitopes, demonstrating that ANT is the primary target of AAb-ANT. The most significant epitopes belong to the M2 and M3 hydrophilic loops of ANT suggesting that apart from being essential for its activity, these loops are highly immunogenic.


Facilitating robot-assisted training in MS patients with arm paresis: a procedure to individually determine gravity compensation.
Gravity compensation (GC) of the arm is used to facilitate arm movements in conventional therapy as well as in robot-assisted rehabilitation of neurologically impaired persons. Positive effects of GC on Range of Motion (ROM) have been demonstrated in stroke. In Multiple Sclerosis (MS), research regarding this topic is lacking. Since an active participation of the patient is required for effective training, full support of the arm might not be advisable. The present study reports on the development of a procedure to measure actively the individual need for GC and to estimate the influence of GC on ROM during reaching, lifting and transporting in severely affected Persons with MS (PwMS). Ten PwMS were tested with the procedure for determination of GC. Maximal reaching movements were performed in a 3D space in three conditions: No support (NS), with GC by the HapticMaster (GC-HM) and with GC by the HapticMaster combined with a sling suspension system (GC-HMS). For the total sample, significant correlations were found between the amount of GC and clinical tests for upper limb function. In four subjects with severe arm dysfunction it was found that mean ROM is larger in the GC-HMS condition compared to the GC-HM condition, and in the GC-HM condition compared to the NS condition, suggesting positive effects of GC on active ROM in PwMS. Therefore, GC could have a positive effect on arm rehabilitation by enabling the PwMS to actively reach a larger ROM during training.


UTP allosterically regulates transcription by Escherichia coli RNA polymerase from the bacteriophage T7 A1 promoter.
In the case of Escherichia coli RNA polymerase, UTP at elevated concentrations suppresses terminated transcript accumulation during multiple-round transcription from a DNA construct containing the T7 A1 promoter and T(e) terminator. The step that is affected by UTP at elevated concentrations is promoter clearance. In an attempt to understand better the mechanism by which UTP regulates this step, we analyzed the effect of UTP on the formation of pppApU in the presence of only UTP and ATP. At elevated concentrations, UTP is a non-competitive inhibitor with respect to ATP in the formation of pppApU. This indicates that the effect of UTP on the formation of pppApU is mediated through an allosteric site. Moreover, the magnitude of the inhibition of pppApU formation is sufficient to account for the decrease in terminated transcript accumulation at elevated UTP concentrations. Thus, it appears that UTP modulates terminated transcript accumulation during multiple-round transcription from this DNA construct by allosteric regulation of promoter clearance at the point of transcription initiation.


Progress on Exploring the Luminescent Properties of Organic Molecular Aggregates by Multiscale Modeling.
Luminescent molecular aggregates have attracted worldwide attention because of their potential applications in many fields. The luminescent properties of organic aggregates are complicated and highly morphology-dependent, unraveling the intrinsic mechanism behind is urgent. This review summarizes recent works on investigating the structure-property relationships of organic molecular aggregates at different environments, including crystal, cocrystal, amorphous aggregate, and doped systems by multiscale modeling protocol. We aim to explore the influence of intermolecular non-covalent interactions on molecular packing and their photophysical properties and then pave the effective way to design, synthesize, and develop advanced organic luminescent materials.


Time trends in prostate cancer surgery: data from an Internet-based multicentre database.
To report our experience with an Internet-based multicentre database that enables tumour documentation, as well as the collection of quality-related parameters and follow-up data, in surgically treated patients with prostate cancer. The system was used to assess the quality of prostate cancer surgery and to analyze possible time-dependent trends in the quality of care. An Internet-based database system enabled a standardized collection of treatment data and clinical findings from the participating urological centres for the years 2005-2009. An analysis was performed aiming to evaluate relevant patient characteristics (age, pathological tumour stage, preoperative International Index of Erectile Function-5 score), intra-operative parameters (operating time, percentage of nerve-sparing operations, complication rate, transfusion rate, number of resected lymph nodes) and postoperative parameters (hospitalization time, re-operation rate, catheter indwelling time). Mean values were calculated and compared for each annual cohort from 2005 to 2008. The overall survival rate was also calculated for a subgroup of the Berlin patients. A total of 914, 1120, 1434 and 1750 patients submitted to radical prostatectomy in 2005, 2006, 2007 and 2008 were documented in the database. The mean age at the time of surgery remained constant (66 years) during the study period. More than half the patients already had erectile dysfunction before surgery (median International Index of Erectile Function-5 score of 19-20). During the observation period, there was a decrease in the percentage of pT2 tumours (1% in 2005; 64% in 2008) and a slight increase in the percentage of patients with lymph node metastases (8% in 2005; 10% in 2008). No time trend was found for the operating time (142-155 min) or the percentage of nerve-sparing operations (72-78% in patients without erectile dysfunction). A decreasing frequency was observed for the parameters: blood transfusions (1.9% in 2005; 0.5% in 2008), postoperative bleeding (2.6%; 1.2%) and re-operations (4.5%; 2.8%). The mean hospitalization time decreased accordingly (10 days in 2005; 8 days in 2008). The examined subcohort had an overall mortality of 1.5% (median follow-up of 3 years). An Internet-based database system for tumour documentation in patients with prostate cancer enables the collection and assessment of important parameters for the quality of care and outcomes. The participating centres show an improvement in the quality of surgical management, including a reduction of the complication rate.


A murine skeletal adaptation that significantly increases cortical bone mechanical properties. Implications for human skeletal fragility.
Mov13 mice carry a provirus that prevents transcription initiation of the alpha 1(I) collagen gene. Mutant mice homozygous for the null mutation produce no type I collagen and die at mid-gestation, whereas heterozygotes survive to adulthood. Dermal fibroblasts from heterozygous mice produce approximately 50% less type I collagen than normal littermates, and the partial deficiency in collagen production results in a phenotype similar to osteogenesis imperfecta type I (an inherited form of skeletal fragility). In this study, we have identified an adaptation of Mov13 skeletal tissue that significantly improves the bending strength of long bone. The adaptive response occurred over a 2-mo period, during which time a small number of newly proliferated osteogenic cells produced a significant amount of matrix components and thus generated new bone along periosteal surfaces. New bone deposition resulted in a measurable increase in cross-sectional geometry which, in turn, led to a dramatic increase in long bone bending strength.


Caenorhabditis elegans As a Promising Alternative Model for Environmental Chemical Mixture Effect Assessment-A Comparative Study.
A key challenge of mixture toxicity testing is that a multitude of substances with even more combinations need to be tested in a broad dose range. Consequently testing in rodent bioassays, the current gold standard of toxicity testing, is hardly feasible. High-throughput compatible cell culture systems, however, suffer from limitations with respect to toxicokinetics, tissue interactions, and compensatory mechanisms. Therefore, simple organisms like the nematode Caenorhabditis elegans, combining relevant advantages of complex in vivo and fast in vitro assays might prove highly valuable within a testing strategy for mixtures. To investigate the comparability between results obtained with C. elegans and traditional rodent assays, we used five azole fungicides as well investigated model substances. Our findings suggest that azoles act additively in C. elegans which is in line with previous results in rats. Additionally, we show that toxicokinetics are one important factor for the differences in the relative toxicity of the azoles in both species. Importantly, we also demonstrate that in contrast to most rodent in vivo studies, C. elegans assays provide well-defined concentration-response relationships which are a very good basis for the prediction of mixture effects. We conclude that C. elegans may be an appropriate model for mixture toxicity testing at least within a first step to identify and prioritize relevant mixtures for further testing.


Patients' satisfaction and maintenance of fixed partial denture.
The aims of this study were to evaluate patient satisfaction with fixed prosthesis following placement and to assess the oral health and oral hygiene practices awareness by survey questionnaire. One hundred and ninety-two questionnaires were filled by patients wearing fixed prosthesis; the questionnaire included the subjective perception of treatment with fixed prosthesis, patients' perception of clinical outcome, regarding esthetics, masticatory function, speech, and together patient's attitude toward oral hygiene measures. Results showed that 84% of the patients were satisfied with their fixed prosthesis, while only 46.4% of patients were satisfied with the chewing ability. In concern, with esthetic outcome, 80% of patients showed that they were satisfied with the esthetic. The results showed that a high significantly number of patients did not use any form of interdental aids' to clean their fixed prosthesis (94%). The main reason for not using any dental aids' (91.1%) was a lack of post fixed prosthodontics instructions and not been informed by the dentist. High percentages of patients were satisfied with their fixed prosthesis. The most important finding of this study was that majority of patients showed a lack of knowledge regarding post fixed prosthodontics instructions and the significance of maintenance of fixed prosthesis using dental aids'. Of particular concern was the majority of dentists did not pay attention to the post treatment instructions concerning the maintenance of fixed prosthesis.


Management of malignant melanoma of the head and neck.
A total of 91 patients with melanoma of the head and neck treated between 1973 and 1991 were studied prospectively with regard to prognostic features, treatment and outcome. Other than Breslow thickness, the only important prognostic feature was the less aggressive nature of lentigo maligna melanoma. A policy of selective excision margins, 1 cm for impalpable and 2 cm for palpable lesions, was found to be safe, although preliminary biopsy should be used if there is diagnostic uncertainty or where the expected extent of surgery entails a mutilating procedure. Local recurrence rates were not affected by the method of wound closure, which should be determined by the best functional and cosmetic outcome. These results support the trend against prophylactic neck dissection. Such dissection, when indicated for lesions of the face, pinna, anterior scalp and parotid area, should routinely include superficial parotidectomy. Uncontrolled symptomatic loco-regional recurrence is an uncommon complication that may occur despite radical primary surgery. The role of preoperative radiotherapy for high-risk melanoma in this situation warrants investigation.


Computational and spectroscopic studies of organic mixed-valence compounds: where is the charge?
This article discusses recent progress by a combination of spectroscopy and quantum-chemical calculations in classifying and characterizing organic mixed-valence systems in terms of their localized vs. delocalized character. A recently developed quantum-chemical protocol based on non-standard hybrid functionals and continuum solvent models is evaluated for an extended set of mixed-valence bis-triarylamine radical cations, augmented by unsymmetrical neutral triarylamine-perchlorotriphenylmethyl radicals. It turns out that the protocol is able to provide a successful assignment to class II or class III Robin-Day behavior and gives quite accurate ground- and excited-state properties for the radical cations. The limits of the protocol are probed by the anthracene-bridged system 8, where it is suspected that specific solute-solvent interactions are important and not covered by the continuum solvent model. Intervalence charge-transfer excitation energies for the neutral unsymmetrical radicals are systematically overestimated, but dipole moments and a number of other properties are obtained accurately by the protocol.


Exploring PM2.5 Environmental Efficiency and Its Influencing Factors in China.
In China, air pollution, especially fine particulate matter (PM2.5) pollution, has become increasingly serious with the rapid economic growth that has occurred over the past 40 years. This paper aims to introduce PM2.5 pollution as a constraint in the environmental efficiency research framework through the use of panel data covering the Chinese provinces from 2001-2018. PM2.5 environmental efficiency is measured with the slack-based measure (SBM)-Undesirable-variable returns-to-scale (VRS) model, and the results show that the average PM2.5 environmental efficiency score is 0.702, which indicates inefficiency, and is U-shaped over time. The PM2.5 environmental efficiency scores are unbalanced across the eight regions and 30 provinces of China. Additionally, the relationship between PM2.5 environmental efficiency and its influencing factors is examined with a tobit model, and the empirical findings indicate that the relationship between economic development and PM2.5 environmental efficiency is an inverted U, which is the opposite of the traditional environmental Kuznets curve (EKC). In addition, technological innovation, trade dependency, and regional development each have a significantly positive effect on PM2.5 environmental efficiency. However, environmental regulations, the industrial structure, and population density have significantly negative effects on PM2.5 environmental efficiency. Finally, this paper fails to prove that foreign direct investment (FDI) has created a PM2.5 "pollution haven" in China.


The familial support system of Thai elderly: an overview.
"The present study is intended as an overview of the familial system of support for the elderly as it currently exists in Thailand. The focus is on living arrangements and material support of the elderly Thais in relation to their children. Data come from a nationally representative survey of the elderly in private households conducted in 1986....[The authors find that] the most prominent feature of the living arrangements of the Thai elderly and the most crucial aspect of the familial system of support and assistance as it currently exists in Thailand is co-residence with an adult child."


Lymphoplasmacytic lymphoma and IgA nephropathy in a patient with hepatitis C infection.
Hepatitis C virus (HCV) infection is known to be associated with lymphoplasmacytic lymphoma. Reports are available of IgA nephropathy along with HCV infection. We are reporting the case of a 44 years old male who was diagnosed to have Hepatitis C infection with lymphoplasmacytic lymphoma and IgA nephropathy.


Two sequential outbreaks of rotavirus gastroenteritis: evidence for symptomatic and asymptomatic reinfections.
In two sequential outbreaks of rotavirus gastroenteritis that occurred in a kibbutz in southern Israel (the Negev), 32 persons (9% of the population) were ill in the first and 45 (13% of the population) in the second. Excretion of virus, changes in titers of rotavirus-specific serum IgG, or both implicated rotavirus in 72% of the illnesses in outbreak 1 and in 56% of the illnesses in outbreak 2. In both outbreaks the age-specific morbidity rate decreased with increasing age. Half (six of 12) of the children six to 27 months of age who were ill with rotavirus in outbreak 1 were ill with rotavirus again in outbreak 2, whereas two were asymptomatically infected; older children who were ill in outbreak 1 were not ill in outbreak 2. Serotype determination by enzyme-linked immunosorbent assay using monoclonal antibodies to VP7 implicated a serotype 3 virus in outbreak 1 and a serotype 1 virus in outbreak 2.


Effectiveness of Acupuncture Therapies to Manage Musculoskeletal Disorders of the Extremities: A Systematic Review.
Study Design Systematic review. Background Little is known about the effectiveness of acupuncture therapies for musculoskeletal disorders. Objective To assess the effectiveness and safety of acupuncture therapies for musculoskeletal disorders of the extremities. Methods We searched MEDLINE, Embase, CINAHL, PsycINFO, and Cochrane Central Register of Controlled Trials from 1990 to 2015 for randomized controlled trials, cohort studies, and case-control studies. Eligible studies were appraised with Scottish Intercollegiate Guidelines Network criteria. A best-evidence synthesis was performed to synthesize results from included studies with a low risk of bias. A sensitivity analysis was conducted to determine the impact of excluding studies with a high risk of bias. Results The search revealed 5180 articles; 15 were included (10 with a low risk of bias, 5 with a high risk of bias). The studies with a low risk of bias suggested that (1) traditional needle acupuncture was superior to oral steroids (1 RCT, n = 77) and may be superior to vitamin B1/B6 supplements (1 RCT, n = 64) for carpal tunnel syndrome (CTS), and was superior to exercise for Achilles tendinopathy (1 RCT, n = 64). Traditional needle acupuncture did not provide important benefit over placebo for upper extremity pain (1 RCT, n = 128), or no intervention for patellofemoral pain (1 RCT, n = 75), and was inconclusive for shoulder pain (2 RCTs, n = 849), suggesting no important benefit; (2) electroacupuncture may be superior to placebo for shoulder injuries (1 RCT, n = 130) and may not be superior to night splinting for persistent CTS (1 RCT, n = 78); and (3) dry needling may be superior to placebo for plantar fasciitis (1 RCT, n = 84). Sensitivity analysis suggests that including studies with a high risk of bias might have impacted the evidence synthesis in support of managing shoulder pain with traditional needle acupuncture, and that would suggest traditional needle acupuncture may be effective for lateral epicondylitis and piriformis syndrome. Conclusion Evidence for the effectiveness of acupuncture for musculoskeletal disorders of the extremities was inconsistent. Traditional needle acupuncture may be beneficial for CTS and Achilles tendinopathy, but not for nonspecific upper extremity pain and patellofemoral syndrome. Electroacupuncture may be effective for shoulder injuries and may show similar effectiveness to that of night wrist splinting for CTS. The effectiveness of dry needling for plantar fasciitis is equivocal. Level of Evidence Therapy, 1a-. J Orthop Sports Phys Ther 2016;46(6):409-429. Epub 26 Apr 2016. doi:10.2519/jospt.2016.6270.


Targeting of circulating Th17 cells by β-D-mannuronic acid (M2000) as a novel medication in patients with rheumatoid arthritis.
This study aimed at investigating the inhibitory effect of β-D-mannuronic acid (M2000) on the Th17 circulating levels and IL-17 a related cytokine in rheumatoid arthritis (RA) patients. The study included 27 patients with RA who had failed response to treatment. All patients were treated orally by M2000 at a dose of 500 mg twice daily for 12 weeks (Clinical trial identifier: IRCT2014011213739N2). The patients based on anti-tumor necrosis factor alpha (TNFα) blocker treatment were classified into two groups (conventional group and etanercept group). They were then allowed to continue their treatment excluding non-steroidal anti-inflammatory drugs (NSAIDs). The frequency of circulating Th17 cells and IL-17 serum level were determined before and 12 weeks after M2000 therapy and were compared to the healthy controls by using flow cytometry analysis and ELISA method, respectively. At baseline, higher circulating Th17 and IL-17 serum levels were significantly observed in both groups of RA patients than in the healthy controls (all P < 0.001). The frequency of Th17 cells significantly decreased in the conventional group as well as in the etanercept group after M2000 therapy but the level of reduction was higher in the conventional group compared to the etanercept group (P < 0.03 and P < 0.04, respectively). The IL-17 serum level significantly decreased in both groups after M2000 therapy (P < 0.01 and P < 0.02, respectively). Furthermore, the frequency of Th17 cells was positively correlated with Disease Activity Score (DAS28) (r = 0.34, P = 0.02). M2000 shows the inhibitory effect on the frequency of circulating Th17 cells as well as in the production of IL-17 in RA patients.