Nucleotide excision repair and chromatin remodeling.
The organization of DNA within eukaryotic cell nuclei poses special problems and opportunities for the cell. For example, assembly of DNA into chromatin is thought to be a principle mechanism by which adventitious general transcription is repressed. However, access to genomic DNA for events such as DNA repair must be facilitated by energy-intensive processes that either directly alter chromatin structure or impart post-translational modifications, leading to increased DNA accessibility. The assembly of DNA into chromatin affects both the incidence of damage to DNA and repair of that damage. Correction of most damage to DNA caused by UV irradiation occurs via the nucleotide excision repair (NER) process. NER requires extensive involvement of large multiprotein complexes with relatively large stretches of DNA. Here, we review recent evidence suggesting that at least some steps of NER require ATP-dependent chromatin remodeling activities while perhaps others do not.


Short communication: radio frequency dielectric heating of nonfat dry milk affects solubility and whey protein nitrogen index.
The US infant formula market is estimated at over $3.5 billion, of which 75% are dairy-based formulas. Dried dairy powders pose a significant food safety risk, with Cronobacter sakazakii and Salmonella spp. being pathogens of particular concern. Radio frequency dielectric heating (RFDH) can provide rapid, uniform heat treatment of dry powders; thus, it potentially may be used as a postprocess lethality treatment for nonfat dry milk (NDM) or powdered infant formula. Because RFDH is a heat treatment, the functionality of the NDM may be altered and should be evaluated. High heat- and low heat-NDM were RFDH processed at temperatures ranging from 75 to 90°C for 5 to 125 min. Products were then assessed for whey protein nitrogen index (WPNI), solubility, and color. In low heat-NDM, RFDH decreased WPNI and solubility if the process was done at ≥ 80°C; however, in high heat-NDM, RFDH had a greater effect on solubility than WPNI and some color properties were altered. Further investigation of RFDH is merited to validate its application as a pathogen control process for NDM across processing parameters that result in acceptable functional properties for infant formula and other food products containing NDM.


Irradiation increases the interactions of platelets with the endothelium in vivo: analysis by intravital microscopy.
Adhesion of platelets to the endothelium is believed to be a major factor contributing to thrombosis and vascular occlusion after radiotherapy or endovascular irradiation. In the present study, platelet-endothelium interactions were analyzed in vivo by intravital microscopy in mesenteric venules of mice according to three parameters: (1) platelet rolling, (2) platelet adhesion, and (3) the presence of platelet clusters. A 10-Gy total-body irradiation of mice resulted in an increase in the frequency of appearance of these three types of platelet-endothelium interactions in postcapillary venules 6 and 24 h after exposure, whereas only minor alterations were seen in large venules. In addition, the duration of platelet adhesion was increased 24 h after irradiation in both postcapillary and large venules. However, P-selectin was not up-regulated on the platelet membrane and platelet-leukocytes were not seen rolling together, suggesting that changes in platelet-endothelial cell interaction result from endothelial cell activation rather than platelet activation. Our data suggest that irradiation transforms resting endothelial cells to a pro-adhesive surface for platelets, which could ultimately lead to thrombosis.


Adapting radiotherapy to hypoxic tumours.
In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO(2)-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO(2)-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO(2) Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO(2) values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields and step-and-shoot intensity levels). Simulated random and systematic errors in the pO(2)-related images reduced the TCP for the non-uniform dose prescription. In conclusion, improved tumour control of hypoxic tumours by dose redistribution may be expected following hypoxia imaging, tumour control predictions, inverse treatment planning and IMRT.


Accuracy of nodal staging is influenced by sidedness in colon cancer.
Adequate lymph node (LN) sampling is critical for accurate nodal staging in colon cancer (CC), particularly for T3N0 disease as current guidelines recommend considering adjuvant chemotherapy when less than 12 LNs are examined. The impact of sidedness on nodal staging accuracy in patients with T3N0 disease has not been previously studied. Patients with pathologic T3 CC were identified from a prospective multicenter international trial of ultrastaging in CC. The probability of true nodal negativity (TNN) based on the number of LN examined was calculated for right and left CC. These results were then validated in a cohort of patients with similar inclusion criteria selected from the National Cancer Database (NCDB) between 2006 and 2014. Three hundred and seventy patients met the inclusion criteria in the trial cohort; 48% were LN-negative. Of 153,945 patients in the NCDB, 57% were LN-negative. The probability of TNN when 12 LNs were examined was 68% for right and 64% for left CC in the trial cohort and 77% and 72% in the NCDB. The number of LNs needed to achieve any given probability of TNN was significantly different between right and left CC in both the trial (P<0.001) and the NCDB (P<0.001). In both a prospective multicenter trial and the NCDB, sidedness influences the number of LNs needed to predict nodal negativity in CC. Current guidelines regarding the minimum number of LNs needed to accurately stage patients with T3N0 CC may need to be re-evaluated by taking into consideration the tumor sidedness.


Development of sucking in term infants from birth to four hours postbirth.
The development of sucking response was investigated in 30 clinically normal infants from 1 or 5 minutes postbirth until their first feeding 4 hours later. Maximum sucking pressures were measured with a research nipple attached to a portable electronic suckometer. Mean suction (negative pressure) began at 5 Torr at birth, peaked at 103 Torr at 90 minutes, and decreased thereafter to 65 Torr at 4 hours. Expression (positive pressure) began at 12 Torr, rose to 29, and decreased to 25. Mean expression pressures correlated with feeding scale scores, r = +.44(24); p less than .025, but suction pressures did not, r = +.26(24); p less than .1. Normative data were gathered on 10 additional stabilized newborns who had been fed twice successfully. Suction pressures were 96 Torr on Day 1, and 103 Torr on Day 2; expression pressures were 25 and 24 Torr, respectively. These pressures approximate those recorded in newborns between 1 and 2 hours postbirth.


G protein subunit α q regulates gastric cancer growth via the p53/p21 and MEK/ERK pathways.
Genetic alterations in G protein subunit α q (GNAQ) have been reported in numerous types of human cancer. However, the role of GNAQ in human gastric cancer (GC) has not been explored. In the present study, we found that GNAQ was highly expressed in GC patient samples and GNAQ expression was related to patient age, GC differentiation status and adjuvant therapy, as determined by immunohistochemical assay. Lentivirus delivery of short hairpin RNA (shRNA) targeting GNAQ was used to explore the function of GNAQ in GC cells. Silencing of GNAQ markedly suppressed proliferation and colony formation in GC cells, and arrested the cell cycle at the S phase. Mechanistic analysis revealed that knockdown of GNAQ significantly increased the expression of p53 and p21, and decreased cyclin A and p-CDK2 protein expression. Moreover, the phosphorylation of ERK and MEK was also decreased after knockdown of GNAQ as determined by western blotting assay. Overall, our results suggest that GNAQ plays a critical role in regulating GC cell growth and survival via canonical oncogenic signaling pathways including MAPK and p53, and therefore serves as a promising new therapeutic target in GC.


The effects of concomitant administration of theophylline and toborinone on the pharmacokinetics of both compounds in poor and extensive metabolizers via CYP2D6.
This study investigated the effects of the concomitant administration of theophylline and toborinone on the pharmacokinetics of both compounds in poor and extensive metabolizers via CYP2D6. In period 1, a single dose of 3.5 mg/kg theophylline was administered orally. In period 2, a single dose of 1.0 microg/kg/min toborinone was infused over 6 hours. In period 3, 3.5 mg/kg theophylline was coadministered with 1.0 microg/kg/min toborinone. Serial blood and pooled urine samples were collected before and after toborinone administration for the quantification of toborinone and its metabolites in plasma and urine. Serial blood samples were collected before and after theophylline administration for the quantification of theophylline and its metabolites in plasma. No significant differences were observed in toborinone pharmacokinetics between poor and extensive metabolizers via CYP2D6. Toborinone coadministration with theophylline did not result in a substantive effect on the disposition of theophylline and vice versa.


Distinct anisotropy and a high power factor in highly textured TiS2 ceramics via mechanical exfoliation.
Polycrystalline bulk of TiS2 with a remarkable enhancement of the texture degree was obtained by densifying powders refined by a liquid-based mechanical exfoliation process. As compared to the pristine TiS2, the in-(a-b)-plane mobility in the exfoliation sample increased from 5.9 to 9.8 cm2 V-1 s-1 with an almost unaffected carrier concentration, in spite of the increased scattering due to grain boundaries. As a result, a tremendously high power factor of up to 16 μW cm-1 K-2 at 673 K was achieved, which is 60% higher than that of the pristine TiS2 and is the highest for bulk TiS2 at high temperatures.


Time course of visuospatial neglect early after stroke: a longitudinal cohort study.
The aim of the current study was to investigate recovery of visuospatial neglect during the first year after stroke. Visuospatial neglect was measured using two frequently and widely used tests: the letter cancellation test (LCT) and the line bisection test (LBT). This was a prospective cohort study of 101 stroke patients. Of these 101 patients, 51 patients showed visuospatial neglect. All time-dependent measures were taken weekly, starting from within 14 days after stroke onset. From week 10-20 biweekly measurements were obtained. Follow-up measurements were performed at weeks 26, 38, and finally 52. For the present study, number of misses in the LCT, split on contralesional versus ipsilesional side, as well as the deviation from the actual midpoint in mm in the LBT were used. The longitudinal relationship of (bi)weekly time on improvement in LBT and LCT were investigated using random coefficient analysis and joinpoint analyses. Results indicated that progress of time is an independent covariate that reflects neurological recovery of visuospatial neglect. Additionally, trend changes were obtained in between 12 and 14 weeks post-stroke with respect to the neglected side. This is the first prospective cohort study in which the time course of neglect is investigated by using intensive serial measurements in the early months post-stroke.


Seed maturity differentially mediates metabolic responses in black soybean.
The soybean seed is placed in the middle of the morphological and developmental alterations, such as changes in seed size, weight, and colour, and alteration of the composition and contents of metabolites during maturation. In this study, we used black soybean seeds to investigate the effect of maturity on metabolite levels at different maturity stages. Seeds were sorted into five maturity categories, from M1 to M5, based on seed size and external pigmentation. Maturity stages M1, M3, and M5 are equivalent to R6, R7, and R8 on the soybean reproductive growth stage scale, indicating full seed, beginning maturity, and full maturity, respectively. As seed maturation progressed, the seed size decreased and the water soluble extract changed, indicating that a change of seed pigmentation occurred. At the same time, numerous metabolites responded differentially to seed maturation. The partial least squares (PLS) scores plot indicated that the metabolic alteration during maturation was clearly visible. Furthermore, isoflavones were highly associated with seed maturity on the PLS loading plot while fatty acids, glucose, fructose, and sucrose were less linked with seed maturity, indicating that those metabolites responded less to seed maturation. Overall, the results indicate that each category of metabolites is mediated differentially during maturation in black soybean seeds.


Simultaneous detection of multiple point mutations using fluorescence-coupled competitive primer extension.
We report the development of a method for the simultaneous genotyping of several distinct nucleotide positions by means of fluorescence-coupled competitive primer extension. We demonstrate the application of this method for the simultaneous detection of three point mutations in the human mitochondrial genome, at nucleotide positions 3460, 11778 and 14484, which account for about 90% of cases with Leber's hereditary optic neuropathy. mtDNA fragments encompassing these nucleotide positions are initially amplified in a multiplex PCR assay. Genotyping is then carried out by a simultaneous primer extension assay using wild-type-specific (FAM-labeled) and mutant-specific (JOE-labeled) oligonucleotides. Primer extension products are separated on a 6% polyacrylamide/8 M urea gel on a fluorescence DNA sequencer. Patients' genotypes can be derived from the peak color of the different-sized extension products. As little as 10% mutant DNA can be detected in heteroplasmic mixtures of wild-type and mutant mtDNA, a degree that is sufficient for routine clinical practice.


RF absorption and ion heating in helicon sources.
Experimental data are presented that are consistent with the hypothesis that anomalous rf absorption in helicon sources is due to electron scattering arising from parametrically driven ion-acoustic waves downstream from the antenna. Also presented are ion temperature measurements demonstrating anisotropic heating (T( perpendicular)>T(parallel)) at the edge of the discharge. The most likely explanation is ion-Landau damping of electrostatic slow waves at a local lower-hybrid-frequency resonance.


Evaluation of effect of selected trace elements on dynamics of sperm DNA fragmentation.
Lead and cadmium can lead to negative effects on sperm chromatin DNA integrity. Copper, zinc and selenium are essential components of many enzymes which are important for reproduction. The aim of this research was to evaluate the influence of lead, cadmium, zinc, copper and selenium on the dynamics of semen DNA fragmentation. The present study concerned 85 fertile and 131 infertile men aged 25-35. DNA fragmentation in the samples was determined after 3 h, 6 h and 12 h. The Pb, Cd, Cu, Zn, and Se measurements were performed by the electrothermal-atomic absorption spectrometry method. We found that sperm DNA fragmentation was a dynamic process which was intensified with an increase in the level of lead in seminal plasma. The levels of lead and cadmium were higher in seminal plasma of infertile men, compared to fertile men. The levels of zinc, copper and selenium in seminal plasma were higher in men with proven fertility, compared to infertile men, and did not exert a significant effect on the dynamics of sperm DNA fragmentation. The level of cadmium had no significant effect on intensification of sperm DNA fragmentation in time. Reports in the literature which concern the effect of trace elements on human reproduction are equivocal. The present study confirmed an unfavourable effect, especially that of lead, on the dynamics of sperm DNA fragmentation; however, these studies need to be expanded and continued in the future.


[Value of mechanographic studies in neuromuscular function diagnosis].
Mechanographic examinations have hitherto played only a minor role in general clinical neuromuscular functional diagnostics. The purpose of this contribution is, therefore, to present an appropriate recording apparatus (W. Zett , 1969), to report on the values that can be considered normal and to outline the diagnostic value of the method using clinical applications as examples. Special value is attached to simultaneous recording of the EMG and the mechanograph because this method permits differentiated conclusions to be drawn regarding disturbances in muscular activity, the electromechanical coupling and the actual process of contraction. The method is also important for pharmacological investigations and should be used principally in connection with musclepathology for objectifying the effects of medication.


[Efficacy of early combined high-dose steroid + PGE1 treatment for sudden deafness].
The efficacy of combined high-dose steroid and PGE1 treatment initiated immediately after the onset of sudden deafness was analyzed with the outcome of 174 patients begun on treatment within 7 days of the onset of sudden deafness. Four potential prognostic factors (days from onset to treatment, age, initial hearing level, presence of vertigo) and hearing outcome were examined with a multiple logistic regression analysis. Days from onset to treatment and age significantly correlated with hearing improvement. The efficacy of the treatment of patients begun on treatment within 3 days of the onset was significantly better than that of patients on treatment 4-7 days after the onset (p < 0.001). In the examination of patients younger than 50 years, the efficacy of the treatment of patients begun on treatment within 3 days of the onset didn't differ significantly from that of patients on treatment 4-7 days after the onset. On the other hand, in the examination of patients aged 50 years and older, the efficacy of the treatment of patients begun on treatment within 3 days of the onset was significantly better than that of patients on treatment 4-7 days after the onset (p < 0.001). These results suggest that significant efficacy may be expected from the combined high-dose steroid + PGE1 treatment, if its use is started within 7 days of the onset of sudden deafness, and started within 3 days of the onset of sudden deafness in patients 50 years old and older.


In vitro induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 expression in keratinocytes by boron and manganese.
Matrix metalloproteinase (MMP)-2 and MMP-9 are involved in keratinocyte migration and granulation tissue remodeling during wound healing. Thermal water cures are sometimes proposed as complementary treatment for accelerating healing of wounds resulting from burns and/or surgery, but their mechanisms of action remain unknown. Some thermal waters are rich in trace elements such as boron and manganese. Interestingly, clinical studies have shown the beneficial effects of trace elements such as boron and manganese for human wound healing. To try to specify the role of trace elements in cutaneous healing, the present study investigated the effects of these trace elements on the production of MMP-2 and MMP-9 by normal human keratinocytes cultured in vitro. Immunohistochemistry and Western blot showed that intracellular MMP-9 expression in keratinocytes was induced when incubated for 6 h with boron at 10 micro g/ml or manganese at 0.2 micro g/ml. Moreover, gelatin zymography on keratinocyte supernatants showed an increase of gelatinase secretion after 24 h of incubation of keratinocytes with boron or manganese, regardless of concentration. Gelatinase secretion was not associated with keratinocyte proliferation induced by trace elements. Thus, our results suggest that boron and manganese could play a role in the clinical efficiency of thermal water on wound healing.


Kinetics and mechanism of formation of the platinum-thallium bond: the [(CN)(5)Pt-Tl(CN)(3)](3)(-) complex.
Formation kinetics of the metal-metal bonded [(CN)(5)PtTl(CN)(3)](3)(-) complex from Pt(CN)(4)(2)(-) and Tl(CN)(4)(-) has been studied in the pH range of 5-10, using standard mix-and-measure spectrophotometric technique at pH 5-8 and stopped-flow method at pH > 8. The overall order of the reaction, Pt(CN)(4)(2)(-) + Tl(CN)(4)(-) right harpoon over left harpoon [(CN)(5)PtTl(CN)(3)](3)(-), is 2 in the slightly acidic region and 3 in the alkaline region, which means first order for the two reactants in both cases and also for CN(-) at high pH. The two-term rate law corresponds to two different pathways via the Tl(CN)(3) and Tl(CN)(4)(-) complexes in acidic and alkaline solution, respectively. The two complexes are in fast equilibrium, and their actual concentration ratio is controlled by the concentration of free cyanide ion. The following expression was derived for the pseudo-first-order rate constant of the overall reaction: k(obs) = (k(1)(a)[Tl(CN)(4)(-) + (k(1)(a)/K(f)))(1/(1 + K(p)[H(+)]))[CN(-)](free) + k(1)(b)[Tl(CN)(4)(-)] + (k(1)(b)/K(f)), where k(1)(a) and k(1)(b) are the forward rate constants for the alkaline and slightly acidic paths, K(f) is the stability constant of [(CN)(5)PtTl(CN)(3)](3)(-), and K(p) is the protonation constant of cyanide ion. k(1)(a) = 143 +/- 13 M(-)(2) s(-)(1), k(1)(b) = 0.056 +/- 0.004 M(-)(1) s(-)(1), K(f) = 250 +/- 54 M(-)(1), and log K(p) = 9.15 +/- 0.05 (I = 1 M NaClO(4), T = 298 K). Two possible mechanisms were postulated for the overall reaction in both pH regions, which include a metal-metal bond formation step and the coordination of the axial cyanide ion to the platinum center. The alternative mechanisms are different in the sequence of these steps.


An exploration of the 6Cs as a set of values for nursing practice.
In 2012, after several high-profile cases of poor quality care in England and concerns about a lack of compassion and a need to refocus on values, the Department of Health in England published a new strategy for nursing, midwifery and care staff: Compassion in Practice. The strategy included the 6Cs (care, compassion, courage, communication, competence and commitment) and in the follow-on framework, produced by NHS England in 2016, the 6Cs were included again. This article explains the background to the 6Cs and highlights the other values frameworks that nurses and midwives must work within too. Nursing theorists have studied caring extensively and the earlier set of 6Cs, produced by a Canadian nurse Sister Simone Roach, is explained in the article. The meaning of the DH's 6Cs is then explored in detail with reference to previous research and nursing theory.


HMTase Inhibitors as a Potential Epigenetic-Based Therapeutic Approach for Friedreich's Ataxia.
Friedreich's ataxia (FRDA) is a progressive neurodegenerative disorder caused by a homozygous GAA repeat expansion mutation in intron 1 of the frataxin gene (FXN), which instigates reduced transcription. As a consequence, reduced levels of frataxin protein lead to mitochondrial iron accumulation, oxidative stress, and ultimately cell death; particularly in dorsal root ganglia (DRG) sensory neurons and the dentate nucleus of the cerebellum. In addition to neurological disability, FRDA is associated with cardiomyopathy, diabetes mellitus, and skeletal deformities. Currently there is no effective treatment for FRDA and patients die prematurely. Recent findings suggest that abnormal GAA expansion plays a role in histone modification, subjecting the FXN gene to heterochromatin silencing. Therefore, as an epigenetic-based therapy, we investigated the efficacy and tolerability of two histone methyltransferase (HMTase) inhibitor compounds, BIX0194 (G9a-inhibitor) and GSK126 (EZH2-inhibitor), to specifically target and reduce H3K9me2/3 and H3K27me3 levels, respectively, in FRDA fibroblasts. We show that a combination treatment of BIX0194 and GSK126, significantly increased FXN gene expression levels and reduced the repressive histone marks. However, no increase in frataxin protein levels was observed. Nevertheless, our results are still promising and may encourage to investigate HMTase inhibitors with other synergistic epigenetic-based therapies for further preliminary studies.


Enzymatic and chemical synthesis of 3-dehydroecdysterone, a metabolite of the moulting hormone of insects.
3-Dehydroecdysterone, a less polar metabolite of ecdysterone, was synthesized in vitro using either an enzyme (edcysone oxidase, EC 22.214.171.124) or the chemical catalyst platinum. 3-Dehydroecdysterone was purified and characterized by its chromatographic behaviour, its staining properties and by UV, IR, NMR and mass spectroscopy. The compound is 1/15 as active as ecdysone in the Calliphora moulting hormone bioassay. Its biological relevance is discussed.


22 GW peak-power fiber chirped-pulse-amplification system.
In this Letter, we report on a femtosecond fiber chirped-pulse-amplification system based on the coherent combination of the output of four ytterbium-doped large-pitch fibers. Each single channel delivers a peak power of about 6.2 GW after compression. The combined system emits 200 fs long pulses with a pulse energy of 5.7 mJ at 230 W of average power together with an excellent beam quality. The resulting peak power is 22 GW, which to the best of our knowledge is the highest value directly emitted from any fiber-based laser system.


Correlation of prolactin serum concentrations with clinical activity and remission in patients with systemic lupus erythematosus. Effect of conventional treatment.
The role of prolactin (PRL) in the pathogenesis of systemic lupus erythematosus (SLE) is controversial. The effect of conventional treatment (steroids, antimalarials, immunosuppressor drugs) on PRL concentrations is unclear. We investigated correlation of PRL levels with lupus activity in patients at entry and after 6 months of conventional treatment. We studied 43 female patients with active SLE, who were divided in 2 groups; Group 1: 16 patients with minor organ involvement (cutaneous and articular involvement), and Group 2: 27 patients with major organ involvement (glomerulonephritis). Controls were 36 healthy individuals. PRL levels were determined by an immunoradiometric assay at entry and after 6 months of treatment. PRL levels were correlated with SLE Disease Activity Index (SLEDAI) score. Mild hyperprolactinemia (HPRL, 20-40 ng/ml) was found in 30/43 (69.7%) SLE patients. After 6 months of treatment a reduction in PRL levels was found in both groups: Group 1: 24.3 +/- 10.8 to 16.96 +/- 10.87 ng/ml (p < 0.001); and Group 2: 23.6 +/- 5.7 to 12.07 +/- 11.13 ng/ml (p < 0.001). The SLEDAI score also decreased after treatment: Group 1: 16.5 +/- 5.9 to 2.1 +/- 1.3 (p < 0.001); Group 2: 16.8 +/- 5.4 to 1.6 +/- 1.4 (p < 0.001). At entry and after treatment, a significant correlation between PRL levels and SLEDAI score was found in all patients (r = 0.4946, p = 0.0007, and r = 0.9086, p = 0.0001, respectively). HPRL was associated with SLE disease activity. Conventional immunosuppressive therapy decreased PRL levels in direct correlation with decreased SLE activity. This finding emphasizes that PRL may play a role in the pathogenesis and clinical expression of SLE.


Relevance of clinical and autoantibody profiles in systemic sclerosis among Thais.
Autoantibody profiles in systemic sclerosis (SSc) and their relative clinical association vary between studies. The rate for being anti-topoisomerase-I (ATA) positive and the association with diffuse cutaneous the SSc subset (dcSSc) is higher among Thais than among Caucasians. The objective was to evaluate the relevance of clinical presentation, namely being positive for one or more autoantibodies among Thai SSc patients. A retrospective, cohort study was performed among SSc patients over 18 years of age at Srinagarind Hospital, Khon Kaen University, Thailand, during January 2006 to December 2013. Autoantibodies comprising 13 SSc-specific antigens were evaluated using the EUROIMMUN AG (Lübeck, Germany) in order to define their clinical association(s). Two hundred and eighty-five scleroderma patients (200 female; 85 male) were included. The majority (66.7%) were dcSSc subset. ATA was the most common antibody profile in our patients (231 cases; 81.1%), followed by anti-Ro 52 (87 cases; 30.5%). Eleven of our patients (3.9%) were negative for all antibody profiles and 44 cases (15.4%) were negative for ATA and anti-centromere antibody (anti-CENP). Almost 40% (112 cases) were positive for at least two autoantibodies. There was an association between the presence of ATA and hand deformity (odds ratio [OR] 3.94; 95% CI 1.12-13.84), anti-CENP and hand deformity (OR 0.20; 95% CI 0.02-0.90), anti-Ku and scleroderma-polymyositis overlap syndrome (OR 6.58; 95% CI 2.16-19.39) and the absence of both ATA and anti-CENP with female sex (OR 2.90; 95% CI 1.12-7.51), limited cutaneous SSc subset (OR 2.70; 95% CI 1.30-5.55) and scleroderma-polymyositis overlap syndrome (OR 2.53; 95% CI 1.04-6.16). Neither ATA nor anti-CENP were associated with the SSc subset. ATA and anti-CENP were not helpful in differentiating the SSc subset in Thai SSc patients, albeit they were good for predicting hand function. Coexisting ATA and anti-CENP negativity were associated with less extensive skin tightness and SSc overlap syndrome.


Primary, Enduring Negative Symptoms: An Update on Research.
We previously proposed that people with schizophrenia who have primary, enduring negative symptoms have a disease-deficit schizophrenia (DS)-that is separate from that affecting people with schizophrenia without these features. Additional evidence consistent with the separate disease hypothesis has accumulated in recent years. White matter changes may be widespread in deficit compared to nondeficit patients and may relate to problems in early brain migration. These 2 patient groups also appear to differ on metabolic measures prior to antipsychotic treatment. Studies of reward and defeatist beliefs provide the basis for future treatment trials. The 2 factors or groups within negative symptoms broadly defined (both primary and secondary) have also been found in DS, and recent evidence suggests these 2 symptom groups have different correlates and reflect the existence of 2 groups with in DS. Negative symptoms are found in disorders other than schizophrenia, and excess summer birth, a deficit risk factor, has been found in a non-patient group with deficit-like features. It may be useful in future research to determine whether findings in DS extend to patients with other neuropsychiatric disorders who also have negative symptoms.


Improving general practitioners' interviewing skills in managing patients with depression and anxiety: a randomized controlled clinical trial.
Studies regarding the effectiveness of CME programmes on physicians' behaviour and communication skills showed inconsistent results. Few randomized controlled trials have been conducted in Asia. To evaluate the effectiveness of a 4 2-hour education programme to improve GP interviewing behaviours, 16 general practitioners were randomized to the intervention and control groups, respectively. Physicians assigned to the intervention group received 8 hours of training emphasizing interviewing behaviours in the diagnosis and treatment of depression and generalized anxiety disorders (GDS). Those assigned to the control group did not receive any training until the completion of study. Standardized patients were used to evaluate the performance of physicians. Two consultations before and after enrolling in the education programme were videotaped. Independent evaluations of consultations were made by a trained clinical psychologist and a social worker blinded to the study status of physicians. The rating schedule for the videotapes was based on the tasks listed on the Calgary Cambridge Observation Guide. The change of score between the intervention and control physicians was significantly different in 'active listening and facilitating patients' response' (p = 0.011) with the intervention physicians having improvement of score. For 'non-verbals', 'understanding patient's perspective' and 'negotiating mutual plan of action', positive change of score in the intervention physicians were seen when compared to that of the control, although the difference did not reach statistical significance (p = 0.06, p = 0.05, p = 0.06, respectively). However, for 'opening', 'structuring the consultation', 'explanation and planning' and 'closure', there were no statistical significant differences between control and intervention group. Our results showed that only certain communication skills, such as active listening and facilitating patient's response, can be taught in the management of depression and generalized anxiety disorder (GAD) in Chinese primary care physicians.


Endothelial dysfunction and oxidant status in pediatric patients with hemoglobin E-beta thalassemia.
Thalassemia major is characterized by anemia, iron overload, and oxidant damage to major organs, especially the cardiovascular system. Oxidative stress is ultimately involved in endothelial dysfunction, a condition which is evident in adults suffering from various cardiovascular diseases including thalassemia. We investigated endothelial function in pediatric patients with hemoglobin E-beta thalassemia (HbE-beta thalassemia), who have been exposed to excessive iron and oxidative stress for much shorter period than adults with thalassemia. We recruited 22 blood transfusion-dependent HbE-beta thalassemia patients aged 11.8 +/- 2.9 years and 20 healthy controls aged 12.1 +/- 1.7 years. Oxidant status was determined, and endothelial function was assessed by a forearm blood flow technique. Oxidative stress was increased in the thalassemic patients, as blood glutathione (GSH) and ratios of reduced GSH to GSH disulfide were markedly reduced, and superoxide anion released from blood cells was highly elevated. Oxidative stress response, assessed by gamma-glutamylcysteine ligase activity, was increased approximately twofold in thalassemia patients. Basal forearm blood flow was significantly increased in patients compared with controls (7.3 +/- 1.8 vs 6.0 +/- 1.8 ml/100 ml tissue/min, respectively), whereas forearm vasodilatory response to reactive hyperemia was depressed by 50% in patients compared with controls. Endothelial function is impaired in young thalassemia patients, and impaired endothelial function is associated with oxidant stress.


3D Printing Ultraflexible Magnetic Actuators via Screw Extrusion Method.
Soft magnetic actuators with programmable structure design and controllable deformation ability based on 3D printing technology have attracted extensive attention. In this paper, a novel 3D printing strategy is developed to manufacture the ultraflexible magnetic actuator, in which the printed material is composed of magnetic particles and thermoplastic rubber materials. Different from the traditional fused deposition printing, this printing strategy introduces screw extrusion technology to the heating components of the printer to overcome the problem of filament buckling in the flexible material. Thus, the tensile modulus of the printed products can be reduced to as low as ≈2 MPa. Based on the above method, biomimetic magnetic actuators of the sucker and the pump are constructed for adhering and releasing object and pumping liquid. The contraction performance of the magnetic actuator is studied via a series of experiments and the magnetic field-induced deformation is analyzed by the multiphysics-based finite element model. This work proves that ultraflexible magnetic actuators fabricated by this 3D printing strategy show broad prospects in the fields of soft robotics and bionics.


Heme oxygenase-1 regulates the major route involved in formation of immune hepatic fibrosis in rats.
Heme oxygenase (HO) plays roles in some liver diseases, but what it does in immune liver fibrosis is rarely reported. We investigated the regulation mechanisms of HO-1 in rat immune liver fibrosis to find routes for intervention. Male Sprague-Dawley rats were randomly divided into control group (N, n = 12), fibrosis group (F, n = 20), cobalt protoporphyrin (CoPP) inducing group (Co, n = 20) and zinc protoporphyrin (ZnPP) inhibiting group (Zn, n = 20). In groups F, Co and Zn, immune liver fibrosis was established with human serum albumin. At the attacked stage, CoPP (5 mg/kg) and ZnPP (5 mg/kg) were intraperitoneally injected in groups Co and Zn, respectively. After establishment of rat models, the numbers of rats reduced to 11, 15, 17 and 12 in groups N, F, Co and Zn respectively, because of death during the process. HO-1 in liver was detected by Western blotting and immunohistochemistry. The indexes of fibrosis were assessed by radioimmunoassay. Concentrations of serum transforming growth factor-β1 (TGF-β1), and tissue inhibitor of metalloproteinses (TIMP-1) were detected using enzyme-linked immunosorbent assay. Hepatic stellate cell (HSC) and proliferation degree of fibrosis were assessed by pathological examination. Data analysis was performed by SPSS 10.0 software. The expression of HO-1 in group F was significantly higher than that in group N, but lower than that in group Co (P < 0.05); while that in group Zn was lower than in group F (P < 0.05), but still higher than that in group N (P < 0.01). Compared with group N, liver functional and liver fibrosis indicators were increased in group F (P < 0.01), while comparing to group F, they were decreased in group Co (P < 0.05) and increased in group Zn (P < 0.05). CoPP reduced the extent of hepatocellular injury and hepatic fibrosis in comparison with group F (P < 0.01), being the opposite effect of ZnPP (P < 0.01). HSC was observed using indirect method and the result showed that the number of HSC in group F increased more than that in groups N and Co, while much less than in group Zn. The concentration of TGF-β1 decreased when HO-1 expressed increasingly (group Co: (3.5 ± 1.0) ng/ml, group F: (7.8 ± 1.3) ng/ml, P < 0.01) and enhanced (group Zn: (9.6 ± 13.6) ng/ml) when HO-1 presented less (P < 0.01). The concentrations of TIMP-1 were (151.1 ± 32.0), (472.0 ± 34.8), (232.3 ± 41.3) and (533.2 ± 37.2) ng/g liver wet weight in groups N, F, Co, and Zn, respectively. It was reduced in group Co (P < 0.01) and increased in group Zn compared with group F (P < 0.05). Inducing HO-1 expression appropriately may lighten hepatic fibrosis, and in contrast, inhibiting it strengthens the lesion. HO-1 interferes with the main ways to form liver fibrosis.


Visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in pre-eclampsia than in healthy pregnancys.
Obesity increases pre-eclampsia (PE) risk. Adipose tissue inflammation may contribute to the clinical syndrome of PE. We compared adipose tissue macrophage infiltration and release of pro-inflammatory adipokines in PE and healthy pregnancy. Subcutaneous and visceral adipose tissue biopsies were collected from healthy (n=13) and PE (n=13) mothers. Basal and lipopolysaccharide (LPS) stimulated adipocyte TNFα, IL-6, CCL-2, and CRP release was measured. Adipose tissue cell densities of activated (cfms+) and total (CD68+) macrophages were determined. In PE only, visceral adipose tissue TNFα release was increased after LPS stimulation (57 [76] versus 81 [97] pg/ml/µg DNA, P=0.030). Basal TNFα release was negatively correlated insulin sensitivity of visceral adipocytes (r = -0.61, P=0.030) in PE. Visceral adipocyte IL-6 release was increased after LPS stimulation in PE only (566 [696] versus 852 [914] pg/ml/µg DNA, P=0.019). Visceral adipocyte CCL-2 basal (67 [61] versus 187 [219] pg/ml/µgDNA, P=0.049) and stimulated (46 [46] versus 224 [271] pg/ml/µg DNA, P=0.003) release was greater than in subcutaneous adipocytes in PE only. In PE, median TNF mRNA expression in visceral adipose tissue was higher than controls (1.94 [1.13-4.14] versus 0.8 [0.00-1.27] TNF/PPIA ratio, P=0.006). In visceral adipose tissue, CSF1R (a marker of activated macrophages) mRNA expression (24.8[11.0] versus 51.0[29.9] CSF1R/PPIA ratio, P=0.011) and activated (cfms+) macrophage count (6.7[2.6] versus 15.2[8.8] % cfms+/adipocyte, P=0.031) were higher in PE than in controls. In conclusion, our study demonstrates dysregulation of inflammatory pathways predominantly in visceral adipose tissue in PE. Inflammation of visceral adipose tissue may mediate many of the adverse metabolic effects associated with PE.


Persistent ischemic stroke disparities despite declining incidence in Mexican Americans.
To determine trends in ischemic stroke incidence among Mexican Americans and non-Hispanic whites. We performed population-based stroke surveillance from January 1, 2000 to December 31, 2010 in Corpus Christi, Texas. Ischemic stroke patients 45 years and older were ascertained from potential sources, and charts were abstracted. Neurologists validated cases based on source documentation blinded to ethnicity and age. Crude and age-, sex-, and ethnicity-adjusted annual incidence was calculated for first ever completed ischemic stroke. Poisson regression models were used to calculate adjusted ischemic stroke rates, rate ratios, and trends. There were 2,604 ischemic strokes in Mexican Americans and 2,042 in non-Hispanic whites. The rate ratios (Mexican American:non-Hispanic white) were 1.94 (95% confidence interval [CI] = 1.67-2.25), 1.50 (95% CI = 1.35-1.67), and 1.00 (95% CI = 0.90-1.11) among those aged 45 to 59, 60 to 74, and 75 years and older, respectively, and 1.34 (95% CI = 1.23-1.46) when adjusted for age. Ischemic stroke incidence declined during the study period by 35.9% (95% CI = 25.9-44.5). The decline was limited to those aged ≥60 years, and happened in both ethnic groups similarly (p > 0.10), implying that the disparities seen in the 45- to 74-year age group persist unabated. Ischemic stroke incidence rates have declined dramatically in the past decade in both ethnic groups for those aged ≥60 years. However, the disparity between Mexican American and non-Hispanic white stroke rates persists in those <75 years of age. Although the decline in stroke is encouraging, additional prevention efforts targeting young Mexican Americans are warranted.


Development and characterization of prototypes for in vitro and in vivo mouse models of ibrutinib-resistant CLL.
Although ibrutinib improves the overall survival of patients with chronic lymphocytic leukemia (CLL), some patients still develop resistance, most commonly through point mutations affecting cysteine residue 481 (C481) in Bruton's tyrosine kinase (BTKC481S and BTKC481R). To enhance our understanding of the biological impact of these mutations, we established cell lines that overexpress wild-type or mutant BTK in in vitro and in vivo models that mimic ibrutinib-sensitive and -resistant CLL. MEC-1 cell lines stably overexpressing wild-type or mutant BTK were generated. All cell lines coexpressed GFP, were CD19+ and CD23+, and overexpressed BTK. Overexpression of wild-type or mutant BTK resulted in increased signaling, as evidenced by the induction of p-BTK, p-PLCγ2, and p-extracellular signal-related kinase (ERK) levels, the latter further augmented upon IgM stimulation. In all cell lines, cell cycle profiles and levels of BTK expression were similar, but the RNA sequencing and reverse-phase protein array results revealed that the molecular transcript and protein profiles were distinct. To mimic aggressive CLL, we created xenograft mouse models by transplanting the generated cell lines into Rag2-/-γc-/- mice. Spleens, livers, bone marrow, and peripheral blood were collected. All mice developed CLL-like disease with systemic involvement (engraftment efficiency, 100%). We observed splenomegaly, accumulation of leukemic cells in the spleen and liver, and macroscopically evident necrosis. CD19+ cells accumulated in the spleen, bone marrow, and peripheral blood. The overall survival duration was slightly lower in mice expressing mutant BTK. Our cell lines and murine models mimicking ibrutinib-resistant CLL will serve as powerful tools to test reversible BTK inhibitors and novel, non-BTK-targeted therapeutics.


Punish the thief-coevolution of defense and cautiousness stabilizes ownership.
Ownership of non-controllable resources usually has to be maintained by costly defense against competitors. Whether defense and thus ownership pays in terms of fitness depends on its effectiveness in preventing theft. We show that if the owners' willingness to defend varies in the population and information about it is available to potential thieves then the ability to react to this information and thus avoid being attacked by the owner is selected for. This can lead to a positive evolutionary feedback between cautiousness in intruders and aggressiveness in owners. This feedback can maintain ownership when the actual direct effectiveness of defense in reducing theft is very low or even absent, effectively turning defense into punishment. We conclude that the deterrence effect of defense in many situations could be stronger than that of prevention and that for many real-world scenarios the purpose of defense of resources might be to punish rather than to drive away intruders. Many animals defend resources against conspecifics. Resource defense can usually only evolve if its costs are paid for by foiling attempts at theft. We show that if potential thieves can detect differences in aggressiveness between owners then cautious intruders and aggressive owners coevolve so that in the end even ineffective defense deters thieves and maintains ownership. This result greatly extends the number of situations in which we expect resource defense to evolve and has the potential to unify the concepts of defense and punishment.


The Bulbocavernosus Reflex in the Differential Diagnosis of Multiple System Atrophy with Predominant Parkinsonism and Parkinson's Disease.
Multiple system atrophy with predominant parkinsonism (MSA-P) is a degenerative disorder that presents with autonomic dysfunction, atypical parkinsonism, and ataxia. Parkinson's disease (PD) is an age-related neurological disorder of the central nervous system. Differentiation between MSA-P and PD is important because treatments, complications, and prognoses differ. The bulbocavernosus reflex (BCR) tests the afferent and efferent signals of the pudendal nerve as well as the sacral cord. In this study, we investigated differences in BCR parameters between MSA-P and PD patients. Thirty-eight MSA-P patients and 32 PD patients were selected to participate in our electrophysiological investigations. The Keypoint EMG/EP system was used to induce the BCR, and latencies and amplitudes were recorded for systematic statistical analyses. Area under the curve of the receiver operating characteristic was used to assess the specificity and sensitivity of the BCR parameters. A BCR was elicited in 76.32% of MSA-P patients and 93.75% of PD patients. The BCR latencies of the MSA-P group were longer than those of the PD group (p < 0.001). In addition, the MSA-P group had a lower BCR amplitude compared to the PD and control groups (p < 0.001). We discovered the difference between MSA-P and PD through BCR latencies and amplitudes. Compared to PD patients, MSA-P patients have longer latencies and lower amplitudes. Therefore, the BCR may be used to discriminate between MSA-P and PD in some cases.


[Multiple tics and Gilles de la Tourette syndrome].
Tic disorders are frequent in childhood, varying from transient motor tics over multiple chronic tic disorders to full-blown Gilles de la Tourette syndrome (GTS). GTS is genetically determined. In affected families, relatives of the patient(s) with GTS may show minor symptoms only. The clinical picture is extremely variable, extending from the well known motor tics over complex compulsive obsessive behavior to purely sensory tics. The optimal treatment today is the use of dopamine antagonists.


Method for assessment of the reporting standard of clinical trials with roentgen contrast media.
A procedure for assessing the methodologic standard of the reports of contrast medium trials is described. Each report was assessed and scored on 11 different items important for evaluating the methodologic strength of a given trial. Although the method was rough, the first experiences indicate that reliable, comparative evaluations can be obtained. The method may be used for improving the reporting standard.


Imipramine treatment of painful diabetic neuropathy.
Twelve patients with severe, painful diabetic neuropathy in the lower extremities were treated with imipramine and placebo in a fixed-dose, double-blind, crossover study of five plus five weeks. Seven patients experienced notable improvement while receiving imipramine and none while receiving placebo. The rating of specific symptoms at the end of each treatment period showed a beneficial effect of imipramine on pain, paresthesia, dysesthesia, numbness, and nocturnal aggravation. The plasma levels of imipramine and its metabolite desipramine were significantly higher in patients who benefited from imipramine treatment.


Coincidental FCoincidental Feeding Artery Aneurysm Presenting during Glioblastoma Surgery: A Case Report and Literature Revieweeding Artery Aneurysm Presenting during Glioblastoma Surgery: A Case Report and Literature Review.
The medical literature reports an association between cerebral neoplasms and aneurysm formation. Some related aneurysms are detected during preoperative screening, whereas others are detected during or after surgery. We report a patient with de novo cerebral feeding artery aneurysm that we managed during glioblastoma surgery. We present a brief review of the literature on the coexistence of brain tumors, particularly that related to high-grade glioma and aneurysms. The literature discusses several mechanisms underlying tumor formation accompanied by aneurysm formation. Some classifications were also proposed for grouping such aneurysms. We question the necessity of the routine use of vascular imaging for patients with glioblastoma.


[Application value of corneal hysteresis in diagnosis and treatment of glaucoma].
Glaucoma is the first leading cause of irreversible blindness world widely, but the pathogenesis was still unclear. The collagen fibers from cornea and sclera connect to each other and both of them have similar extracellular matrix components. The biomechanical characteristics of optic nerve lamina cribrosa may associated with the biomechanical properties of the cornea. Therefore, the study of corneal physiological can indirectly reflex the compression and damage in optic nerve lamina cribrosa. The technical developments in corneal hysteresis examination had been updated these years constantly. Many researches implicated that low corneal hysteresis involved in pathogenesis and progression of glaucoma which refresh our recognition of the relationship between cornea and glaucoma. This review summarized the characteristics of corneal hysteresis, the examination and the connection with glaucoma to provide the reference for clinical work. (Chin J Ophthalmol, 2017, 53: 140-143).


Effects of dietary supplementation with detoxified Rhus verniciflua sap on egg production, yolk lipid and intestinal microflora in laying hens.
This study was conducted to investigate the effects of dietary detoxified Rhus verniciflua sap (RVS) on production performance, egg quality, lipid fractions of egg yolk, liver and serum, and the profile of cecal microflora in laying hens. Two hundred 52-week-old Hy-Line Brown layers were randomly divided into 4 groups with 5 replicates per group (2 hens per cage, 5 cages per replicate) and were provided with one of 4 experimental diets containing 0%, 0.05%, 0.1%, or 0.2% RVS, for 6 weeks. Due to unequal intervals of RVS doses, the interactive matrix language procedure of the SAS program was used to correct the contrast coefficients of orthogonal polynomials. There were no differences in feed intake and egg weight among the groups. Egg production increased (linearly and quadratically, p<0.05) with increasing levels of RVS. Eggshell thickness increased (linear, p<0.05) as the level of RVS in diets increased. The levels of blood cholesterol and activities of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase were not altered by dietary treatments. Increasing level of RVS increased (linear, p<0.05) the populations of cecal lactic acid bacteria. The content of yolk cholesterol decreased (linear, p< 0.05) with increasing levels of dietary RVS, although there were no significant differences in each lipid fraction of the liver. This study indicates that dietary RVS could improve laying performance and eggshell quality, and affect cecal lactic acid bacteria in a dose-dependent manner.


Immunocytochemical profile of benign and carcinomatous effusions. A practical approach to difficult diagnosis.
One of the great challenges in the cytodiagnosis of effusions is the distinction between reactive mesothelium/histiocytes and cancer cells. This is notably true in patients having undergone radiation and/or chemotherapy. To establish whether monoclonal antibodies (MoAbs) could be used as reliable diagnostic adjuvants, the authors retrospectively and blindly studied 60 cases diagnosed by standard cytologic criteria (malignant, benign, and equivocal), with a panel of seven readily available MoAbs (cytokeratins, vimentin, EMA, B72.3, alpha-CEA, HMFG-2, and Leu-M1) and the lectin Ulex europaeus I. All 18 (100%) malignant cases showed reactivity with EMA and HMFG, whereas 17 (95%) and 11 (61%) reacted with B72.3 and alpha-CEA, respectively. Combinations of (1) EMA + B72.3, (2) EMA + alpha-CEA, and (3) EMA + alpha-CEA + B72.3 displayed positivity in 17 (95%), 11 (61%), and 10 (56%) malignant cases, respectively. Of the 18 benign cases, 7 reacted with HMFG and 2 each with EMA and B72.3. Only one case (5.5%) reacted with both EMA and B72.3. Based on these results, the 24 equivocal cases were regrouped into 14 malignant and 10 benign cases. Follow-up effusions obtained within the ensuing three months in all these patients allowed the authors to unequivocally confirm the diagnosis in all but five. The combination of EMA and B72.3 MoAbs detected malignant cells in 95% of the cases, with a 3.5% incidence of false positive cases in this study. A panel of EMA, B72.3, and alpha-CEA MoAbs should prove the most useful and simple approach to the correct diagnosis in most questionable effusions. Some of the potential pitfalls are discussed.


The effect of beta-aminoproprionitrile on the periodontal ligament: II. Radioautographic study of collagen secretion from fibroblasts.
Fibroblasts are distributed evenly throughout the periodontal ligament (PDL) of normal mice. In mice fed beta-aminoproprionitrile (beta-APN) the fibroblasts undergo aggregation to form palisades of closely juxtaposed cells abutting pools of acellular collagenous matrix. Individual fibroblasts within these aggregates retain their polarized cytoplasmic organization and continue to synthesize and secrete collagen. However, unlike normal PDL fibroblasts, the beta-APN-treated cells appear immobilized by well-developed cell-to-cell adherens-type junctions along their lateral surfaces. We studied collagen secretion from beta-APN-treated fibroblasts by light and electron microscopic radioautography after injection of 3H-proline. Newly synthesized collagen was secreted from the distal ends of the beta-APN-aggregated fibroblasts as a distinct band of labeled material, resembling the pattern of matrix deposition seen in osteogenesis and dentinogenesis. The radioactive band of collagenous matrix was displaced further away from the fibroblasts at 2 and 4 days after 3H-proline injection as more collagen was secreted. This pattern of radiolabeled collagen secretion confirmed previous observations that PDL fibroblasts are highly polarized and that collagen secretory granules are extruded from the distal or secretory pole of the cell. In normal PDL the even distribution of fibroblasts and the complex interrelationship of their distal cell processes leads to a diffuse pattern of silver grain deposition, masking the oriented flow of new collagen from the distal ends of individual fibroblasts. Analysis of electron microscopic radioautographs revealed that newly synthesized collagen was packaged and secreted from beta-APN-treated fibroblasts via the normal cytoplasmic pathways but at a slower rate.


The effective and selective separation of (-)-epigallocatechin gallate by molecularly imprinted chitosan beads.
The (-)-epigallocatechin gallate (EGCG) imprinted chitosan beads (EICBs) were fabricated for the effective and selective separation of EGCG. The EGCG molecules interacted with the amino groups of chitosan in the imprinting process, resulting in a highly porous structure of EICBs and more adsorption sites. Consequently, EICBs exhibited better adsorption performance than non-imprinted chitosan beads. The maximum adsorption capacity of EGCG onto EICBs reached 135.50 mg/g at 313 K. The imprinting factor of EICBs was 4.22, indicating that EICBs possess good recognition ability and selectivity for EGCG. After five cycles of reuse, only a slight decrease (7.77%) in the adsorption capacity was observed, demonstrating the satisfactory reusability of EICBs. Furthermore, the adsorption of EGCG onto EICBs is deduced to be the monolayer adsorption on an energetically homogeneous surface; the hydrogen bonding between EGCG and EICBs is the main driving force for the adsorption. Our studies suggest that EICBs have a great potential for the effective and selective separation of EGCG.


(S)-2-Benzyl-N-(2,6-diisopropyl-phen-yl)-1,2,3,4-tetra-hydro-isoquinoline-3-carboxamide.
The asymmetric unit of the title compound, C(29)H(34)N(2)O, contains two mol-ecules in which the N-containing six-membered rings assume different conformations viz. half-chair and envelope. Inter-molecular N-H⋯O hydrogen bonding via the amide groups cross-link the mol-ecules in the crystal structure.


Paediatric orbital and periorbital infections.
This study is a review of recent literature in the diagnosis and management of preseptal cellulitis, orbital cellulitis and dacryocystitis, including causative organisms, diagnosis and medical or surgical therapy and potential complications. Advances in vaccination against Haemophilus influenzae B have resulted in a shift in the most common causative organisms of preseptal and orbital cellulitis. Management of orbital cellulitis has been advanced by adjuvant corticosteroids, and subperiosteal abscess volumes of more than 1250 ml has been shown as predictive for requiring potential surgical intervention. Periorbital infections require prompt evaluation and management. Although the infectious organisms in both preseptal and orbital cellulitis include Staphylococcus/Streptococcus species, management may differ significantly on the basis of the nidus of infection, presenting signs and symptoms, and response to initial medical management.


Brownian motion in confinement.
This research modifies an earlier approach based on the single-wall reflection method to predict the perpendicular and parallel diffusion coefficients of a Brownian sphere in confinement. The modified version provides predictions that match experimental data reported in the literature more accurately than those provided by other available models, including the linear superposition approximation, the coherent superposition approximation, and Oseen's equation.


The oligoadenylate synthetase family: an ancient protein family with multiple antiviral activities.
The 2'-5' oligoadenylate synthetases (OAS) are interferon-induced antiviral enzymes that recognize virally produced dsRNA and initiate RNA destabilization through activation of RNase L within infected cells. However, recent evidence points toward several RNase L-independent pathways, through which members of the OAS family can exert antiviral activity. The crystal structure of OAS led to a novel insight into the catalytic mechanism, and revealed a remarkable similarity between OAS, Polyadenosine polymerase, and the class I CCA-adding enzyme from Archeoglobus fulgidus. This, combined with a variety of bioinformatic data, leads to the definition of a superfamily of template independent polymerases and proved that the OAS family are ancient proteins, which probably arose as early as the beginning of metazoan evolution.


Wound care in the accident and emergency department.
Wound assessment in the accident and emergency (A&E) department has a different focus from that in other clinical areas because of the lack of available clinical information about the patient. A wound may have had a greater-physical impact than is immediately apparent and therefore a comprehensive skin assessment is often necessary. The wound will require thorough exploration and debridement to enable healing to take place with minimal complications. The methods of debridement and cleansing used in the A&E department are often unique because of the complexity of wound contamination. The variety of wounds encountered in this setting necessitate a large repertoire of dressing regimens. Modern wound management products can be adapted to meet the needs of the wounded patient in the A&E department.


[Clinical phenotype characteristics and genetic analysis in children with nephronophthisis and related syndromes caused by different gene mutations].
To improve the understanding of the clinical phenotypes and genetic characteristics of nephronophthisis (NPHP) and related syndromes in children. A retrospective analysis was performed on the medical data of eight children with NPHP and related syndromes who were diagnosed and treated in the Department of Pediatrics of the Second Hospital of Hebei Medical University, from January 2018 to November 2022. The clinical characteristics and genetic testing results were analyzed. Among these eight children, there were five boys and three girls, with an age of onset ranging from 15 months to 12 years. All 8 children exhibited different degrees of renal function abnormalities when they attended the hospital. Among the eight children, two had the initial symptom of delayed development, two had the initial symptom of anemia, and two were found to have abnormal renal function during physical examination. The extrarenal manifestations included cardiovascular abnormalities in two children, skeletal dysplasia in two children, liver dysfunction in one child, retinitis pigmentosa in one child, and visceral translocation in one child. All eight children had renal structural changes on ultrasound, and four children had mild to moderate proteinuria based on routine urine test. Of all eight children, five had NPHP1 gene mutations and one each had a gene mutation in the NPHP3, IFT140, and TTC21B genes, and four new mutation sites were discovered. Children with NPHP and related syndromes often have the initial symptom of delayed development or anemia, and some children also have extrarenal manifestations. NPHP and related syndromes should be considered for children with unexplained renal dysfunction, and high-throughput sequencing may help to make a confirmed diagnosis.


The effect of school year and summer break in health-related cardiorespiratory fitness: A 2-year longitudinal analysis.
This study aimed to assess the trends of health-related cardiorespiratory fitness (CRF) during two school years with a 3-month summer break in children and adolescents. A 2-year longitudinal study, including 440 6th to 8th graders (218 boys), mean age 12.3 years, was conducted. The Progressive Aerobic Cardiovascular Endurance Run (PACER) was used to assess CRF. Physical activity was measured using accelerometers. Repeated measures linear models were used to analyses differences and trends in VO2peak and health-related CRF. Overall differences between time-point VO2peak were significant for both boys (p<0.001) and girls (p=0.003). Pairwise comparisons showed that VO2peak improved from the beginning to the end of the same school year for boys (school-year 1: 1.53 ml/kg/min, 95%CI=0.98, 2.09; school-year 2: 1.81 ml/kg/min, 95%CI=1.28, 2.34) and girls (school-year 1: 0.85 ml/kg/min, 95%CI=0.43, 1.27; school-year 2: 1.05 ml/kg/min, 95%CI=0.73, 1.36), while, differences in CRF during summer break were not significant. However, significance was only maintained for girls when performing monthly adjusted analysis. Improvements in CRF were observed during school year and remained unchanged during summer break. These findings provide relevant information for the health education community, suggesting the need for additional efforts to counteract the summer break effects on CRF, especially for girls.


Pathogenesis of Hypertrophic Cardiomyopathy is Mutation Rather Than Disease Specific: A Comparison of the Cardiac Troponin T E163R and R92Q Mouse Models.
In cardiomyocytes from patients with hypertrophic cardiomyopathy, mechanical dysfunction and arrhythmogenicity are caused by mutation-driven changes in myofilament function combined with excitation-contraction (E-C) coupling abnormalities related to adverse remodeling. Whether myofilament or E-C coupling alterations are more relevant in disease development is unknown. Here, we aim to investigate whether the relative roles of myofilament dysfunction and E-C coupling remodeling in determining the hypertrophic cardiomyopathy phenotype are mutation specific. Two hypertrophic cardiomyopathy mouse models carrying the R92Q and the E163R TNNT2 mutations were investigated. Echocardiography showed left ventricular hypertrophy, enhanced contractility, and diastolic dysfunction in both models; however, these phenotypes were more pronounced in the R92Q mice. Both E163R and R92Q trabeculae showed prolonged twitch relaxation and increased occurrence of premature beats. In E163R ventricular myofibrils or skinned trabeculae, relaxation following Ca2+ removal was prolonged; resting tension and resting ATPase were higher; and isometric ATPase at maximal Ca2+ activation, the energy cost of tension generation, and myofilament Ca2+ sensitivity were increased compared with that in wild-type mice. No sarcomeric changes were observed in R92Q versus wild-type mice, except for a large increase in myofilament Ca2+ sensitivity. In R92Q myocardium, we found a blunted response to inotropic interventions, slower decay of Ca2+ transients, reduced SERCA function, and increased Ca2+/calmodulin kinase II activity. Contrarily, secondary alterations of E-C coupling and signaling were minimal in E163R myocardium. In E163R models, mutation-driven myofilament abnormalities directly cause myocardial dysfunction. In R92Q, diastolic dysfunction and arrhythmogenicity are mediated by profound cardiomyocyte signaling and E-C coupling changes. Similar hypertrophic cardiomyopathy phenotypes can be generated through different pathways, implying different strategies for a precision medicine approach to treatment.


Significant enhanced superoxide anion (O2-) production in vitro by peripheral blood monocytes of lepromatous leprosy patients stimulated with liposome and suppression by C-reactive protein (CRP).
Peripheral blood monocytes (PBM) from normal individuals, infectious mononucleosis (IM) and leprosy patients were stimulated with liposome. The mean and standard error of superoxide anion (O2-) generated in nm/1.5 X 10(5) PBM/well for 5 normal subjects and 3 IM patients was 2.9 +/- 0.5 and 3.1 +/- 0.2, respectively. Monocytes stimulated with 100 ng C-reactive protein (CRP) incorporated into liposome gave values of 3.3 +/- 0.3 and 2.7 +/- 0.1 nm O-2/1.5 X 10(5) PBM/well for normals and IM, respectively. No significant differences in O2- production between liposome and liposome with incorporated CRP were shown. PBM from lepromatous patients demonstrated a significant (p less than 0.01) increase in O2- production with liposome alone compared with tuberculoid patients (3.5 +/- 0.4 vs 1.8 +/- 0.3). The most dramatic suppression of O2- shown when purified CRP was added to the mixtures in all groups examined [0.4 +/- 0.1 (500 ng), 0.3 +/- 0.0 (500 ng), 1.5 +/- 0.1 (100 ng), and 1.3 +/- 0.6 (100 ng) nm O2-/1.5 X 10(5) PBM/well for normals, IM, lepromatous, and tuberculoid, respectively]. Results of O2- formation with incorporation of CRP into liposome as compared with liposome alone had no significant effect on PBM of lepromatous or tuberculoid patients. It is suggested that CRP may play a significant role in regulation of oxygen free radicals formed during acute and chronic inflammatory episides.


Epidemiology of urinary tract infections in type 2 diabetes mellitus patients: An analysis based on a large sample of 456,586 German T2DM patients.
This analysis was conducted to investigate urinary tract infection (UTI) incidence among Type 2 Diabetes mellitus (T2DM) patients in Germany in a real-world setting and to identify risk factors associated with UTI incidence/recurrence. Our cohort study was conducted based on an anonymized dataset from a regional German sickness fund (2010-2012). A UTI event was mainly identified through observed outpatient/inpatient UTI diagnoses. We reported the number of UTI events per 1000 patient-years. Furthermore, the proportion of patients affected by ≥1 and ≥2 UTI events in the observational period was separately reported. Finally, three multivariate Cox regression analyses were conducted to identify factors that may be associated with UTI event risk or recurrent UTI event risk. A total of 456,586 T2DM-prevalent patients were identified (mean age 72.8years, 56.1% female, mean Charlson Comorbidity Index (CCI) of 7.3). Overall, the UTI event rate was 87.3 events per 1000 patient-years (111.8/55.8 per 1000 patient-years for women/men (p<0.001)). The highest UTI event rates were observed for those aged >89years. After 730days after first observed T2DM diagnosis, the proportion of women/men still UTI-event-free was 80.9%/90.2% (p<0.001). Most important factors associated with UTI risk in our three models were older age (Hazard Ratio (HR)=1.56-1.70 for >79years), female gender (HR=1.38-1.57), UTIs in the previous two years (HR=2.77-5.94), number of comorbidities as measured by the CCI (HR=1.32-1.52 for CCI>6) and at least one cystoscopy in the previous year (HR=2.06-5.48). Furthermore, high HbA1c values in the previous year (HR=1.29-1.4 referring to HbA1c>9.5%) and a poor kidney function (HR=1.11-1.211 referring to glomerular filtration rate (GFR)<60ml/min) increased the UTI event risk. Our study confirms that UTI event risk is high in T2DM patients. Older female patients having experienced previous UTIs face an above-average UTI risk, especially if these risk factors are associated with poor glycemic control and poor kidney function.


Assembly of an adult type acetylcholine receptor in a mouse cell line transfected with rat muscle epsilon-subunit DNA.
The mouse muscle cell line BC3H-1 expresses an acetylcholine receptor (AChR) composed of alpha-, beta-, gamma- and delta-subunits. The functional characteristics of this AChR are comparable to the non-synaptic AChR subtype in mouse muscle. To investigate the role of the epsilon-subunit, which is believed to replace the gamma-subunit in forming the adult AChR subtype, BC3H-1 cells were stably transfected with cDNA encoding the rat muscle AChR epsilon-subunit. Expression of this cDNA was under the control of a heat shock promoter, and the plasmid carried the neomycin resistance gene for selection. Several clones were isolated that had integrated the plasmid DNA in a stable form and produced epsilon-subunit specific RNA after heat induction. Single-channel current recording from cells which contained abundant epsilon-subunit mRNA identified a novel AChR channel having a larger conductance than the native AChR in these cells. These results suggest that the rat muscle epsilon-subunit may assemble with mouse muscle alpha-, beta- and delta-subunits to form a mouse-rat hybrid AChR with properties similar to that of end-plate channels in the mature mammalian neuromuscular synapse. The novel AChR channel appears in the surface membrane within a few hours following the rise in epsilon-subunit mRNA. Thus, the notion that replacement of the gamma-subunit by the epsilon-subunit during development is the result of the postnatal rise in the level of epsilon-subunit specific mRNA is further supported.


Do QEEG topographic map data have a multivariate normal distribution? Implications for tests of individual maps.
The study was designed to test whether topographic map data expressed in log power units have a multivariate normal (MVN) distribution in a healthy population, and to determine if any deviation from normality poses serious difficulties for the use of standard multivariate statistical tests in assessing the significance of deformations of the map in individual cases. Data on 361 healthy adults using 20 electrodes in the classic 10/20 configuration were recorded in six frequency bands. The log-transformed power data were shown to deviate markedly from MVN. The actual distributions of multivariate tests were computed for the sample using the 'jackknife' method, and shown to deviate markedly from the F-distributions that would be expected for MVN data. These 'jackknife' sampling distributions were then used to demonstrate significant deformations in the topographic maps of a patient who had sustained traumatic head injury.


Alkali-aided protein extraction from chicken dark meat: textural properties and color characteristics of recovered proteins.
Textural properties, water-holding capacity, and color characteristics of alkali-extracted chicken dark meat have been studied. Alkali extraction was carried out at 4 different pH values (10.5, 11.0, 11.5, and 12.0). At higher pH of extraction, cooking loss and water loss were found to be significantly decreased (P < 0.05). The lightness (L* value) of the recovered samples treated at higher pH was found to be significantly lower (P < 0.05). Whiteness of uncooked samples also decreased significantly at higher extraction pH values. Protein samples extracted at higher pH values were found to be harder, and the maximum (4,956 g of force) value was shown by samples prepared at pH 11.5. Chewiness values were significantly increased (P < 0.05) for protein samples extracted at pH values of 11.5 and 12.0. Dynamic viscoelastic behavior of samples was assessed in the temperature range of 7 to 100 degrees C. The dynamic viscoelastic behavior of raw chicken dark meat as revealed by storage modulus indicated considerable gel-forming ability. The maximum storage modulus (G') value of 439 kPa was measured at 66.7 degrees C. Storage modulus was found to decrease for the recovered protein samples and be lowest at higher pH values. However, the recovered protein samples did show substantial gel-forming ability when stored with cryoprotectants. Tan delta values denoted 2 clear transitions for raw dark meat; however, only 1 major transition at 50.1 degrees C was evident for pH-treated samples, probably reflecting the loss of collagen in processing. In conclusion, this process of protein recovery may offer the possibility to use the underused poultry resources for preparation of functional foods.


Role of the leukocyte function antigen-1 conformational state in the process of human immunodeficiency virus type 1-mediated syncytium formation and virus infection.
Human immunodeficiency virus type 1 (HIV-1)-mediated syncytium formation is recognized as being highly dependent on intercellular adhesion molecule (ICAM)-1-leukocyte function-associated molecule 1 (LFA)-1 interaction, whereas the process of infection with cell-free virions is independent of such complementary interaction. Our group has recently demonstrated that an antibody-mediated induction of the high affinity state of LFA-1 for ICAM-1 renders target T cells more prone to HIV-1-dependent syncytium formation and infection by ICAM-1-bearing virions. To further substantiate these results, we made use of mutant cell lines expressing LFA-1 in either a low (parental HPB-ALL and HAmut) or a high affinity state for ICAM-1 (HAP4) and compared syncytium formation and virus infection. Cells expressing the activated form of LFA-1 were found to be more susceptible to HIV-1-induced syncytium formation and to infection by ICAM-1-bearing HIV-1 particles. The observed increase was solely due to the LFA-1 activation state because it was abrogated by anti-LFA-1 or anti-ICAM-1 antibodies and not due to variations in surface expression of LFA-1, CD4, or the chemokine coreceptor CXCR4. However, a linear relation was seen between the level of CXCR4 surface expression and susceptibility to syncytium formation/virus infection when ICAM-1-LFA-1 interaction was either absent (i.e., infection with ICAM-1-negative virions) or abrogated (treatment with anti-LFA-1 or anti-ICAM-1 antibodies). These results emphasize the important role of the LFA-1 activation state with respect to virus-induced syncytium formation and HIV-1 infection.


[Isotope angiography in peripheral arterial pathology].
On the basis of 67 isotope angiograms, the results of which were compared with those of arteriography, the authors present the advantages, indications and limitations of this technique.


Abatacept to induce remission of peanut allergy during oral immunotherapy (ATARI): protocol for a phase 2a randomized controlled trial.
While oral immunotherapy (OIT) has been shown to promote the remission of mild peanut allergy in young children, there is still an unmet need for a disease-modifying intervention for older patients and those with severe diseases. In mice models, abatacept, a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) immunoglobulin fusion protein, has been shown to promote immune tolerance to food when used as an adjuvant to allergen immunotherapy. The goal of this study is to explore the potential efficacy of abatacept in promoting immune tolerance to food allergens during OIT in humans. In this phase 2a proof-of-concept study (NCT04872218), 14 peanut-allergic participants aged from 14 to 55 years will be randomized at a 1:1 ratio to abatacept vs. placebo for the first 24 weeks of a peanut OIT treatment (target maintenance dose of 300 mg peanut protein). The primary outcome will be the suppression of the OIT-induced surge in peanut-specific IgE/total IgE at 24 weeks, relative to the baseline. Sustained unresponsiveness will be assessed as a secondary outcome starting at 36 weeks by observing incremental periods of peanut avoidance followed by oral food challenges. This is the first study assessing the use of abatacept as an adjuvant to allergen immunotherapy in humans. As observed in preclinical studies, the ability of abatacept to modulate the peanut-specific immune response during OIT will serve as a proxy outcome for the development of clinical tolerance, given the small sample size. The study will also test a new patient-oriented approach to sustained tolerance testing in randomized controlled trials.


Influence of oral health attitude of mothers on the gingival health of their school age children.
We investigated the influence of mothers' oral health attitudes on their children's gingival health level, in 257 pairs of mothers and children from an elementary school in Hiroshima. The Oral Rating Index for Children (ORI-C) was used for the gingival health examination, and the Hiroshima University Dental Behavioral Inventory (HU-DBI) was used to assess the oral health attitude of each mother. Subjects in mother and child pairs were divided into a lower grade group (L-group) (grades 1-3), and upper grade group (U-group) (grades 4-6). Gingival health i L-group children was 3.42 times higher in those whose mothers noticed plaque, and 2.68 times higher in those who received dental check-ups. However, ORI-C scores were not correlated to HU-DBI scores in the U-group. We concluded that the gingival health of children could be significantly influenced by the oral health attitude of their mothers up to approximately ten years of age.


[Timing of dressing removal in the healing of surgical wounds by primary intention: a meta-analysis].
An appropriate postoperative wound management helps to prevent surgical site infections. However, ideal timing of dressing removal is an unresolved issue in current practice. The objective of this systematic review therefore was to provide a comprehensive synthesis of existing evidence concerning the efficacy of different periods of postoperative dressing removal in surgical wounds which are healing by primary intention. We searched MEDLINE, EMBASE, CINAHL, The Cochrane Library (all in August 2011), and hand-searched additional sources. All randomised controlled trials that were comparing different periods of leaving dressings in place, including not dressing the surgical site at all, and covering wounds until suture removal were included. We conducted our systematic review and meta-analysis in accordance with the recommendations of the Cochrane Collaboration. Eight trials with a total of 2097 participants were included in our meta-analysis. All studies were at high or unclear risk of bias. This meta-analysis did not show a higher rate of wound infections or other wound complications associated with an early dressing removal in wounds that are healing by primary intention: risk difference (RD) -0.01; 95%-confidence interval (CI) -0.03, 0.01. However, conclusions are limited due to bad study quality of included studies. Finally more sound research is needed.


Formation of Ent-isophleichrome by Cladosporium herbarum Isolated from Sugar Beet.
An isolate of Cladosporium herbarum obtained from leaves of sugar beet produced a phytotoxic red pigment which was identified as ent-isophleichrome (1). Production of the pigment was dependent on composition of the culture medium. The toxicity of ent-isophleichrome to sugar beet was strongly influenced by light. The polyketide biosynthetic origin of ent-isophleichrome in C. herbarum was demonstrated by (13)C acetate labelling/(13)C NMR studies.


Evaluation of a 3-hour indium-111 leukocyte image as a surrogate for a technetium-99m nanocolloid marrow scan in the diagnosis of orthopedic infection.
This is a retrospective study to evaluate a 3-hour In-111-labeled leukocyte image as a surrogate for a Tc-99m nanocolloid marrow scan in the investigation of suspected orthopedic infection using In-111 leukocyte scintigraphy. Images from 51 patients who had received contemporaneous In-111-labeled leukocyte scintigraphy and Tc-99m nanocolloid marrow scintigraphy were reviewed. Initially, the 3-hour and 22-hour In-111-labeled leukocyte images were compared. Sites of abnormal uptake on the 22-hour image were correlated with the 3-hour image and were graded according to the level of concordance or discordance. One week later, the Tc-99m nanocolloid images and 22-hour In-111-labeled leukocyte images of the same patients were compared and graded for concordance or discordance. When discrepancies in grading arose between the observers, a consensus opinion was achieved after additional review of the images a week later. On inspection of the 22-hour In-111 leukocyte images, 93 sites of focal, potentially abnormal leukocyte accumulation were identified. When the grading system was reduced to simply "concordant" or "discordant," there was good agreement between the observers in the majority of cases, with kappa statistics 0.77 for Tc-99m nanocolloid versus 22-hour In-111-labeled leukocyte images and 0.78 for 3-hour versus 22-hour In-111-labeled leukocyte images. Using the comparison of the Tc-99m nanocolloid marrow scan and the 22-hour In-111-labeled leukocyte images to identify concordance or discordance as the "gold standard" for scintigraphic evaluation of suspected orthopedic infection, comparison of the 3-hour In-111-labeled leukocyte images with the 3-hour In-111-labeled leukocyte images gave a sensitivity of 77%, a specificity of 77%, and an accuracy of 77%. A 3-hour image is helpful using In-111-labeled leukocyte scintigraphy.


Heat shock cognate protein 70 isoform D is required for clathrin-dependent endocytosis of Japanese encephalitis virus in C6/36 cells.
Japanese encephalitis virus (JEV), one of encephalitic flaviviruses, is naturally transmitted by mosquitoes. During infection, JEV generally enters host cells via receptor-mediated clathrin-dependent endocytosis that requires the 70 kDa heat-shock protein (Hsp70). Heat-shock cognate protein 70 (Hsc70) is one member of the Hsp70 family and is constitutively expressed; thus, it may be expressed under physiological conditions. In C6/36 cells, Hsc70 is upregulated in response to JEV infection. Since Hsc70 shows no relationship with viruses attaching to the cell surface, it probably does not serve as the receptor according to our results in the present study. In contrast, Hsc70 is evidently associated with virus penetration into the cell and resultant acidification of intracellular vesicles. It suggests that Hsc70 is highly involved in clathrin-mediated endocytosis, particularly at the late stage of viral entry into host cells. Furthermore, we found that Hsc70 is composed of at least three isoforms, including B, C and D; of these, isoform D helps JEV to penetrate C6/36 cells via clathrin-mediated endocytosis. This study provides relevant evidence that sheds light on the regulatory mechanisms of JEV infection in host cells, especially on the process of clathrin-mediated endocytosis.


Picosecond Dynamics of Excitonic Magnetic Polarons in Colloidal Diffusion-Doped Cd(1-x)Mn(x)Se Quantum Dots.
Spontaneous magnetization is observed at zero magnetic field in photoexcited colloidal Cd(1-x)Mn(x)Se (x = 0.13) quantum dots (QDs) prepared by diffusion doping, reflecting strong Mn(2+)-exciton exchange coupling. The picosecond dynamics of this phenomenon, known as an excitonic magnetic polaron (EMP), are examined using a combination of time-resolved photoluminescence, magneto-photoluminescence, and Faraday rotation (TRFR) spectroscopies, in conjunction with continuous-wave absorption, magnetic circular dichroism (MCD), and magnetic circularly polarized photoluminescence (MCPL) spectroscopies. The data indicate that EMPs form with random magnetization orientations at zero external field, but their formation can be directed by an external magnetic field. After formation, however, external magnetic fields are unable to reorient the EMPs within the luminescence lifetime, implicating anisotropy in the EMP potential-energy surfaces. TRFR measurements in a transverse magnetic field reveal rapid (<5 ps) spin transfer from excitons to Mn(2+) followed by coherent EMP precession at the Mn(2+) Larmor frequency for over a nanosecond. A dynamical TRFR phase inversion is observed during EMP formation attributed to the large shifts in excitonic absorption energies during spontaneous magnetization. Partial optical orientation of the EMPs by resonant circularly polarized photoexcitation is also demonstrated. Collectively, these results highlight the extraordinary physical properties of colloidal diffusion-doped Cd(1-x)Mn(x)Se QDs that result from their unique combination of strong quantum confinement, large Mn(2+) concentrations, and relatively narrow size distributions. The insights gained from these measurements advance our understanding of spin dynamics and magnetic exchange in colloidal doped semiconductor nanostructures, with potential ramifications for future spin-based information technologies.


Construction of pyrazolodiazepines using AuI, a dual functional gold catalyst.
N,N'-5,7-Fused compounds are important molecules exhibiting medicinal potential. Herein, we report a practical and robust method for synthesising pyrazolodiazepines from N-piperidinyl alkynylhydrazides using a AuI catalyst. The broad substrate scope of alkynylhydrazides and synthetic application of pyrazolodiazepines are demonstrated. In addition, control experiments provide detailed information on the reaction mechanism, in which AuI promotes both the sequential intramolecular nucleophilic addition and the double nucleophilic substitution reaction as a π-acidic and nucleophilic dual functional catalyst.


Cultural effects on the association between election outcomes and face-based trait inferences.
How competent a politician looks, as assessed in the laboratory, is correlated with whether the politician wins in real elections. This finding has led many to investigate whether the association between candidate appearances and election outcomes transcends cultures. However, these studies have largely focused on European countries and Caucasian candidates. To the best of our knowledge, there are only four cross-cultural studies that have directly investigated how face-based trait inferences correlate with election outcomes across Caucasian and Asian cultures. These prior studies have provided some initial evidence regarding cultural differences, but methodological problems and inconsistent findings have complicated our understanding of how culture mediates the effects of candidate appearances on election outcomes. Additionally, these four past studies have focused on positive traits, with a relative neglect of negative traits, resulting in an incomplete picture of how culture may impact a broader range of trait inferences. To study Caucasian-Asian cultural effects with a more balanced experimental design, and to explore a more complete profile of traits, here we compared how Caucasian and Korean participants' inferences of positive and negative traits correlated with U.S. and Korean election outcomes. Contrary to previous reports, we found that inferences of competence (made by participants from both cultures) correlated with both U.S. and Korean election outcomes. Inferences of open-mindedness and threat, two traits neglected in previous cross-cultural studies, were correlated with Korean but not U.S. election outcomes. This differential effect was found in trait judgments made by both Caucasian and Korean participants. Interestingly, the faster the participants made face-based trait inferences, the more strongly those inferences were correlated with real election outcomes. These findings provide new insights into cultural effects and the difficult question of causality underlying the association between facial inferences and election outcomes. We also discuss the implications for political science and cognitive psychology.


Long-term functional recovery and health-related quality of life of elderly out-of-hospital cardiac arrest survivors.
Understanding the prognosis of elderly out-of-hospital cardiac arrest (OHCA) patients is vital to informing resuscitation and advanced care planning decisions. However, short-term outcomes such as survival to hospital discharge do not account for post-arrest quality of life. We describe the 12-month functional recovery and health-related quality of life (HR-QOL) of elderly OHCA survivors, including those arresting in aged care facilities. We conducted a retrospective analysis of Victorian Ambulance Cardiac Arrest Registry data for all OHCA survivors to hospital discharge aged ≥65 years between 1 January 2010 and 30 June 2016. The influence of age on functional recovery and independent living was assessed using multivariable logistic regression. During the study period, 20,103 elderly OHCAs were attended, 9016 (44.9%) of whom received a resuscitation attempt. In total, 876 (9.7%) patients survived to hospital discharge and 777 were alive 12 months post-arrest. Of these, 651 participated in 12-month follow-up (response rate 83.8%). Most (60.6%) resided at home without additional care and 66.6% reported a good functional recovery, however both measures decreased with increasing age (p < 0.001). Mental HR-QOL increased with increasing age and was significantly better than the age- and sex-matched Australian population. Each 10-year increase in age was associated with a 40.8% (95%CI 25.6-53.0%) reduction in the odds of good functional recovery, and a 65.8% (95%CI 55.8-73.5%) reduction in the odds of living independently. Of the 2575 OHCAs in an aged care facility, 2.2% survived to hospital discharge, however no patient reported a good 12-month functional recovery. Most elderly OHCA survivors resided independently with good functionality 12 months post-arrest. However, increasing age was associated with less favourable outcomes. New strategies are needed with regard to resuscitation in aged care facilities.


Rexin-G®, a tumor-targeted retrovector for malignant peripheral nerve sheath tumor: A case report.
Soft tissue sarcoma is a rare neoplasm of mesenchymal origin, accounting for only ~1% of all adult cancers and consisting of 75 histological subtypes. In the present report, the unique case of a 14 year-old female with metastatic malignant peripheral nerve sheath tumor (formerly, malignant melanotic schwannoma) of the parotid gland, who experienced a durable response and sustained tumor control with Rexin-G®, a tumor-targeted retroviral expression vector encoding an anti-cyclin G1 construct, is described. Post-parotidectomy, and prior to the administration of Rexin-G®, the patient received various chemotherapy regimens, including doxorubicin, ifosfamide, temozolomide, sorafenib, and an immunological therapy with interleukin-2, which only resulted in the further progression of lung metastases. The patient subsequently participated in a Phase 1/2 gene therapy study, during which she received intravenous Rexin-G® as monotherapy for two years with minimal drug-associated adverse events. Currently, the patient has no evidence of active disease 9 years after commencing the Rexin-G® treatment, and with no additional anti-cancer therapy. In conclusion, Rexin-G® may be a viable therapeutic option for malignant peripheral nerve sheath tumors, and should be further investigated in prospective histology-specific clinical trials for this type, and possibly other types, of chemotherapy-resistant sarcoma.


Psychiatry in Spain: past and present.
The authors discuss the contributions and history of psychiatry in Spain on the basis of extensive literature review and on-site observations. The history of Spanish psychiatry is a rich one, including pioneering efforts in the establishment of mental institutions and a strong traditional alliance between psychiatry and literature. However, the authors note that Spanish psychiatrists today are less innovative than their counterparts in other countries. They emphasize the historical and cultural context of the discipline, with illustrations of the importance of the church, attitudes toward the family, and other sociocultural factors.