Localization of FtsZ in Helicobacter pylori and consequences for cell division.
Of the various kinds of cell division, the most common mode is binary fission, the division of a cell into two morphologically identical daughter cells. However, in the case of asymmetric cell division, Caulobacter crescentus produces two morphologically and functionally distinct cell types. Here, we have studied cell cycle progression of the human pathogen Helicobacter pylori using a functional green fluorescent protein (GFP) fusion of FtsZ protein and membrane staining. In small cells, representing newly divided cells, FtsZ localizes to a single cell pole. During the cell cycle, spiral intermediates are formed until an FtsZ ring is positioned with very little precision, such that central as well as acentral rings can be observed. Daughter cells showed considerably different sizes, suggesting that H. pylori divides asymmetrically. Fluorescence recovery after photobleaching (FRAP) analyses demonstrate that the H. pylori FtsZ ring is about as dynamic as that of Escherichia coli but that polar assemblies show less turnover. Strikingly, our results demonstrate that H. pylori cell division follows a different route from that in E. coli and Bacillus subtilis. It is also different from that in C. crescentus, where cytokinesis regulation proteins like MipZ play a role. Therefore, this report provides the first cell-biological analysis of FtsZ dynamics in the human pathogen H. pylori and even in epsilonproteobacteria to our knowledge. In addition, analysis of the filament architecture of H. pylori and E. coli FtsZ filaments in the heterologous system of Drosophila melanogaster S2 Schneider cells revealed that both have different filamentation properties in vivo, suggesting a unique intrinsic characteristic of each protein.


Production Task Queue Optimization Based on Multi-Attribute Evaluation for Complex Product Assembly Workshop.
The production task queue has a great significance for manufacturing resource allocation and scheduling decision. Man-made qualitative queue optimization method has a poor effect and makes the application difficult. A production task queue optimization method is proposed based on multi-attribute evaluation. According to the task attributes, the hierarchical multi-attribute model is established and the indicator quantization methods are given. To calculate the objective indicator weight, criteria importance through intercriteria correlation (CRITIC) is selected from three usual methods. To calculate the subjective indicator weight, BP neural network is used to determine the judge importance degree, and then the trapezoid fuzzy scale-rough AHP considering the judge importance degree is put forward. The balanced weight, which integrates the objective weight and the subjective weight, is calculated base on multi-weight contribution balance model. The technique for order preference by similarity to an ideal solution (TOPSIS) improved by replacing Euclidean distance with relative entropy distance is used to sequence the tasks and optimize the queue by the weighted indicator value. A case study is given to illustrate its correctness and feasibility.


Combination of B-type natriuretic peptide and peak oxygen consumption improves risk stratification in outpatients with chronic heart failure.
Peak oxygen consumption is a cornerstone for prognostic determination in patients with congestive heart failure. The purpose of this study was to assess whether plasma B-type natriuretic peptide (BNP) provided any additional prognostic information. Plasma concentrations of atrial natriuretic peptide, N terminal pro-atrial natriuretic peptide, BNP, endothelin-1, norepinephrine, and peak VO2 were measured in 250 consecutive outpatients with mild to moderate heart failure (96% in New York Heart Association [NYHA] class II or III) and left ventricular ejection fraction (LVEF) <45%. During a median follow-up of 584 days, 42 patients died (19 from sudden death) and 5 underwent urgent heart transplantation. Multivariate stepwise regression analysis showed that, among 13 variables including NYHA and LVEF, plasma BNP (chi2 = 11.9, P =.0001) was the strongest independent predictor of death or urgent transplantation, followed by serum sodium (chi2 = 8, P =.0046), resting heart rate (chi2 = 7.5, P =.0062), plasma endothelin-1 (chi2 = 7.2, P =.007), and peak VO2 (chi2 = 6.2, P =.012). Patients with plasma BNP above the upper quartile value (260 pg/mL) had a 1-year rate of death or urgent transplantation of 31%. The 1- and 2-year survival rates without urgent transplantation in patients with a peak VO2 < or =14 mL x kg(-1) x min(-1) were 71% and 59%, respectively, when plasma BNP was >137 pg/mL (median value), compared with 100% and 89%, respectively, when plasma BNP was < or =137 pg/mL (P =.008). Furthermore, plasma BNP was the only independent predictor of sudden death (chi2 = 19.9, P =.00001). Plasma BNP provides additive independent prognostic information compared to peak VO2 alone in outpatients with mild to moderate heart failure.


Environmental economics of lignin derived transport fuels.
This paper explores the environmental and economic aspects of fast pyrolytic conversion of lignin, obtained from 2G ethanol plants, to transport fuels for both the marine and automotive markets. Various scenarios are explored, pertaining to aggregation of lignin from several sites, alternative energy carries to replace lignin, transport modalities, and allocation methodology. The results highlight two critical factors that ultimately determine the economic and/or environmental fuel viability. The first factor, the logistics scheme, exhibited the disadvantage of the centralized approach, owing to prohibitively expensive transportation costs of the low energy-dense lignin. Life cycle analysis (LCA) displayed the second critical factor related to alternative energy carrier selection. Natural gas (NG) chosen over additional biomass boosts well-to-wheel greenhouse gas emissions (WTW GHG) to a level incompatible with the reduction targets set by the U.S. renewable fuel standard (RFS). Adversely, the process' economics revealed higher profits vs. fossil energy carrier.


Evaluation of interprofessional education: lessons learned through the development and implementation of an interprofessional seminar on team communication for undergraduate health care students in Heidelberg - a project report.
This project report describes the development, "piloting" and evaluation of an interprofessional seminar on team communication bringing together medical students and Interprofessional Health Care B.Sc. students at the Medical Faculty of Heidelberg University, Germany. A five-member interprofessional team collaborated together on this project. Kolb's experiential learning concept formed the theoretical foundation for the seminar, which explored three interprofessional competency areas: team work, communication and values/ethics. Evaluation for the purposes of quality assurance and future curricula development was conducted using two quantitative measures: descriptive analysis of a standardized course evaluation tool (EvaSys) ANOVA analysis of the German translation of the University of the West of England Interprofessional Questionnaire (UWE-IP-D). The key finding from the standardized course evaluation was that the interprofessional seminars were rated more positively [M=2.11 (1 most positive and 5 most negative), SD=1, n=27] than the monoprofessional seminars [M=2.55, SD=0.98, n=90]. The key finding from the UWE-IP-D survey, comparing pre and post scores of the interprofessional (IP) (n=40) and monoprofessional (MP) groups (n=34), was that significant positive changes in mean scores for both groups towards communication, teamwork and interprofessional learning occurred. Lessons learnt included: a) recognising the benefit of being pragmatic when introducing interprofessional education initiatives, which enabled various logistical and attitudinal barriers to be overcome; b) quantitative evaluation of learning outcomes alone could not explain positive responses or potential influences of interprofessional aspects, which highlighted the need for a mixed methods approach, including qualitative methods, to enrich judgment formation on interprofessional educational outcomes.


[Effect of electric stimulation on denervated skeletal muscle atrophy].
To study the influence of the electric stimulation of denervated muscle atrophy. Sixteen SD rats were made the model of denervated skeletal muscle in two lower limbs by cutting off the sciatic nerve and femoral nerve. The right gastrocnemius muscle was stimulated with JNR-II nerve & muscle recovery instrument by skin as the experimental side and the left was not treated as the control side. The muscle histology, ultrastructure, fibrillation potential amplitude, Na(+)-K(+)-ATPase and Ca(2+)-ATPase activities were observed 2 weeks and 4 weeks after operation. Electric stimulation could protect mitochondria and sarcoplasmic reticulum from the degeneration. The reduction rates of muscle cell diameter and cross section in the experimental side were slower significantly than those in control side. There was no influence on fibrillation potential amplitude in the both sides after electric stimulation. The reduction rates of Na(+)-K(+)-ATPase activity in the experimental side were slower 15.59% and 27.38% respectively than those in the control side. The reduction rates of Ca(2+)-ATPase activity in the experimental side were slower 4.83% and 21.64% respectively than those in the control side. The electric stimulation can protect muscle histology, electrophysiology and enzymic histochemistry of denervated skeletal muscle from the degeneration. The electric stimulation is an effective method to prevent and treat muscle atrophy.


Siaα2-3Galβ1- Receptor Genetic Variants Are Associated with Influenza A(H1N1)pdm09 Severity.
Different host genetic variants may be related to the virulence and transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the ST3GAL1 gene, which encodes the Siaα2-3Galβ1- receptor to which influenza A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the six exons encoding the ST3GAL1 gene were sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of the study, the rs113350588 and rs1048479 polymorphisms identified in this sample were genotyped in a sample of 356 subjects from the northern and northeastern regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of the polymorphisms was performed in silico and the influence of these variants on the severity of infection was evaluated. The results suggest that rs113350588 and rs1048479 may alter the function of ST3GAL1 either directly through splicing regulation alteration and/or indirectly through LD with SNP with regulatory function. In the study the rs113350588 and rs1048479 polymorphisms were in linkage disequilibrium in the population studied (D' = 0.65). The GC haplotype was associated with an increased risk of death in subjects with influenza (OR = 4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476, 95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the association of ST3GAL1 gene haplotypes on the risk of more severe disease and death in patients infected with Influenza A(H1N1)pdm09 virus.


[Asperger Syndrome and/or Clinical High Risk of Psychosis? A Differential Diagnostic Challenge].
Asperger Syndrome and/or Clinical High Risk of Psychosis? A Differential Diagnostic Challenge This case-study deals with the often difficult differential diagnosis of Asperger syndrome and a clinical high risk state of psychosis, in particular as indicated by attenuated psychotic symptoms, as well as with its therapeutic implications. The presented case is a 10-year old girl, who has not been diagnosed with an autism spectrum disorder before being referred to a specialized center for early detection of psychosis due to possible hallucinatory experiences and delusional ideas. We demonstrate how to perform a context-sensitive differential diagnosis to distinguish between specific interests as well as related behaviors and unusual thought content as well as perceptive abnormalities, between paranoid ideas and biased interpretations of the behaviors of others typical for autism, and between disorganized symptoms and autistic unusual communication and social behavior. The resulting dual diagnoses in our case-study formed the basis for a complex differential indication, which considered both the increased stress vulnerability associated with an increased risk for the development of psychosis as well as the rigid thinking style associated with autism. Our case-report shows that such a precise differential indication can lead to stabilization over the long-term, even in patients with dual diagnoses.


Large tandem chromosome expansions facilitate niche adaptation during persistent infection with drug-resistant Staphylococcus aureus.
We used genomics to study the evolution of meticillin-resistant Staphylococcus aureus (MRSA) during a complex, protracted clinical infection. Preparing closed MRSA genomes from days 0 and 115 allowed us to precisely reconstruct all genetic changes that occurred. Twenty-three MRSA blood cultures were also obtained during treatment, yielding 44 colony morphotypes that varied in size, haemolysis and antibiotic susceptibility. A subset of 15 isolates was sequenced and shown to harbour a total of 37 sequence polymorphisms. Eighty per cent of all mutations occurred from day 45 onwards, which coincided with the appearance of discrete chromosome expansions, and concluded in the day 115 isolate with a 98 kb tandem DNA duplication. In all heterogeneous vancomycin-intermediate Staphylococcus aureus isolates, the chromosomal amplification spanned at least a 20 kb region that notably included mprF, a gene involved in resistance to antimicrobial peptides, and parC, an essential DNA replication gene with an unusual V463 codon insertion. Restoration of the chromosome after serial passage under non-selective growth was accompanied by increased susceptibility to antimicrobial peptide killing and reduced vancomycin resistance, two signature phenotypes that help explain the clinical persistence of this strain. Elevated expression of the V463 parC was deleterious to the cell and reduced colony size, but did not alter ciprofloxacin susceptibility. In this study, we identified large DNA expansions as a clinically relevant mechanism of S. aureus resistance and persistence, demonstrating the extent to which bacterial chromosomes remodel in the face of antibiotic and host immune pressures.


Factors related to patient selection and initiation of peritoneal dialysis.
The majority of dialysis patients initiate dialysis using hemodialysis, rather than peritoneal dialysis (PD), although they may be candidates for either modality.Multiple factors account for this selection, including pre-dialysis education, physician familiarity with hemodialysis versus PD, and patient-related factors. This paper will discuss the various considerations by both providers and patients in the selection of PD as a modality.


[Experiences with parenteral administration of diltiazem in coronary surgery patients].
Diltiazem is a calcium channel blocker whose effects lie between those of the two other important calcium antagonists nifedipine and verapamil. In addition to vasodilation, it has a negative dromotropic effect with prolongation of the A-V interval. In animal experiments and human investigations, diltiazem improves the function of ischemic myocardium due to a direct dilating effect on coronary vessels. The purpose of the present study was to investigate the hemodynamic effects of diltiazem in patients before and during coronary revascularization. METHODS. The study included 60 consenting male patients with coronary heart disease. Twenty premedicated patients randomly received 0.3 mg/kg diltiazem or placebo within 3 min before induction of anesthesia. Hemodynamic measurements (arterial pressure, heart rate, mean pulmonary arterial pressure, pulmonary capillary pressure, right atrial pressure and cardiac output) were taken during the following 21 min. Before cannulation of the great vessels for institution of extracorporeal circulation (ECC), 20 other patients received 0.014 mg diltiazem or placebo/kg per min over 20 min. In addition to the above mentioned hemodynamic measurements, left ventricular parameters (LVP, LVEDP, dp/dt) were directly registered, and 5 min after the end of ECC the measurements were repeated with the same preload as before the ECC. Twenty additional patients received 0.014 mg diltiazem or placebo/kg per min within 21 min during ECC observing arterial perfusion pressure and oxygenator volume. RESULTS. Pre- and intraoperatively diltiazem caused a decrease in mean arterial pressure; cardiac index increased only during the preoperative investigation period (Tables 1, 2), whereas stroke volume index increased pre- and intraoperatively; heart rate decreased in all patients as well as dp/dt (Fig. 1).(ABSTRACT TRUNCATED AT 250 WORDS)


Toxicity of a monoclonal F(ab')2:ricin A conjugate for retinoblastoma in vitro.
The toxic A chain of the poison ricin has been conjugated to the F(ab')2 fragment of a retinoblastoma-specific murine monoclonal antibody. The conjugate was toxic in vitro to Y-79 retinoblastoma cells at a concentration of approximately 5 X 10(-10) M; Y-79 retinoblastoma cells were the immunizing cells in the production of the monoclonal antibody. Against a second retinoblastoma cell line, the conjugate was toxic at a concentration of approximately 10(-9) M. Ricin A chain alone was not toxic to either of these cell lines at concentrations less than 4 X 10(-8) M. The conjugate was no more toxic than was ricin A chain against five control cell lines in vitro. The effect of the conjugate on retinoblastoma-derived cells was concentration dependent. Concentrations less than a "minimum" concentration were not cytotoxic, despite an excess of conjugate molecules over target cells. Concentrations greater than the minimum toxic concentration rapidly reached maximal toxicity, suggesting that antigenic sites were saturated. No clinical, hematologic, or renal toxicity was noted when mice were given injections of the conjugate at 1 mg/kg, or free ricin A chain at 0.375 mg/kg.


Alterations in antioxidant enzyme activities in cerebrospinal fluid related with severity of hypoxic ischemic encephalopathy in newborns.
The antioxidant status of the tissue affected by ischemia-reperfusion is of great importance for the primary endogenous defense against the free-radical-induced injury. In this study, we aimed to evaluate the relationship between the activities of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT)] in cerebrospinal fluid (CSF) and severity of hypoxic-ischemic encephalopathy (HIE) in newborns. Thirty full-term asphyxiated infants (gestational age >37 weeks) and 11 full-term infants (none of whom showed any signs of asphyxia) were included in this study. Activities of SOD, GPX, and CAT in CSF were measured within the first 72 h of life in infants with HIE and controls. Activity of SOD in CSF was significantly higher in infants with HIE compared with controls (p<0.05). GPX and CAT activities were higher in infants with HIE than they were in controls; however, the differences were not statistically significant (p > 0.05). The activities of GPX and CAT were significantly increased in severe HIE as compared with mild HIE and controls (p < 0.05). Both the duration of the hypoxic-ischemic insult and the severity of HIE modulate elevations of enzymatic activity as an adaptive response to excessive free radical production in CSF in newborn infants with HIE. The activities of antioxidant enzyme alterations in CSF correspond highly to the severity of HIE, and these patterns may be useful for diagnostic and prognostic purposes.


Information transfer in biological systems: targeting of proteins to specific organelles or to the extracellular environment (secretion).
Orderliness is the salient characteristic of living systems. Cells are intolerant of disorder. They express this by rapidly eliminating or degrading out-of-place molecules. When cells are broken apart and their constituent organelles separated and analysed, the same types of macromolecules are always associated with the same subcellular structures. One finds, for example, the same proteins in mitochondria time after time, and these differ from the sets of proteins found in nuclei, secretory granules, or plasma membranes. The information necessary to target each protein to its appropriate intracellular destination is determined primarily by the gene for that protein. Encoded within the DNA structure of genes are signals that specify where each protein molecule belongs. Thus, it is the transfer of information from one macromolecule to another that maintains the integrity and orderliness of living cells.


Composite electrospun nanofibers of reduced graphene oxide grafted with poly(3-dodecylthiophene) and poly(3-thiophene ethanol) and blended with polycaprolactone.
In this paper, an effective method was employed for preparation of nanofibers using conducting polymer-functionalized reduced graphene oxide (rGO). First, graphene oxide (GO) was obtained from graphite by Hommer method. GO was reduced to rGO by NaBH4 and covalently functionalized with a 3-thiophene acetic acid (TAA) by an esterification reaction to reach 3-thiophene acetic acid-functionalized reduced graphene oxide macromonomer (rGO-f-TAAM). Afterward, rGO-f-TAAM was copolymerized with 3-dodecylthiophene (3DDT) and 3-thiophene ethanol (3TEt) to yield rGO-f-TAA-co-PDDT (rGO-g-PDDT) and rGO-f-TAA-co-P3TEt (rGO-g-PTEt), which were confirmed by Fourier transform infrared spectra. The grafted materials depicted better electrochemical properties and superior solubilities in organic solvents compared to GO and rGO. The soluble rGO-g-PDDT and rGO-g-PTEt composites blended with polycaprolactone were fabricated by electrospinning, and then cytotoxicity, hydrophilicity, biodegradability and mechanical properties were investigated. The grafted rGO composites exhibited a good electroactivity behavior, mainly because of the enhanced electrochemical performance. The electrospun nanofibers underwent degradation about 7 wt% after 40 days, and the fabricated scaffolds were not able to induce cytotoxicity in mouse osteoblast MC3T3-E1 cells. The soluble conducting composites developed in this study are utilizable in the fabrication of nanofibers with tissue engineering application.


A Review on Adsorption Technologies for Mercury Emission Control.
This study summarized existing adsorption technologies for the removal of elemental mercury in the flue gas. Both carriers (e.g., active carbon (AC), pyrolyzed char, inorganic adsorbents and fly ash) and various modification methods (pore structure improvement, oxygen-containing functional groups addition and new active reagents impregnation) were compared to shed light on the development of future adsorption technology. AC and char possibly performed more mercury adsorption capacity (MAC) compared with fly ash and inorganic adsorbents since carbon atom existence was easier to form the active halogen groups (C-X) and oxygen containing groups. Though both pore structure improvement and chemical group formation improved the MAC of adsorbents, the chemical modification methods (oxygen-containing functional groups addition and new active reagents impregnation) were more effective. The impregnation of halogen, sulfur and metal chloride could distinctly form lots of active sites on the adsorbents and developed high effective mercury adsorbents. In the future, the adsorption researches possibly focus on SO2 and H2O resistance of adsorbents, separable adsorbents, low-cost chemical modification methods, and utilization potential of fly ash.


Moderate drinking: no impact on female fecundity.
To determine the effect of moderate alcohol intake on probability of conception. Prospective cohort study. Normal healthy women enrolled in an artificial donor insemination program. Women starting artificial donor insemination for the very first time were selected. Alcohol exposure was measured through a self-administered questionnaire at intake of study. A first positive pregnancy test as indicative for conception. Women with moderate alcohol intake had a slightly higher, though not significant, probability of conception compared with nondrinkers (Hazard Ratio 1.20; 95% confidence interval 0.90 to 1.60). Moderate alcohol intake has no negative impact on female fecundity.


Reciprocal uniparental disomy in yeast.
In the diploid cells of most organisms, including humans, each chromosome is usually distinguishable from its partner homolog by multiple single-nucleotide polymorphisms. One common type of genetic alteration observed in tumor cells is uniparental disomy (UPD), in which a pair of homologous chromosomes are derived from a single parent, resulting in loss of heterozygosity for all single-nucleotide polymorphisms while maintaining diploidy. Somatic UPD events are usually explained as reflecting two consecutive nondisjunction events. Here we report a previously undescribed mode of chromosome segregation in Saccharomyces cerevisiae in which one cell division produces daughter cells with reciprocal UPD for the same pair of chromosomes without an aneuploid intermediate. One pair of sister chromatids is segregated into one daughter cell and the other pair is segregated into the other daughter cell, mimicking a meiotic chromosome segregation pattern. We term this process "reciprocal uniparental disomy."


Circulatory effects of carbon dioxide in experimental endotoxic shock.
In seven anaesthetized dogs the central circulatory effects of changes in Paco2 were studied before and after an intravenous injection of E. coli endotoxin 1.0 mg kg-1. The animals were on controlled ventilation with constant minute volumes, and Paco2 was changed by variations in the inspired gas mixture. Before endotoxin was given, cardiac output, mean aortic pressure, mean pulmonary artery pressure, total peripheral resistance and stroke volume were little affected by the changes in Paco2 from 3.9 +/- 0.4 to 7.2 +/- 0.4 kPa (mean +/- s.e.mean). Only heart rate decreased significantly (P less than 0.05). The intravenous endotoxin injection resulted in a decreased cardiac output (P less than 0.01), a decreased mean aortic pressure (P less than 0.01) and a decreased stroke volume (P less than 0.05). Mean pulmonary artery pressure, total peripheral resistance and heart rate showed only minor changes. In endotoxic shock an increase in Paco2 from 4.4 +/- 0.4 to 7.8 +/- 0.3 kPa (mean +/- s.e.mean) resulted in a significant increase in cardiac output (P less than 0.05), stroke volume (P less than 0.05) and mean pulmonary artery pressure (P less than 0.05), while the other parameters remained unchanged. It can be concluded that the carbon dioxide tension is of importance for the cardiac performance in experimental endotoxic stock in a manner not seen in control animals. The mechanisms behind these findings need further investigation.


[Immunological and histological analyses of transarterial immuno-embolization therapy (TIE) in operable patients with hepatocellular carcinoma].
Immunological and histological analyses were performed on 14 patients with hepatocellular carcinoma treated by transcatheter immunoembolization (TIE) and subsequently by hepatic resection. They were compared with the cases treated by transcatheter arterial embolization (TAE). Exceptionally high plasma levels of inflammatory cytokines, such as IL-6 and IL-8, were noted 3 hours after TIE insults in the majority of the cases. On the contrary, exceptionally high levels of TNF-alpha were also observed in some cases of TIE treatment. In addition, light microscopically, the lytic necrosis of the tumor and massive infiltration of mononuclear cells were the histological characteristics of this treatment. Interestingly, the population of the infiltrates has altered after TIE treatment. It thus consisted mainly of neutrophils in early phase, subsequently of the mixture of lymphocytes, eosinophils, and plasma cells, and finally of lymphocytes. These results may suggest that certain inflammatory responses caused by TIE may play important roles in this new therapeutic modality.


Physiological properties of astroglial cell lines derived from mice with high (SAMP8) and low (SAMR1, ICR) levels of endogenous retrovirus.
Previous studies have reported that various inbred SAM mouse strains differ markedly with regard to a variety of parameters, such as capacity for learning and memory, life spans and brain histopathology. A potential cause of differences seen in these strains may be based on the fact that some strains have a high concentration of infectious murine leukemia virus (MuLV) in the brain, whereas other strains have little or no virus. To elucidate the effect of a higher titer of endogenous retrovirus in astroglial cells of the brain, we established astroglial cell lines from SAMR1 and SAMP8 mice, which are, respectively, resistant and prone to deficit in learning and memory and shortened life span. MuLV-negative astroglial cell lines established from ICR mice served as controls. Comparison of these cell lines showed differences in: 1) levels of the capsid antigen CAgag in both cell lysates and culture media, 2) expression of genomic retroelements, 3) the number of virus particles, 4) titer of infectious virus, 5) morphology, 6) replication rate of cells in culture and final cell concentrations, 7) expression pattern of proinflammatory cytokine genes. The results show that the expression of MuLV is much higher in SAMP8 than SAMR1 astrocyte cultures and that there are physiological differences in astroglia from the 2 strains. These results raise the possibility that the distinct physiological differences between SAMP8 and SAMR1 are a function of activation of endogenous retrovirus.


What can patients tell us about the quality and safety of hospital care? Findings from a UK multicentre survey study.
Patient safety measurement remains a global challenge. Patients are an important but neglected source of learning; however, little is known about what patients can add to our understanding of safety. We sought to understand the incidence and nature of patient-reported safety concerns in hospital. Feedback about the experience of safety within hospital was gathered from 2471 inpatients as part of a multicentre, waitlist cluster randomised controlled trial of an intervention, undertaken within 33 wards across three English NHS Trusts, between May 2013 and September 2014. Patient volunteers, supported by researchers, developed a classification framework of patient-reported safety concerns from a random sample of 231 reports. All reports were then classified using the patient-developed categories. Following this, all patient-reported safety concerns underwent a two-stage clinical review process for identification of patient safety incidents. Of the 2471 inpatients recruited, 579 provided 1155 patient-reported incident reports. 14 categories were developed for classification of reports, with communication the most frequently occurring (22%), followed by staffing issues (13%) and problems with the care environment (12%). 406 of the total 1155 patient incident reports (35%) were classified by clinicians as a patient safety incident according to the standard definition. 1 in 10 patients (264 patients) identified a patient safety incident, with medication errors the most frequently reported incident. Our findings suggest that patients can provide insight about safety that complements existing patient safety measurement, with a frequency of reported patient safety incidents that is similar to those obtained via case note review. However, patients provide a unique perspective about hospital safety which differs from and adds to current definitions of patient safety incidents. ISRCTN07689702; pre-results.


Comparison between 18F-FDG PET image-derived indices for early prediction of response to neoadjuvant chemotherapy in breast cancer.
The goal of this study was to determine the best predictive factor among image-derived parameters extracted from sequential (18)F-FDG PET scans for early tumor response prediction after 2 cycles of neoadjuvant chemotherapy in breast cancer. 51 breast cancer patients were included. Responder and nonresponder status was determined by histopathologic examination according to the tumor and node Sataloff scale. PET indices (maximum and mean standardized uptake value [SUV], metabolically active tumor volume, and total lesion glycolysis [TLG]), at baseline and their variation (Δ) after 2 cycles of neoadjuvant chemotherapy were extracted from the PET images. Their predictive value was investigated using Mann-Whitney U tests and receiver-operating-characteristic analysis. Subgroup analysis was also performed by considering estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, triple-negative, and HER2-positive tumors separately. The impact of partial-volume correction was also investigated using an iterative deconvolution algorithm. There were 24 pathologic nonresponders and 27 responders. None of the baseline PET parameters was correlated with response. After 2 neoadjuvant chemotherapy cycles, the reduction of each parameter was significantly associated with response, the best prediction of response being obtained with ΔTLG (96% sensitivity, 92% specificity, and 94% accuracy), which had a significantly higher area under the curve (0.91 vs. 0.82, P = 0.01) than did ΔSUVmax (63% sensitivity, 92% specificity, and 77% accuracy). Subgroup analysis confirmed a significantly higher accuracy for ΔTLG than ΔSUV for ER-positive/HER-negative but not for triple-negative and HER2-positive tumors. Partial-volume correction had no impact on the predictive value of any of the PET image-derived parameters despite significant changes in their absolute values. Our results suggest that the reduction after 2 neoadjuvant chemotherapy cycles of the metabolically active volume of primary tumor measurements such as ΔTLG predicts histopathologic tumor response with higher accuracy than does ΔSUV measurements, especially for ER-positive/HER2-negative breast cancer. These results should be confirmed in a larger group of patients as they may potentially increase the clinical value and efficiency of (18)F-FDG PET for early prediction of response to neoadjuvant chemotherapy.


Ozone interactions with carpet: secondary emissions of aldehydes.
Ozone-induced formation of aldehydes was studied on the surface and in the gas phase above carpets and on carpet components. Samples of four carpets were exposed to 100 ppb ozone. Emission rates of aldehydes and other organic compounds were measured from exposed and unexposed samples. Surface interactions of ozone with carpets produced C1-C13 n-aldehydes and several unsaturated aldehydes. Total aldehyde emission rates increased markedly with ozone exposure, from 1 to 70 microg m(-2) h(-1) for unexposed samples, to 60-800 microg m(-2) h(-1) during exposure. One exposed sample emitted large amounts of 2-nonenal (180-230 microg m(-2) h(-1)), a compound with a low odor threshold. Material balance modeling of a residence with this high emitting carpet suggests (1) that the concentration of 2-nonenal would be well above its odor threshold even in areas with only moderate ambient ozone levels and (2) that odorous levels of 2-nonenal could persist for years. Reactions of ozone with gas-phase primary emissions from carpet significantly reduced the levels of 4-phenylcyclohexene and produced small amounts of branched ketones. Separately measured patterns of aldehyde emissions from ozone exposure of linseed and tung oils were similar but not identical to those observed from ozone-exposed carpets.


Binaural phase differences and binaural auditory adaptation.
In order to determine the relationship between binaural phase localization and auditory adaptation, subjects were asked to perform a series of phase-based localization tasks, as well as an SDLB adaptation task. A binaurally presented 400 Hz tone was used for midplane localization tasks, and adaptation balances. The tone was presented monaurally during adaptation after binaural localization and the SDLB pre-test. Following 7 min exposure, subjects readjusted phase to centre the binaural stimulus in the midline, and then adjusted intensity to determine dB of adaptation. No consistent or statistically significant change in phase settings occurred. There was a significant decline in the balance intensity as a function of adaptation. A further re-establishment of the midline by phase manipulation also showed no localization effect. For the stimulus values used in the present study, there was no inter-effect of binaural phase localization, and SDLB auditory adaptation.


Development of noise controls for longwall shearer cutting drums).
Noise-induced hearing loss is the second most pervasive disease in the mining industry. The exposure of miners to noise levels above the permissible exposure level results in hearing loss of approximately 80% of coal miners by retirement age. In addition, between 2002 and 2011, approximately 48% of longwall shearer operators were overexposed in coal mines in the United States. Previous research identified the two rotating cutting drums used by the longwall shearer to extract coal as the most significant sound-radiating components. In this context, the National Institute for Occupational Safety and Health conducted research to develop noise controls for longwall mining systems. To this end, structural and acoustic numerical models of a single cutting drum were developed to assess its dynamic and acoustic response, respectively. Once validated, these models were used to explore various noise control concepts including force isolation, varying structural damping and varying component stiffness. Upon multiple simulations, it was determined that structural modifications to increase the stiffness of the outer vane plates were the most practical and durable approach to reduce the sound radiated by the cutting drums. Furthermore, these modifications did not adversely affect the cutting performance, nor the loading ability of the drums. As a result, these structural modifications were implemented into an actual set of drums for evaluation purposes. Results from the underground evaluation, when the modified cutting drums were used under normal operation conditions, showed noise reduction across the entire frequency spectrum with an overall noise reduction of 3 dB in the sound pressure level at the operator location, confirming the validity of the developed noise controls.


Response Surface Optimization of Supercritical Carbon Dioxide Extraction of Tea Polyphenols from Green Tea Scraps.
Background: The green tea scraps are the waste materials during the process of green tea production, and it is significant to extract valuable tea polyphenols (TP) for reuse. Objective: The objective of this study was to extract valuable TP from green tea scraps, and the extraction conditions were optimized to obtain maximum yield of TP. Methods: The TP were extracted by supercritical carbon dioxide (SC-CO₂) with 65% (v/v) aqueous ethanol solution as cosolvent. The content of TP was determined with the Folin-Ciocalteu method. The key factors of the extraction process, including temperature (313.15-323.15 K), pressure (20-30 Mpa), and amount of cosolvent (50-150 mL) were optimized by response surface methodology (RSM). Results: These key factors showed the extremely complex effects on the extraction yield of TP. A second-order polynomial mathematical model was developed for the response with high R-squared value (R² = 0.9946) and used to predict the optimal conditions (i.e., temperature of 322.15 K, pressure of 23.60 MPa, and amount of cosolvent of 150 mL). The verification experiments showed that the maximum yield of TP was 23.07 ± 0.82% under the optimal conditions, which was in good agreement with the predicted value. Conclusions: TP can be successfully extracted from green tea scraps by SC-CO₂, and RSM could be used to optimize the extraction process. Highlights: SC-CO₂ extraction of TP from green tea scraps was developed. The operating conditions, including pressure, temperature, and amount of cosolvent, were optimized. RSM could successfully predict the optimal operating conditions.


Optimized Nuclear Pellet Method for Extracting Next-Generation Sequencing Quality Genomic DNA from Fresh Leaf Tissue.
Next-generation sequencing (NGS) is a revolutionary advancement allowing large-scale discovery of functional molecular markers that has many applications, including plant breeding. High-quality genomic DNA (gDNA) is a prerequisite for successful NGS library preparation and sequencing; however, few reliable protocols to obtain such plant gDNA exist. A previously reported nuclear pellet (NP) method enables extraction of high-yielding gDNA from fresh leaf tissue of maize (Zea mays L.), but the quality does not meet the stringent requirements of NGS. In this study, we optimized the NP method for whole-genome sequencing of rice (Oryza sativa L.) through the integration of simple purification steps. The optimized NP method relied on initial nucleus enrichment, cell lysis, extraction, and subsequent gDNA purification buffers. The purification steps used proteinase K, RNase A, phenol/chloroform/isoamyl alcohol (25:24:1), and chloroform/isoamyl alcohol (24:1) treatments for protein digestion and RNA, protein, and phenol removal, respectively. Our data suggest that this optimized NP method allowed extraction of consistently high-yielding and high-quality undegraded gDNA without contamination by protein and RNA. Moreover, the extracted gDNA fulfilled the quality metrics of NGS library preparation for the Illumina HiSeq X Ten platform by the TruSeq DNA PCR-Free Library Prep Kit (Illumina). We provide a reliable step-by-step guide to the extraction of high-quality gDNA from fresh leaf tissues of rice for molecular biologists with limited resources.


Acute suicidal intoxication with tacrolimus in a kidney transplant patient.
A case of a 23-year-old female, after renal transplant, who had tried to commit suicide with 100 mg of Prograf was described. In the presented case despite the relatively high tacrolimus blood concentration level (>30 microg/l) only severe 5-hour lasting headache and short-term mild hyperglycaemia (7.22 mmol/l), hyperkalemia (5.4 mmol/l) and considerable leukocytosis (19.52 x 10(3)) were observed. In this case there was mild clinical course of intoxication despite tacrolimus high blood concentration. It could not be excluded that early administration of gastric lavage and activated carbon was partly responsible for mild course of poisoning.


Control of growth and differentiation of normal human epithelial cells through the manipulation of reactive nitrogen species.
In this work, we addressed the issue of whether exogenous NO and ONOO- (peroxynitrite) are able to alter growth, viability and/or differentiation of normal epithelial cells using cultured normal human keratinocytes as a model. 3-Morpholino-sydnonimine (SIN-1), a donor of both NO and O2(-)., leading to the production of ONOO-, dose-dependently inhibited growth of human keratinocytes without loss of viability. This inhibitory effect was lowered when SIN-1 was transformed into a pure NO donor by scavenging O2(-). with superoxide dismutase/catalase. Finally, scavenging NO release from SIN-1 with carboxy-1H-imidazol-1-yloxy,2-(4-carboxyp henyl)-4,5-dihydro-4,4,5,5 -tetramethyl-3-oxide (PTIO) resulted in a loss of the inhibitory effect of SIN-1. Together these findings suggest that both ONOO- and NO exert a growth inhibitory effect on human keratinocytes without cytotoxicity. Further support for this conclusion came from the treatment of human keratinocytes with the NO. donor propanamine 3-(2-hydroxy-2-nitroso-1-propyl hydrazino) or with authentic peroxynitrite. Moreover, only SIN-1 or peroxynitrite, and not NO, was able to trigger the expression of markers of terminal differentiation in human keratinocytes. From a physiological perspective, the ability of peroxynitrite, a known genotoxic and potentially carcinogenic agent, to direct proliferating keratinocytes towards terminal differentiation may be crucial to protect the genomic stability of this barrier epithelium.


Solitary intraosseous neurofibroma of mandible.
Solitary intraosseous neurofibroma is a rare benign non-odontogenic tumor. Although neurofibromas occur predominantly as a feature of neurofibromatosis affecting the soft tissue, a few cases of solitary intraosseous neurofibromas of the jaw have been reported. We herewith report a case of solitary intraosseous neurofibroma of mandible in a middle-aged woman with a discussion on its clinical, radiological, and histopathological presentation along with review of cases.


Obesity and supermarket access: proximity or price?
We examined whether physical proximity to supermarkets or supermarket price was more strongly associated with obesity risk. The Seattle Obesity Study (SOS) collected and geocoded data on home addresses and food shopping destinations for a representative sample of adult residents of King County, Washington. Supermarkets were stratified into 3 price levels based on average cost of the market basket. Sociodemographic and health data were obtained from a telephone survey. Modified Poisson regression was used to test the associations between obesity and supermarket variables. Only 1 in 7 respondents reported shopping at the nearest supermarket. The risk of obesity was not associated with street network distances between home and the nearest supermarket or the supermarket that SOS participants reported as their primary food source. The type of supermarket, by price, was found to be inversely and significantly associated with obesity rates, even after adjusting for individual-level sociodemographic and lifestyle variables, and proximity measures (adjusted relative risk=0.34; 95% confidence interval=0.19, 0.63) Improving physical access to supermarkets may be one strategy to deal with the obesity epidemic; improving economic access to healthy foods is another.


Long Non-Coding RNA LINC00525 Promotes the Stemness and Chemoresistance of Colorectal Cancer by Targeting miR-507/ELK3 Axis.
This study aims to explore the effects of a long non-coding RNA, LINC00525, on colorectal cancer (CRC) and its underlying molecular mechanisms. The qPCR, MTT, colony formation, Western blotting, Luciferase reporter and biotin pull-down, shRNA knockdown and DNA fragmentation assays were performed in this study. High expressions of LINC00525 were associated with poor prognosis of CRC patients. LINC00525 knockdown decreased stemness properties and increased sensitivities to oxaliplatin. MiR-507 was a direct target of LINC00525 and overexpression of miR-507 significantly decreased abilities of tumorsphere formation and cell growth. Overexpression of miR-507 resulted in a decrease of expression of cancer stem cell markers and the increase of apoptosis rates. MiR-507 regulated the expression of ELK3. In addition, LINC00525 knockdown decreased the expression of ELK3. Restoration of ELK3 expression abrogated the effects of LINC00525 knockdown. LINC00525 could be served as prognostic marker of CRC. LINC00525 enhanced stemness properties and increased sensitivities of CRC cells to oxaliplatin by targeting miR-507/ELK3 axis.


Anatomic diagnosis of congenital heart disease. A practical approach based on the sequentiality principle.
Based on the sequentiality principle, this review proposes a practical method that allows the systematization of the anatomic diagnosis of congenital heart disease. We emphasize the need to use sequential connection between the different cardiac segments: atria, ventricles and great arteries. Five ordered steps are defined, which include determination of atrial situs and of the connection features between the ventricles and the great arteries. Related lesions and some additional special features are a second stage in the sequential analysis of congenital heart disease, which is also important for the integral diagnosis.


Elemental sulphur recovery from a sulphate-rich aqueous stream in a single hybrid linear flow channel reactor is mediated through microbial community dynamics and adaptation to reactor zones.
The coupled application of biological sulphate reduction (BSR) and partial sulphide oxidation to treat sulphate-rich wastewater is an effective strategy to mitigate pollution and recover elemental sulphur for repurposing. The recent development of the hybrid linear flow channel reactor (LFCR) achieves simultaneous BSR and partial sulphide oxidation with biosulphur recovery via a floating sulphur biofilm (FSB). Here, we explore the microbial community zoning and dynamics facilitating the process. A total of three continuous LFCRs were used to evaluate the effect of reactor zones, hydraulic residence time (HRT), carbon source, namely lactate and acetate, as well as reactor geometry and scale on process performance and microbial community dynamics. Community composition of sessile and planktonic microbial consortia were resolved at a 5- and 2-day HRT through 16S rRNA amplicon sequencing. Preferential attachment and prevalence of specific phylotypes within the sessile and planktonic communities revealed clear adaptation of key microorganisms to different microenvironments. Key microbial taxa affiliated with sulphate reduction and sulphide oxidation as well as those implicated in fermentation and syntrophic metabolism, fluctuated in response to changes in HRT and process performance. Through understanding the relationship between microbial community dynamics and process performance, this research will inform better process design and optimization of the hybrid LFCR.


Neuroprotective and axonal outgrowth-promoting effects of tetramethylpyrazine nitrone in chronic cerebral hypoperfusion rats and primary hippocampal neurons exposed to hypoxia.
Chronic cerebral hypoperfusion is an important risk factor for vascular dementia and other brain dysfunctions, for which there are currently no effective medications available. We investigated the neuroprotective and axonal outgrowth promoting effects of tetramethylpyrazine nitrone (TBN) in a permanent bilateral occlusion of the common carotid arteries (2VO) rat model and in primary hippocampal neurons exposed to oxygen glucose deprivation (OGD). At 6th week after 2VO, TBN increased the time spent in novel arms in the Y-maze test and improved the discrimination ratio in object reorganization task. TBN attenuated axonal damage, and reduced oxidative DNA injury and lipid peroxidation in white matter. TBN also attenuated the neuronal apoptosis and ameliorated accumulation of astrocytes in parietal cortex and CA1 region of hippocampus. Western blot analyses indicated that TBN increased Bcl-2 expression, decreased Bax and Caspase 3 expressions, and upregulated the phosphorylation levels of high-molecular weight neurofilament (p-NFH), Akt (p-Akt) and glycogen synthase kinase-3β (p-GSK3β) in hippocampus at 6th week after chronic hypoperfusion. In vitro, TBN rescued hippocampal neuronal viability and axonal elongation from OGD damage. The p-Akt and p-GSK3β upregulation by TBN was abolished by a specific phosphoinositide 3-kinase (PI3K) inhibitor LY294002, resulting in suppression of axonal outgrowth. Collectively, the results showed that TBN alleviated white matter lesion and impairment of cortex and hippocampus, attenuated oxidative damage and enhanced axonal outgrowth through the regulation of PI3K/Akt/GSK3β signaling pathway, leading to improved cognitive deficit in a rat chronic hypoperfusion model.


POTENTIATION OF THE LETHAL EFFECT OF ENDOTOXIN BY HETEROLOGOUS PLASMA.
The intravenous injection of endotoxin in human plasma into rabbits produces a marked potentiation of lethal effect, when compared to the mortality associated with comparable doses of endotoxin in saline alone. A similar enhancement was noted with other heterologous plasma (guinea pig, rat) but not with homologous plasma. The potentiating factor is not in the albumin or gamma globulin fractions, is not concerned with fibrinogen, and is heat-labile. Tolerance of the recipient animal to endotoxin destroys the lethal effect. Within a period of 3 hours, endotoxin and human plasma may be administered separately, without regard to timing or sequence, without loss of the lethal effect. The enhancement of lethal effect is not avoided by pretreatment with heparin or cortisone. Preliminary experiments indicate that the loss of lethal effect found after incubation of endotoxin-plasma mixtures may be due to a separate inhibitor, but is not due to loss of the potentiating factor.


Antidipsogenic effect of endotoxin in the rat.
Escherichia coli LPS (640-1280 mcg/Kg, intravenously) showed a powerful, dose-dependent and long-lasting inhibitory effect on drinking behavior stimulated by 48 h water deprivation, subcutaneous injection of isoprenaline (33.3 mcg/Kg) and intracerebroventricular injection of hypertonic NaCl (2.9%) solution, carbachol (250 ng) and angiotensin II (100 ng). The antidipsogenic effect was neither a consequence of behavioral alterations, nor due to endotoxin peripheral vasodilating activity. Naloxone (60-120-240 mcg/Kg, subcutaneously) did not influence endotoxin inhibition of water intake, thus ruling out an endorphin-mediated effect. When prostaglandin synthesis was inhibited, the effect of endotoxin was reduced. Since prostaglandins do not seem to be involved in the regulation of thirst, the mechanism of the antidipsogenic effect elicited by endotoxin needs further study.


Long-term medical outcomes and quality-of-life assessment of patients with chronic myeloid leukemia followed at least 10 years after allogeneic bone marrow transplantation.
Benchmark analysis of patients with chronic myeloid leukemia (CML) alive for more than 10 years after allogeneic bone marrow transplantation (BMT) including data on disease status, bone marrow reserve, long-term complications, and quality of life (QOL). Eighty-nine patients (46 in first chronic phase, 43 in advanced phase) received an allogeneic BMT for CML during the study period. Medical outcomes and QOL of patients were analyzed retrospectively. Twenty-eight (31.5%) of 89 patients were alive at 10 years and included in this analysis. Thirteen (46.4%) of 28 long-term survivors never relapsed. Fifteen patients relapsed between 0.5 and 16 years after transplantation. Ten patients showed a hematologic relapse and received salvage treatment. Five patients showed transient low levels of BCR-ABL-positive cells by Southern blot with no subsequent hematologic relapse. One of the 28 patients died in blast crisis at 12 years. The most frequent long-term complications were chronic graft-versus-host disease, osteoporosis, and cataracts. Frequency of clonogenic progenitors remained persistently decreased. QOL assessment yielded lower scores in physical performance as compared with an age-matched normative population, whereas social functioning was equivalent. A high degree of satisfaction was noted with interpersonal relationships. Patients with CML surviving their BMT long term do well in terms of medical outcomes. A constant rate of relapse was noted, with a high salvage rate of affected patients, suggesting the need for lifelong monitoring. QOL is perceived as good, particularly as related to social functioning; however, it is inferior to a normative population with regard to physical performance.


Splitting p63.
Causative TP63 mutations have been identified in five distinct human developmental disorders that are characterized by various degrees of limb abnormalities, ectodermal dysplasia, and facial clefts. The distribution of mutations over the various p63 protein domains and the structural and functional implications of these mutations establish a clear genotype-phenotype correlation.


The effect of P-glycoprotein and cytochrome P450 3a on the oral bioavailability of vinorelbine in mice.
This study was designed to determine the effects of P-glycoprotein (P-gp) and cytochrome P450 3a metabolism on the oral bioavailability of the vinca alkaloid Vinorelbine (Navelbine; VRL). Pharmacokinetics of VRL were determined in FVB wild-type and mdr1a/1b (-/-) mice after oral and intravenous administration of 10 mg/kg VRL with or without oral ritonavir (5 mg/kg) prior to VRL. Serial blood samples were drawn for a period of up to 48 hours using mice with a cannulated jugular vein. Feces was collected for a period of 96 hours. VRL was determined by ion-exchange HPLC in combination with fluorescence detection. The oral bioavailability in wild-type was 16.0+/-1.4% (mean+/-SE) and was not significantly higher in mdr1a/1b (-/-) mice (17.9+/-0.7%). Both after intravenous and oral administration, the AUC was not significantly different between wild-type and mdr1a/1b(-/-) mice. When RTV was co-administered the AUC of intravenous VRL increased significantly by 30% (p = 0.012). Because RTV increased the AUC of oral VRL by 83% the oral bioavailability was increased to 22.5+/-2.3% (p = 0.016). The fecal recovery of unchanged VRL was about 34 and 6% of the dose in wild-type and mdr1a/1b(-/-) mice, respectively, and was not altered by RTV. This study shows that P-gp has little effect on the disposition and oral bioavailability of VRL. A substantial fraction of an oral dose of VRL is absorbed from the gut of wild-type mice. Consequently, first-pass metabolism is the most important factor for explaining the modest oral bioavailability, but the results with RTV suggest that cyp3a plays only a modest role in metabolic breakdown in mice. Apparently, other routes of metabolic elimination are more important. These results suggest that also in patients the oral bioavailability may not gain substantially from the co-administration of a potent P-gp and/or Cyp3a inhibitor.


Randomized Study of Early Continuous Positive Airways Pressure in Acute Respiratory Failure in Children With Impaired Immunity (SCARF) ISRCTN82853500.
Previous trials in adults with impaired immunity and respiratory failure suggest that early noninvasive ventilation avoids endotracheal intubation and improves survival. No randomized clinical trials have addressed this question in children. We undertook an open, parallel-group randomized trial in three pediatric hospitals. Children with impaired immunity and acute respiratory failure defined as tachypnoea (> 90th centile); a new requirement for supplemental oxygen; and new chest radiograph infiltrates. Children were randomly assigned to early PICU admission for continuous positive airways pressure (early continuous positive airways pressure) or to standard care. The primary outcome was endotracheal intubation by 30 days. One-hundred fourteen children met inclusion criteria of whom 42 were randomized between January 2013 and January 2016. There was no significant difference in endotracheal intubation by 30 days with early continuous positive airways pressure (10/21; 48%) compared with standard care (5/21; 24%), odds ratio 2.9 (0.8-10.9), p value equals to 0.11. However, 30-day mortality was significantly higher with early continuous positive airways pressure (7/21; 33%) compared with standard care (1/21; 5%), odds ratio 10.0 (1.1-90.6), p value equals to 0.041. Mortality at 90 days was early continuous positive airways pressure (11/21; 52%) versus standard care (4/21; 19%), odds ratio 4.7 (1.2-18.6), p value equals to 0.029, whereas mortality at 1 year was similar early continuous positive airways pressure (13/21; 61.9%) versus standard care (9/21; 42.7%), odds ratio 2.2 (0.6-7.4), p value equals to 0.22. There were two serious adverse events: early continuous positive airways pressure (pneumothorax) and standard care (hemothorax). This study provided no evidence to support early PICU admission for continuous positive airways pressure in children with acute respiratory failure and impaired immunity. There was a trend toward increased endotracheal intubation and a higher early mortality in the early continuous positive airways pressure group.


Prevention of congenital toxoplasmosis in Slovenia by serological screening of pregnant women.
A programme for the prevention of congenital toxoplasmosis in Slovenia involving the screening of pregnant women for Toxoplasma infection is presented. Of 21,270 pregnant women screened for toxoplasmosis between, 1996 and the end of 1999, 13,987 (66%) were seronegative, 7,151 (34%) seropositive and 132 had primary infection; approximately 9/1,000 women were at risk of acquiring the primary infection. One hundred live-born infants of primary infected women were available for follow-up. Nine infected but asymptomatic children were born to mothers who were screened and treated in time and two congenitally infected babies were born to mothers in whom infection was detected too late in pregnancy and who therefore received no adequate treatment. It is suggested that the results obtained in this study outweigh the cost of screening for toxoplasmosis in pregnancy. Pregnant women should always be tested at the beginning of pregnancy and, in cases of seronegativity, should be re-tested in the second and third trimesters of the pregnancy. Toxoplasma primary infected pregnant women and neonates should be treated as soon as possible. However, long-term follow-up of children born to primary infected women would be necessary for an accurate evaluation of the effectiveness of the screening because of the possibility of late onset of symptoms.


Radio-tracking reveals how wind and temperature influence the pace of daytime insect migration.
Insects represent the most diverse and functionally important group of flying migratory animals around the globe, yet their small size makes tracking even large migratory species challenging. We attached miniaturized radio transmitters (less than 300 mg) to monarch butterflies ( Danaus plexippus) and common green darner dragonflies ( Anax junius) and tracked their autumn migratory movements through southern Ontario, Canada and into the United States using an automated array of over 100 telemetry towers. The farthest estimated distance a monarch travelled in a single day was 143 km at a wind-assisted groundspeed of 31 km h-1 (8.7 m s-1) and the farthest estimated distance a green darner travelled in a single day was 122 km with a wind-assisted groundspeed of up to 77 km h-1 (21.5 m s-1). For both species, increased temperature and wind assistance positively influenced the pace of migration, but there was no effect of precipitation. While limitations to tracking such small animals remain, our approach and results represent a fundamental advance in understanding the natural history of insect migration and environmental factors that govern their movements.


Visualizing tactile feedback: an overview of current technologies with a focus on ultrasound elastography.
Tissue elasticity remains an essential biomarker of health and is indicative of irregularities such as tumors or infection. The timely detection of such abnormalities is crucial for the prevention of disease progression and complications that arise from late-stage illnesses. However, at both the bedside and the operating table, there is a distinct lack of tactile feedback for deep-seated tissue. As surgical techniques advance toward remote or minimally invasive options to reduce infection risk and hasten healing time, surgeons lose the ability to manually palpate tissue. Furthermore, palpation of deep structures results in decreased accuracy, with the additional barrier of needing years of experience for adequate confidence of diagnoses. This review delves into the current modalities used to fulfill the clinical need of quantifying physical touch. It covers research efforts involving tactile sensing for remote or minimally invasive surgeries, as well as the potential of ultrasound elastography to further this field with non-invasive real-time imaging of the organ's biomechanical properties. Elastography monitors tissue response to acoustic or mechanical energy and reconstructs an image representative of the elastic profile in the region of interest. This intuitive visualization of tissue elasticity surpasses the tactile information provided by sensors currently used to augment or supplement manual palpation. Focusing on common ultrasound elastography modalities, we evaluate various sensing mechanisms used for measuring tactile information and describe their emerging use in clinical settings where palpation is insufficient or restricted. With the ongoing advancements in ultrasound technology, particularly the emergence of micromachined ultrasound transducers, these devices hold great potential in facilitating early detection of tissue abnormalities and providing an objective measure of patient health.


The neurobiology of adaptive learning in reading: a contrast of different training conditions.
fMRI was used to investigate the separate influences of orthographic, phonological, and semantic processing on the ability to learn new words and the cortical circuitry recruited to subsequently read those words. In a behavioral session, subjects acquired familiarity for three sets of pseudowords, attending to orthographic, phonological, or (learned) semantic features. Transfer effects were measured in an event-related fMRI session as the subjects named trained pseudowords, untrained pseudowords, and real words. Behaviorally, phonological and semantic training resulted in better learning than did orthographic training. Neurobiologically, orthographic training did not modulate activation in the main reading regions. Phonological and semantic training yielded equivalent behavioral facilitation but distinct functional activation patterns, suggesting that the learning resulting from these two training conditions was driven by different underlying processes. The findings indicate that the putative ventral visual word form area is sensitive to the phonological structure of words, with phonologically analytic processing contributing to the specialization of this region.


Recovery from a variegate porphyria by a liver transplantation.
The porphyrias are a group of inherited or acquired enzymatic defects of heme biosynthesis. Each type of porphyria has a characteristic pattern of overproduction and accumulation of heme precursors based on the location of dysfunctional enzyme in the heme synthetic pathway. Variegate porphyria, one of the acute hepatic porphyrias, is characterized by a partial reduction in protoporphyrinogen oxidase, the seventh enzyme of the heme biosynthetic pathway. A case of liver transplantation is described with a recovery from a variegate porphyria. Acute porphyria is commonly worsened by a wide variety of medications. We describe a step-by-step perioperative management protocol.


Autoregulation of RBM10 and cross-regulation of RBM10/RBM5 via alternative splicing-coupled nonsense-mediated decay.
Mutations in the spliceosomal RNA binding protein RBM10 cause TARP syndrome and are frequently observed in lung adenocarcinoma (LUAD). We have previously shown that RBM10 enhances exon skipping of its target genes, including its paralog RBM5. Here, we report that RBM10 negatively regulates its own mRNA and protein expression and that of RBM5 by promoting alternative splicing-coupled nonsense-mediated mRNA decay (AS-NMD). Through computational analysis and experimental validation, we identified RBM10-promoted skipping of exon 6 or 12 in RBM10 and exon 6 or 16 in RBM5 as the underlying AS-NMD events. Importantly, we showed that LUAD-associated mutations affecting splice sites of RBM10 exons 6 or 12 abolished exon inclusion and correlated with reduced expression of RBM10 RNA. Together, our investigations have revealed novel molecular mechanisms underlying RBM10 autoregulation and cross-regulation of RBM5, thereby providing insights concerning the functions of RBM10 under various physiological and pathological conditions. Our combined computational and experimental approach should be useful for elucidating the role of AS-NMD in auto- and cross-regulation by other splicing regulators.


Applications of artificial intelligence in clinical management, research, and health administration: imaging perspectives with a focus on hemophilia.
Joints of persons with hemophilia are frequently affected by repetitive hemarthrosis. In this paper, concepts, perks, and quirks of the use of artificial intelligence (AI), machine learning (ML), and deep learning are reviewed within clinical and research contexts of hemophilia and other blood-induced disorders' patient care, targeted to the imaging diagnosis of hemophilic joints, under the perspective of different stakeholders (radiologists, hematologists, nurses, physiotherapists, technologists, researchers, managers, and patients/caregivers). Rubrics that determine the suitability of the utilization of AI in blood-induced disorders' patient care, including diagnosis and follow-up of patients are discussed, focusing on features in which AI can replace or augment the role of radiology in the clinical management and in research of patients. Insights on features in the design and conduct of AI projects in which the human intervention remains critical are provided. The author discusses research concepts in radiogenomics, and challenges for the utilization of AI in different healthcare fields such as patient safety, data sharing and privacy regulations, workforce education and future jobs' shortage. Finally, the author proposes alternatives and potential solutions to mitigate challenges in successfully deploying ML algorithms into clinical practice.


Comparison of Prehospital Assessment by Paramedics and In-Hospital Assessment by Physicians in Suspected Stroke Patients: Results From 2 Prospective Cohort Studies.
It is unknown if ambulance paramedics adequately assess neurological deficits used for prehospital stroke scales to detect anterior large-vessel occlusions. We aimed to compare prehospital assessment of these stroke-related deficits by paramedics with in-hospital assessment by physicians. We used data from 2 prospective cohort studies: the LPSS (Leiden Prehospital Stroke Study) and PRESTO study (Prehospital Triage of Patients With Suspected Stroke). In both studies, paramedics scored 9 neurological deficits in stroke code patients in the field. Trained physicians scored the National Institutes of Health Stroke Scale (NIHSS) at hospital presentation. Patients with transient ischemic attack were excluded because of the transient nature of symptoms. Spearman rank correlation coefficient (rs) was used to assess correlation between the total prehospital assessment score, defined as the sum of all prehospital items, and the total NIHSS score. Correlation, sensitivity and specificity were calculated for each prehospital item with the corresponding NIHSS item as reference. We included 2850 stroke code patients. Of these, 1528 had ischemic stroke, 243 intracranial hemorrhage, and 1079 stroke mimics. Correlation between the total prehospital assessment score and NIHSS score was strong (rs=0.70 [95% CI, 0.68-0.72]). Concerning individual items, prehospital assessment of arm (rs=0.68) and leg (rs=0.64) motor function correlated strongest with corresponding NIHSS items, and had highest sensitivity (arm 95%, leg 93%) and moderate specificity (arm 71%, leg 70%). Neglect (rs=0.31), abnormal speech (rs=0.50), and gaze deviation (rs=0.51) had weakest correlations. Neglect and gaze deviation had lowest sensitivity (52% and 66%) but high specificity (84% and 89%), while abnormal speech had high sensitivity (85%) but lowest specificity (65%). The overall prehospital assessment of stroke code patients correlates strongly with in-hospital assessment. Prehospital assessment of neglect, abnormal speech, and gaze deviation differed most from in-hospital assessment. Focused training on these deficits may improve prehospital triage.


US regional and demographic differences in prescription opioid and heroin-related overdose hospitalizations.
US opioid overdose death rates have increased between 2000 and 2014. While, the increase in prescription opioid use has been linked to the increase in heroin use, there are reasons to view this relationship as a partial explanation for the recent increase in heroin-related harms. This study documents the differences in trends in prescription opioid overdose-related (POD) and heroin overdose-related (HOD) hospitalizations. Data come from the National Inpatient Sample (NIS) for the years 2000 through 2014. POD and HOD hospitalizations were abstracted from ICD-9 codes. Rates of POD and HOD by census region and census division were constructed along with separate rates for age and race. Regression analysis analyzing trends across region were estimated along with graphs for documenting differences in POD and HOD rates. POD hospitalization rates were highest in the South and lowest in the Northeast. HOD hospitalization rates were highest in the Northeast region and grew the fastest in the Midwest. There was statistically significant heterogeneity in HOD trends but not POD trends across the four regions between 2000 and 2014. Between 2012 and 2014 POD rates decreased in eight of the nine census divisions, with only New England showing an increase. HOD hospitalization rates increased in all nine census divisions between 2012 and 2014. Both POD and HOD rates show different demographic patterns across the nine census divisions. Comparing POD and HOD hospitalization trends reveals significant disparities in geographic as well as demographic distributions. These epidemics are evolving and the simple opioid-to-heroin transition story is both supported and challenged by this paper. The opioid pill, heroin and fentanyl crises are intertwined yet increasingly have drivers and outcomes that support examining them as distinct. Addressing these complex and interrelated epidemics will require innovative public health research and interventions which need to consider local and regional contexts.


EFFECT OF THE ANTIPARASITIC DRUG MEBENDAZOLE ON CHOLANGIOCARCINOMA GROWTH.
Mebendazole (MBZ) is an anthelmintic drug which inhibits tubulin polymerization and eventually causes apoptosis in target organisms. Antitumor activity of MBZ has been reported in various cancers. The aim of this study was to investigate the effect of MBZ on cholangiocarcinoma (CCA) cells in vitro and in vivo. MBZ reduced cell proliferation in the KKU-M213 cell line associated with a remarkable enhancement of caspase-3 gene expression and enzyme activity. Oral administration of MBZ slightly reduced the growth rate of subcutaneously xeno-grafted KKU-M213 in nude mice. The TUNEL assay showed an increase of apoptotic cell numbers in the xenograft tumor tissue of MBZ-treated mice. The data obtained in this study suggested that MBZ can suppress CCA cell proliferation via caspase-3 activated apoptosis. Further investigation of the antitumor effects of MBZ might support the use of MBZ as an alternative drug for CCA treatment.


Basic fibroblast growth factor evokes a rapid glutamate release through activation of the MAPK pathway in cultured cortical neurons.
We examined the possibility that basic fibroblast growth factor (bFGF) is involved in synaptic transmissions. We found that bFGF rapidly induced the release of glutamate and an increase in the intracellular Ca2+ concentration through voltage-dependent Ca2+ channels in cultured cerebral cortical neurons. bFGF also evoked a significant influx of Na+. Tetanustoxin inhibited the bFGF-induced glutamate release, revealing that bFGF triggered exocytosis. The mitogen-activated protein kinase (MAPK) pathway was required for these acute effects of bFGF. We also found that pretreatment with bFGF significantly enhanced high K+-elicited glutamate release also in a MAPK activation-dependent manner. Therefore, we propose that bFGF exerts promoting effects on excitatory neuronal transmission via activation of the MAPK pathway.


A critical role for long-term potentiation mechanisms in the maintenance of object recognition memory in perirhinal cortex revealed by the infusion of zeta inhibitory pseudosubstrate.
Object recognition, the ability to discriminate between a novel and a familiar stimulus, is critically dependent upon the perirhinal cortex. Neural response reductions upon repetition of a stimulus, have been hypothesized to be the mechanism within perirhinal cortex that supports recognition memory function. Thus, investigations into the mechanisms of long-term depression (LTD) in perirhinal cortex has provided insight into the mechanism of object recognition memory formation, but the contribution of long-term potentiation (LTP) to object recognition memory formation has been less studied. Inhibition of atypical PKC activity by Zeta Inhibitory Pseudosubstrate (ZIP) impairs the maintenance of LTP but not LTD, thus here infusion of ZIP into the perirhinal cortex allowed us to investigate the contribution of LTP-like mechanisms to object recognition memory maintenance. Infusion of ZIP into the perirhinal cortex of rats 24 h after the sample phase impaired performance in an object recognition but not an object location task, in contrast infusion of ZIP into the hippocampus impaired performance in an object location but not an object recognition task. The impairment in object recognition by ZIP was prevented by administration of the peptide GluA23y, which blocks the endocytosis of GluA2 containing AMPA receptors. Finally, performance in a perceptual oddity task, which requires perirhinal cortex function, was not disrupted by ZIP. Together these results demonstrate the importance of LTP-like mechanisms to the maintenance of object recognition memory in the perirhinal cortex.


Investigate pathogenic mechanism of TXNDC5 in rheumatoid arthritis.
Hypoxia stimulates synovial hypoperfusion in rheumatoid arthritis (RA). TXNDC5 stimulates cellular proliferation in hypoxic conditions. We previously detected increased TXNDC5 expression in synovial tissues and blood from RA patients and demonstrated that the gene encoding TXNDC5 increased RA risk. The present study investigated the pathogenic roles of TXNDC5 in RA. Transgenic mice that over-expressed TXNDC5 (TXNDC5-Tg) were generated using C57BL/6J mice and treated with bovine collagen II to induce arthritis (CIA). Synovial fibroblasts from RA patients (RASFs) were cultured and incubated with TXNDC5-siRNA or CoCl(2), a chemical that induces hypoxia. CIA was observed in 80% of the TXNDC5-Tg, but only 20% of the wild-type mice (WT) developed CIA. The clinical arthritis scores reached 5 in the TXNDC5-Tg, but this index only reached 2 in the control mice. CIA TXNDC5-Tg exhibited clear pannus proliferation and bone erosion in joint tissues. A significant increase in CD4 T cells was observed in the thymus and spleen of TXNDC5-Tg during CIA. Serum levels of anti-collagen II IgG, IgG1 and IgG2a antibodies were significantly elevated in the mice. Increased cell proliferation, cell migration and TXNDC5 expression were observed in RASFs following incubation with 1 µM CoCl(2). However, this effect was diminished when TXNDC5 expression was inhibited with 100 nM siRNA. TNF-alpha, IL-1α, IL-1β and IL-17 levels were significantly increased in the blood of TXNDC5-Tg mice, but the levels of these cytokines declined in the supernatant of RASFs that were treated with TXNDC5 siRNA. The expression of adiponectin, a cytokine-like mediator, decreased significantly in RASFs following TXNDC5 siRNA treatment. These results suggest that TXNDC5-over-expressing mice were susceptible to CIA. This study also suggests that hypoxia induced TXCNDC5 expression, which contributed to adiponectin expression, cytokine production and the cellular proliferation and migration of fibroblasts in RA.


Sustained release of vancomycin from a new biodegradable glue to prevent methicillin-resistant Staphylococcus aureus graft infection.
Prosthetic graft infection with methicillin-resistant Staphylococcus aureus (MRSA) is one of the most serious complications of cardiovascular surgery. Seeking to prevent graft infection, we evaluated the efficacy of a new biodegradable hydrogel glue (new-glue) composed of aldehyded dextran and epsilon-poly(L-lysine) which acts as a local sustained-release carrier of vancomycin. Rats (n=40) were implanted with 1-cm(2) Dacron grafts in the subcutaneous pockets. Groups (n=10 each) were as follows: no treatment (group A), topical vancomycin solution (group B), new-glue without vancomycin (group C) or new-glue containing 1 mg of vancomycin (group D). Twenty-four h after the implantation, 2.0x10(7) colony-forming units of MRSA was inoculated onto the graft surface. Seven days thereafter, the graft was sampled and cultured. The quantity of MRSA was significantly lower in group D than in the other groups (P<0.0001). About 95% of the total vancomycin was released from the new-glue over the 72 h experimental period, and the tissue concentration of vancomycin remained above the minimum inhibitory concentration for the MRSA strain throughout the experiment. This new vancomycin-containing glue effectively prevented prosthetic graft infection and thus may be a promising biodegradable drug vehicle.


Isolation and complete amino-acid sequence of the small polypeptide from light-harvesting pigment-protein complex I (B870) of Rhodopseudomonas capsulata.
The small bacteriochlorophyll-binding polypeptide of the light-harvesting complex B870 was extracted from the intracytoplasmic membrane of the strain A1a+ of Rhodopseudomonas capsulata with chloroform/methanol/ammonium acetate and separated by chromatography on Sephadex LH60 using the same solvent. The polypeptide obtained from the peak fraction III was found to be homogeneous and identical with the small polypeptide isolated from the B870 complex as shown by dodecyl sulfate/polyacrylamide gel electrophoresis, amino acid composition and N-terminal sequence. The complete amino acid sequence is given. The relative molecular mass based on the amino acid sequence is 5341. The polarity of amino acids is 35.42%. The C-terminal part of the peptide chain from residue 29 to 48 is hydrophobic and includes one His residue.


Immunological effects of yeast- and mushroom-derived beta-glucans.
Glucans have a long history as nonspecific biological modulators. We compared the effects of three different glucans on immune reactions. Using two different administrations (intraperitoneal and oral) and two different animal models, we showed that yeast-derived Betamune (Biorigin, São Paulo, Brazil) caused significant stimulation of phagocytic activity as well as potentiation of synthesis and release of interleukin (IL)-1, IL-2, IL-4, IL-6, IL-8, IL-13, and tumor necrosis factor-alpha. In addition, Betamune inhibited growth of tumor cells in vivo and affected expression of several important genes in breast cancer cells. Compared to adult mice, young animals showed different sensitivity to glucan action.


Growth of Highly Epitaxial YBa2Cu3O(7-δ) Films from a Simple Propionate-Based Solution.
Intensive investigations have been conducted to develop epitaxial oxide thin films with superior electromagnetic performance by low-cost chemical solution deposition routes. In this paper, a novel propionate-based precursor solution without involving any other additive was proposed and employed to grow superconducting YBa2Cu3O(7-δ) (YBCO) films on LaAlO3 (LAO) single crystals. The precursor solutions are stable with a long shelf life of up to several months. Since the primary compositions are propionates after evaporating the solvent, the toxic reagents and evolved gases during solution synthesis and heat treatment can be eliminated completely. In this process, rapid pyrolysis and high conversation rate can also be achieved during growth of YBCO films in comparison with the conventional trifluoroacetate metal organic deposition routes. Remarkably, a 210 nm YBCO film exhibits high superconducting performance with a Jc value of 3.7 MA/cm(2) at 77 K, self-field. Nucleation and growth behaviors in the chemical solution process have also been studied. It is revealed that the amount of liquid phase (Ba-Cu-O) is sufficient through the entire thickness within a very short time at high growth temperatures, which results in pronounced densification and fast conversion of the YBCO phase.


The Arabidopsis Cytosolic Ribosomal Proteome: From form to Function.
The cytosolic ribosomal proteome of Arabidopsis thaliana has been studied intensively by a range of proteomics approaches and is now one of the most well characterized eukaryotic ribosomal proteomes. Plant cytosolic ribosomes are distinguished from other eukaryotic ribosomes by unique proteins, unique post-translational modifications and an abundance of ribosomal proteins for which multiple divergent paralogs are expressed and incorporated. Study of the A. thaliana ribosome has now progressed well beyond a simple cataloging of protein parts and is focused strongly on elucidating the functions of specific ribosomal proteins, their paralogous isoforms and covalent modifications. This review summarises current knowledge concerning the Arabidopsis cytosolic ribosomal proteome and highlights potentially fruitful areas of future research in this fast moving and important area.


Coexistence of celiac disease & type 1 diabetes mellitus in children.
Type 1 diabetes mellitus (T1DM) and celiac disease (CD) tend to co-exist due to similar underlying genetic predisposition. Failure to recognize CD in patients with T1DM predisposes them to complications. The present study was aimed to assess children with T1DM for the presence of CD. This was a retrospective analysis of the records of children with T1DM attending paediatric endocrinology clinic at a tertiary care hospital in north India from January 2006 to May 2014. All children were screened for CD at the time of diagnosis of T1DM using IgA anti-tissue transglutaminase (anti-tTG) levels in serum. Seropositive children were subjected to upper gastrointestinal endoscopy and duodenal biopsy for histopathological confirmation. The children also underwent thyroid function testing (TFT); those with deranged TFT were evaluated for thyroid-specific antibodies. Positive serology for CD was present in 43 of 126 children with T1DM whose records were reviewed [34.1%; 95% confidence interval (CI): 25.9-43.1]. Confirmed CD was diagnosed in 17 (13.5%; CI: 8.1-20.7) of the children screened and 17 of 40 (42.5%; CI: 27.1-59.1) seropositive participants. Four out of 17 children with coexisting CD and T1DM also had autoimmune thyroiditis with overt hypothyroidism. The children with confirmed CD were more likely to have short stature [odds ratios (OR)-3.16; 95% CI: 1.09-9.20, P<0.05] and hypothyroidism (OR-6.4; 95% CI: 1.52-26.90, P<0.05). Our study showed a higher proportion of CD in children with T1DM as compared to that reported in general population. Regular screening of children with T1DM for CD is needed to improve metabolic control and prevent long-term complications.


Spontaneous thigh hematoma associated with diclofenac.
Spontaneous nongastrointestinal bleeding in patients treated with nonsteroidal anti-inflammatory drugs is an extremely rare occurrence. Herein, the case of a 60-year-old woman with severe bilateral hip osteoarthritis treated with diclofenac sodium, who presented with manifestations of a spontaneous hematoma of the right thigh, is described. There was no history of trauma or family history of bleeding disorder. Thorough investigation excluded a hemorrhagic disorder. The patient was treated conservatively with success and was advised to discontinue diclofenac.


Magnetic diagnostics for the first plasma operation in Korea Superconducting Tokamak Advanced Research.
Magnetic diagnostics for the first plasma operation in the Korea Superconducting Tokamak Advanced Research device are described. The main discussion is the feasibility studies from the magnetic flux and field measurements utilizing the superconducting poloidal field coils before the first plasma generation.


Effectiveness of pre-operative routine blood tests in predicting complicated acute appendicitis.
Early prediction and diagnosis of perforation in acute appendicitis allow surgeons to choose the most appropriate treatment. The purpose of this study is to evaluate whether pre-operative routine laboratory examinations have a role in predicting complicated acute appendicitis. In the study, 783 patients operated with the diagnosis of acute appendicitis between the years 2014 and 2019 were analyzed retrospectively. Among the patients with non-perforated and perforated acute appendicitis, pre-operative laboratory tests include leukocyte (WBC), neutrophil, lymphocyte, platelet (PLT), mean platelet volume (MPV), platelet distribution width (PDW), C-reactive protein (CRP), and neutrophil-to-lymphocyte rate (NLR) parameters were compared. Appendicitis was not detected histopathologically in 81 cases. In the study, 89.9% (n=631) of the 702 patients were non-perforated and 10.1% (n=71) were perforated acute appendicitis cases. Perforation rate was higher in elderly patients (p<0.01). It was seen that lymphocyte count was significantly lower in the perforated group, and CRP and NLR were significantly higher (p=0.048, p=0.001, p=0.028, respectively). In the diagnosis of perforated acute appendicitis, cutoff values were 44.0 mg/dL for CRP, 7.65 for NLR and 1.7/mm3 for lymphocytes. There was no statistical difference between the groups in terms of WBC, neutrophil, PLT, MPV, and PDW values. Low lymphocyte count, high CRP, and high NLR were found to be reliable and strong predictive parameters in the diagnosis of complicated acute appendicitis.


Shifting meanings of time, productivity and social worth in the life course in Meru, Kenya.
Formal 'age sets' and 'age grades' no longer function as integral components of social organization among the Meru of Mt. Kenya. Three analytic perspectives-historical time, life time, and social time-reveal the changes in the life course which accompany the decline of age set social organization in Meru. These changes include: (1) an increasingly flexible and informal age grade structure for both men and women and (2) a fundamental shift in the meanings of time and social worth. In the past, the life course was conceptually organized around age-graded variations in reciprocal kinship interactions. Today, age-related abilities to produce and reproduce provide the underlying conceptual anchor.


[Herbal textual research on origin and development of traditional Chinese medicine "duhuo" and "qianghuo"].
To clarify the origin and development of the traditional Chinese medicine "Duhuo" and "Qianghuo" with medicinal literatures. Medical literatures of past dynasties were analysed and combined with the modern material. The "Duhuo" in Herbal writing Shen Nong Ben Cao Jing include traditional Chinese medicine "Duhuo" and "Qianghuo", "Qianghuo" was separated from "Duhuo" due to the distinguish of clinical application. The origin of "Qianghuo" is Notopterygium incisum and N. forbesii, However, The origin of "Duhuo" is very complex, Angelica pubescens f. biserrata as authentic "Duhuo" was used from Song Dynasty. "Qianghuo" was originated from "Duhuo".


In situ detection of H1-receptor mRNA and absence of apoptosis in the transient histamine system of the embryonic rat brain.
In the developing brain, histamine is one of the first neurotransmitters to appear. The concentration of histamine in the prenatal brain is fivefold that of adult levels. During the prenatal development a large transiently histamine-immunoreactive cell population distinct from the adult histaminergic system can be found within a subpopulation of the developing serotonergic raphe nuclei neurons. Also histamine-immunoreactive nerve fibers are widely distributed already during the prenatal development extending to the diencephalon, the thalamus, the cortex, and the spinal cord. Large numbers of histamine-containing mast cells also migrate into the brain during the late prenatal life. The wide distribution and high prenatal concentrations imply important functions for the histaminergic system during intrauterine development. However, little is known about the actual functions of histamine during development, and which of the histamine receptors are present in the prenatal rat brain is currently unknown. In the present study, we used in situ hybridization to study the distribution of H1-receptor (H1R) mRNA in the embryonic rat brain and spinal cord. H1R mRNA could be detected in rat brain and in spinal cord on embryonic day (E) 14, and the expression pattern seemed to partially localize in areas containing histamine-immunoreactive nerve fibers through E14-E20. H1R mRNA was also detected by reverse transcriptase polymerase chain reaction from embryonic brain samples and by Northern hybridization. The possible involvement of apoptosis in the disappearance of the developing transiently histaminergic system was studied by using apoptosis detection based on the terminal dUTP nick end labeling (TUNEL) technique and with c-Fos immunostaining. Although histamine immunoreactivity disappears dramatically from the developing raphe nuclei after E18, only occasional apoptotic nuclei could be seen in the histamine-immunoreactive cell bodies. The presence of H1R mRNA during the embryonic development renders it possible that histamine could exert an H1R-specific function at the time of the embryonic histamine peak.


Efficient ECG Compression and QRS Detection for E-Health Applications.
Current medical screening and diagnostic procedures have shifted toward recording longer electrocardiogram (ECG) signals, which have traditionally been processed on personal computers (PCs) with high-speed multi-core processors and efficient memory processing. Battery-driven devices are now more commonly used for the same purpose and thus exploring highly efficient, low-power alternatives for local ECG signal collection and processing is essential for efficient and convenient clinical use. Several ECG compression methods have been reported in the current literature with limited discussion on the performance of the compressed and the reconstructed ECG signals in terms of the QRS complex detection accuracy. This paper proposes and evaluates different compression methods based not only on the compression ratio (CR) and percentage root-mean-square difference (PRD), but also based on the accuracy of QRS detection. In this paper, we have developed a lossy method (Methods III) and compared them to the most current lossless and lossy ECG compression methods (Method I and Method II, respectively). The proposed lossy compression method (Method III) achieves CR of 4.5×, PRD of 0.53, as well as an overall sensitivity of 99.78% and positive predictivity of 99.92% are achieved (when coupled with an existing QRS detection algorithm) on the MIT-BIH Arrhythmia database and an overall sensitivity of 99.90% and positive predictivity of 99.84% on the QT database.


Multiple autoimmune syndrome revealed by nephrogenic diabetes insipidus and hypokalaemic paralysis.
A presentation of postpartum polydipsia and polyuria followed by periodic weakness led to the diagnosis of nephrogenic diabetes insipidus and hypokalaemic paralysis, both of which are complications of primary Sjögren's syndrome (pSS). The clinically dominant pSS was taken to coexist with long-latent systemic lupus erythematosus and asymptomatic autoimmune thyroid disease. This case of multiple autoimmune syndrome is a distinctive subgroup of autoimmune disorders that is increasingly recognized. Female hormone levels appeared to play a role in disease pathogenesis in this case. The patient was predicted to have a favourable prognosis due to the absence of major organ involvement. This case revealed an uncommon form of complex polyautoimmune phenomena and should prompt physicians to extend immunological screening, particularly for females with multiple illnesses.


Polycationic photosensitizer conjugates: effects of chain length and Gram classification on the photodynamic inactivation of bacteria.
We have shown previously that a polycationic conjugate between poly-L-lysine and the photosensitizer chlorin(e6) was effective in photodynamic inactivation (PDI) of both Gram-positive and Gram-negative bacteria. In this report we explore the relationship between the size of the polylysine chain and its effectiveness for mediating the killing of Gram-negative and Gram-positive bacteria. Conjugates were prepared by attaching precisely one chlorin(e6) molecule to the alpha-amino group of poly-(epsilon-benzyloxycarbonyl)lysines of average length eight and 37 lysine residues, followed by deprotection of the epsilon-amino groups, and were characterized by iso-electric focusing. The uptake of these conjugates and free chlorin(e6) by Gram-positive Staphylococcus aureus (ATCC 27659) and Gram-negative Escherichia coli (ATCC 29181) after washing was measured as a function of photosensitizer concentration (0-4 microM chlorin(e6) equivalent) and incubation time. After incubation the bacteria were exposed to low fluences (10-40 J/cm(2)) of 660 nm light delivered from a diode laser, and viability was assessed after serial dilutions by a colony-forming assay. S. aureus and E. coli took up comparable amounts of the two conjugates, but free chlorin(e6) was only taken up by S. aureus. After illumination S. aureus was killed in a fluence-dependent fashion when loaded with the 8-lysine conjugate and free chlorin(e6) but somewhat less so with the 37-lysine conjugate. In contrast, PDI of E. coli was only effective with the 37-lysine conjugate at concentrations up to 4 microM. PDI using the 8-lysine conjugate and free chlorin(e6) on E. coli was observed at a concentration of 100 microM. Transmission electron micrographs showed internal electron-lucent areas consistent with chromosomal damage. These results can be explained by the necessity of a large polycation to penetrate the impermeable outer membrane of Gram-negative E. coli, while Gram-positive S. aureus is more easily penetrated by small molecules. However, because S. aureus is more sensitive overall than E. coli the 37-lysine conjugate can effectively kill both bacteria.