Characterization of the altered cutaneous reactivity of transgenic mice whose keratinocytes overexpress B7-1.
B7-1 (CD80) is a second signal molecule usually associated with "professional" APCs that prevents the induction of T-cell clonal anergy and induces IL-2 production during antigen presentation. Tg mice whose epidermal KC overexpress B7-1 exhibit exaggerated and persistent CHS to a variety of haptens that lasts up to 8 weeks after hapten challenge. These Tg mice also exhibit significantly enhanced ear-swelling responses to irritants that are not persistent. Exaggerated CHS was not reflected in the draining lymph node. T-lymphocyte proliferative responses after sensitization and local challenge with haptens, as there were no significant differences between the B7-1 Tg and the NTg mice. However, RT-PCR analysis of mouse ear skin at the hapten challenge site indicated that B7-1 Tg mice had an alteration in the kinetics of in situ lymphokine transcripts compared to NTg mice: IFN-gamma transcripts were first detectable in Tg mouse skin at 2 weeks versus 24 h for NTg mice. RNase protection assays to detect inflammatory cytokine transcripts at hapten application sites indicated that B7-1 Tg mice responded to hapten application with increased TNF-alpha, IL-6, and TNF-beta transcripts compared to NTg mice. Thus, hapten-induced ear swelling in these Tg mice may be mediated by enhanced inflammatory cytokines during the early phase (1-14 days). IFN-gamma-producing lymphocytes may be responsible for the late phase of the ear-swelling response (14-42 days). These data indicate that B7-1 overexpression by KC in mouse skin directly or indirectly affects the nature of cutaneous inflammation induced by haptens and irritants.


Depth extension and sidelobe suppression in optical coherence tomography using pupil filters.
We demonstrate a new focus engineering scheme to achieve both extended depth of focus (DOF) and sidelobe suppression in spectral-domain optical coherence tomography (SD-OCT) system. Each of the illumination pupil function and the detection pupil function is modulated using an annular pupil filter implemented by center obscuration. The two pupil filters are arranged in a dark-field configuration such that the first sidelobe of the illumination point-spread function (PSF) matches the first minimum of the detection PSF in the lateral focal plane. We tested the feasibility of the proposed scheme numerically, and then constructed a dark-field OCT (DF-OCT) system to further verify its effectiveness experimentally. Simulation results show that a DOF gain of 4.2 can be achieved compared with a full aperture OCT (FA-OCT) system, with a suppression ratio of 2.9 dB for the first sidelobe compared with an annular-aperture bright-field OCT (BF-OCT) system. Experimental results show that the constructed DF-OCT extends the DOF by three-fold compared with the constructed FA-OCT, and suppresses the first sidelobe by 3.1 dB compared with the BF-OCT. The penalty for the extended DOF is an ~11.6 dB drop in sensitivity compared with the FA-OCT system.


Nanoscale-engineered LiCoO2as a high energy cathode for wide temperature lithium-ion battery applications-role of coating chemistry and thickness.
Extending the charge cutoff voltage of LiCoO2(LCO) beyond 4.2 V is considered as a key parameter to obtain higher energy densities. Following gaps have been identified based on a thorough literature survey especially for higher cutoff voltage of nanoscale engineered LCO cathodes, (i) different metal oxides and metal fluoride surface coatings have been mostly done independently by different groups, (ii) room temperature performance was the focus with limited investigations at high temperature, (iii) nonexistence of low temperature cycling studies and (iv) no reports on high rate capability of LCO beyond 4.5 V (especially at 4.8 V) needs to be investigated. Herein, we report the effect of nanoscale engineering of LCO along with the role of coating chemistry and thickness to study its electrochemical performance at higher voltages and at wide operating temperatures. Surface coating was implemented with different metal oxides and a metal fluoride with tunable thickness. At 4.5 V, 5 wt% Al2O3coated LiCoO2(LCO@Al2O3-5) delivered a reversible capacity of 169 mAh g-1at 100 mA g-1and 151 mAh g-1at high rate of 10 C (2 A g-1) and 72% retention at the end of 500 cycles. At 55 °C, it exhibited better stability over 500 cycles at 5 C and even at -12.5 °C it maintained 72% of its initial capacity after 100 cycles at 200 mA g-1. At 4.8 V cut-off, LCO@Al2O3-5 rendered reversible capacity of 213 mAh g-1at 100 mA g-1, a high value compared to literatures reported for LCO. Also noted that it delivered a capacity of 126 mAh g-1at a current density of 1 A g-1, whereas bare could only exhibit 66 mAh g-1under same testing conditions. Enhanced performance of LCO@Al2O3-5 can be ascribed to the lower charge transfer resistance derived from the stable solid solution formation on the interface.Ex situXRD andex situRaman analysis at different stages of charge/discharge cycles correlates the enhanced performance of LCO@Al2O3-5 with its structural stability and minimal structural degradation.


Endogenous Retrovirus 3 - History, Physiology, and Pathology.
Endogenous viral elements (EVE) seem to be present in all eukaryotic genomes. The composition of EVE varies between different species. The endogenous retrovirus 3 (ERV3) is one of these elements that is present only in humans and other Catarrhini. Conservation of ERV3 in most of the investigated Catarrhini and the expression pattern in normal tissues suggest a putative physiological role of ERV3. On the other hand, ERV3 has been implicated in the pathogenesis of auto-immunity and cancer. In the present review we summarize knowledge about this interesting EVE. We propose the model that expression of ERV3 (and probably other EVE loci) under pathological conditions might be part of a metazoan SOS response.


DELETERIOUS MUTATION AND THE EVOLUTION OF GENETIC LIFE CYCLES.
It is often proposed that the ability of diploids to mask deleterious mutations leads to an evolutionary advantage over haploidy. In this paper, we studied the evolution of the relative duration of haploid and diploid phases using a model of recurrent deleterious mutations across the entire genome. We found that a completely diploid life cycle is favored under biologically reasonable conditions, even when prolonging the diploid phase reduces a population's mean fitness. A haploid cycle is favored when there is complete linkage throughout the genome or when mutations are either highly deleterious or partially dominant. These results hold when loci interact multiplicatively and for synergistic epistasis. The strength of selection generated on the life cycle can be substantial because of the cumulative effect of selection against mutations across many loci. We did not find conditions that support cycles that retain both phases, such as those found in some plants and algae. Thus, selection against deleterious mutations may be an important force in the evolution of life cycles but may not be sufficient to explain all the patterns of life cycles seen in nature.


Mechanisms of the deep, slow-wave, sleep-related increase of upper airway muscle tone in healthy humans.
Upper airway muscle activity is reportedly elevated during slow-wave sleep (SWS) when compared with lighter sleep stages. To uncover the possible mechanisms underlying this elevation, we explored the correlation between different indices of central and reflex inspiratory drive, such as the changes in airway pressure and end-expiratory CO2 and the changes in the genioglossus (GG) and tensor palatini (TP) muscle activity accompanying transitions from the lighter N2 to the deeper N3 stage of non-rapid eye movement (NREM) sleep in healthy young adult men. Forty-six GG and 38 TP continuous electromyographic recordings were obtained from 16 men [age: 20 ± 2.5 (SD) yr; body mass index: 22.5 ± 1.8 kg/m2] during 32 transitions from NREM stages N2 to N3. GG but not TP activity increased following transition into N3 sleep, and the increase was positively correlated with more negative airway pressure, increased end-tidal CO2, increased peak inspiratory flow, and increased minute ventilation. None of these correlations was statistically significant for TP. Complementary GG and TP single motor unit analysis revealed a mild recruitment of GG units and derecruitment of TP units during the N2 to N3 transitions. These findings suggest that, in healthy individuals, the increased GG activity during SWS is driven primarily by reflex stimulation of airway mechanoreceptors and central chemoreceptors.NEW & NOTEWORTHY The characteristic increase in the activity of the upper airway dilator muscle genioglossus during slow-wave sleep (SWS) in young healthy individuals was found to be related to increased stimulation of airway mechanoreceptors and central chemoreceptors. No evidence was found for the presence of a central SWS-specific drive stimulating genioglossus activity in young healthy individuals. However, it remains to be determined whether a central drive exists in obstructive sleep apnea patients.


An apparatus for immersing trapped ions into an ultracold gas of neutral atoms.
We describe a hybrid vacuum system in which a single ion or a well-defined small number of trapped ions (in our case Ba(+) or Rb(+)) can be immersed into a cloud of ultracold neutral atoms (in our case Rb). This apparatus allows for the study of collisions and interactions between atoms and ions in the ultracold regime. Our setup is a combination of a Bose-Einstein condensation apparatus and a linear Paul trap. The main design feature of the apparatus is to first separate the production locations for the ion and the ultracold atoms and then to bring the two species together. This scheme has advantages in terms of stability and available access to the region where the atom-ion collision experiments are carried out. The ion and the atoms are brought together using a moving one-dimensional optical lattice transport which vertically lifts the atomic sample over a distance of 30 cm from its production chamber into the center of the Paul trap in another chamber. We present techniques to detect and control the relative position between the ion and the atom cloud.


[The role of cations and surface membrane proteins in the adhesion of rat liver parenchymal cells. II. The influence of calcium ions on the structure of cell contacts].
The structural interrelations of hepatocytes, under the rat liver perfusion with calciumless solutions, were studied with the electron microscopy. Lantanum chloride, alcian blue and ruthenium red were used for revealing the intercellular space, specialized junctions and cell coats. Significant alterations in the interelations of the hepatocytes after a long liver perfusion (1.5h) were discovered. The structure of the specialized cell junctions and the space intercellular width under a 15-20 min. liver perfusion remained unchanged. The results obtained suggest the important role of Ca2+-ions and supramembranic material in the cellular adhesion.


Examination for intestinal parasites and enteric bacteria in the wastewater and treated wastewater from the city of Chiang Mai, Thailand.
An attempt to use treated wastewater for agriculture in the Chiang Mai area was made, but the re-use process had to be performed under a condition that limited the risks liable to leave pathogens present in the water. The objective of our study was to examine the intestinal parasites and enteric bacteria in the wastewater and treated wastewater from the Chiang Mai University campus as well as the treated wastewater from the Chiang Mai municipality. The raw wastewater (RW), primary treatment effluent water (PE), treated wastewater using the activated sludge system (AS) from the Chiang Mai University campus and treated wastewater using the aerated lagoon (AL) system from the Chiang Mai municipality were examined for intestinal parasites and enteric bacteria by using the centrifugal sedimentation and conventional methods respectively. The ground water (GW) and the irrigation water (IW) were used for comparison. All kinds of water were collected and examined twice a month for 6 months (February to July 2000). None of human intestinal parasites were found from any wastewater, whereas the RW and PE water contained hookworm larva, Ascaris egg and Taenia egg on some occasions. A small amounts of pathogenic bacteria that can cause severe diarrhea were detected. Salmonella enteritidis gr E was isolated from the AL water in April, while Vibrio cholerae type O139 was detected from the PE water in June. Some pathogenic bacteria that might cause gastroenteritis, such as Aerobacter spp, Citrobacter spp, Pseudomonas spp and Escherichia coli were also found in all kinds of water. Between the two types of treated wastewater, the bacteria found in AS water was less than that in AL water in terms of both amount and type of bacteria. The treated wastewater from the city of Chiang Mai, compared to natural water such as irrigation water, appears to be safe to use for agriculture.


Effects of concentration and steric configuration of propranolol on AV conduction and ventricular repolarization in the dog.
To investigate the electrophysiological effects of propranolol in vivo over a wide range of plasma concentrations and to distinguish effects due to beta-blockade from those due to a direct membrane action, His bundle electrograms were recorded, and ventricular effective refractory periods (VERP) and monophasic action potential duration (MAP) were measured in anesthetized control dogs and in dogs given three graded infusions of d- or dl-propranolol. Dogs were excluded if the plasma concentrations attained did not fall in predefined ranges of 25--125, 125--700, and 700--3,000 ng/ml. Isoproterenol sensitivity tests were performed to determine the relative beta-blocking potency of the isomers at the three concentration ranges. The highest concentration of d-propranolol had approximately the same beta-blocking potency as the lowest concentration of dl-propranolol. Mean AH and HV intervals in the His bundle electrogram increased with the concentration of dl-propranolol, and the increase was greater than with d-propranolol (p less than 0.03) at the first and second concentration steps but not significantly different at the highest concentrations of d- and dl-propranolol. VERP and MAP increased directly with concentration of d- and dl-propranolol. Although the mean increases of VERP and MAP tended to be greater in the dl-propranolol group, the differences between d- and dl-propranolol were not statistically significant at any concentration. We conclude that prolongations of atrioventricular and His-Purkinje conduction are stereospecific responses and are due to beta-blockade. The specific mechanism for the prolongation of ventricular repolarization and refractoriness are effects of propranolol that could not be definitively classified in this study.


Exploration of genetic diversity among medicinally important genus Epimedium species based on genomic and EST-SSR marker.
Epimedium species has gained prime importance due to their medicinal and economic values. Therefore, in this study, 26 genomic SSR and 10 EST-SSR markers were developed for 13 medicinal species of the Epimedium genus and one out-group species Vancouveria hexandra W. J. Hooker to explore the existing genetic diversity. A total of 100 alleles by genomic SSR and 65 by EST-SSR were detected. The genomic SSR markers were presented between 2-7 alleles per locus. The observed heterozygosity (Ho) and expected heterozygosity (He) ranged from 0.00 to 4.5 and 0.0254 to 2.8108, respectively. Similarly, for EST-SSR, these values were ranged from 3.00 to 4.00 and 1.9650 to 2.7142. The number of alleles for EST-SSR markers ranged from 3 to 10 with an average of 3.51 per loci. It has been concluded that medicinally important species of the genus Epimedium possesses lower intraspecific genetic variation.


CD13hi Neutrophil-like myeloid-derived suppressor cells exert immune suppression through Arginase 1 expression in pancreatic ductal adenocarcinoma.
Perineural invasion and immunosuppressive tumor microenvironment are the distinct features of pancreatic ductal adenocarcinoma (PDAC). Heterogeneous myeloid-derived suppressor cells (MDSCs) are potent suppressors of antitumor immunity, posing obstacles for cancer immunotherapy. Increasing evidences have demonstrated the accumulation of MDSCs in PDAC patients. However, the role of MDSCs in perineural invasion of PDAC and the existence of novel MDSC subsets during PDAC remain unclear. This study found that lymphocytic perineural cuffs were frequently present in chronic pancreatitis (CP) tissues and adjacent non-neoplastic pancreatic tissues (ANPTs), but not in PDAC with perineural invasion. Meanwhile, we found that neutrophil-like MDSCs (nMDSCs), but not monocyte-like MDSCs (mMDSCs), were significantly increased in PBMCs and tumor tissues of PDAC patients. Further observation identified two distinct subsets of nMDSCs, CD13hi and CD13low nMDSCs in PDAC patients, which have not been reported previously. Despite a similar morphology, CD13hi nMDSCs expressed higher levels of CD11b, CD33, CD16 and arginase 1 but lower levels of CD66b than CD13low nMDSCs. Importantly, CD13hi MDSCs, compared with CD13low nMDSCs, more effectively suppressed alloreactive T cell responses via an arginase-1-related mechanism. After tumor resection, the circulating CD13hi nMDSCs were decreased markedly. PDAC patients with more CD13hi nMDSCs had a shorter overall survival than those with less CD13hi nMDSCs. To conclude, we identified two novel MDSC subsets with different characteristics and functions in PDAC, demonstrated the association of the two MDSC subsets with cancer progression, and explored their roles in perineural invasion and immune escape of PDAC.


Fundamental limitations to gain enhancement in periodic media and waveguides.
A common strategy to compensate for losses in optical nanostructures is to add gain material in the system. By exploiting slow-light effects it is expected that the gain may be enhanced beyond its bulk value. Here we show that this route cannot be followed uncritically: inclusion of gain inevitably modifies the underlying dispersion law, and thereby may degrade the slow-light properties underlying the device operation and the anticipated gain enhancement itself. This degradation is generic; we demonstrate it for three different systems of current interest (coupled-resonator optical waveguides, Bragg stacks, and photonic crystal waveguides). Nevertheless, a small amount of added gain may be beneficial.


Offering statins to a population attending health checks with a 10-year cardiovascular disease risk between 10% and 20.
In 2014 the UK National Institute for Health and Care Excellence recommended reducing the threshold for offering statin therapy to patients from a 10-year modelled risk of cardiovascular disease (CVD) of 20% to 10%. To describe the response of patients in UK primary care with a CVD risk between 10% and 20% to an invitation to attend a consultation to discuss statins. Review of electronic medical records at one GP practice in the East of England. We invited all patients who had attended an NHS Health Check at the practice, had a QRisk(®) score between 10% and 20%, and were not prescribed statins to attend designated clinics in the practice to discuss starting statins. We reviewed the medical records to identify those who had attended the clinics and those who had chosen to start a statin. Of 410 patients invited, 100 (24.4%) patients attended the designated clinics and 45 (11%) chose to start a statin. Those who chose to start a statin were older and with a higher QRisk(®) than those who did not. Among those who attended, individuals who started a statin had a higher QRisk(®) than those who did not and were more likely to be current or ex-smokers. The proportion choosing to start a statin was substantially lower than previously estimated. Large population-based studies with long-term follow-up are needed to assess the impact on health and workload of this change in guidance.


High-normal free thyroxine level is related with decreased bone mineral density in nonobese male patients with type 2 diabetes over 50 years old.
The prevalence of 'low bone mineral density (BMD)' in Type 2 diabetes (T2DM), especially stratified by body mass index, is seldom reported. The relation of the euthyroid range and low BMD in T2DM remains to be further elucidated. We aim to investigate the thyroid hormones' impact on BMD among euthyroid patients with T2DM. A total of 1452 hospitalized T2DM patients with normal thyroid function (43.6% males aged over 50 and 56.4% postmenopausal females) were enrolled in this cross-sectional study. BMD was measured at lumbar spine by GE lunar dual-energy X-ray absorptiometry system, and 'low BMD' was defined as T-score <-1.0 SD. The prevalence of 'low BMD' was compared between obese and nonobese (body mass index < 25 kg/m2) groups for both sexes, and the relation of low BMD and free T4 quartiles was explored by multiple logistic regression. The general prevalence of 'low BMD' was 12.3% for male patients aged over 50 (15.5% in the nonobese group and 8.0% in the obese group) and 49.8% for postmenopausal females (56.7% in the nonobese group and 48.9% in the obese group). After adjustment in multiple linear regression, free T4 level remained significantly related to decreased BMD in nonobese male subgroup. Multiple logistic regression revealed that BMD of the highest free T4 quartile (1.12-1.48 ng/dL) decreased significantly than other three quartiles after adjusting for confounding factors including age, body mass index, serum calcium and creatinine level, fasting glucose, alkaline phosphatase, glycosylated hemoglobin, total cholesterol, and smoking history (OR = 2.724, 95% CI = 1.085-6.840, p = 0.033). No significant relation was found in obese male or postmenopausal female groups. High-normal free T4 is a potential independent risk factor for 'low BMD' in nonobese male T2DM patients aged over 50. Close attention should be paid to thyroid function profile, even within normal range, in nonobese men with underlying higher fracture risks on diabetes status.


Computer-guided implant surgery: analysis of dynamic navigation systems and digital accuracy.
After the static computer-guided implant surgery, borns the concept of "navigated implantology" (NI) that offers significant advantages in the treatment planning and help clinicians to perform successful implant rehabilitation. NI allows an optimal final location, to avoid the risk of damaging the noble anatomical structures near the site and allows the achievement of satisfactory aesthetics. The aim of this study is analyze three different systems: the RoboDent® system (Berlin, Germany, 2001), today not for sale, was the first implant navigation system introduced on the market and made the history of dynamic surgery; X-Guide (Nobel Biocare, 2017), a dynamic computer assisted system that uses the principles of stereoscopic triangulation by optical video cameras. And last, the Navident® dynamic navigation system (Toronto, Canada, 2015), produced by the Canadian company ClaroNav, evolved from the Navient brand used in orthopaedic surgery, neurosurgery and otolaryngology, sharing the motion tracking technology. Dynamic computer assisted surgery systems allow more accurate implant placement when based on an accurate 3D CT-based image data and an implant planning software which minimizes errors and simplify the surgical technique.


Diagnosing boredom and confusion.
An interview schedule to determine whether individuals could be diagnosed psychologically as being in a bored, confused, or adaptive state of mind was constructed and tested. Boredom and confusion were viewed as two distinct maladaptive states of mind. Objectivity, reliability, and validity were demonstrated for the interview schedule. The schedule was effective in diagnosing maladaptive and adaptive states of mind in outpatients who sought help at a family practice clinic and in detecting changes from maladaptive states to an adaptive state of mind after four weeks of psychological treatment.


RapidHRV: an open-source toolbox for extracting heart rate and heart rate variability.
Heart rate and heart rate variability have enabled insight into a myriad of psychophysiological phenomena. There is now an influx of research attempting using these metrics within both laboratory settings (typically derived through electrocardiography or pulse oximetry) and ecologically-rich contexts (via wearable photoplethysmography, i.e., smartwatches). However, these signals can be prone to artifacts and a low signal to noise ratio, which traditionally are detected and removed through visual inspection. Here, we developed an open-source Python package, RapidHRV, dedicated to the preprocessing, analysis, and visualization of heart rate and heart rate variability. Each of these modules can be executed with one line of code and includes automated cleaning. In simulated data, RapidHRV demonstrated excellent recovery of heart rate across most levels of noise (>=10 dB) and moderate-to-excellent recovery of heart rate variability even at relatively low signal to noise ratios (>=20 dB) and sampling rates (>=20 Hz). Validation in real datasets shows good-to-excellent recovery of heart rate and heart rate variability in electrocardiography and finger photoplethysmography recordings. Validation in wrist photoplethysmography demonstrated RapidHRV estimations were sensitive to heart rate and its variability under low motion conditions, but estimates were less stable under higher movement settings.


Stable carbon isotopes of woods during carbonization and their correlation with climatic factors.
To explore the applicability of the carbon isotope composition (δ13C) of fossil charcoal for the quantitative reconstruction of paleoclimates, we selected five points in Shaanxi province, from north to south, to collect modern Pinus species and Quercus species to sample covering areas with obvious climatic differences. In order to reveal the relationships between δ13C of charcoal and climate variables on the basis of carbonization experiments, we evaluated the fractionation mechanism of δ13C of charcoal, and compared the differences between δ13C of charcoal in wildfire experiments and indoor experiments regarding genera and species. The results showed significant differences in δ13C between genera but no significant differences among species. Additionally, the δ13C of charcoal was significantly negatively correlated with precipitation and positively correlated with evaporation, which could be determined from δ13C values in the study area to reconstruct ancient precipitation and evaporation in the future.


Patient characteristics associated with buprenorphine/naloxone treatment outcome for prescription opioid dependence: Results from a multisite study.
Prescription opioid dependence is a growing problem, but little research exists on its treatment, including patient characteristics that predict treatment outcome. A secondary analysis of data from a large multisite, randomized clinical trial, the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study (POATS) was undertaken to examine baseline patient characteristics (N=360) associated with success during 12-week buprenorphine/naloxone treatment for prescription opioid dependence. Baseline predictor variables included self-reported demographic and opioid use history information, diagnoses assessed via the Composite International Diagnostic Interview, and historical opioid use and related information from the Pain And Opiate Analgesic Use History. In bivariate analyses, pre-treatment characteristics associated with successful opioid use outcome included older age, past-year or lifetime diagnosis of major depressive disorder, initially obtaining opioids with a medical prescription to relieve pain, having only used opioids by swallowing or sublingual administration, never having used heroin, using an opioid other than extended-release oxycodone most frequently, and no prior opioid dependence treatment. In multivariate analysis, age, lifetime major depressive disorder, having only used opioids by swallowing or sublingual administration, and receiving no prior opioid dependence treatment remained as significant predictors of successful outcome. This is the first study to examine characteristics associated with treatment outcome in patients dependent exclusively on prescription opioids. Characteristics associated with successful outcome after 12 weeks of buprenorphine/naloxone treatment include some that have previously been found to predict heroin-dependent patients' response to methadone treatment and some specific to prescription opioid-dependent patients receiving buprenorphine/naloxone.


The emerging novel Middle East respiratory syndrome coronavirus: the "knowns" and "unknowns".
A novel lineage C betacoronavirus, originally named human coronavirus EMC/2012 (HCoV-EMC) and recently renamed Middle East respiratory syndrome coronavirus (MERS-CoV), that is phylogenetically closely related to Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5, which we discovered in 2007 from bats in Hong Kong, has recently emerged in the Middle East to cause a severe acute respiratory syndrome (SARS)-like infection in humans. The first laboratory-confirmed case, which involved a 60-year-old man from Bisha, the Kingdom of Saudi Arabia (KSA), who died of rapidly progressive community-acquired pneumonia and acute renal failure, was announced by the World Health Organization (WHO) on September 23, 2012. Since then, a total of 70 cases, including 39 fatalities, have been reported in the Middle East and Europe. Recent clusters involving epidemiologically-linked household contacts and hospital contacts in the Middle East, Europe, and Africa strongly suggested possible human-to-human transmission. Clinical and laboratory research data generated in the past few months have provided new insights into the possible animal reservoirs, transmissibility, and virulence of MERS-CoV, and the optimal laboratory diagnostic options and potential antiviral targets for MERS-CoV-associated infection.


Quantification of salsolinol enantiomers by stable isotope dilution liquid chromatography with tandem mass spectrometric detection.
Salsolinol, 1-methyl-6,7-dihydroxy-2,3,4,5-tetrahydroisoquinoline (SAL), is a precursor of a Parkinsonian neurotoxin, N-methysalsolinol (N-methyl-SAL). Previous studies have shown that individual enantiomers of N-methyl-SAL possess distinct neurotoxicological properties. In this work, a chiral high-performance liquid chromatography (HPLC) method with electrospray ionization tandem mass spectrometric (ESI-MS/MS) detection was developed for the quantification of (R/S)-SAL enantiomers. Enantioseparation was achieved on a beta-cyclodextrin-bonded silica gel column, and the resolved enantiomers were detected by ESI-MS/MS operated in positive ion mode. The ESI collision-induced dissociation (CID) mass spectrum of SAL was studied together with that of its deuterium-labeled analog (i.e. salsolinol-alpha,alpha,alpha,1-d(4), SAL-d(4)) so that the fragmentation pathways could be elucidated. Further, using SAL-d(4) as internal standard in HPLC/MS/MS analysis of SAL improved significantly assay accuracy and reliability. Determination of (R/S)-SAL enantiomers present in food samples such as dried banana chips was demonstrated.


Gallic acid improves liver cirrhosis by reducing oxidative stress and fibrogenesis in the liver of rats induced by bile duct ligation.
Disturbance in the production and excretion of bile acid causes cholestatic liver disease. Liver cirrhosis is a disease that occurs if cholestasis continues. This study evaluated the protective effect of gallic acid (GA) on liver damage caused by biliary cirrhosis. Rats were randomly divided into 4 groups, each with 8 subjects: 1) control, 2) BDL, 3) BDL + GA 20, and 4) BDL + GA 30. The rats were anesthetized 28 days after the BDL, followed by collecting their blood and excising their liver. Their serum was used to measure liver enzymes, and the liver was used for biochemical analysis, gene expression, and histopathological analysis. Serum levels of liver enzymes, total bilirubin, liver Malondialdehyde level (MDA), expression of inflammatory cytokines and caspase-3, necrosis of hepatocytes, bile duct proliferation, lymphocytic infiltration, and liver fibrosis showed an increase in the BDL group compared to the control group (p < 0.05). In addition, BDL decreased the activity of liver antioxidant enzymes and glutathione (GSH) levels compared to the control group (p < 0.05). The groups receiving GA indicated a decrease in liver enzymes, total bilirubin, MDA, the expression of inflammatory cytokines and caspase-3, and a reduction in liver tissue damage compared to the BDL group (p < 0.05). The level of GSH in the BDL + GA 20 group showed a significant increase compared to the BDL group (p < 0.05). Moreover, it was found that GA, with its anti-fibrotic and anti-inflammatory properties, reduces liver damage caused by biliary cirrhosis.


Learning through collaboration: the NEXus consortium as a winning collaborative.
The Nursing Education Exchange (NEXus) is a consortium of academic doctoral programs in nursing, initiated in response to a national shortage of well-qualified nurse educators and the need to increase the number of doctoral faculty in nursing programs across the United States. The vision for the consortium was to use distance-accessible delivery methods to provide rural nurse educators and clinical nurses with access to quality doctoral programs in nursing while remaining in their home environments. In addition, smaller or newly established doctoral programs would be able to offer a wider variety of elective coursework without recruiting and hiring additional faculty, further decreasing their limited available resources. This article describes the initiation and implementation of a successful nursing education collaborative that has gained increasing influence across the country and is recognized by its acronym, NEXus.


The effect of silica nanoparticle-modified surfaces on cell morphology, cytoskeletal organization and function.
Chemical and morphological characteristics of a biomaterial surface are thought to play an important role in determining cellular differentiation and apoptosis. In this report, we investigate the effect of nanoparticle (NP) assemblies arranged on a flat substrate on cytoskeletal organization, proliferation and metabolic activity on two cell types, Bovine aortic endothelial cells (BAECs) and mouse calvarial preosteoblasts (MC3T3-E1). To vary roughness without altering chemistry, glass substrates were coated with monodispersed silica nanoparticles of 50, 100 and 300 nm in diameter. The impact of surface roughness at the nanoscale on cell morphology was studied by quantifying cell spreading, shape, cytoskeletal F-actin alignment, and recruitment of focal adhesion complexes (FAC) using image analysis. Metabolic activity was followed using a thiazolyl blue tetrazolium bromide assay. In the two cell types tested, surface roughness introduced by nanoparticles had cell type specific effects on cell morphology and metabolism. While BAEC on NP-modified substrates exhibited smaller cell areas and fewer focal adhesion complexes compared to BAEC grown on glass, MC3T3-E1 cells in contrast exhibited larger cell areas on NP-modified surfaces and an increased number of FACs, in comparison to unmodified glass. However, both cell types on 50 nm NP had the highest proliferation rates (comparable to glass control) whereas cells grown on 300 nm NP exhibited inhibited proliferation. Interestingly, for both cell types surface roughness promoted the formation of long, thick F-actin fibers, which aligned with the long axis of each cell. These findings are consistent with our earlier result that osteogenic differentiation of human mesenchymal progenitor cells is enhanced on NP-modified surfaces. Our finding that nanoroughness, as imparted by nanoparticle assemblies, effects cellular processes in a cell specific manner, can have far reaching consequences on the development of "smart" biomaterials especially for directing stem cell differentiation.


Chronic N-acetylcysteine administration prevents development of hypertension in N(omega)-nitro-L-arginine methyl ester-treated rats: the role of reactive oxygen species.
The aim of this study was to evaluate the production of superoxide anions as well as their role in the induction and/or maintenance of high blood pressure in rats with N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. In the preventive study, we compared adult Wistar rats treated with L-NAME for 4 weeks with L-NAME-treated rats that were simultaneously given N-acetylcysteine (NAC) in their drinking water. Basal blood pressure, superoxide production, conjugated dienes concentration and NO synthase (NOS) activity were measured at the end of the experiment. Chronic NOS inhibition by L-NAME treatment increased blood pressure, enhanced superoxide production in the aorta and elevated the concentration of conjugated dienes in the heart and kidney. All these changes were prevented by simultaneous NAC administration, which augmented NOS activity in L-NAME-treated rats. In the therapeutic study, the effects of chronic NAC treatment were studied in rats with established hypertension which developed during 4 weeks of L-NAME administration. The blood pressure effects of chronic NAC treatment in established L-NAME hypertension were only moderate, although this treatment also restored NOS activity and lowered conjugated dienes in the heart and kidney. Since chronic NAC treatment had better preventive than therapeutic effects, it seems that reactive oxygen species play a more important role in the induction than in the maintenance of L-NAME hypertension.


Shallow-water Ascidians from Matua Island (central Kuril Islands, NW Pacific).
Fifteen species of ascidians were identified in the material collected at Matua Island. Two species are new, Botryllus flavus n. sp. and Distaplia matua n. sp. The first species occurs also at Kamchatka waters, while the second is probably an endemic of Kuril Islands. The genus Macrenteron Redikorzev, 1927 is synonymized with Aplidium Savigny, 1816 and a new name Aplidium macrenteron nom. nov. is proposed for its type species.


The Effects of Dark Incubation on Cellular Metabolism of the Wild Type Cyanobacterium Synechocystis sp. PCC 6803 and a Mutant Lacking the Transcriptional Regulator cyAbrB2.
The cyAbrB2 transcriptional regulator is essential for active sugar catabolism in Synechocystis sp. PCC 6803 grown under light conditions. In the light-grown cyabrB2-disrupted mutant, glycogen granules and sugar phosphates corresponding to early steps in the glycolytic pathway accumulated to higher levels than those in the wild-type (WT) strain, whereas the amounts of 3-phosphoglycerate, phosphoenolpyruvate and ribulose 1,5-bisphosphate were significantly lower. We further determined that accumulated glycogen granules in the mutant could be actively catabolized under dark conditions. Differences in metabolite levels between WT and the mutant became less substantial during dark incubation due to a general quantitative decrease in metabolite levels. Notable exceptions, however, were increases in 2-oxoglutarate, histidine, ornithine and citrulline in the WT but not in the mutant. The amounts of cyAbrBs were highly responsive to the availability of light both in transcript and protein levels. When grown under light-dark cycle conditions, diurnal oscillatory pattern of glycogen content of the mutant was lost after the second dark period. These observations indicate that cyAbrB2 is dispensable for activation of sugar catabolism under dark conditions but involved in the proper switching between day and night metabolisms.


Real-Time Imaging and Quantitative Evolution for Pyrolysis of Carbon Dots-Encapsulated Metal-Organic Frameworks at the Nanoscale by In Situ Environmental Transmission Electron Microscopy.
The pyrolysis of metal-organic frameworks (MOF) has been widely used approach to generate hierarchical structures with the corresponding metal, metal carbide, or metal oxide nanoparticles embedded in a porous carbon matrix with a high specific surface area for industrial catalysis, energy storage and transfer, etc. MOF-derived heterogeneous catalysts can be constructed by the encapsulation of carbon dots (CDs) with plenty of hydroxyl and amine groups to enhance the performance of the final product. Controlled formation of metallic carbon structures at the nanoscale, especially matter cycling and transformation on the nanoscale interface, is important for the production of industrial catalysts as well as the research of materials science and engineering progress. However, the mass transfer at the nanoscale during the processing of MOF pyrolysis remains less understood due to the lack of direct observation. Herein, by using in situ environmental transmission electron microscopy, real-time imaging and quantitative evolution of porous carbon decorated with metal species by the pyrolysis of CDs-encapsulated zeolitic imidazolate framework-67 are achieved. The migration of Co, the flow of aggregates, and the growth of carbon nanotubes observed in the nanoscale pyrolysis laboratory working at 600 °C with an air atmosphere are present. Experimental studies based on reduction and oxidation reaction models reveal that the synergistic effect between doped graphite nitrogen and confined Co nanoparticles is beneficial for boosting catalytic performance.


Sensitive detection of trace hemoglobin using fluorescence method based on functionalized quantum dots.
The fluorescence quenching of quantum dots by hemoglobin has been demonstrated to depend on surface functionalization, and this property has been utilized to construct a novel fluorescent method for rapid, sensitive, and selective detection of trace hemoglobin in urine at microgram level. This method shows low interference and high selectivity for hemoglobin with a limit of detection of 4.3 μg L(-1) in water and 66.1 μg L(-1) in urine, which are lower than those of currently used methods in labs and clinics. Spike and recovery tests in raw, acidified, and alkalized urine samples exhibit good recovery rates for the spiked concentrations close to the limit of detection.


Transcapillary permeability and subendothelial distribution of endothelial and amniotic fluid insulin-like growth factor binding proteins in the rat heart.
Insulin-like growth factor (IGF) binding proteins (IGFBP) were purified from conditioned media of cultured bovine endothelial cells (ECBP) and from human amniotic fluid (IGFBP-1), and then labeled by radioiodination. 125I-ECBP and 125I-IGFBP-1 were perfused through isolated beating rat hearts for 1 and 5 min, and the hearts fixed and analyzed for 125I-BP content and distribution. One to 4% of the perfused 125I-ECBP and 125I-IGFBP-1 crossed the capillary boundary. The ECBPs predominantly localized as intact 125I-BP in connective tissue elements of the heart with less 125I-BP in cardiac muscle. The ratio of 125I-ECBP in connective tissue: muscle (normalized to percent vol of these compartments) was greater than or equal to 10:1. In contrast, the IGFBP-1 had a greater affinity for cardiac muscle with ratios of 125I-IGFBP-1 in connective tissue:muscle of approximately 1:2. When 125I-IGF-I, in the absence of any BPs, was perfused through the hearts approximately 3-5% left the microcirculation and was found in subendothelial tissues. 125I-IGF-I localized primarily to cardiac muscle with a distribution of connective tissue:cardiac muscle of about 1:3. The findings in the isolated perfused heart were confirmed in intact animals. After 125I-IGFBP-1 was injected into anesthetized rats and allowed to circulate for 5 min, substantial radioactivity was associated with the heart. As in the isolated heart, the IGFBP-1 preferentially localized to cardiac muscle with a connective tissue:cardiac muscle ratio of 1:3. We conclude that IGFBPs produced by endothelial cells and the IGFBP-1 contained in amniotic fluid can cross the capillary boundaries of the rat heart, and that the ECBPs preferentially localize in connective tissue elements of the myocardium, whereas IGFBP-1 predominantly localizes in cardiac muscle.


[Screening for EXT1 and EXT2 gene mutations in a ethnic Han Chinese family from Shanxi with hereditary multiple exostoses].
To screen for potential mutations in an ethnic Han Chinese family from Shanxi with hereditary multiple exostoses. Polymerase chain reaction and DNA sequencing were used to screen potential mutations in EXT1 and EXT2 genes. For EXT1 gene, two synonymous mutations (P477P and E587E), three intronic mutations (c.1537 -48A>G, c.1721 +203A>G and c.1722 -103C>G) were detected. For EXT2 gene, five intronic mutations (c.-29 -148A>T, c.1080 -18T>A, c.1336 -93C>T, c.1526 -166C>T, and c.1526 -195C>T) were identified. Among these, EXT1 P477P, EXT1 E587E and EXT2 c.1080 -18T>A are polymorphisms listed by Multiple Osteochondroma Mutation Database, whilst the other 7 sites have not been reported. No mutations have been found among all exons of the EXT1 and EXT2 genes in this family. Linkage analysis is necessary for identifying the cause of this disease.


Inflammation: a possible mechanism for a causative role of hyperuricemia/gout in cardiovascular disease.
Hyperuricemia and gout are independent risk factors associated with the development of hypertension, metabolic syndrome, vascular damage, and renal disease. Whether these risk factors are causally related to these important chronic co-morbidities remains uncertain, but inflammation may provide a mechanistic explanation. Hyperuricemia and gout negatively affect vascular function by exerting pro-oxidant effects and by decreasing nitric oxide bioavailability, thus inducing inflammation and endothelial dysfunction, which may promote hypertension, metabolic syndrome, and cardiovascular (CV) disease. This paper presents and discusses current understanding of the diverse influences promoting hyperuricemia and gout and the basis of acute and chronic hyperuricemia/gout-related inflammation. This review is based on a PubMed/Embase database search for articles on hyperuricemia and its impact on cardiovascular and renal function.


Animal models of human tissue expansion.
Although tissue expansion is being used extensively in humans, many fundamental scientific questions remain to be addressed which can best be answered using an animal model. Presently, no single animal has been identified for research of this kind which is comparable both subjectively and objectively to humans. This study evaluates the skin of the rat, guinea pig, pig, and dog and identifies the dog as the best model based on biomechanical and practical considerations.


Differential inducibility of human and porcine dental pulp-derived cells into odontoblasts.
A robust method for generating odontoblasts from cultured dental pulp cells has not been established. In this study, efficient methods for deriving odontoblasts from cultured human and porcine dental pulp-derived cells were investigated with special attention to species differences. Cultured human cells showed relatively low alkaline phosphatase (ALP) activity in the presence of dexamethasone (Dex) and beta-glycerophosphate (beta-Gly). In contrast, the addition of 1,25-dihydroxyvitaminD(3) (VitD3) significantly increased the ALP activity. In porcine cells, beta-Gly alone or a combination of Dex and beta-Gly significantly increased ALP activity; however, addition of VitD3 reduced this activity. RT-PCR and Western blotting analysis revealed that the combination of three induction reagents on human cells significantly upregulates the expression of osteocalcin mRNA, and dentin sialoprotein. We propose that the combination of Dex, beta-Gly, and VitD3 is critical for differentiation of human dental pulp-derived cells into odontoblasts. In addition, the inducibility of dental pulp-derived cells presented remarkable species differences.


A high-cholesterol, n-3 polyunsaturated fatty acid diet causes different responses in rats and hamsters.
This study was designed to investigate the response to a high-cholesterol, n-3 polyunsaturated fatty acid (PUFA) or n-6 PUFA diet in rats and hamsters. Animals were fed n-3 or n-6 PUFA with a cholesterol-free diet, or with a diet enriched with cholesterol (0.5%, w/w) for 2 weeks. In rats and hamsters fed a cholesterol-free diet, plasma cholesterol, triglycerides and very-low-density lipoprotein (VLDL)-triglyceride levels in n-3 PUFA group were significantly lower than those in n-6 PUFA group. In contrast, when diets were supplemented with 0.5% cholesterol, the plasma cholesterol- and triglyceride-lowering effect of dietary n-3 PUFA disappeared. In hamsters fed with the atherogenic diet (0.5% dietary cholesterol) for 2 weeks, n-3 PUFA induced hypercholesterolemia more than n-6 PUFA, the increase being in the VLDL and low-density lipoprotein (LDL) fractions. Our data thus indicate that elevation of VLDL- and LDL-cholesterol in hamsters by n-3 PUFA, compared with n-6 PUFA, is dependent on 0.5% dietary cholesterol supplementation. In rats, on the other hand, dietary n-3 PUFA did not induce hypercholesterolemia more than n-6 PUFA when 0.5% cholesterol was supplemented. Although the effects of n-3 PUFA on plasma cholesterol, triglycerides and VLDL-triglycerides were similar in hamsters and rats, the interactive effects of n-3 PUFA and cholesterol on plasma and lipoprotein cholesterol levels differed in the two species. It was also found that plasma triglycerides, cholesterol and lipoprotein cholesterol levels in hamsters are higher than in rats in the presence and absence of dietary cholesterol. In addition, cholesterol feeding induces hypertriglyceridemia and hypercholesterolemia only in hamsters. Moreover, liver triglyceride concentrations increased in rats fed a cholesterol-rich diet and hepatic triglyceride levels of the n-3 PUFA-fed rats were significantly lower than those in the n-6 PUFA-fed rats in the presence and absence of dietary cholesterol. However, triglycerides did not accumulate in the liver in hamsters fed a cholesterol-rich diet and hepatic triglyceride levels of the n-3 PUFA-fed hamsters were not significantly different from those in the n-6 PUFA-fed hamsters in the presence and absence of dietary cholesterol. Therefore, these studies confirm marked species differences in response to the interactive effects of dietary n-3 PUFA and cholesterol.


Triiodothyronine acutely stimulates glucose transport into L6 muscle cells without increasing surface GLUT4, GLUT1, or GLUT3.
Thyroid hormones (THs) act genomically to stimulate glucose transport by elevating glucose transporter (Slc2a) expression and glucose utilization by cells. However, nongenomic effects of THs are now emerging. Here, we assess how triiodothyronine (T(3)) acutely affects glucose transport and the content of GLUT4, GLUT1, and GLUT3 at the surface of muscle cells, and possible interactions between T(3) and insulin action. Differentiated L6 myotubes transfected with myc-tagged Slc2a4 (L6-GLUT4myc) or Slc2a1 (L6-GLUT1myc) and wild-type L6 myotubes were studied in the following conditions: control, hypothyroid (Tx), Tx plus T(3), Tx plus insulin, and Tx plus insulin and T(3). Glucose uptake and GLUT4 content at the cell surface decreased in the Tx group relative to controls. T(3) treatment for 30 minutes increased glucose transport into L6-GLUT4myc cells without altering surface GLUT4 content, which increased only thereafter. The total amount of GLUT4 protein remained unchanged among the groups studied. The surface GLUT1 content of L6-GLUT1myc cells also remained unaltered after T(3) treatment; however, in these cells glucose transport was not stimulated by T(3). In wild-type L6 cells, although T(3) treatment increased the total amount of GLUT3, it did not change the surface GLUT3 content. Moreover, within 30 minutes, T(3) stimulation of glucose uptake was additive to that of insulin in L6-GLUT4myc cells. As expected, insulin elevated surface GLUT4 content and glucose uptake. However, interestingly, surface GLUT4 content remained unchanged or even dropped with T(3) plus insulin. These data reveal that T(3) rapidly increases glucose uptake in L6-GLUT4myc cells, which, at least for 30 minutes, did not depend on an increment in GLUT4 at the cell surface yet potentiates insulin action. We propose that this rapid T(3) effect involves activation of GLUT4 transporters at the cell surface, but cannot discount the involvement of an unknown GLUT.


Fixation of heavy metals onto lignocellulosic sorbent prepared from paddy straw.
The sorption behavior of biosorbent prepared from paddy straw with nine different heavy metals has been studied. The binding mechanisms involving adsorption and the cation-exchange process have also been investigated. Characterization of biosorbent through a scanning electron microscope revealed no major surface deformity resulting from the chemical treatment. X-ray photo electron spectroscopy was also used to determine the presence of exchangeable cations in the sorbent and the speciation of bound chromium, cadmium, and mercury. The maximum sorption capacity (millimoles/gram) obtained from the Langmuir model for Pb2+, Cd2+, Hg2+, Co2+, Ni2+, Mn2+, Zn2+, and Cu2+ were 0.286, 0.147, 0.226, 0.181, 0.196, 0.189, 0.219, and 0.248, respectively. Interpretation of Dahlquist (1978) and Scatchard (1949) was also used for the binding site heterogeneity. The unique ability of the biosorbent to bind nine different metals has been attributed to the presence of surface heterogeneity and Ca2+ ions, which attract and sequester metal ions. Biosorption results are useful for the development of low-cost biosorbent.


[Research into the prevention and treatment of burns due to specific causes should be highly strengthened].
So far there is no clear and accurate definition for burns due to specific causes, though they are encountered sometimes. Burns due to specific causes sometimes are neglected because of their low incidence, and many surgeons, even burn specialists are not familiar with them because of low incidence, thus leading to poor results in the treatment. Burns due to specific causes are often involved in complicated and compound injuries. The treatment is often difficult, leading to delayed wound healing. In this paper, the definition, classification, and clinical characteristics of burns due to specific causes are described. Problems involved in diagnosis and treatment of common ones such as electrical, chemical, and compound burns are discussed. Facing an increase of those burns with specific causes, the author suggests that the research into the prevention and treatment should be highly strengthened.


Adherence to treatment guidelines and survival in older women with early-stage breast cancer in Denmark 2008-2012.
Objectives: The aims of this study were to compare patients 70 years or older with younger patients, to examine whether Danish patients with early-stage breast cancer aged 70 years or more received treatment according to guidelines, the reasons for deviating from the guidelines, and to analyze whether such deviations affected survival.Methods: From the Danish Breast Cancer Cooperative Group (DBCG) database we identified 23,247 women diagnosed with early-stage breast cancer in Denmark from 2008 to 2012. 17,391 were aged less than 70 years and 5856 were 70+ years. We reviewed medical charts of 441 patients aged 70+ years from Funen (a region of Denmark) to ascertain whether treatment was given according to the guidelines of DBCG and if not, the reason for deviating. Overall survival was analyzed by Cox proportional hazards models.Results: Up to age 80 years most women (94%) had surgery according to guidelines, decreasing to 41% in women aged 85+ years, the main reason for omitting surgery being patients' requests. Patients with breast cancer over the age of 80 years did not have an excess mortality compared with the general population in Funen. Compared with women who had surgery according to guidelines, women who did not have surgery had a significantly higher risk of dying with a hazard ratio (HR) of 8.38 (95% Confidence Intervals (CI) 4.46-15.8) if they were less than 80 years and HR = 2.56 (95% CI 1.63-4.01) if they were 80 years or more (p = .003 for interaction).Conclusions: Adherence to treatment according to guidelines decreases with increasing age, mainly for patients aged 80+ years. Our results suggest that surgery is important for the survival of patients aged less than 80 years.


[Neuropsychological performance in anorexia and bulimia nervosa].
Anorexia nervosa and Bulimia nervosa are common chronic psychiatric diseases afflicting in particular female adolescents. During the acute phase of starvation a number of hormonal, neuropsychological and cerebral morphological changes occur. Some of these abnormalities are only partly reversible. Psychiatric comorbidities complicate the clinical picture and aggravate appropriate therapeutic interventions. The following review describes in detail the neuropsychological impairments in eating disorders, potential factors influencing cognitive performance, and resulting implications for clinical every day life.


Mesenchymal Stromal Cells for Treatment of Acute Steroid-Refractory Graft Versus Host Disease: Clinical Responses and Long-Term Outcome.
Acute graft-versus-host disease (aGvHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Steroid-resistant aGvHD is associated with poor outcome, and no commonly accepted salvage therapy is available for its treatment. Here, we report 58 adult patients treated with mesenchymal stromal cells (MSCs) as salvage therapy for steroid-refractory aGvHD. Third-party MSCs expanded in platelet lysate-containing medium were transfused at a median dose of 0.99 × 10(6) cells per kg b.wt. A median of two MSC infusions were administered to each patient. Median time between the onset of aGvHD and the first infusion of MSCs was 12 days (range, 6-62 days). Most patients (79%) had grade IV aGvHD. Five patients showed complete response, five showed very good partial response, 17 showed partial response, and 31 showed no response. The estimated probability of survival after 1 year was 19%, and median survival was 69 days. Overall survival was not significantly different from that of a historical cohort of patients receiving alternative salvage therapy and no MSC infusions. In conclusion, MSC treatment on top of conventional immunosuppression was associated with an overall response rate of 47% but improved outcome in terms of survival remains to be shown.


3-D computer modelling of malunited posterior malleolar fractures: effect of fragment size and offset on ankle stability, contact pressure and pattern.
The positioning of the fracture fragment of a posterior malleolus fracture is critical to healing and a successful outcome as malunion of a posterior malleolar fracture, a condition seen in clinical practice, can affect the dynamics of the ankle joint, cause posterolateral rotational subluxation of the talus and ultimately lead to destruction of the joint. Current consensus is to employ anatomic reduction with internal fixation when the fragment size is larger than 25 to 33% of the tibial plafond. A 3-dimensional finite element (FE) model of ankle was developed in order to investigate the effect of fragment size (6-15 mm) and offset (1-4 mm) of a malunited posterior malleolus on tibiotalar joint contact area, pressure, motion of joint and ligament forces. Three positions of the joint were simulated; neutral position, 20° dorsiflexion and 30° plantarflexion. Compared to the intact joint our model predicted that contact area was greater in all malunion scenarios considered. In general, the joint contact area was affected more by section length than section offset. In addition fibula contact area played a role in all the malunion cases. We found no evidence to support the current consensus of fixing posterior malleolus fractures of greater than 25% of the tibial plafond. Our model predicted joint instability only with the highest level of fracture in a loaded limb at an extreme position of dorsiflexion. No increase of peak contact pressure as a result of malunion was predicted but contact pattern was modified. The results of our study support the view that in cases of posterior malleolar fracture, posttraumatic osteoarthritis occurs as a result of load on areas of cartilage not used to loading rather than an increase in contact pressure. Ankle repositioning resulted in increased force in two ankle ligaments. Our finding could explain commonly reported clinical observations.


[Raynaud syndrome complicated by digital gangrene during treatment with interferon-alpha].
In a 43-year old male suffering from idiopathic hypereosinophilic syndrome (HES) since 1984, successfully treated with alpha interferon (alpha IFN) for 32 months, a severe Raynaud's phenomenon of the four extremities occurred and eventually evolved into digital necrosis within a few weeks. The arterial echography/doppler and plethysmography patterns were suggestive of isolated small-to medium-size digital artery occlusions. An extensive search for an aetiology of digital necrosis, including complete tests of autoimmunity, remained negative. Two months later, despite alpha IFN withdrawal and intravenous infusions of ilomedin, the digital ischemia evolved to extensive necrosis that necessitated several amputations and a definitive spinal chord stimulation. Pathologic examination of arteries showed no vasculitis but diffuse arterial occlusions by thrombi.


sRNA154 a newly identified regulator of nitrogen fixation in Methanosarcina mazei strain Gö1.
Trans-encoded sRNA154 is exclusively expressed under nitrogen (N)-deficiency in Methanosarcina mazei strain Gö1. The sRNA154 deletion strain showed a significant decrease in growth under N-limitation, pointing toward a regulatory role of sRNA154 in N-metabolism. Aiming to elucidate its regulatory function we characterized sRNA154 by means of biochemical and genetic approaches. 24 homologs of sRNA154 were identified in recently reported draft genomes of Methanosarcina strains, demonstrating high conservation in sequence and predicted secondary structure with two highly conserved single stranded loops. Transcriptome studies of sRNA154 deletion mutants by an RNA-seq approach uncovered nifH- and nrpA-mRNA, encoding the α-subunit of nitrogenase and the transcriptional activator of the nitrogen fixation (nif)-operon, as potential targets besides other components of the N-metabolism. Furthermore, results obtained from stability, complementation and western blot analysis, as well as in silico target predictions combined with electrophoretic mobility shift-assays, argue for a stabilizing effect of sRNA154 on the polycistronic nif-mRNA and nrpA-mRNA by binding with both loops. Further identified N-related targets were studied, which demonstrates that translation initiation of glnA2-mRNA, encoding glutamine synthetase2, appears to be affected by sRNA154 masking the ribosome binding site, whereas glnA1-mRNA appears to be stabilized by sRNA154. Overall, we propose that sRNA154 has a crucial regulatory role in N-metabolism in M. mazei by stabilizing the polycistronic mRNA encoding nitrogenase and glnA1-mRNA, as well as allowing a feed forward regulation of nif-gene expression by stabilizing nrpA-mRNA. Consequently, sRNA154 represents the first archaeal sRNA, for which a positive posttranscriptional regulation is demonstrated as well as inhibition of translation initiation.


The utility of recanalized umbilical vein graft to the hepato-pancreato-biliary surgeon.
The authors recently published their experience of recanalizing umbilical veins in deceased liver donors, with recanalized umbilical veins as vascular conduits for meso-Rex bypass procedures. They have since found recanalized umbilical veins to be an excellent, easy to harvest vascular conduit that can be used for multiple vascular procedures and repair. Here, they report their experience using this vessel for bypass and vascular reconstruction. They have recanalized umbilical veins and used them in a total of 5 Meso-Rex bypasses; 5 pancreaticoduodenectomies; 1 left hepatic trisegmentectomy with right portal vein (PV) resection and reconstruction; 1 right hepatectomy and 1 adrenalectomy, both with partial inferior vena cava (IVC) resection and reconstruction; 1 coronary-Rex bypass shunt for extrahepatic PV thrombosis; and 1 orthotopic liver transplantation with infrahepatic IVC anastomotic dehiscence patched with umbilical vein graft. Umbilical veins were dilated mechanically and used in situ for the meso-Rex bypass surgery; they were ligated in the space of Rex and then dilated ex vivo otherwise to be used as interposition grafts or a vein patch. A total of 15 hepato-pancreato-biliary procedures were done using the recanalized umbilical vein as graft; 2 patients required thrombectomy postoperatively with reexploration, venotomy, thrombectomy with fogarty catheter, and venotomy closure. The umbilical vein graft is a fine vascular conduit and can serve many purposes in hepatobiliary surgery.


Effects of water content on reactive transport of 85Sr in Chernobyl sand columns.
It is known that under unsaturated conditions, the transport of solutes can deviate from ideal advective-dispersive behaviour even for macroscopically homogeneous porous materials. Causes may include physical non-equilibrium, sorption kinetics, non-linear sorption, and the irregular distribution of sorption sites. We have performed laboratory experiments designed to identify the processes responsible for the non-ideality of radioactive Sr transport observed under unsaturated flow conditions in an Aeolian sandy deposit from the Chernobyl exclusion zone. Miscible displacement experiments were carried out at various water contents and corresponding flow rates in a laboratory model system. Results of our experiments have shown that breakthrough curves of a conservative tracer exhibit a higher degree of asymmetry when the water content decreases than at saturated water content and same Darcy velocity. It is possible that velocity variations caused by heterogeneities at the macroscopic scale are responsible for this situation. Another explanation is that molecular diffusion drives the solute mass transfer between mobile and immobile water regions, but the surface of contact between these water regions is small. At very low concentrations, representative of a radioactive Sr contamination of the pore water, sorption and physical disequilibrium dominate the radioactive Sr transport under unsaturated flow conditions. A sorption reaction is described by a cation exchange mechanism calibrated under fully saturated conditions. The sorption capacity, as well as the exchange coefficients are not affected by desaturation. The number of accessible exchange sites was calculated on the basis that the solid remained in contact with water and that the fraction of solid phase in contact with mobile water is numerically equal to the proportion of mobile water to total water content. That means that for this type of sandy soil, the nature of mineral phases is the same in advective and non-advective domains. So sorption reaction parameters can be estimated from more easily conducted saturated experiments, but hydrodynamic behaviour must be characterized by conservative tracer experiments under unsaturated flow conditions.


DLC1: a significant GAP in the cancer genome.
Rho GTPases are believed to make important contributions to the development and progression of human cancer, but direct evidence in the form of somatic mutations analogous to those affecting Ras has been lacking. A recent study in Genes & Development by Xue and colleagues (1439-1444) now provides in vivo evidence that DLC1, a negative regulator of Rho, is a tumor suppressor gene deleted almost as frequently as p53 in common cancers such as breast, colon, and lung.


Outcomes of lobectomy on pulmonary function for early stage non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD).
Lung cancer is the first cause of cancer mortality worldwide. Chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer. An epidemiological survey discovered that the presence of COPD increases the risk of lung cancer by 4.5-fold. Lobectomy is considered to be the standard surgical method for early stage non-small cell lung cancer (NSCLC). However, the influence of lobectomy on the loss of pulmonary function has not been fully investigated in NSCLC patients with COPD. We searched the PubMed database using the following strategies: COPD and pulmonary function test (MeSH term) and lobectomy (MeSH term) from 01 January 1990 to 01 January 2019. We selected the articles of patients with COPD. A total of six studies, including 195 patients with COPD, provided lung function values before and after surgery. Five out of six studies focused on the short-term change of pulmonary function (within 3-6 months) after lobectomy, and the average loss of FEV1 was 0.11 L (range: -0.33-0.09 L). One study investigated the long-term change of pulmonary function (within 1-2 years) after lobectomy, and the average loss of FEV1 was 0.15 L (range: -0.29-0.05 L). A short-term (3-6 months) loss of pulmonary function after operation is acceptable for lung cancer patients with COPD. However, there may be a high risk of postoperative complications in NSCLC patients with COPD. Therefore, surgical treatment needs to be carefully considered for these patients.


Memory updating after retrieval: when new information is false or correct.
We conducted three experiments testing the malleability of memory in incorporating new information following retrieval. All experiments used associative lists typical of the DRM paradigm [Deese, J. (1959). On the prediction of occurrence of particular verbal intrusions in immediate recall. Journal of Experimental Psychology, 58(1), 17-22; Roediger, H. L., & McDermott, K. B. (1995). Creating false memories: Remembering words not presented in lists. Journal of Experimental Psychology: Learning, Memory, and Cognition, 21(4), 803-814]. This paradigm enabled the evaluation of the integration of false information and correct information with the original information. In Experiment 1, participants studied DRM lists, and in a later phase either retrieved or restudied the lists and were presented with never-presented critical lures. The results of Experiment 1 showed that compared to restudy, retrieval enhanced the integration of subsequent false information, as measured by later recall in a follow-up test. In Experiments 2 and 3, after initial study, participants retrieved or studied incorrect information and received corrective feedback. The results showed that retrieval led to more error correction than restudy, when feedback was presented immediately. In general, this research suggests retrieval facilitates incorporation of new, related information, regardless of whether it is false or correct.


The efficacy of honey for ameliorating pain after tonsillectomy: a meta-analysis.
Postoperative pain and wound healing following tonsillectomy can result in dissatisfaction for the patient. However, there is no consensus on whether postoperatively administered honey effectively reduces morbidity after tonsillectomy. Therefore, a systematic review with a meta-analysis of the efficacy of honey as a treatment for postoperative pain and wound healing was performed. Two authors independently searched the database records (MEDLINE, SCOPUS, and Cochrane databases) dating from inception to June 2014. Studies comparing postoperative oral administration of honey with administration of placebo where the outcomes of interest were pain and wound healing on postoperative days were included. Baseline study characteristics, study quality, numbers of patients in steroid-treated and control groups, and treatment outcomes were extracted. Sufficient data for meta-analysis were retrieved from 4 trials with a total of 264 patients. We analyzed patient-reported pain scores and quantities of administered analgesics during the first 5 postoperative days. The pain score was significantly decreased in the honey-treated patients in comparison with the placebo-treated patients on postoperative day 1 only, but the analgesic intake of the honey-treated patients on the first 5 postoperative days was significantly less than that of the placebo-treated patients. In addition, honey significantly increased tonsillectomy bed wound healing in comparison with placebo during the first 2 weeks after surgery. This meta-analysis shows that postoperative administration of honey after tonsillectomy significantly reduces pain and promotes wound healing. Further trials comparing honey with good research methodology should be conducted to confirm these results.


Reduction in Renal Ischemia-Reperfusion Injury in Mice by a Phosphoinositide 3-Kinase p110gamma-Specific Inhibitor.
Although renal ischemia-reperfusion injury (IRI) can cause delayed graft function, a targeted therapy is not yet available. Because phosphoinositide 3-kinases (PI3K) p110γ and p110δ play important roles in immune cell migration and function, we investigated the effects of PI3K p110γ- and p110δ-specific inhibitors in a murine renal IRI model. Renal function was assessed by serum creatine and hematoxylin-eosin staining. Immune cell migration was assessed by flow cytometry and an in vitro cell migration assay using Transwell plates. Gene expression analysis and a multiplex cytokine/chemokine assay were performed to find cytokines/chemokines whose expression was upregulated in renal IRI and affected by p110γ-specific inhibitor. The PI3K p110γ-specific inhibitor, but not p110δ-specific inhibitor, significantly reduced serum creatine levels and acute tubular necrosis. These were accompanied by reduced infiltration of B cells and reduced expression of CXCL9, a CXCR3 ligand, suggesting that p110γ plays an important role in B-cell migration toward injured kidneys. An in vitro cell migration assay revealed for the first time that B-cell migration to injured kidney cells and to CXCL9 requires p110γ. p110γ-specific inhibitor ameliorates renal IRI by reducing necrosis and immune cell migration. This inhibitor may have the potential to reduce renal graft failure caused by renal IRI.


[Transcatheter ablation with high-frequency currents as a method for creating useful experimental models in the study of cardiac conduction and automatism].
analyze the utility of transcatheter ablation with high-frequency currents to create different experimental models of altered cardiac automatism and conduction. the results were obtained in six anesthetized dogs subjected to electrophysiological study after selectively applying transcatheter radiofrequency ablation to different zones of the specific cardiac conduction system. Ablation was carried out using conventional bipolar 7F catheter-electrodes. High-frequency currents (0.7 MHz) were emitted through the distal electrode, with variable intensity and duration according to the aim of the experiment. Anatomic (fluoroscopic) and electrophysiological criteria were used to position the electrode within the ablation zone. selective radiofrequency application to the atrioventricular junction zone affords complete A-V blocks with escape rhythms located in the A-V node or His-Purkinje system, together with different degrees of infra- and intra-hisian and intranodal blocks. The modification of intranodal refractoriness and conduction without interrupting atrial pulse transmission may manifest atypical patterns with truncated nodal conduction curves. The abolition of sinus function through ablation in the zone of the sulcus terminalis makes it possible to obtain supraventricular subsidiary rhythms. The obtaining of intranodal complete blocks with supra-Hisian escape rhythms demonstrates phenomena such as the modulation of subsidiary automatism by non-transmitted atrial pulses, analyzed by constructing phase-response curves. transcatheter ablation using high-frequency currents is useful in demonstrating phenomena related to intranodal and His-Purkinje conduction, subsidiary pacemaker automatism or the modulation of automatism and conduction via non-transmitted pulses.


Penrose drain tube as a guide for endostaplers during lobectomy via video-assisted thoracoscopic surgery.
Endostaplers are widely used in pulmonary lobectomy procedures performed through video-assisted thoracoscopic surgery (VATS). Using them to approach fused pulmonary fissures during VATS lobectomy procedures is safer and quicker than manual techniques. However, the direction of endostaplers is sometimes limited by the location of the working ports, which may result in difficulties in positioning the endostaplers or even traction or laceration of peripheral lung tissue. We describe here a useful surgical technique that uses a Penrose drain tube as a guide for the endostapler, making its use to divide fused pulmonary fissures during VATS lobectomy easier and safer.


Sequential expression of phenotype markers for osteoclasts during differentiation of precursors for multinucleated cells formed in long-term human marrow cultures.
Long-term human marrow cultures form multi-nucleated cells (MNC) which express the osteoclast phenotype. Mononuclear precursors for these MNC can be identified and highly enriched. We tested early (bipotent) and late (unipotent) precursors of these MNC for expression of several osteoclast differentiation markers: 1) the osteoclast vitronectin receptor, identified by the 23c6 monoclonal antibody, 2) the vacuolar-type proton pump, identified by the E11 monoclonal antibody, and 3) the calcitonin (CT) receptor, by autoradiography with 125I-labeled salmon calcitonin. We wished to determine if the proton pump was expressed in cells in long term marrow cultures and if its expression correlated with expression of the CT receptor and the vitronectin receptor. About 30% of early precursor cells reacted with the 23c6 monoclonal antibody, but none expressed CT receptors or showed amplified proton pump expression. The CT receptor and amplified proton pump expression were detected first on the late precursor, a stage in which every cell reacted strongly with the 23c6 monoclonal antibody. Over 80% of MNC formed from these late precursors expressed abundant CT receptors, and all MNC expressed the vitronectin receptor and showed amplified proton pump expression. In contrast, macrophage polykaryons and mononuclear macrophages formed in vitro failed to express the osteoclast vitronectin and CT receptors and expressed the proton pump at levels indistinguishable from those of surrounding cells.


[Regulatory effect of zengmian mixture on T-lymphocyte dysfunction in children with repeated lower respiratory tract infection of both Qi-Yin deficiency type].
To explore the T-lymphocyte dysfunction in children with repeated infection of lower respiratory tract of both Qi-Yin deficiency type (RIR-QYD) and the immune regulatory effect of zengmian mixture (ZMM), to provide theoretical basis for the effective therapy. Peripheral T-lymphocyte subsets and expressions of T-lymphocyte activating related surface molecules (CD3+/HLA-DR+ and CD3+/CD25+, etc.) in children with RIR-QYD, 31 of mild type and 28 of severe type cases, were investigated before administration of ZMM and after treatment of ZMM for 3-6 months (non-infectious stage), using immune fluorescent labelling and flow cytometric technique. In the patients with mild RIR-QYD, the expression rate of CD4+ and CD3+/HLA-DR+ activated T-cells before treatment were all obviously lowered, after 3 months treatment, the positive rate of CD4+, CD3+/HLA-DR- resting T-cell, CD3+/HLA-DR+ activated T-cell and CD3+/CD25+ express IL-2R T-cells were all obviously lowered, but after treatment for 6 months, only that of CD3+/HLA-DR+ activated T-cells was lower than that in the control group. In the patients with severe RRI-QYD before treatment, the expression rate of CD3+, CD4+, CD3+/HLA-DR-, CD3+/HLA-DR+ and CD3+/CD25+ all lowered, while after 3-6 months treatment, some recoveries were shown in these parameters but still lower than those in the control group. The total effective rate of ZMM for mild patients was 100%, and the markedly effective rate 78.9%, while for severe cases, the total effective rate was 90.9% and the markedly effective rate 68.2%. In patients with RIR-QYD, the T-cells decreased with activating dysfunction, the severity of disease is in accordance with the degree of T-cell activating dysfunction. ZMM shows markedly clinical effect in treating RIR-QYD and evident regulatory effect on T-cell dysfunction, but a long-term treatment is needed for the recovery of laboratory parameters.


Effect of antiviral treatment on the outcome of secondary bacterial pneumonia after influenza.
Secondary bacterial pneumonia is an important cause of influenza-associated death. Although antibacterial therapy is standard, antiviral therapy has been ignored because viral infections usually resolve by the time bacterial pneumonia presents. In the present study, antiviral compounds were tested in a mouse model of secondary pneumococcal pneumonia after influenza. Treatment with oseltamivir improved survival in mice from 0% to 75%, even when therapy was delayed for up to 5 days after infection with influenza virus. In mice, treatment with rimantadine had no effect on survival. Treatment with ampicillin cleared infection but, in the absence of treatment with oseltamivir, did not improve survival. Pneumonia developed in only 7 of the 22 mice receiving oseltamivir, and subsequent treatment with ampicillin resulted in cure (100% survival). Treatment of the predisposing influenza-virus infection with inhibitors specific for the viral neuraminidase may improve the efficacy of antibiotics and increase survival in persons who are at high risk for complications and mortality during influenza.


Accuracy of interpretation of preparticipation screening electrocardiograms.
To evaluate the accuracy of pediatric cardiologists' interpretations of electrocardiograms (ECGs). A series of 18 ECGs that represented conditions causing pediatric sudden cardiac death or normal hearts were interpreted by 53 members of the Western Society of Pediatric Cardiology. Gold-standard diagnoses and recommendations were determined by 2 electrophysiologists (100% concordance). The average number of correct ECG interpretations per respondent was 12.4 ± 2.2 (69%, range 34%-98%). Respondents achieved a sensitivity of 68% and a specificity of 70% for recognition of any abnormality. The false-positive and false-negative rates were 30% and 32%, respectively. Based on actual ECG diagnosis, sports participation was accurately permitted in 74% of cases and accurately restricted in 81% of cases. Respondents gave correct sports guidance most commonly in cases of long QT syndrome and myocarditis (98% and 90%, respectively) and least commonly in cases of hypertrophic cardiomyopathy, Wolff-Parkinson-White syndrome, and pulmonary hypertension (80%, 64%, and 38%, respectively). Respondents ordered more follow-up tests than did experts. Preparticipation screening ECGs are difficult to interpret. Mistakes in ECG interpretation could lead to high rates of inappropriate sports guidance. A consequence of diagnostic error is overuse of ancillary diagnostic tests.


Lipid-lowering therapy after coronary revascularization: the interventional cardiologist's perspective.
Despite the success of coronary interventions in the treatment of stenosis due to coronary atherosclerosis, it behooves cardiologists to treat the underlying disease by decreasing patients' cholesterol levels. Intravascular ultrasound has made it possible to detect plaque accumulation not visible on angiography. Although advanced lesions that are fibrous and calcific can be treated with atherectomy and lasers, it is the soft, lipid-laden plaque that is particularly vulnerable to rupture and leads to coronary events. Therefore, attention must also focus on decreasing atherosclerotic progression in patients who have undergone coronary interventions. Studies have clearly shown the value of cholesterol reduction in decreasing coronary events. However, a review of cardiologists' practices shows that more aggressive lipid-lowering therapy is needed. One way to achieve this goal is to treat and monitor patients who have undergone revascularization procedures and to encourage patients to become more involved in their own care.


[Inequality, poverty, and childhood health and nutritional conditions in Northeast Brazil].
This cross-sectional study analyzes the relationship between gradients of social inequalities and the household environment and health and nutritional conditions among 2,001 preschool children in ten counties (municipalities) in the State of Bahia, Brazil. The analysis used multinomial multivariate logistic regression. Children in the middle and lower tertiles on the poverty scale had significant and increasing odds of living in a household headed by a woman, an unemployed father, a mother with </= years of schooling, more than one child sharing the same bed, severe stunting, and retinol consumption below the median as compared to those in the upper tertile. More than one child in the home, weight deficit, and lipid consumption below the median were also significantly associated with the poorest tertile. Specific emergency health policies and measures must be implemented to minimize the burden imposed by poverty and social inequalities on childhood health and nutrition.


The first specimen of Camarasaurus (Dinosauria: Sauropoda) from Montana: The northernmost occurrence of the genus.
A partial skeleton from the Little Snowy Mountains of central Montana is the first referable specimen of the Morrison Formation macronarian sauropod Camarasaurus. This specimen also represents the northernmost occurrence of a sauropod in the Morrison. Histological study indicates that, although the specimen is relatively small statured, it is skeletally mature; this further emphasizes that size is not a undeviating proxy to maturity in dinosaurs, and that morphologies associated with an individual's age and stature may be more nebulous in sauropods.


[Relationship between paraoxonase/glutathione S-transferase gene polymorphism and health conditions of floriculture farmers].
In this study we conducted a cross-sectional study and reported on the distribution of two common genetic polymorphisms of the PON1 gene and two common genetic polymorphisms of the GST gene as well as the association between those polymorphisms and other predictors in a population of floriculture workers from Kunming city. 136 pesticide-exposed farmers were recruited. PON1 and GST T1, M1 genotype were determined by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). (1) Compared with exposure group, the GLB in control group was higher (β = -0.16, t = -2.30, P = 0.02), but the A/G in control group was lower (β = 0.14, t = 2.09, P = 0.04); (2) Compared with the persons who carried QQ genotype, the accumulative symptom scores were lower in the persons who carried RR genotype (t = -2.78, P = 0.006); (3) Compared with GST T1 carriers, non-carriers' GLB (β = -0.20, t = -3.01, P = 0.00) and IgG (β = -0.20, t = -3.01, P = 0.00) were higher, but the A/G was lower; (4) The abnormities of cardiograms among people who had been exposed to pesticides were higher compared to people who did not expose to any pesticides (β = 1.147, P = 0.042). PON1-192 and GST T1 gene were associated with the farmers health condition after pesticides exposure.


Immunoproteasomes and immunosenescence.
Aging is a complex process which is accompanied with the decline and the reshaping of different functions of the body. In particular the immune system is characterized, during ageing (immunosenescence) by a remodeling of innate immunity (well preserved, up-regulated) and clonotypical immunity (severely altered) and by the occurrence of a chronic inflammatory process (inflammaging) which are, at least in part, genetically controlled. In this scenario, it can be anticipated that a crucial role is played by age-related structural and functional alterations and modifications of proteasomes and immunoproteasomes, the last being a key component of antigen processing and MHC class I antigen presentation. A variety of experimental data are available, suggesting that proteasomes are affected by age, and that in centenarians they are relatively preserved. On the contrary, few data are available on immunoproteasomes, likely as a consequence of the poverty of suitable cellular models. Lymphoblastoid cell lines from EBV immortalized B cells from old donors is envisaged as a possible model for the study of immunoproteasomes in humans and their changes with age. Thus, basic questions such as those related to possible consequences, for immune responses in infectious diseases and cancer, of age-related alterations of antigen processing and presenting, change with age of self-antigen repertoire, and the genetic basis of immunoproteasome activity and its change with age, remain largely unanswered.


Electroosmosis of Powell-Eyring fluids under interfacial slip.
We investigate the EOF of a Powell-Eyring fluid through a slit microchannel, employing Navier slip boundary condition. Using an analytical scheme consistent with the homotopy perturbation method, we bring out the alteration in the underlying flow dynamics as attributable to the nonlinear interactions between fluid rheology and electrostatics over interfacial scales. We validate the approximate analytical solutions by comparing those with results from numerical analysis. We unveil a regime of phenomenal amplification in the net volumetric flow rate, realized as a consequence of an intricate interplay between interfacial electromechanics, slipping hydrodynamics, and the flow rheology. Our results may have far ranging consequences in the design of various biomicrofluidic devises/systems, which are often used for the manipulation of non-Newtonain fluids.


Measurement Properties of the NIH-Minimal Dataset Dutch Language Version in Patients With Chronic Low Back Pain.
Validation study with cross-sectional and longitudinal measurements. To translate the US National Institutes of Health (NIH)-minimal dataset for clinical research on chronic low back pain into the Dutch language and to test its validity and reliability among people with chronic low back pain. The NIH developed a minimal dataset to encourage more complete and consistent reporting of clinical research and to be able to compare studies across countries in patients with low back pain. In the Netherlands, the NIH-minimal dataset has not been translated before and measurement properties are unknown. Cross-cultural validity was tested by a formal forward-backward translation. Structural validity was tested with exploratory factor analyses (comparative fit index, Tucker-Lewis index, and root mean square error of approximation). Hypothesis testing was performed to compare subscales of the NIH dataset with the Pain Disability Index and the EurQol-5D (Pearson correlation coefficients). Internal consistency was tested with Cronbach α and test-retest reliability at 2 weeks was calculated in a subsample of patients with Intraclass Correlation Coefficients and weighted Kappa (κω). In total, 452 patients were included of which 52 were included for the test-retest study. factor analysis for structural validity pointed into the direction of a seven-factor model (Cronbach α = 0.78). Factors and total score of the NIH-minimal dataset showed fair to good correlations with Pain Disability Index (r = 0.43-0.70) and EuroQol-5D (r = -0.41 to -0.64). Reliability: test-retest reliability per item showed substantial agreement (κω=0.65). Test-retest reliability per factor was moderate to good (Intraclass Correlation Coefficient = 0.71). The Dutch language version measurement properties of the NIH-minimal were satisfactory. N/A.


Direct detection of drug-resistant Mycobacterium tuberculosis using targeted next generation sequencing.
Mycobacterium tuberculosis complex (MTBC) infections are treated with combinations of antibiotics; however, these regimens are not as efficacious against multidrug and extensively drug resistant MTBC. Phenotypic (growth-based) drug susceptibility testing on slow growing bacteria like MTBC requires many weeks to months to complete, whereas sequencing-based approaches can predict drug resistance (DR) with reduced turnaround time. We sought to develop a multiplexed, targeted next generation sequencing (tNGS) assay that can predict DR and can be performed directly on clinical respiratory specimens. A multiplex PCR was designed to amplify a group of thirteen full-length genes and promoter regions with mutations known to be involved in resistance to first- and second-line MTBC drugs. Long-read amplicon libraries were sequenced with Oxford Nanopore Technologies platforms and high-confidence resistance mutations were identified in real-time using an in-house developed bioinformatics pipeline. Sensitivity, specificity, reproducibility, and accuracy of the tNGS assay was assessed as part of a clinical validation study. In total, tNGS was performed on 72 primary specimens and 55 MTBC-positive cultures and results were compared to clinical whole genome sequencing (WGS) performed on paired patient cultures. Complete or partial susceptibility profiles were generated from 82% of smear positive primary specimens and the resistance mutations identified by tNGS were 100% concordant with WGS. In addition to performing tNGS on primary clinical samples, this assay can be used to sequence MTBC cultures mixed with other mycobacterial species that would not yield WGS results. The assay can be effectively implemented in a clinical/diagnostic laboratory with a two to three day turnaround time and, even if batched weekly, tNGS results are available on average 15 days earlier than culture-derived WGS results. This study demonstrates that tNGS can reliably predict MTBC drug resistance directly from clinical specimens or cultures and provide critical information in a timely manner for the appropriate treatment of patients with DR tuberculosis.


Autophagic cell death of human hepatoma G2 cells mediated by procyanidins from Castanea mollissima Bl. Shell-induced reactive oxygen species generation.
The autophagy of human hepatoma G2 (HepG2) cells induced by procyanidins from chestnut (Castanea mollissima Bl.) shell (CSPCs) was investigated, and the inherent relationship between autophagic levels and reactive oxygen species (ROS) generation was studied. The results showed that CSPCs induced HepG2 cell death in a time- and concentration-dependent manner, increased the accumulation of autophagolysosomes and microtubule-associated proteins light chain 3-II (LC3-II, a marker of autophagy). However, these phenomena were not observed in the group pretreated with the autophagy inhibitor 3-MA, suggesting that CSPCs induced HepG2 cell autophagy. Furthermore, we found that CSPCs triggered ROS generation in cells, while the levels of ROS decreased in the N-acetylcysteine (Nac) co-treatment, revealing that CSPCs-mediated autophagy was partly blocked by Nac. In addition, treatment with CSPCs decreased the mitochondrial membrane potential of HepG2 cells. These results suggested CSPCs could trigger autophagy via ROS generation, which may be associated with the mitochondria-dependent signaling way.


Factors associated with hydrocarbon ingestion in children.
To investigate the types of hydrocarbon ingested by children and identify factors associated with hydrocarbons ingestion. It was a hospital based case control study in which medical records of sixty seven children with hydrocarbon ingestion, admitted through emergency department between January 2001 to December 2005 of Aga Khan Hospital were reviewed. Variables such as age, sex, types of hydrocarbons, amount ingested, socioeconomic status, family size, number of children, type of containers, trend of ingestion during hot weather, length of stay at hospital along with the outcomes were evaluated. Out of 67 patients, 53 (79%) were male and 14 (21%) were female. Majority of children 36 (54%) were between the ages 2-5 years. Kerosene oil 59 (88%) was the most commonly ingested hydrocarbons. Socioeconomically 48 (71%) children belonged to lower middle class. Children with large family size (> or = 3 siblings/family) were more commonly affected. Hydrocarbon were mostly 41 (61%) stored in beverages and mineral water bottles. The accident occurred in 43 (65%) during summer, whereas 34 (56%) patients had presented with fever and cough. Consolidation of lungs was found in 38 (56%) cases. Majority 53 (79%) of the patients were discharged from the hospital within the first 24 hours of admission. Male, age < 2 years, large family size, poor socioeconomic status, hot weather (afternoon and summer vacations), kerosene oil, unsafe containers were the major factors loading to hydrocarbon ingestion in this study. There is a need for strategic planning with parent awareness programs to reduce the hydrocarbon poisoning in our children.


A Case of Rheumatoid Vasculitis Involving Hepatic Artery in Early Rheumatoid Arthritis.
Rheumatoid vasculitis is a rare, but most serious extra-articular complications of long-standing, seropositive rheumatoid arthritis (RA). Vasculitis of hepatic artery is an extremely rare but severe manifestation of rheumatoid vasculitis. A 72-year-old woman who presented with polyarthralgia for 2 months was diagnosed with early RA. Since she had manifestations of livedo reticularis, and liver dysfunction which was atypical for RA patients, a percutaneous needle liver biopsy was performed revealing arteritis of a medium-sized hepatic artery. Extensive investigations did not reveal evidences of other systemic causes such as malignancy or systemic vasculitis. The patient was diagnosed with rheumatoid vasculitis involving hepatic arteries based on Bacon and Scott criteria for rheumatoid vasculitis. With high dose corticosteroid and cyclophosphamide induction and methotrexate and tacrolimus maintenance treatment, she was successfully recovered. Association of rheumatoid vasculitis at very early stages of the disease may represent an early aggressive form of RA.