Comparative radiographic assessment of a new bioceramic-based root canal sealer.
The aim of this study was to assess the radiopacity of two bioceramic-based root canal sealers, the conventional TotalFill BC sealer (FKG Dentaire Switzerland) and a new experimental filling material developed in collaboration with 'Raluca Ripan' Institute for Research in Chemistry, Cluj-Napoca. Five disc samples were prepared using both materials (10 mm diameter × 1 mm thickness), being subjected to digital radiography together with aluminum step wedges (1 to 12 mm in thickness), in accordance with ISO 6876: 2012. Radiopacity was determined by the computer analysis of the images obtained. Four different areas were selected for each sample, corresponding to a disk-sample quadrant. Statistical analysis was performed using ANOVA. Both materials showed a radiopacity that was 3 mm greater than the equivalent thickness of aluminum. Total Fill BC showed greater radiopacity than the experimental material, but the differences were not statistically significant. Both materials comply with ISO 6876: 2012 recommendations on minimum radiopacity.


[Clinical characteristics of children with B cell type acute lymphoblastic leukemia carrying different fusion gene].
To investigate whether there were differences in the clinical characteristics, cytogenetic characteristics, immunophenotype and prognosis in children with B cell type acute lymphoblastic leukemia (B-ALL) carrying different fusion genes. The research included 80 children with B-ALL from Peking University People's Hospital between March 2006 and December 2008. Eighteen children were positive for TEL/AML1, 14 for E2A/PBX1, 11 for BCR/ABL,and 2 cases for MLL/AF4, and 35 cases were negative for all of the 4 fusion genes. Data including clinical characteristics, morphology, immunophenotype and cytogenetic characteristics were collected, and the disease-free survival (DFS) was evaluated. The children were followed up until April 2009. In the 18 children with TEL/AML1+B-ALL, 66.7% were younger than 5 years old. They had low tumor load. FAB-L2 morphology was commonly observed, but t(12;21) was often absence in these children. Up to now,17 children who survived were disease-free. In the 14 children with E2A/PBX1+B-ALL, the majority were female. Thirteen children showed FAB-L1 morphology. Twelve children showed pre-B-ALL immunophenotype. The EFS was close to 80%. In the 11 children with BCR/ABL+B-ALL, 10 children showed common B type immunophenotype. FAB-L1 and FAB-L2 morphology was found in 4 children respectively. The DFS was less than 20%. Two children with MLL/AF4 positive B-ALL had high tumor load. Their morphologic diagnosis was FAB-L1. Both showed the Pro-B-ALL immunophenotype. One child discontinued treatment at the early stage of chemotherapy, and the other child survived disease-free until now. The B-ALL children with different fusion genes have different clinical characteristics, immunophenotypes and prognosis.


Intralesional collagenase Clostridium histolyticum in the management of Peyronie's disease: current best practice.
The use of Clostridium histolyticum collagenase (CCH) has become increasingly widespread for the treatment of Peyronie's disease (PD) in recent years. Numerous trials have confirmed both its safety and efficacy in appropriately selected patients with this condition. The purpose of this review is to examine pivotal trials demonstrating the efficacy of CCH, revisit viable candidates for treatment with intralesional injection therapy, and provide a summary of injection technique and appropriate management of patients receiving this treatment at the time of therapy and in follow up.


Stem cells and motor recovery after stroke.
In stroke patients with severe persistent neurological deficits, alternative therapeutic modalities are limited. Stem cell therapy might be an opportunity when the safety profile of this approach will be achieved. This review will give possible mechanisms of restoration of function in animals and a statement of clinical trials in humans. The sources of neural stem cells for therapeutic use will be detailed. Potentials mechanisms of transplanted cell-mediated recovery are described with a particular emphasis on ipsilesional post-stroke plasticity. The optimal conditions for cell transplant therapy after stroke are evoked but not yet clearly defined. Finally, since multimodality imaging will be crucial in the post-transplantation patient assessment, the final part describes recent advances in the in vivo monitoring of repair progress.


High-resolution imaging reveals how the spindle midzone impacts chromosome movement.
In the spindle midzone, microtubules from opposite half-spindles form bundles between segregating chromosomes. Microtubule bundles can either push or restrict chromosome movement during anaphase in different cellular contexts, but how these activities are achieved remains poorly understood. Here, we use high-resolution live-cell imaging to analyze individual microtubule bundles, growing filaments, and chromosome movement in dividing human cells. Within bundles, filament overlap length marked by the cross-linking protein PRC1 decreases during anaphase as chromosome segregation slows. Filament ends within microtubule bundles appear capped despite dynamic PRC1 turnover and submicrometer proximity to growing microtubules. Chromosome segregation distance and rate are increased in two human cell lines when microtubule bundle assembly is prevented via PRC1 knockdown. Upon expressing a mutant PRC1 with reduced microtubule affinity, bundles assemble but chromosome hypersegregation is still observed. We propose that microtubule overlap length reduction, typically linked to pushing forces generated within filament bundles, is needed to properly restrict spindle elongation and position chromosomes within daughter cells.


Predictive factors for long-term outcome in polymyositis/dermatomyositis-associated interstitial lung diseases.
Interstitial lung disease (ILD) is strongly associated with polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM). It is also related to mortality. Previous studies have highlighted that the acute form of PM/DM/CADM-associated ILD (PM/DM/CADM-ILD) has a poor short-term prognosis. However, little is known about the long-term clinical features of patients with PM/DM/CADM-ILD. The aim of the present study is to clarify the clinical characteristics and the predictive factors for long-term outcomes in patients with PM/DM/CADM-ILD. Thirty-four patients with PM/DM/CADM-ILD who were followed up for more than 12 months were analyzed retrospectively. The patients were classified as "stable" or "deterioration" according to respiratory symptoms, serial changes in forced vital capacity (FVC) or arterial oxygen pressure, and radiologic findings during the follow-up period. Twenty-six patients (76%) were in the stable group and eight patients (24%) were in the deterioration group. Home oxygen therapy was performed in six cases in the deterioration group because of chronic respiratory failure due to progression of ILD. The deterioration group, in comparison to the stable group, had a significantly lower %FVC and a higher positive rate for the anti-PL-7 antibody. Multivariate logistic regression analysis revealed that a positive anti-PL-7 antibody test and a lower %FVC were independently associated with deterioration during long-term follow-up. Patients with PM/DM/CADM-ILD are at risk for chronic respiratory failure due to the deterioration of ILD during long-term follow-up. The presence of anti-PL-7 antibody and a lower %FVC at initial diagnosis may predict long-term deterioration in patients with PM/DM/CADM-ILD.


"Omics" insights into plastid behavior toward improved carotenoid accumulation.
Plastids are a group of diverse organelles with conserved carotenoids synthesizing and sequestering functions in plants. They optimize the carotenoid composition and content in response to developmental transitions and environmental stimuli. In this review, we describe the turbulence and reforming of transcripts, proteins, and metabolic pathways for carotenoid metabolism and storage in various plastid types upon organogenesis and external influences, which have been studied using approaches including genomics, transcriptomics, proteomics, and metabonomics. Meanwhile, the coordination of plastid signaling and carotenoid metabolism including the effects of disturbed carotenoid biosynthesis on plastid morphology and function are also discussed. The "omics" insight extends our understanding of the interaction between plastids and carotenoids and provides significant implications for designing strategies for carotenoid-biofortified crops.


Methionine availability in plasma of dairy cows supplemented with methionine hydroxy analog isopropyl ester.
Adequate Met supply is especially important in the dairy cow for milk protein synthesis. Because of insufficient Met contents in the most frequently used feed-stuffs, Met becomes limiting in the diet of the dairy cow. To restore the amino acid balance of the diet and consequently to optimize lactation performance, Met must be supplied in a protected form because of its high degradability as a free amino acid by rumen microorganisms. A new chemical derivative of Met, the isopropyl ester of the 2-hydroxy-4-(methylthio)-butanoic acid (HMBi) was tested for its metabolic fate by following the evolution of plasma concentrations of its metabolites (2-hydroxy-4-(methylthio)-butanoic acid (HMB), Met, isopropyl alcohol, and acetone) after spot-dose supplementation (50 g Met equivalent) to 15 cows. Results indicated that HMBi would be quickly absorbed and hydrolyzed into HMB and isopropyl alcohol, and then converted to Met and acetone, respectively. In our experimental conditions, the Met availability for cows was estimated to be 48.34 +/- 2.05% using a calibration curve established by modeling the area under the curve response to increasing doses of Met supplied as Smartamine M, whose bioavailability (80%) is considered the reference value. Plasma kinetics and bioavailability of Met were compared between HMBi and Smartamine M in the same cows. Comparison of the kinetics suggests that HMBi would be absorbed through the rumen wall providing good protection against rumen microorganisms. It can thus be concluded that HMBi is a new source of Met for ruminants with an acceptable bioavailability.


Defect-Induced Near-Infrared Photoluminescence of Single-Walled Carbon Nanotubes Treated with Polyunsaturated Fatty Acids.
Single-walled carbon nanotubes (SWCNTs) have been incorporated in many emerging applications in the biomedical field including chemical sensing, biological imaging, drug delivery, and photothermal therapy. To overcome inherent hydrophobicity and improve their biocompatibility, pristine SWCNTs are often coated with surfactants, polymers, DNA, proteins, or lipids. In this paper, we report the effect of polyunsaturated fatty acids (PUFAs) on SWCNT photoluminescence. A decrease in the SWCNT bandgap emission (E11) and a new red-shifted emission (E11-) were observed in the presence of PUFAs. We attribute the change in SWCNT photoluminescence to the formation of oxygen-containing defects by lipid hydroperoxides through photo-oxidation. The observed changes in near-infrared emission of SWCNTs are important for understanding the interaction between SWCNTs and lipid biocorona. Our results also indicate that photoexcited SWCNTs can catalyze lipid peroxidation similarly to lipoxygenases.


Selective disruption of the recognition of facial expressions of anger.
Appetitive aggression occurs in the context of resource/dominance disputes in a wide variety of species. Hence, the possibility arises that a specific neural system may have evolved to detect and coordinate responses to this specific form of challenge or threat. The dopamine system has been implicated in the processing of signals of aggression in social-agonistic encounters in several species. Here we report that dopaminergic antagonism in healthy male volunteers, following acute administration of the dopamine D2-class receptor antagonist sulpiride, leads to a selective disruption in the recognition of facial expressions of anger (signals of appetitive aggression in humans), but leaves intact recognition of other emotions and the matching of unfamiliar faces.


Subterminal key pinch dynamometry: a new method to quantify strength deficit in ulnar nerve paralysis.
Precise pre- and postoperative assessments are fundamental to recording the quality of recovery after ulnar nerve repair. Because of its imprecision, manual muscle testing is being replaced by dynamometry to measure grasping and key-pinch strengths. However, both grasping and key pinch are dependent not only on the ulnar nerve but also the median and radial nerves. We propose to measure strength using a new sort of pinch, called the 'subterminal key pinch'. Strength was measured using a commercially available pinch meter. Patients applied pressure on the dynamometer with the interphalangeal joint of the thumb, maintaining the joint in extension to avoid enhancement of strength by the flexor pollicis longus. We examined 17 patients before ulnar nerve repair. Preoperatively, grasping strength was 46% of normal, while key pinch was 58%, pinch-to-zoom strength was 26% and subterminal key pinch only 7%. Subterminal key pinch was the most affected pinch with a strength deficit of over 90%.Level of evidence: IV.


Extension of High-Resolution Optical Absorption Spectroscopy to Divalent Neodymium: Absorption Spectra of Nd2+ Ions in a SrCl2 Host.
There is a lack of information on electronic spectra of divalent neodymium, and thus the synthesis and characterization of Nd2+ systems is now reported. Stabilization of neodymium is observed in a chloride host, which importantly has been accomplished with Nd ions introduced in a divalent state during synthesis, unlike by γ-irradiation of Nd3+ system employed previously. This method yields good-quality SrCl2 :Nd2+ single crystals. For the first time the electronic absorption spectra of Nd2+ doped in SrCl2 have been recorded with high resolution at liquid helium temperature (4.2 K). Identification of the absorption bands occurring in the spectral range of 5000-40 000 cm-1 (2000-250 nm) has been achieved and their tentative assignment proposed. This uniquely detailed Nd2+ absorption spectrum provides basis for fingerprinting method enabling identification of the presence of Nd2+ ions in future spectra as well as in existing but as-yet not fully resolved spectra.


Chloride losing diarrhoea and metabolic alkalosis in an infant with cystic fibrosis.
A case of hypochloraemic metabolic alkalosis in an infant with chloride losing ileostomy drainage and cystic fibrosis is described. It is speculated that intestinal loss of chloride played a major role in the development of metabolic alkalosis.


Dynamic cost-effectiveness of oncology drugs.
To develop a methodology for computing cost-effectiveness measures of a drug throughout its life cycle. We developed a set of models that measure the long-term cost-effectiveness of 2 oncology drugs, paclitaxel and docetaxel, throughout their life cycles. The study combined pricing history of the drugs, US Food and Drug Administration approval dates, drug utilization from Medicare claims, and clinical effectiveness information from phase III studies reported in the scientific literature. These data were used to estimate the incremental cost-effectiveness ratio (ICER) at the time of market entry and by year thereafter. The study population included patients with cancer who were treated with paclitaxel or docetaxel. The prices of paclitaxel and docetaxel dropped substantially due to patent expirations, while the number of users increased several fold because of subsequent empirical evidence and approval of new indications that resulted in greater efficacy. The ICER over a 10-year period was approximately 60% of the ICER at product launch for both drugs, and was further decreased when a longer-term perspective was taken. We demonstrated that the ICER of a drug can decrease substantially over its life cycle. Thus, cost-effectiveness at drug launch might be a poor indicator of the longterm value of the drug. The results of this study are based on the analysis of 2 prominent oncology drugs, paclitaxel and docetaxel. The results may not be generalizable to other drug classes or other oncology drugs for which new indications are less common.


Silencing of SbPPCK1-3 Negatively Affects Development, Stress Responses and Productivity in Sorghum.
Phosphoenolpyruvate carboxylase (PEPC) plays central roles in photosynthesis, respiration, amino acid synthesis, and seed development. PEPC is regulated by different post-translational modifications. Between them, the phosphorylation by PEPC-kinase (PEPCk) is widely documented. In this work, we simultaneously silenced the three sorghum genes encoding PEPCk (SbPPCK1-3) by RNAi interference, obtaining 12 independent transgenic lines (Ppck1-12 lines), showing different degrees of SbPPCK1-3 silencing. Among them, two T2 homozygous lines (Ppck-2 and Ppck-4) were selected for further evaluation. Expression of SbPPCK1 was reduced by 65% and 83% in Ppck-2 and Ppck-4 illuminated leaves, respectively. Expression of SbPPCK2 was higher in roots and decreased by 50% in Ppck-2 and Ppck-4 in this tissue. Expression of SbPPCK3 was low and highly variable. Despite the incomplete gene silencing, it decreased the degree of phosphorylation of PEPC in illuminated leaves, P-deficient plants, and NaCl-treated plants. Both leaves and seeds of Ppck lines had altered metabolic profiles and a general decrease in amino acid content. In addition, Ppck lines showed delayed flowering, and 20% of Ppck-4 plants did not produce flowers at all. The total amount of seeds was lowered by 50% and 36% in Ppck-2 and Ppck-4 lines, respectively. The quality of seeds was lower in Ppck lines: lower amino acid content, including Lys, and higher phytate content. These data confirm the relevance of the phosphorylation of PEPC in sorghum development, stress responses, yield, and quality of seeds.


[Predictive value of Ages & Stages Questionnaires for cognitive performance at early years of schooling].
The Ages and Stages questionnaires (ASQ) has been recently validated in our country for developmental screening. The objective of this study is evaluate the validity of ASQ to predict low cognitive performance in the early years of schooling. Diagnostic test studies conducted on a sample of children of medium-high socioeconomic level were evaluated using ASQ at least once at 8, 18 and/or 30 months old, and later, between 6 and 9 years old, reevaluated using the Wechsler Intelligence Scale for Children-third edition (WISC-III). Each ASQ evaluation was recorded independently. WISC-III was standardized, considering underperformance when the total score were under -1 standard deviation. 123 children, corresponding to 174 ASQ assessments (42 of them were 8 months old, 55 were 18 months and 77 were 30 months of age) were included. An area under the ROC curve of 80.7% was obtained, showing higher values at 8 months (98.0%) compared to 18 and 30 months old (78.1 and 79.3%, respectively). Considering different ASQ scoring criteria, a low sensitivity (27.8 to 50.0%), but a high specificity (78.8 to 96.2%) were obtained; the positive predictive value ranged between 21 and 46%, while the negative value was 92.0-93.2%. Conclusion ASQ has low sensitivity but excellent specificity to predict a low cognitive performance during the first years of schooling, being a good alternative to monitor psychomotor development in children who attend the private sector healthcare in our country.


Rapid method for measuring extracellular water in yeast preparations.
A rapid procedure for the quantitative determination of extracellular water in bulk bakers' yeast was developed on the basis of the solute dilution principle. A reagent is prepared by synthesizing the diazonium ion of p-aminobenzoic acid and coupling it to peptone. This "azopeptone reagent" permits direct colorimetric measurement, which accounts for the rapidity and simplicity of the test. Potential errors due to osmotic effects are avoided by supplementing the reagent with saline and, more importantly, minimizing the duration of contact between reagent and cells. The new method has acceptable accuracy and precision, and may also be suitable for use with other microorganisms.


Identification of a Novel Transcription Factor Required for Osteogenic Differentiation of Mesenchymal Stem Cells.
Osteogenic differentiation is a complex and still poorly understood biological process regulated by intrinsic cellular signals and extrinsic microenvironmental cues. Following appropriate stimuli, mesenchymal stem cells (MSCs) differentiate into osteoblasts through a tightly regulated multistep process driven by several transcription factors and characterized by the expression of a number of bone-specific proteins. In this study, we describe a novel transcription factor that we named osteoblast inducer (ObI)-1, involved in MSC differentiation toward the osteogenic lineage. ObI-1 encodes for a nuclear protein subjected to proteasomal degradation and expressed during osteoblast differentiation both in a murine multipotent mesenchymal cell line (W20-17) and in primary murine MSCs. RNA interference-mediated knockdown of ObI-1 expression significantly impairs osteoblast differentiation and matrix mineralization with reduced expression of the osteogenic markers, Runt-related transcription factor 2 (Runx2) and osteopontin. Conversely, ObI-1 overexpression enhances osteogenic differentiation and bone-specific markers expression. ObI-1 stimulates bone morphogenetic protein (BMP)-4 expression and the consequent activation of the Smad pathway; treatment with a BMP receptor type I antagonist completely abolishes ObI-1-mediated stimulation of osteogenic differentiation. Collectively, our findings suggest that ObI-1 modulates osteogenic differentiation, at least in part, through the BMP signaling pathway, increasing Runx2 activation and leading to osteoblast commitment and maturation.


The problem of induction in clinical decision making.
This article is a discussion of the consequences of "the problem of induction" as manifested in clinical decision making. All data, statistics, and probabilities are concerned with groups, generalizing from samples to other populations. It is not self-evident what such processes mean at the level of the individual patient. Some discussion of this problem is followed by a formulation of subjective probability that may contribute to the application and acceptance of clinical decision analysis.


Application of a Varied-Line-Spacing Grating in a High-Performance Soft X-ray Monochromator.
The design and experimental evaluation of a high-resolution varied-line-spacing-grating monochromator constructed at the Photon Factory are described. Various applications of a varied-line-spacing grating in a high-performance soft X-ray monochromator are discussed.


Within- and between-pen transmission of Classical Swine Fever Virus: a new method to estimate the basic reproduction ratio from transmission experiments.
We present a method to estimate basic reproduction ratio R0 from transmission experiments. By using previously published data of experiments with Classical Swine Fever Virus more extensively, we obtained smaller confidence intervals than the martingale method used in the original papers. Moreover, our method allows simultaneous estimation of a reproduction ratio within pens R0w and a modified reproduction ratio between pens R'0b. Resulting estimates of R0w and R'0b for weaner pigs were 100 (95% CI 54.4-186) and 7.77 (4.68-12.9), respectively. For slaughter pigs they were 15.5 (6.20-38.7) and 3.39 (1.54-7.45), respectively. We believe, because of the smaller confidence intervals we were able to obtain, that the method presented here is better suited for use in future experiments.


Testosterone and the aging male.
The number and magnitude of studies involving testosterone-supplementation therapy in older men are limited. In addition, many studies to date have not been blinded or controlled, were reported in abstract form only, and had involved a variety of androgen-replacement regimens and outcomes measurements. Nonetheless, an overview of the data suggests there is real potential for supplementation therapy to improve bone mass and muscle mass and strength in this age group. Affects on mood, sexual function, and cognition are less clear but may be meaningful in certain men. Questions still remain, however, on the magnitude and longevity of the beneficial effects of testosterone supplementation in the older man and whether only certain subgroups of men would truly benefit from therapy. More importantly, the long-term risks of androgen therapy in this age group really are not known, especially in the areas of cardiovascular disease and prostate diseases. Presently, men who use androgen-supplementation therapy for age-related "testosterone deficiency" should consider this as a gamble.


[Prognosis factors for death within 90 days of discharge in patients with acute kidney injury requiring continuous renal replacement therapy after surgery for Stanford type A acute aortic dissection].
Objective: To investigate the prognosis factors for death within 90 days after discharge in patients with acute kidney injury(AKI) treated requiring continuous renal replacement therapy(CRRT) undergoing surgery for acute Standford type A aortic dissection. Methods: The clinic data of 126 patients undergoing CRRT for postoperative AKI after acute type A aortic dissection surgery in the Center for Cardiac Intensive Care, Beijing Anzhen Hospital from July 2016 to February 2019 were analyzed retrospectively. There were 83 males and 43 females, aging (52.9±11.2) years(range: 25 to 70 years). The patients' demographic characteristics, disease-related information, perioperative data, laboratory indexes during CRRT, complications, and survival information within 90 days after discharge were recorded. Independent prognosis factors for death within 90 days of discharge were determined by Kaplan-Meier survival analysis, univariate and multifactorial Cox regression analysis. Results: Totally 57 of 126 patients(45.2%) died over the first 90 days after discharge. Kaplan-Meier survival analysis and univariate Cox regression analysis showed that there were significant differences between the non-survival and survival group including ≥65 years old, high lactate values 12 hours after CRRT, pulmonary infection, liver dysfunction, presence of permanent neurological complications, and postoperative ejection fraction(EF)<45%. Multifactorial Cox regression analysis revealed that ≥65 years old(HR=2.14, 95%CI: 1.09 to 4.21, P=0.03), high lactate values 12 hours after CRRT(HR=1.13, 95%CI: 1.06 to 1.20, P=0.01) and postoperative EF<45%(HR=2.21, 95%CI: 1.09 to 4.51, P=0.03) were independent prognosis factors for patients' death within 90 days after hospital discharge. Conclusions: ≥65 years old, high lactate values 12 hours after CRRT and postoperative EF<45% are independent prognosis factors for death within 90 days after discharge in patients undergoing CRRT for AKI after acute type A aortic dissection surgery. Proper identification and management of prognosis factors could be beneficial to improve patients' outcomes.


In silico approach towards designing virtual oligopeptides for HRSV.
HRSV (human respiratory syncytial virus) is a serious cause of lower respiratory tract illness in infants and young children. Designing inhibitors from the proteins involved in virus replication and infection process provides target for new therapeutic treatments. In the present study, in silico docking was performed using motavizumab as a template to design motavizumab derived oligopeptides for developing novel anti-HRSV agents. Additional simulations were conducted to study the conformational propensities of the oligopeptides and confirmed the hypothesis that the designed oligopeptide is highly flexible and capable of assuming stable confirmation. Our study demonstrated the best specific interaction of GEKKLVEAPKS oligopeptide for glycoprotein strain A among various screened oligopeptides. Encouraged by the results, we expect that the proposed scheme will provide rational choices for antibody reengineering which is useful for systematically identifying the possible ways to improve efficacy of existing antibody drugs.


Visible-light-mediated α-amino alkylation of ketimines and aldimines for the synthesis of 1,2-diamines.
A visible-light-mediated protocol to prepare 1,2-diamines has been successfully explored based on the photoredox/Brønsted acid co-catalyzed α-amino alkylations of imines with tertiary amines. Both ketimines and aldimines are applicable to this transformation. Various 1,2-diamines with different functional groups were produced in moderate to excellent yields. Moreover, this approach could be performed on a gram scale, showing its practicality.


Comparison of two post-column derivatization systems, ultraviolet irradiation and electrochemical determination, for the liquid chromatographic determination of aflatoxins in food.
This study compared 2 post-column derivatization (PCD) techniques for the determination of aflatoxins B1, B2, G1, and G2 (AFB1, AFB2, AFG1, and AFG2) by fluorescence detection after liquid chromatographic separation: ultraviolet (UV) irradiation (PCD(UV)) and electrochemical bromination (PCD(EC)). Photochemical fluorescence enhancement was obtained with 2 different commercially available systems (PCD(UV1) and PCD(UV2)). An electrochemical bromination apparatus was used for bromination. Analyses of naturally contaminated or spiked samples of corn, pistachio paste, peanut butter, fig paste, and animal feed showed that neither of the techniques resulted in derivatization-specific matrix interferences for any of the matrixes under study, even when extracts were not completely purified. The response ratios PCD(UV)/PCD(EC) for AFB1, AFB2, AFG1, and AFG2 were 0.86, 0.96, 0.70, and 0.96, respectively, for PCD(UV1) and 0.82, 0.95, 0.60, and 0.90, respectively, for PCD(UV2). The long-term use of the UV lamps (300 h for PCD(UV1) and 343 h for PCD(UV2)) in the photochemical detectors showed that these ratios remained stable throughout the time frame investigated. The relative standard deviation obtained for each of the devices during the in-house validation study ranged from 0.3 to 1.8% for PCD(UV1), from 0.8 to 1.3% for PCD(UV2), and from 0.9 to 2.0% for PCD(EC).


Experimental investigations on characteristics of stable water electrospray in air without discharge.
An experimental study was conducted to resolve previous conflicting results on water electrospray in air at atmospheric pressure. Using a small flow rate relative to that used in previous studies and a small nonmetallic nozzle, we observed stable electrospray of water in air without discharge and distinguished three distinct operating regimes for applied voltage and flow rate. The well-known cone-jet mode was observed and the general scaling law of the generated droplet size in the cone-jet mode was confirmed by direct visualization of the meniscus, jet, and generated droplets. We also observed and analyzed whipping motion in the electrified water jet.


Morphine inhibits nocturnal oxytocin secretion and uterine contractions in the pregnant baboon.
Morphine is a potent inhibitor of nocturnal uterine contractions (UCs) in the pregnant baboon, and these contractions are known to be induced by oxytocin (OT). The purpose of this study was to determine the mode of action of morphine in inhibiting nocturnal UCs by examining the effect of morphine on OT secretion, OT clearance, and uterine responsiveness to OT. A tethered pregnant baboon model during the last third of gestation was used for these experiments. In study 1, the effects of morphine or control saline on OT release and on spontaneous nocturnal UCs were examined. Study 2 determined the effects of morphine or control saline on the pharmacokinetics of OT after a bolus injection of OT. To exclude/include direct opiate effects on UCs, study 3 examined the responsiveness of the uterus to exogenous OT after morphine or control saline administration. Plasma OT levels were analyzed by RIA after extraction. UCs were assessed by frequency, amplitude, duration, and area under the curve. During nocturnal UCs, morphine, but not saline, administration resulted in the precipitous suppression of integrated OT levels (p < 0.05) to 42% of pretreatment values at 0-15 min postinjection and 17% at 30-45 min. Simultaneously, UCs were significantly suppressed (p < 0.05) by 75% at the 30- to 45-min interval. By 1 h, 5 of 7 animals showed no UCs. In study 2, morphine consistently increased the metabolic clearance rate (MCR) of OT in all trials (p < 0.05), although the magnitude of this effect was small (median 9%). Finally, study 3 demonstrated that myometrial responsiveness to the challenge of exogenous OT was not depressed by opiate administration (p > 0.05). To summarize, the decrease in nocturnal UCs after morphine is primarily due to an inhibition of OT release, and perhaps, but to a much lesser extent, an increase in OT MCR. There was no evidence of a direct tocolytic effect of morphine on the uterus. In conclusion, opioids such as morphine are potent inhibitors of nocturnal UCs and act by suppressing OT release in the pregnant baboon.


A pull versus push framework for reputation.
Reputation is a powerful driver of human behavior. Reputation systems incentivize 'actors' to take reputation-enhancing actions, and 'evaluators' to reward actors with positive reputations by preferentially cooperating with them. This article proposes a reputation framework that centers the perspective of evaluators by suggesting that reputation systems can create two fundamentally different incentives for evaluators to reward positive reputations. Evaluators may be pulled towards 'good' actors to benefit directly from their reciprocal cooperation, or pushed to cooperate with such actors by normative pressure. I discuss how psychology and behavior might diverge under pull versus push mechanisms, and use this framework to deepen our understanding of the empirical reputation literature and suggest ways that we may better leverage reputation for social good.


Active XY model on a substrate: Density fluctuations and phase ordering.
We explore the generic long-wavelength properties of an active XY model on a substrate, consisting of a collection of nearly phase-ordered active XY spins in contact with a diffusing, conserved species, as a representative system of active spinners with a conservation law. The spins rotate actively in response to the local density fluctuations and local phase differences, on a solid substrate. We investigate this system by Monte Carlo simulations of an agent-based model, which we set up, complemented by the hydrodynamic theory for the system. We demonstrate that this system can phase-synchronize without any hydrodynamic interactions. Our combined numerical and analytical studies show that this model, when stable, displays hitherto unstudied scaling behavior: As a consequence of the interplay between the mobility, active rotation, and number conservation, such a system can be stable over a wide range of the model parameters characterized by a novel correspondence between the phase and density fluctuations. In different regions of the phase space where the phase-ordered system is stable, it displays generalized quasi-long-range order (QLRO): It shows phase ordering which is generically either logarithmically stronger than the conventional QLRO found in its equilibrium limit, together with "miniscule number fluctuations," or logarithmically weaker than QLRO along with "giant number fluctuations," showing a novel one-to-one correspondence between phase ordering and density fluctuations in the ordered states. Intriguingly, these scaling exponents are found to depend explicitly on the model parameters. We further show that in other parameter regimes there are no stable, ordered phases. Instead, two distinct types of disordered states with short-range phase order are found, characterized by the presence or absence of stable clusters of finite sizes. In a surprising connection, the hydrodynamic theory for this model also describes the fluctuations in a Kardar-Parisi-Zhang (KPZ) surface with a conserved species on it, or an active fluid membrane with a finite tension, without momentum conservation and a conserved species living on it. This implies the existence of stable fluctuating surfaces that are only logarithmically smoother or rougher than the Edward-Wilkinson surface at two dimensions (2D) can exist, in contrast to the 2D pure KPZ-like "rough" surfaces.


Low frequency variants, collapsed based on biological knowledge, uncover complexity of population stratification in 1000 genomes project data.
Analyses investigating low frequency variants have the potential for explaining additional genetic heritability of many complex human traits. However, the natural frequencies of rare variation between human populations strongly confound genetic analyses. We have applied a novel collapsing method to identify biological features with low frequency variant burden differences in thirteen populations sequenced by the 1000 Genomes Project. Our flexible collapsing tool utilizes expert biological knowledge from multiple publicly available database sources to direct feature selection. Variants were collapsed according to genetically driven features, such as evolutionary conserved regions, regulatory regions genes, and pathways. We have conducted an extensive comparison of low frequency variant burden differences (MAF<0.03) between populations from 1000 Genomes Project Phase I data. We found that on average 26.87% of gene bins, 35.47% of intergenic bins, 42.85% of pathway bins, 14.86% of ORegAnno regulatory bins, and 5.97% of evolutionary conserved regions show statistically significant differences in low frequency variant burden across populations from the 1000 Genomes Project. The proportion of bins with significant differences in low frequency burden depends on the ancestral similarity of the two populations compared and types of features tested. Even closely related populations had notable differences in low frequency burden, but fewer differences than populations from different continents. Furthermore, conserved or functionally relevant regions had fewer significant differences in low frequency burden than regions under less evolutionary constraint. This degree of low frequency variant differentiation across diverse populations and feature elements highlights the critical importance of considering population stratification in the new era of DNA sequencing and low frequency variant genomic analyses.


Neutrophil sphingosine 1-phosphate and lysophosphatidic acid receptors in pneumonia.
The phospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via transmembrane receptors S1P 1-5 and LPA 1-3, respectively. Both have been implicated in inflammatory responses. S1P and LPA receptor profiles on neutrophils of patients with pneumonia compared with healthy subjects were determined by PCR and Western blotting. Chemotaxis studies were performed to assess functional differences. S1P or LPA receptors were immunoprecipitated from neutrophils to assess receptor heterodimerization with CXCR1, an IL-8 receptor, by Western blotting. Receptors S1P 1, 4, and 5 and LPA 2 were expressed on neutrophils from both subject groups, but S1P 3 and LPA 1 receptor expression was mainly confined to neutrophils of patients with pneumonia. Chemotaxis of neutrophils from patients with pneumonia compared with control subjects was significantly increased in response to S1P and LPA. Pretreatment with S1P or LPA reduced IL-8-induced neutrophil chemotaxis and transcriptional expression of the CXCR1 receptor. Receptors S1P 3 and 4 and LPA 1 formed constitutive heterodimers with CXCR1. LPA treatment reduced the amount of LPA 1/CXCR1 heterodimer. Therefore, profiles of S1P and LPA receptors differ between neutrophils of patients with pneumonia and control subjects, with consequences for neutrophil function.


Coexistence of the loss of heterozygosity at the PTEN locus and HER2 overexpression enhances the Akt activity thus leading to a negative progesterone receptor expression in breast carcinoma.
Serine/threonine kinase Akt/PKB is known to regulate divergent cellular processes, including apoptosis, proliferation, differentiation, and metabolism. Akt is activated by a variety of stimuli, through such growth factor receptors as HER2, in phosphoinositide-3-OH kinase (PI3K)-dependent manner. A loss of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) function also activates Akt. It has recently been shown that Akt activation is associated with a worse outcome among endocrine treated breast cancer patients and that it also inhibits the progesterone receptor (PR) expression via the PI3K/Akt pathway in breast cancer cells. Therefore, the PI3K/Akt signaling pathway has recently attracted considerable attention as a new target for effective therapeutic strategies. In the present study, we investigated the relationship between Akt activation and either HER2 overexpression or PTEN gene alteration, as well as the PR expression. We analyzed the incidence of LOH at the PTEN locus in 138 breast cancer patients, using our new system for microsatellite analysis, called high-resolution fluorescent microsatellite analysis (HRFMA). We showed Akt activation to significantly correlate with HER2 overexpression or LOH at the PTEN gene locus while inversely correlating with the PR expression. In addition, when LOH at the PTEN gene locus and HER2 overexpression occurred simultaneously, the incidence of Akt activation and reduced PR expression was significant. The association between Akt activation and PR negative expression was observed even in the ER-positive cases. Our results suggest that simultaneous PTEN LOH and HER2 overexpression enhances Akt activation and may thus lead to a negative PR expression.


A PHYSICO-CHEMICAL STUDY OF THE MECHANICAL PROPERTIES OF LOW AND INTERMEDIATE MOISTURE FOODS.
A number of textural properties of precooked, freeze-dried beef were examined by a cutting-extrusion test (force) and by a compression test (seven different properties). The tests were performed at different points of the moisture sorption isotherm over the complete range of water activity, Aw . In cutting-extrusion experiments (Allo Kramer Shear Press), a maximum in the force vs. Aw curve was observed at about Aw = 0.85. In compression experiments (Instron Universal Testing Apparatus), important changes of the textural properties were found in the range Aw = 0.15-0.30. These changes were paralleled by changes in the thermodynamic functions of water vapor sorption, especially in the standard differential entropy. Thermodynamic theory and mechanical measurements were used to interpret the textural changes in terms of increased crystallinity and subsequent swelling of the food structure.


1LocusSim a mobile-friendly simulator for teaching population genetics.
Biology students often struggle with the fundamental concepts of evolutionary genetics, including genetic drift, mutation and selection. To address this problem, 1LocusSim was developed to simulate the interaction of different factors, such as population size, mutation, selection and dominance, to study their effect on allelic frequency during evolution. With 1LocusSim, students can compare theoretical results with simulation outputs and solve and analyze different problems of population genetics. The 1LocusSim web has a responsive design which means that it has been specifically designed to be used on smartphones. To demonstrate its use, I review the classical overdominance model of population genetics and highlight a characteristic that is often not explicitly stated. Specifically, it is emphasized that the equilibrium of the model does not depend on the homozygous selection coefficients but rather on the ratio of the selection coefficients. This is already clear from the classical formula but maybe not so much for students. Also it implies that the equilibrium can be expressed solely in terms of the dominance coefficient h. To verify this theoretical prediction, I utilize the simulator and calculate the equilibrium for the well-known case of sickle cell anemia. By utilizing this tool, students can learn at their own pace and convenience, anywhere and anytime. 1LocusSim if freely available at https://1LocusSim-biosdev.pythonanywhere.com/. Website implemented under the Bottle micro web-framework for Python, with all major browsers supported. Supplementary data are available at Bioinformatics Advances online.


Optical characterization of high performance mirrors based on cavity ringdown time measurements with 6 degrees of freedom mirror positioning.
An instrument capable of measuring optical losses, transmission, and the radius of curvature of high reflectivity mirrors is presented. The measurement setup consists of two remote controlled hexapod systems with 6 degrees of freedom placed inside a vacuum enclosure. Mirror loss measurements are performed via the cavity ring-down time method using a linear resonant two-mirror Fabry-Perot cavity configuration. The use of high-precision positioning systems enables cavity loss mapping by transversely scanning the position of the cavity end mirror. Mirror surfaces of up to 30 mm in diameter can be scanned, and the cavity length can be tuned by 120 mm.


[Distribution and degradation of SAS in soil environments in the Taihu Lake region].
Soil samples of different soil types under different land use patterns and environmental impacts were collected in Wuxian City in the Taihu Lake region. The contents of SAS were determined by Azure A colorimeter. Degradation of LAS was studied in the water and soil mediums by using laboratory incubation. The SAS concentration in the studied soils ranged from 2 to 10 mg.kg-1, varied with soil conditions. Profile distribution of SAS showed decreasing trend down to the soil bottom, where 0.7 mg.kg-1 of SAS was still detected. The degradation of LAS in three dominant types of paddy soils obeyed the primary reaction equation like that of soil organic matter with the half residence time in range of 9-16 days. The data indicates the relative accumulation of SAS in the soils in the Taihu Lake region and longer residence of such synthetic organic compounds in the soil environments.


Experimental infection of domestic swine with Baylisascaris procyonis from raccoons.
Six 8-week-old ascarid-naive pigs which were experimentally infected with 72,000 embryonated Baylisascaris procyonis eggs of raccoon origin developed lesions limited to the intestines and liver. Intestinal lesions consisted of multifocal areas of inflammation by macrophages, eosinophils, and lymphocytes in the mucosa and submucosa, in association with Baylisascaris larvae; similar lesions were seen in the mesenteric lymph nodes. Typical white, granulation type, multifocal interstitial hepatitis ("milk-spots"), 1 to 5 mm in diameter, were seen in the livers by 7 days, with resolution by 47 days. Microscopically, these consisted of multifocal areas of marked periportal and interlobular edema, and influx of eosinophils, and large intralobular aggregates of eosinophils. At 47 days, hundreds to thousands of small white granulomas were seen on the serosa of the intestines; microscopically, they were discrete collections of macrophages, lymphocytes, and eosinophils in the submucosa and muscle layers surrounding nonviable remnants of Baylisascaris larvae. Larvae or lesions were not seen in other tissues, including the brain. These experiments indicated that B procyonis will undergo limited migration in swine and can produce typical white spots in the liver. The larvae were killed by cellular reactions in the intestinal wall and liver, and, unlike the situation in most other animals infected with this parasite, no somatic migration or CNS disease occurred after infection.


Management of metatarsus adductovarus.
A retrospective analysis of 795 patients treated for metatarsus adductovarus by a standardized outpatient approach by one of the authors (D.S.W.) from 1970 to 1983 was conducted to evaluate the efficacy of a straight metal bar and attached reverse last shoe protocol. Criteria for inclusion were developed excluding those milder cases in which spontaneous resolution was expected and indeed occurred. Nearly uniform excellent results were encountered, with a 99% likelihood of obtaining a fully corrected foot. Surgical intervention was deemed necessary in under 1% of cases seen. The authors also examined birth weights and rank in relation to metatarsus adductovarus. Those children with the deformity had a mean birth weight of 7.6 pounds, without statistical variance from normal average birth weights. We were unable to establish any statistical association with birth rank. In light of the results of this study, which compare favorably with serial casting, we recommend this approach as a more economical and less disruptive and cumbersome technique for parent, patient, and physician.


Electrophysiological significance of QRS alternans in narrow QRS tachycardia.
To investigate the electrophysiological significance of QRS alternans during narrow QRS tachycardia, transesophageal atrial pacing and recording was performed in 24 patients with a history of paroxysmal supraventricular tachycardia. Standard electrocardiograms showed ventricular preexcitation in 15 patients and normal QRS pattern in nine patients. The ventriculoatrial interval during tachycardia, as defined by means of transesophageal electrogram, allowed tentative diagnosis of the tachycardia mechanism. A 12-lead ECG was recorded either during spontaneous or induced tachycardia, as well as during transesophageal atrial pacing at increasing rates. Electrical alternans occurred spontaneously in eight patients (33%, group A): five with accessory pathway reentry (mean VA: 136 +/- 43 msec), and three with AV nodal reentry (mean VA: 48.3 +/- 12 msec). Tachycardia rate ranged between 170 and 230 beats/min (mean 200.7 +/- 16). In two patients, alternation of the QRS occurred only in the presence of a heart rate exceeding 180 and 190 beats/min, respectively. The amplitude of QRS remained stable during tachycardia in 16 patients (67%, group B): 14 had accessory pathway reentry (mean VA: 137.5 +/- 32 msec), and two had AV nodal reentry (mean VA: 45 +/- 7 msec). In this group, the tachycardia rate ranged from 150 to 210 beats/min (mean 175 +/- 12). Incremental transesophageal atrial pacing up to rates equal to that of tachycardia was performed in five patients from group A and in five patients from group B. Electrical alternans could not be induced in both groups with pacing at progressively increasing rates.(ABSTRACT TRUNCATED AT 250 WORDS)


In situ detection of human immunodeficiency virus (HIV) nucleic acid in H9 cells using nonradioactive DNA probes and an image cytophotometry system.
Rapid and sensitive nonradioactive methods to detect human immunodeficiency virus (HIV)-infected cells are needed in clinical medicine. We developed an in situ hybridization test using 2-acetylaminofluorene (AAF)-labeled HIV DNA as a hybridization probe. Hybridized probe was detected using rabbit anti-AAF antibody, followed by alkaline phosphatase-conjugated goat anti-rabbit, and the bromochloroindolyl phosphate-nitroblue tetrazolium reaction. An image cytophotometry system was used to quantitate the percentage of HIV-infected cells. These methods were used to determine the percentage of H9 cells infected with HIV. HIV was detected in 0% of cells on day 1 post infection, 7% on day 4, 41% on day 8, and 5% on day 15. These results paralleled those of the reverse transcriptase assay and an antigen capture ELISA assay for HIV antigen. Thus the AAF modified HIV DNA probe detected HIV nucleic acid in infected H9 cells and the image cytophotometry system improved the sensitivity and objectivity of detection.


[ Active trypanocidal alkaloids, bisbenzylisoquinoles ii. active in vitro against trypanosoma cruzi the agent responsible for trypanosomiasis, south america].
Chagas disease caused by the protozoan Trypanosoma cruzi is an endemic parasitic disease in Central and South America. The chemotherapeutic agents against Trypanosoma cruzi (imidazol compounds, lampit and benznidazol) are not very convenient products. Since it is known that protozoan Trypanosoma are close to Leishmania we studied the action of 14 bisbenzylisoquinoline alkaloids, in vitro, on three strains of T. cruzi (Tulahuen, C8C11, and 1979 CL1). As in the case of Leishmania, gyrocarpine, daphnandrine and obaberine showed an interesting activity and we judge them to be worthy of in vivo assays.


A ten-year observation on experimental infection of periodic Brugia malayi in man.
This paper reports the results of 10 years of observations on the clinical manifestations, pathology and immunity to filariasis and aetiological biology of filariae in three volunteers (first author and his family members) who were inoculated experimentally with infective larvae of periodic Brugia malayi in 1981. The changes in clinical symptoms and signs were recorded systematically. Microfilariae were first detected at 41 and 46 weeks after inoculation in two subjects and remained detectable in small numbers until 8-8.5 years after infection. The microfilarial density fluctuated at 1-2 mf 120 microliters-1. Thereafter no microfilariae were detected in 12 blood sample examinations, suggesting that the adult reproductive period of periodic B. malayi could last up to 8-9 years in the human body. Eosinophilia occurred mainly before and at the initial stage of microfilaraemia. An increase in the lymphocytes was observed to some extent at 2-156 weeks after infection. Biopsy at the inoculation site 6 weeks after inoculation showed infiltration of the lymph node by inflammatory cells, mainly eosinocytes, lymphocytes and monocytes. Lymphangiectasis and lymphostasis were observed in both limbs and pelvic regions by lymphangiogram taken 11 weeks after inoculation. Antibodies against B. malayi first appeared at 2-5 weeks after infection, peaked at 12-56 weeks and thereafter declined gradually. Subjects A and C became antibody free but subject B remained positive to antibody against B. malayi 10 years after infection. E-rosette forming lymphocytes became lower than normal at 11 weeks and recovered to normal within 10 years after infection.


Comparison of a new renin inhibitor and enalaprilat in renal hypertensive dogs.
The hypotensive efficacy of a potent new renin inhibitor (N alpha-isovaleryl-L-histidyl-L-prolyl-L-phenylalanyl-L-histidyl-ACHPA+ ++-L- phenylalanyl amide) containing (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy pentanoic acid (ACHPA) was compared with the converting enzyme inhibitor (enalaprilat) (MK-422) in conscious one-kidney dogs before and after tightening a renal artery clamp. Dose-response curves to 0.003 to 0.1 mg/kg/min i.v. infusions of the ACHPA-containing renin inhibitory peptide or enalaprilat (0.003-0.1 mg/kg i.v. bolus) were obtained in one-kidney dogs before and 3 days and 14 days after renal artery constriction. The ACHPA-containing renin inhibitory peptide and enalaprilat maximally decreased blood pressure by 10 +/- 2 and 9 +/- 2 mm Hg before constriction and by 12 +/- 2 and 12 +/- 4 mm Hg in dogs treated 14 days after renal artery constriction, respectively. Glomerular filtration rate and effective renal plasma flow were unaltered or slightly improved. In sharp contrast, both compounds elicited significant, dose-related decreases in blood pressure (-26 +/- 4 and -20 +/- 4 mm Hg, respectively), glomerular filtration rate (-21 +/- 3 and -23 +/- 3 ml/min), and renal plasma flow (-45 +/- 14 and -48 +/- 13 ml/min) in dogs examined 3 days after renal artery constriction. These data demonstrate that ACHPA-containing renin inhibitory peptide and enalaprilat are equally effective antihypertensive agents in dogs with renin-dependent renovascular hypertension and lend credence to the contention that the renin-angiotensin system supports renal function in hypertensive states in which renin levels are elevated.


Excessive weight gain in rats over extended kindling of the basolateral amygdala.
Previous lesion studies have indicated a role of the amygdala in the central regulation of food intake. In the present experiments, twice-daily electrical stimulation of the basolateral nucleus of the amygdala in female Wistar rats was found to be associated with a significant body weight gain compared to unstimulated controls. On average, significant increases in body weight were observed after 25 amygdala stimulations, using a kindling paradigm for stimulation. Compared to kindled rats, in which amygdala stimulations were terminated after about 20 stimulations, extended kindling of the amygdala with up to 280 stimulations led to progressive weight increases and compulsive hyperphagia. No gross neuronal damage was seen in thionin-stained sections of the amygdala after extended kindling, but degeneration of a specific type of neurons can not be excluded. The results substantiate that amygdaloid nuclei are an important extrahypothalamic site for the regulation of food intake and body weight. The extensive weight gain over extended amygdala kindling provides an interesting new model for experimentally induced obesity.


Postoperative radionuclide monitoring of renal allografts on triple therapy.
Renal allograft dysfunction arising from rejection or cyclosporin A nephrotoxicity in patients on high-dose cyclosporin A administration can currently only be distinguished reliably by allograft biopsy excluding rejection. The renographic course up to 35 days after transplantation or to discharge was followed in 30 patients treated with low-dose azathioprine, prednisone, and cyclosporin A (triple therapy). Routine renographic monitoring combined with intravenous angiography in critical periods proved a valuable aid in the differentiation between post-operative complications such as acute rejection and surgical complications.


Multiple sclerosis in Coloured South Africans.
Detailed case histories of seven Coloured South Africans with multiple sclerosis are presented; the summary of one South African-born Indian is included. Apart from an isolated case report in 1947, this is the first time that multiple sclerosis has been reported in detail in this South African racial group. All the Coloured patients presented for the first time during the last 12 years.


Comparison of fenoprofen calcium, ibuprofen and placebo in primary dysmenorrhea.
This prospective, double-blind, parallel, two clinic study compared fenoprofen calcium, 200 mg; ibuprofen, 400 mg; and placebo in the treatment of pain due to primary dysmenorrhea. By various criteria, the treatment groups, prior to treatment, were not significantly different (P greater than 0.05) in paired comparisons. However, after oral administration of the study medications, the pain scores were significantly greater (P less than 0.05) for the placebo group than for either other group. The posttreatment pain scores for the fenoprofen and ibuprofen treated groups were not significantly different (P greater than 0.05).


Hormonal and non-hormonal oral contraceptives given long-term to pubertal rats differently affect bone mass, quality and metabolism.
We investigated the effects of hormonal and non-hormonal oral contraceptives (OCs) on bone mass, mineralization, composition, mechanical properties, and metabolites in pubertal female SD rats. OCs were given for 3-, and 7 months at human equivalent doses. The combined hormonal contraceptive (CHC) was ethinyl estradiol and progestin, whereas the non-hormonal contraceptive (NHC) was ormeloxifene. MicroCT was used to assess bone microarchitecture and BMD. Bone formation and mineralization were assessed by static and dynamic histomorphometry. The 3-point bending test, nanoindentation, FTIR, and cyclic reference point indentation (cRPI) measured the changes in bone strength and material composition. Bone and serum metabolomes were studied to identify potential biomarkers of drug efficacy and safety and gain insight into the underlying mechanisms of action of the OCs. NHC increased bone mass in the femur metaphysis after 3 months, but the gain was lost after 7 months. After 7 months, both OCs decreased bone mass and deteriorated trabecular microarchitecture in the femur metaphysis and lumbar spine. Also, both OCs decreased the mineral: matrix ratio and increased the unmineralized matrix after 7 months. After 3 months, the OCs increased carbonate: phosphate and carbonate: amide I ratios, indicating a disordered hydroxyapatite crystal structure susceptible to resorption, but these changes mostly reversed after 7 months, indicating that the early changes contributed to demineralization at the later time. In the femur 3-point bending test, CHC reduced energy storage, resilience, and ultimate stress, indicating increased susceptibility to micro-damage and fracture, while NHC only decreased energy storage. In the cyclic loading test, both OCs decreased creep indentation distance, but CHC increased the average unloading slope, implying decreased microdamage risk and improved deformation resistance by the OCs. Thus, reduced bone mineralization by the OCs appears to affect bone mechanical properties under static loading, but not its cyclic loading ability. When compared to an age-matched control, after 7 months, CHC affected 24 metabolic pathways in bone and 9 in serum, whereas NHC altered 17 in bone and none in serum. 6 metabolites were common between the serum and bone of CHC rats, suggesting their potential as biomarkers of bone health in women taking CHC. Both OCs have adverse effects on various skeletal parameters, with CHC having a greater negative impact on bone strength.


Corpus callosum integrity is affected by mood disorders and also by the suicide attempt history: A diffusion tensor imaging study.
Some MRI studies have noted alterations in the corpus callosum (CC) white matter integrity of individuals with mood disorders and also in patients with suicidal behavior. We investigated the specific impact of suicidal behavior on CC integrity in mood disorders. CC structural changes were assessed by diffusion tensor imaging (DTI) in 121 women 18-50-year-old): 41 with bipolar disorder (BD), 50 with major depressive disorder (MDD) and 30 healthy controls (HC). Fractional anisotropy (FA) and DTI metrics were calculated for the genu, body and splenium of CC and compared in the three groups by MANCOVA. Then, they were re-analyzed relative to the suicide attempt history within the MDD and BD groups and to the suicide number/severity. FA values for the CC genu and body were lower in non-suicide attempters with BD than with MDD and in HC. Conversely, FA values for all CC regions were significantly lower in suicide attempters with BD than in HC. Finally, higher number of suicide attempts (>2) and elevated Suicidal Intent Scale score were associated with significant splenium alterations. Limitations include the cross-sectional design (non-causal study), the potential influence of medications and concerns about the generalizability to men. Genu and body are altered in non-suicide attempters with BD, while splenium is specifically altered in suicide attempters, independently from their psychiatric status. History of suicide attempts may be a source of heterogeneity in the association between CC alterations and BD and may partially explain the variable results of previous studies.


Effect of lung irradiation on the incidence of pulmonary metastases and its mechanism.
LP-12 cells injected intravenously into ddY mice result in the formation of visible lung colonies which are introduced as a model for pulmonary metastases. Localized irradiation before tumour cell transplantation significantly increased the incidence of pulmonary metastases in the irradiated lung only. The changes of the vascular permeability of the lung indicate that dilatation of capillaries or increased permeability may be one of the main mechanisms of this phenomenon.


[Identification of mycobacteria species using genetic probes].
Using commercially available probes Gen-Probe (Accu-Probe, Epignost, Austria) labelled with acridinium ester, the authors identified 102 cultures of mycobacteria which are the causal agents of classical tuberculosis or cause mycobacterioses which are difficult to control by therapeutic measures. The cultures were isolated from sputum or lymph nodes and cultivated on Löwenstein-Jensen medium. The authors proved a 100% sensitivity of the probe for isolates of M. tuberculosis and M. kansasii. In a group of 36 strains sent as suspect M. avium 33 strains reacted with the probe for the M. avium complex, 28 strains with the M. avium probe and 4 strains with the M. intracellulare. One isolate hybridized only with the probe for the M. avium complex. In one isolate a positive hybridization value was recorded with the M. gordonae probe and in one pigmented strain with the M. kansasii probe. One isolate did not hybridize with any of the probes used. In one instance a mixed culture of M. tuberculosis and M. avium was involved. The results of hybridization were interpreted in RLU values (relative light unit). Isolates above 30,000 RLU were evaluated positively, as recommended by the manufacturer.


Professional training to reduce children's exposure to second-hand smoke in the home: evidence-based considerations on targeting and content.
Proponents of theory-based evaluations argue that the type of evidence needed by public health decision-makers is not simply whether interventions work or not. A more fruitful approach is to understand the contexts and circumstances associated with effectiveness. This article aims: to firstly understand factors influencing professionals' practice following their participation in training that aimed to reduce children's exposure to second-hand smoke (SHS) in the home via increased usage of brief interventions; and secondly to consider the implications of these factors for improving the skills of a diverse workforce. Questionnaires were issued to the 231 participants pre- and post-training and at three-month follow-up. Four focus groups and four interviews were run with 16 people who had attended the training in the previous four to eight months and who performed a wide range of professional roles, reflecting the diversity of those trained. The three-month follow-up data indicated that some, but not all, participants had engaged in components of the brief intervention and changed their practice. This difference was largely explained by professional role. Those working in a health-visiting role or team were considered better placed to support families through a process of restricting SHS exposure in the home. Triangulated data also indicated that these professionals more often practised elements of the brief intervention. There was also some evidence that the training did not equip participants with the full range of information they wanted, or with the skills that they felt that they needed. Decisions on who to target for training need to be informed by an understanding of the contexts in which professionals work and the opportunities and constraints within these. Those working in a health-visiting team are credible message carriers, have opportunities to develop a relationship with families, and can be well placed to provide families with sustained support. To do so, they need clear messages on precisely how to reduce exposure. In addition, they need the skills to support families through a process of change.


Calcium channel blocker use and mortality among patients with end-stage renal disease.
Patients on dialysis suffer from alarming rates of cardiovascular disease. While calcium channel blockers (CCBs) are prescribed widely to patients with end-stage renal disease (ESRD) for the treatment of hypertension, the long-term outcomes associated with the use of these medications are not known. We sought to determine the association between CCB use and mortality among a cohort of ESRD patients. Data were utilized from the United States Renal Data System Dialysis Morbidity and Mortality Wave II, a randomly selected prospective cohort of 4065 ESRD patients who began dialysis in 1996. Clinical data, including medication information, were collected 60 days after the start of dialysis. Subsequent survival status and cause of death were ascertained. The Cox proportional hazards model was used to estimate the relative risk of death associated with CCB use. Data from 3716 patients (91.4%) were available for analysis. Fifty-one percent of the study patients were prescribed a CCB. The use of a CCB was associated with a 21% lower risk of total mortality (RR 0.79, CI 0.69 to 0.90) and a 26% lower risk of cardiovascular specific mortality (RR 0.74, CI 0.60 to 0.91). For patients with pre-existing cardiovascular disease, CCB use was associated with a 23% (RR 0.77, CI 0.65 to 0.91) and 32% (RR 0.68, CI 0.53 to 0.87) lower risk of total and cardiovascular mortality, respectively. After controlling for known risk factors and potential confounders, CCBs were found to be associated with a lower risk of mortality among ESRD patients.


Phytosociological contrast of ferns and lycophytes from forest fragments with different surroundings matrices in southern Brazil.
Forest edges typically exhibit higher luminosity and lower humidity than the forest interior, resulting in an abiotic gradient. However, the degree of abiotic difference can be affected from the type of the matrix, influencing the selection of species. We compared the floristic and phytosociological structure of understory communities of ferns and lycophytes of the edge and interior of three forest sites influenced by different types of surrounding matrices (natural field, Pinus plantation, and cultivation of crops). In the region of Araucaria Forest, in Rio Grande do Sul, Brazil, twelve 10 × 10 m plots were selected at the edge and interior of each site, totaling 72 plots and to evaluate the phytosociological contrast, using as a parameter coverage and species richness per plot to evaluate this contrast. We recorded a total of 38 species in the studied areas, distributed in 15 families. The results show that the edge effect acts at different intensities in the analyzed sites. In the site with unnatural matrix, the composition was more homogeneous both in the edges and in the interiors and presented lower richness, showing a more pronounced and deep impact. Already in the site with natural matrix surroundings, although the border also presents low richness, the interior was about 3x richer. Based on our results, we concluded that fern conservation efforts should focus on fragments of Araucaria Forest inserted in the natural field, because the conversion of natural field into Pinus planting and cultivation of crops decreases ferns species both in the edges and forest interiors of the studied fragments, besides altering the phytosociological structure leading the communities to simplification.


New wiggler beamlines at BSRF.
A new multipole wiggler has been installed in the ring of the Beijing Electron Positron Collider (BEPC), and two new beamlines were extracted from it for experiments, including LIGA, microprobe fluorescence analysis, high-pressure diffraction and soft X-ray research. The beam profile and photon intensity were measured and compared with the calculated values. The main parameters and characteristics of the two beamlines are illustrated. Some experimental results are presented.


Inefficacy of topical methoxalen plus UVA for palmoplantar pustulosis.
The effect of local application of 8-methoxypsoralen (8-MOP) and subsequent UVA irradiation on palmoplantar pustulosis (PPP) was studied in 10 patients. In 8 patients 8-MOP baths were used, and in 5 patients an 8-MOP ointment was applied, 3 patients receiving both forms of treatment. The number of treatment sessions varied from 15 to 128, with maximal UVA doses of 1.2 to 12 J/cm2, and total cumulative doses of 8 to 348 J/cm2. Two patients experienced a brisk phototoxic erythema and one patient developed a bullous reaction. Only 3 patients responded favourably to the treatment, 2 with moderate and 1 with good clearing of the lesions. In the remaining 7 patients either no effect (5 patients) or an exacerbation of the disease (2 patients) was seen.


Long-term Outcomes of Laparoscopy-assisted Gastrectomy for T4a Advanced Gastric Cancer: A Single-center Retrospective Study.
Laparoscopy-assisted gastrectomy (LAG) has been proven to be feasible and oncologically safe for early gastric cancer. Despite the rapid increase in the number of LAG cases, there are few reports on the long-term outcomes of T4a (serosalinvasion) gastric cancer after LAG. The aim of the present study was to evaluate the long-term clinical outcomes in patients with stage T4a gastric cancer after laparoscopic gastrectomy. A total of 578 patients with gastric cancer were treated with LAG between February 2004 and December 2014. Among these patients, 224 patients were pathologically confirmed with T4a advanced gastric cancer. The clinical and follow-up data were retrospectively analyzed, the survival rates were estimated using the Kaplan-Meier method, and the risk factors for overall and disease-free survival (DFS) were evaluated by Cox regression. Among these 224 patients, 129 patients were above 60 years old, and the male-to-female ratio was 157:67. Furthermore, among these patients, 125 patients received laparoscopy-assisted distal gastrectomy, whereas 99 patients received laparoscopy-assisted total gastrectomy. Forty (17.90%) patients experienced postoperative complications according to the Clavien-Dindo classification. Median follow-up time was 32 months. Recurrence was observed in 99 (44.20%) patients. The cumulative 5-year overall survival (OS) and DFS rates were 47.20% and 43.60%, respectively. The 5-year OS and DFS rates were 72.50% and 70.00% for stage N0, 57.00% and 53.90% for stage N1, 41.60% and 37.00% for stage N2, and 23.30% and 21.30% for stage N3, respectively. In the univariate analysis, tumor size, tumor location, N stage and metastatic lymph node ratio (MLR) were correlated with OS and DFS. The MLR was identified as an independent predictor for OS (P<0.05; hazard ratio=1.828; 95% confidence interval, 1.353-2.469) and DFS (P<0.05; hazard ratio=1.197; 95% confidence interval, 0.945-1.516). The long-term outcomes of LAG for T4a (M0) gastric cancer were acceptable, compared with previous reports. Therefore, this treatment could be considered as an alternative operative approach for T4a gastric cancer. The MLR was an independent predictor for OS and DFS.


Reflecting on the challenges of choosing and using a grounded theory approach.
To explore three different approaches to grounded theory and consider some of the possible philosophical assumptions underpinning them. Grounded theory is a comprehensive yet complex methodology that offers a procedural structure that guides the researcher. However, divergent approaches to grounded theory present dilemmas for novice researchers seeking to choose a suitable research method. This is a methodology paper. This is a reflexive paper that explores some of the challenges experienced by a PhD student when choosing and operationalising a grounded theory approach. Before embarking on a study, novice grounded theory researchers should examine their research beliefs to assist them in selecting the most suitable approach. This requires an insight into the approaches' philosophical assumptions, such as those pertaining to ontology and epistemology. Researchers need to be clear about the philosophical assumptions underpinning their studies and the effects that different approaches will have on the research results. This paper presents a personal account of the journey of a novice grounded theory researcher who chose a grounded theory approach and worked within its theoretical parameters. Novice grounded theory researchers need to understand the different philosophical assumptions that influence the various grounded theory approaches, before choosing one particular approach.


The chemical inventory of the inner regions of planet-forming disks - the JWST/MINDS program.
The understanding of planet formation has changed recently, embracing the new idea of pebble accretion. This means that the influx of pebbles from the outer regions of planet-forming disks to their inner zones could determine the composition of planets and their atmospheres. The solid and molecular components delivered to the planet-forming region can be best characterized by mid-infrared spectroscopy. With Spitzer low-resolution (R = 100, 600) spectroscopy, this approach was limited to the detection of abundant molecules, such as H2O, C2H2, HCN and CO2. This contribution will present the first results of the MINDS (MIRI mid-INfrared Disk Survey, PI:Th Henning) project. Due do the sensitivity and spectral resolution provided by the James Webb Space Telescope (JWST), we now have a unique tool to obtain the full inventory of chemistry in the inner disks of solar-type stars and brown dwarfs, including also less-abundant hydrocarbons and isotopologues. The Integral Field Unit (IFU) capabilities will enable at the same time spatial studies of the continuum and line emission in extended sources such as debris disks, the flying saucer and also the search for mid-IR signatures of forming planets in systems such as PDS 70. These JWST observations are complementary to ALMA and NOEMA observations of outer-disk chemistry; together these datasets will provide an integral view of the processes occurring during the planet-formation phase.


Persistence of erythromycin-resistant group a streptococci in cultured respiratory cells.
A significant association between erythromycin resistance and ability of bacteria to enter human respiratory cells has been documented in group A streptococci (GAS) isolated in Italy from children with pharyngitis. The occurrence of strains combining cell invasiveness with erythromycin resistance raised serious concern because they could escape penicillin by virtue of intracellular location and macrolides by virtue of resistance, resulting in difficulty in eradication. Thirty-one pharyngeal cell-invasive, erythromycin-resistant (ER) GAS, representing that many clones recently identified among Italian GAS carrying the internalization-related gene prtF1, were investigated for intracellular persistence inside cultured respiratory cells (A549) by means of a survival assay and by staining and polymerase chain reaction assays on infected cells. All tested ER GAS could be recovered in culture from infected cells 24 hours from infection with logarithms exceeding 4.0 (4 strains). The highest survival rate (>5.0) was exhibited by strain SP1900 [erm(A)/iMLS-B; high-level erythromycin resistance [minimum inhibitory concentration, > or =128 microg/mL)], the most widespread clone, which was cultivable from infected cells up to day 5. As long as SP1900-infected cells could be maintained in culture, the presence of multiple cocci inside cells was consistently revealed by microscopy. During the same time, DNA sequences internal to both genes prtF1 and erm(A) continued to be amplified by polymerase chain reaction. These results suggest that the ER GAS are capable of persisting in human respiratory cells. This might contribute to clinical problems such as relapsing infection and persistent carriage despite antibiotic treatment and might have facilitated the widespread diffusion of ER GAS in Italy.


Staffing shortages.
The case of a man dying after being given the wrong blood type shows why checking blood components before administration should always be done by two qualified members of staff.


Risk assessment based on FDG-PET imaging in patients with synovial sarcoma.
Synovial sarcoma generally is associated with poor prognosis. With recent advances in molecular biology, it has become apparent not all synovial sarcomas share the same tumor biology. (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is useful for risk assessment in several types of sarcomas. We therefore assessed the clinical value of (18)F-FDG-PET-derived maximum standard uptake value (SUV(max)) for predicting survival in patients with synovial sarcoma. (18)F-FDG-PET was performed in 44 patients with synovial sarcoma before therapy and resection. SUV(max) was calculated for each tumor and then evaluated for prognostic usefulness along with metastasis at presentation, tumor grade, histopathologic subtype, age, gender, postsurgical margins, anatomic location, and tumor size for overall survival and progression-free survival. SUV(max) ranged from 1.2 to 13.0 (median, 4.35). Pretherapy tumor SUV(max) predicted overall survival and progression-free survival. Patients presenting with a SUV(max) greater than 4.35 had a decreased disease-free survival and were therefore at high risk for having local recurrences and metastatic disease. Level I, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.


Risk factors for anal sphincter disruption during child birth.
The objective of our study was to analyse the risk factors in a cohort of women who suffered anal sphincter disruption (third-degree tear) and compare the results with a similar cohort of women who underwent an uncomplicated vaginal delivery (without a clinically detectable laceration) during the same period. A retrospective analysis was carried out on 54 women (group 1) who suffered a third-degree tear and 71 women who had undergone uncomplicated vaginal delivery during the same period (group 2). The risk factors considered were forceps delivery, parity, second stage of labour longer than 1 h, episiotomy, birth weight over 4 kg, gestational age and maternal age at delivery. The Cleveland Incontinence Score was completed. Multiple logistic regression analysis of obstetric risk factors for third-degree perineal tear indicated forceps delivery (p = 0.0001), primiparity (p = 0.004), foetal birth weight over 4 kg (p = 0.030) and delay in the second stage of labour (p = 0.031) to be significant risk factors for a third-degree tear. Mediolateral episiotomy was shown to be a significant protective factor (p = 0.0001). Gestational age and the maternal age at delivery (p = 0.340) were not shown to be significant risk factors (p = 0.336). Primary prevention and identification of women with risk factors is recommended. In some cases, counselling regarding the potential risks and benefits of both vaginal and caesarean delivery may be appropriate.


Modification of Bupivacaine-Induced Myotoxicity with Dantrolene and Caffeine In Vitro.
Local anesthetics, especially bupivacaine, have myotoxic effects in clinically used concentrations and context. Detailed mechanisms of these effects are unknown, but an increase in intracellular calcium levels is suspected to be the most important trigger. Dantrolene and caffeine modify cellular calcium release from the sarcoplasmic reticulum. The aim of our study was to investigate the effect of dantrolene and caffeine on bupivacaine-induced myotoxicity in vitro. A cell culture model of primary muscle cells of BALB/c AnNCrl mice was established. Cells were incubated simultaneously with increasing concentrations of bupivacaine, dantrolene, and caffeine. The fraction of dead cells was calculated after staining with propidium iodide and analysis by flow cytometry. The half-maximal inhibitory concentration of bupivacaine was calculated for each concentration. Group differences were determined by using 1-way analysis of variances with subsequent post hoc 1-way Dunnett t test. Both dantrolene and caffeine alone had no effect on muscle cell survival. Increasing concentrations of bupivacaine caused increasing cell death. Dantrolene dose-dependently reduced the fraction of necrotic cells, whereas caffeine dose-dependently increased the fraction of dead cells. Dantrolene attenuated, and caffeine enhanced, bupivacaine-induced myotoxicity, presumably by modifying sarcoplasmic calcium release. This indicates that intracellular calcium release is an important factor for local anesthetic-induced cell death.


Elevated high-sensitivity troponin does not indicate the presence of coronary artery disease in patients presenting with supraventricular tachycardia.
Patients with supraventricular tachycardia (SVT) and patients with coronary artery disease (CAD) often present with similar symptoms (chest pain, shortness of breath), similar electrocar¬diographic changes and elevated high-sensitivity troponin (Tn). It is not clear whether troponin reflects critical CAD or is elevated due to other causes in patients presenting with SVT. The aim of this study was to assess the role of elevated troponin in patients presenting with SVT. Patients undergoing radiofrequency ablation (RFA) for SVT and simultaneous coronary an¬giography at the Heart Centre Lucerne, Switzerland between January 2010 and October 2014 were in¬cluded in this analysis. Significant CAD was defined as diameter-stenosis ≥ 75% in vessels > 2.0 mm. The level of Tn was compared between patients with the presence or absence of CAD on coronary angi¬ography. A Tn value of ≥ 0.014 μg/L was considered as elevated. During the study period a total of 473 patients underwent RFA for SVT. The study population consisted of 326 patients (69%, mean age 60 ± 12 years) who underwent invasive coronary angiogra¬phy during the same session. The prevalence of significant CAD was 14% (45/326 patients). The highest prevalence of CAD was found in patients with atrial flutter (35%, 18/45 patients). Tn was elevated in 83% (10/12 patients) with significant CAD and in 47% (26/55 patients) without CAD. The prevalence of CAD is low in patients with SVT, which questions the role of routine invasive coronary angiography during RFA. Tn measurement did not reliably exclude or confirm CAD in these patients.


Allergen induced gene expression of airway epithelial cells shows a possible role for TNF-alpha.
Epithelium is more than a physical barrier for pathogens and allergens, as it is also capable of producing mediators in response to these environmental factors. Some of these mediators have an immuno-modulatory function, suggesting that epithelium is an active component of the immune response. Here, we fully characterize the expression profile of airway epithelial cells in response to house dust mite (HDM) allergen. H292 cells were exposed to HDM extract for 24 h, RNA and supernatant was used for microarray analysis and multiplex enzyme-linked immunosorbent assay (ELISA) respectively. A total of 38,500 genes, 813 were differentially expressed by more than twofold and 116 even more than fivefold. Interestingly, among the most up-regulated genes, a large number are involved in cell-to-cell communication. These include chemokines (CCL-8 and -20, CXCL-1, -2 and -3), cytokines (IL-1alpha, -6 and -11), anti-inflammatory factors [PTX-3, interleukin (IL)-13Ralpha, tumour necrosis factor (TNF)-alphaIP3], and factors that are involved in repair of the mucosal tissue (LOXL-2, NID-2, HBEGF, MUC-5AC and MUC-5B). Pathway analysis showed that a number of these genes are transcriptionally regulated by TNF-alpha, which we could detect by quantitative polymerase chain reaction at earlier time points after HDM exposure. In addition, we could detect increased protein levels for TNF-alpha, IL-6, IL8, granulocyte-macrophage colony-stimulating factor, granulocyte colony stimulating factor and interferon (IFN)-gamma using ELISA. Our data show that a broad range of mediators produced upon allergen exposure by these mediators' epithelial cells can participate in the immune response via recruitment and activation of cells of the immune system.


A comparative computer simulation study of three different sparse-sampling methods for the estimation of steady-state area under the concentration-time curve (AUC) and maximum concentration (Cmax) in toxicokinetics.
A limited-sampling method is proposed to estimate the area under the curve (AUC) of concentration versus time and maximum concentration (Cmax) following single or multiple oral doses of a hypothetical drug. The plasma concentration versus time data sets for 50 animals were generated by simulation. The limited-sampling model (LSM) was developed with samples from 10 animals at a single time point. The model was validated in another 40 animals who received either a 500-mg single dose or multiple doses orally. The model provided good population mean estimates of AUC and Cmax. The proposed method was compared with the existing two methods; they are, naive sampling (five time points) and optimal sampling (three time points). The method described here may be useful in estimating AUC and Cmax with one or two samples in toxicokinetic studies following single or multiple oral dosing without detailed pharmacokinetic studies.


Human Health Impact of Cross-Connections in Non-Potable Reuse Systems.
We used quantitative microbial risk assessment (QMRA) to estimate the microbial risks from two contamination pathways in onsite non-potable water systems (ONWS): contamination of potable water by (treated) reclaimed, non-potable water and contamination of reclaimed, non-potable water by wastewater or greywater. A range of system sizes, event durations, fraction of users exposed, and intrusion dilutions were considered (chlorine residual disinfection was not included). The predicted annual microbial infection risk from domestic, non-potable reuse remained below the selected benchmark given isolated, short-duration intrusion (i.e., 5-day) events of reclaimed water in potable water. Whereas, intrusions of wastewater into reclaimed, non-potable water resulted in unacceptable annual risk without large dilutions or pathogen inactivation. We predicted that 1 user out of 10,000 could be exposed to a 5-day contamination event of undiluted wastewater in the reclaimed, non-potable water system each year to meet the annual benchmark risk of 10-4 infections per person per year; whereas, 1 user out of 1000 could be exposed to a 5-day contamination event of undiluted reclaimed water in the potable water each year. Overall, the predicted annual risks support the use of previously derived non-potable reuse treatment requirements for a variety of ONWS sizes and support the prioritization of protective measures to prevent the intrusion of wastewater into domestic ONWS.


Stem cell therapies in post-prostatectomy erectile dysfunction: a critical review.
Erectile dysfunction (ED) is still a common complication of radical prostatectomy. Current treatments of ED are mainly symptomatic. Mesenchymal stem cells (MSCs) have been widely investigated as a potential curative treatment. Although MSC therapy consistently improved erectile functions in the pre-clinical studies the initial expectations seem to be unmet. The aim of this study is to critically review the existing studies on use of stem cells in post-prostatectomy ED and understand factors that preclude clinical translation of the available evidence. A literature search for all pre-clinical and clinical studies investigating MSCs in the treatment of post-prostatectomy ED published between January 2009 and March 2016 was performed using the PubMed database. A total of 24 pre-clinical studies investigated MSC based treatments in cavernous nerve injury (CNI) rodent models. In the majority of these studies intracavernous injection of MSCs at the time injury improved erectile functions. There is less data on the efficacy of MSCs when applied in a chronic disease state. Allogeneic or xenogeneic MSCs were similarly effective with limited data on immunologic response. There is a lack of conclusive data on in vivo fate of MSCs and the best route of MSC administration. MSC therapy consistently improved erectile functions after CNI. There seems to be a consensus on the disease model used and outcome evaluation however further studies focusing on immunologic response to MSCs, their mechanism of action and in vivo fate are needed before their widespread use in clinic.


Effect of anesthetic agent on lung tumor induction in hamsters given benzo[a]pyrene-ferric oxide.
The effects of an anesthetic agent on lung tumor induction in noninbred Syrian golden hamsters were investigated after intratracheal instillation of a benzo[a]pyrene-ferric oxide mixture. Inhalation anesthesia with ether or methoxyflurane was accomplished with a closed recirculatory system that allowed a short induction time for anesthesia and a good control over the concentration of anesthetic. This type of anesthetic induction was compared with systemic induction by Brevital. Survival rates during the 10 weekly instillations were least for the Brevital-treated group and greatest for the methoxyflurane-treated group. Body weight gain was lower in both the ether- and Brevital-treated groups as compared to the group anesthetized with methoxyflurane. The animals anesthetized with Brevital had the shortest tumor latency, but the tumor incidence during the weeks of the experiment was similar in the group treated with this agent and the group treated with ether. Exposure to methoxyflurane and the carcinogen produced a slow onset of deaths from tumors and lower tumor incidence. These results are discussed in relation to retention of the dose of carcinogen in the respiratory tract and effect of inhalation anesthia on consequent lung tissue pathology.


Inflammatory cell responses in biliary mucosa during Opisthorchis viverrini infection: Insights into susceptibility differences among hosts.
Individual host susceptibility is believed to be a risk factor in the interaction between the host and the parasite. Since studying time series in humans is limited, animal models are replaced. This study aims to explore and compare the pattern of inflammatory cell types along the biliary tract and their association with proliferative lesions in the early development of cholangiocarcinoma from susceptible and nonsusceptible animal models. Thirty male Syrian golden hamsters and 30 BALB/c mice, serving as the susceptible and nonsusceptible animal models, were used in this comparative study. The animals were infected with 50 Opisthorchis viverrini metacercariae via gastric intubation. At days 1, 2, 7, 14, 28, and 56 postinfection (p.i.), five animals were randomly selected from each group and humanely sacrificed. The hepatobiliary tissues were collected and processed for histopathological study. Histochemical and immunohistochemical staining were applied to differentiate the inflammatory cell types. Kruskal-Wallis and Mann-Whitney tests were applied to assess all semi-quantitative and quantitative variables. The correlation between each variable was also analyzed using Spearman rank at a p-value < 0.05. The results demonstrated that mice had different patterns of infiltrating cell types when compared to hamsters. This suggested that the cellular response to the infection in mice occurred earlier than that in hamsters. The response in mice reached its peak at D7 to D14 and then rapidly declined at D28. In contrast, although the inflammatory response in hamsters started slowly, the response reached the peak at D28 and maintained a high level until D56. Significant differences in the number of inflammatory cells between mice and hamsters were seen at D1 (p = 0.047), D7 (p = 0.049), D28 (p = 0.040), and D56 (p < 0.040). The inflammatory responses to O. viverrini infection in the nonsusceptible animal model occurred and declined earlier while the response in the susceptible animal model occurred later in a gradual manner. Both rodents are suitable animal models for the studies of opisthorchiasis susceptibility.


Blunt lower-extremity trauma and popliteal artery injuries: revisiting the case for selective arteriography.
Abandoning mandatory angiography in patients with blunt lower-extremity trauma and normal neurovascular examination results does not affect limb salvage. Retrospective, nonrandomized cohort study. Mean follow-up (31 of 52 patients) of 9.5 months (range, 0-96 months). Single-institution, academic level I trauma center. Medical records of patients presenting on an emergency basis with knee dislocation, distal femoral fractures, or proximal tibial fractures during a 20-year period were reviewed. Fifty-three injuries occurred in 52 patients. Patients were predominantly male (81%) and young (mean age, 32.7 years). Mechanisms and side of extremity injury, coincident injuries, and neurovascular status on admission were recorded. Hard signs of arterial insufficiency or compartment syndrome were identified. Angiographic findings and operative and nonoperative interventions were recorded to identify whether angiographic data would alter therapy dictated by clinical findings alone. Limb salvage rate and necessity for vascular surgical intervention based on angiographic data in patients with normal neurovascular examination results. Multiorgan trauma occurred in 11 patients. Pulses were normal in 35, absent in 16, and diminished or identified by Doppler signal in 2. Arterial insufficiency or compartment syndrome was present in 29%. Twenty-seven patients (28 limbs) underwent angiography at the discretion of the attending surgeon. Of 13 abnormal arteriograms, 2 occurred in patients with normal pulses and 11 in patients with abnormal examination results. Thirteen of 36 patients with normal pulses underwent angiography; none had clinically significant arterial injuries that necessitated intervention. No vascular interventions were necessary in 23 patients with normal pulses who did not undergo angiography (P<.001). Normal neurovascular status bore a 100% negative predictive value in determining the necessity of vascular intervention. Angiography is unnecessary in the routine evaluation of the patient with blunt lower-extremity trauma who presents with a normal neurovascular examination result and can be used selectively for patients with diminished pulses who lack associated indications for mandatory operative exploration.