Expression and characterization of a novel propionyl-CoA dehydrogenase gene from Candida rugosa in Pichia pastoris.
The propionyl-CoA dehydrogenase (PACD) gene was firstly cloned from Candida rugosa by the cDNA RACE technique. The 6× His-tagged recombinant PACD gene was expressed in Pichia pastoris GS115 and purified with Ni-NTA affinity chromatography. SDS-PAGE analysis and Western blotting revealed that the molecular mass of the purified PACD was 49 kDa. The results showed that the recombinant protein had the activity of catalyzing propionyl-CoA to acrylyl-CoA. The K (m), k (cat), and V (max) values of the purified PACD were calculated to be 40.86 μM, 0.566 s(-1) and 0.693 U mg(-1) min(-1). The optimal temperature and pH of the purified PACD were 30 °C and 7.0, respectively. The recombinant PACD maintained 76.3%, 30.1%, and 4.3% of its original activity after 2 h incubation in standard buffer at 30, 40, and 50 °C, respectively. Mg(2+) had an activating effect on the enzyme, while Mn(2+), Ca(2+), Zn(2+), and Cu(2+) had weak inhibition. Since PACD catalyzed the key step (from propionyl-CoA to acrylyl-CoA) in the modified β-oxidation pathway from glucose to 3-hydroxypropionic acid (3-HP), the integration of recombinant PACD could benefit the engineered strains for effective production of 3-HP from the most abundant biomass-sugars.


Responses of stoats and least weasels to fluctuating food abundances: is the low phase of the vole cycle due to mustelid predation?
We studied responses of stoats and least weasels to fluctuating vole abundances during seven winters in western Finland. Density indices of mustelids were derived from snow-tracking, diet composition from scat samples, and vole abundances from snap-trapping. Predation rate was estimated by the ratio of voles to mustelids and by the vole kill rate by predators (density of predator x percentage of voles in the diet). We tested the following four predictions of the hypothesis that small mustelids cause the low phase of the microtine cycle. (1) The densities of predators should lag well behind the prey abundances, as time lags tend to have destabilizing effects. The densities of stoats fluctuated in accordance with the vole abundances, whereas the spring densities of least weasels tracked the vole abundances with a half-year lag and the autumn densities with a 1-year lag. (2) Predators should not shift to alternative prey with declining vole densities. The yearly proportion of Microtus voles (the staple prey) in the diet of stoats varied widely (range 16-82%) and was positively correlated with the winter abundance of these voles. In contrast, the same proportion in the food of least weasels was independent of the vole abundance. (3) The ratio of voles to small mustelids should be smallest in poor vole years and largest in good ones. This was also observed. (4) Vole densities from autumn to spring should decrease more in those winters when vole kill rates are high than when they are low. The data on least weasels agreed with this prediction. Our results from least weasels were consistent with the predictions of the hypothesis, but stoats behaved like "semi-generalist" predators. Accordingly, declines and lows in the microtine cycle may be due to least weasel predation, but other extrinsic factors may also contribute to crashes.


Coronary atherothrombotic disease: progress in antiplatelet therapy.
Platelets are now regarded as playing a dominant role in cardiovascular medicine since our recent understanding of acute coronary syndrome as an atherothrombotic process. This development has led to the widespread use of antiplatelet agents, such as aspirin, thienopyridines and glycoprotein-IIb/IIIa receptor blockers, for the prevention of ischemic heart disease. Nevertheless, recent evidence suggests that not all patients receive appropriate antiplatelet therapy because there may be resistance or a variable response to the drug used or because of an increased risk of hemorrhage. Moreover, the reported lack of efficacy of the combination of clopidogrel and aspirin when used for primary prevention has raised concerns about the general concept that greater inhibition implies greater efficacy. At present, research efforts are focused on improving current antiplatelet treatment with the aim of increasing efficacy and safety. Alternative ADP-receptor antagonists (e.g., prasugrel, cangrelor and AZD6140) and thrombin-receptor antagonists (e.g., E5555 and SCH 530348) are being developed. They may provide faster, more potent and more stable platelet inhibition. In addition, new insights into platelet structure and into the mechanisms underlying thrombus formation could lead to the discovery of new therapeutic targets. This article reviews what is known about the pathophysiological role of platelets in the atherothrombotic process, considers the current state of the art in antiplatelet therapy, and provides a commentary on new therapeutic approaches.


Impact of whey protein/surfactant mixture and oil type on the gastrointestinal fate of emulsions: Ingredient engineering.
The engineering of ingredients emerges as a strategy to design emulsified products aiming to control the lipid hydrolysis. In this context, oil-in-water (O/W) emulsions composed of different oil phases (Sunflower oil - LCT or NEOBEE® 1053 - MCT) and stabilized by whey protein isolate - WPI (1% w/w), Tween 80 - T80 (1% w/w) or varied ratios of WPI/T80 (0.9975%WPI/0.0025%T80; 0.75%WPI/0.25%T80; 0.5%WPI/0.5%T80 w/w) were produced and submitted to simulated gastrointestinal conditions. The lipolysis of LCT was influenced by the fatty acid chain length and emulsifier composition, while only the fatty acid chain length affected the lipolysis of MCT. The emulsions produced with LCT and 1%WPI or 09975%WPI/00025%T80 showed the highest release rate of free fatty acids (FFAs), but similar result was observed for the 0.5%WPI/0.5%T80 system. In the 0.5%WPI/0.5%T80 mixture, WPI and T80 worked together and achieved an improved performance during the gastric (stability similar as 1%T80 emulsion) and small intestinal phases (lipolysis similar as 1%WPI emulsion). The rational selection of ingredients is useful to design emulsions with improved performance as a delivery system since the emulsion structural stability during digestion, the oil type and interaction between lipase-interface had a marked impact on the efficiency of lipid digestion.


Iliac conduits for endovascular repair of aortic pathologies.
Challenging iliac access during thoracic endovascular aortic repair (TEVAR) is associated with a higher risk of access site complications such as injury or rupture of the iliac vessels. As a result, the use of iliac conduits is frequently used to facilitate access during TEVAR. This report evaluates the effect of iliac conduits on TEVAR outcomes. The 2005-2010 American College of Surgeons Surgical Quality Improvement Program database was queried to identify vascular patients undergoing elective TEVAR. Patients without conduit (Group A) were compared to patients who underwent TEVAR with conduit (Group B). We identified 1037 patients (90%) in Group A (69 ± 12.7 years, 42% female) and 117 patients (10%) in Group B (70 ± 12.6 years, 68% female). Women received conduits more often than men (Male:5.8%, Female:15.7%, p < 0.001). There was no significant difference in the rate of non-surgical (A:19%,B:25%,p = 0.121), pulmonary (A:11%,B:16%, p = 0.115), renal (A:3.1%, B:1.7%, p = 0.4) and cardiovascular complications (A:8%, B:12%, p = 0.143) between groups. However, any complication (A:24%, B:33%. p = 0.025), surgical complications (A:10%, B:16%, p = 0.035) and mortality (A:4.5%, B:12%. p = 0.001) were significantly higher in Group B. In multivariate analysis, use of conduit was associated with a 3.8 times higher risk of death compared with no conduit after controlling for confounders. Length of in-hospital stay was similar for both groups (A:6.6 ± 8.8, B:7.6 ± 8 days, p = 0.247). The use of conduits had a declining rate over time from 17.9% in 2006 down to 6.5% in 2010. Female patients more frequently require iliac conduits during TEVAR compared to men. Conduits were associated with a higher rate of surgical complications and mortality. The incidence of conduit use has decreased threefold in the last five years. Safer access for TEVAR by use of a conduit should not be abandoned based on these results, but there should be a heightened awareness for the higher rate of mortality in these patients.


Second Harmonic Generation Morphometry of Muscle Cytoarchitecture in Living Cells.
The architectural structure of cells is essential for the cells' function, which becomes especially apparent in the highly "structure functionally" tuned skeletal muscle cells. Here, structural changes in the microstructure can have a direct impact on performance parameters, such as isometric or tetanic force production. The microarchitecture of the actin-myosin lattice in muscle cells can be detected noninvasively in living cells and in 3D by using second harmonic generation (SHG) microscopy, forgoing the need to alter samples by introducing fluorescent probes into them. Here, we provide tools and step-by-step protocols to guide the processes of obtaining SHG microscopy image data from samples, as well as extracting characteristic values from the image data to quantify the cellular microarchitecture using characteristic patterns of myofibrillar lattice alignments.


Clinical placement challenges associated with radiography education in a low-resource setting: A qualitative exploration of the Ethiopian landscape.
Clinical placements (CP) are of paramount importance in the learning and the acquisition of key competencies in terms of knowledge, skill and professional attributes required for clinical radiography practice. This study explored the challenges faced by radiography students and educators in relation to clinical placement and training in Ethiopia. A qualitative approach using focus group discussion and interviews were used to explore the experiences of students and educators, respectively, pertaining to challenges encountered in relation to the clinical placement of students across four university affiliated hospitals. Data obtained was analysed using a structured three step framework and the coding approach employed in a thematic analysis. Participants comprise of third- and fourth-year undergraduate radiography students (n = 14) and educators [academic faculty (n = 7) and clinical practice educators (n = 8)]. Four main themes were identified, which relate to deficiencies of an existing training curriculum and its implementation strategies, inadequate resource and infrastructure within the CP environments and absence of advanced training opportunities. This research showed that there are many and varied challenges encountered by both students and educators in relation to CP and training of radiography students in Ethiopia. These challenges could potentially affect the future performance of students/practitioners and/or the appropriate application of the core clinical radiography skills and competencies in the world of work. Clinical radiography training in resource-limited settings will require urgent attention and support with modern infrastructure including simulation to augment their clinical development to acceptable standards.


Transforming growth factor-beta1 codon 10 polymorphism is associated with acute GVHD after allogenic BMT in Iranian population.
Certain cytokine genotypes are associated with acute graft versus host disease (aGVHD) after bone marrow transplantation (BMT). The present study aimed to determine existing association between TGF-beta1 codon 10 polymorphism and aGVHD after HLA-identical sibling BMT in the Iranian population. In a retrospective case-control study, 168 subjects including 84 Iranian HLA-identical sibling BMT donor/recipient pairs were recruited. All of the patients were affected by hematological malignancies (AML=39, ALL=23 and CML=22). PCR-SSP method was performed to determine TGF-beta1 codon 10 T/C polymorphism genotypes. The frequency of TGF-beta1 codon 10 TT, TC and CC genotypes among all subjects were 26.8%, 33.3% and 39.9% respectively. Recipients with the T allele developed aGVHD significantly less than those without the T allele (odds ratio =0.334, P=0.026). Genetic background of TGF-beta1 may be involved as a protective factor in the development of aGVHD in HLA-matched sibling BMT in Iranian population. Moreover, this finding may indicate that the genetic markers in Iranians are, at least to some extent, linked to distinct genetic event from Japanese.


Opioid-Sparing Anesthetic Technique for Pediatric Patients Undergoing Adenoidectomy: A Pilot Study.
An opioid-sparing anesthetic involves a multi-modal technique with non-opioid medications targeting different analgesic pathways. Such techniques may decrease adverse effects related to opioids. These techniques may be considered in patients at higher risk for opioid-related adverse effects including obstructive sleep apnea or sleep disordered breathing. A prospective, pilot study was performed in 10 patients (3-8 years of age), presenting for adenoidectomy. The perioperative regimen included oral dextromethorphan (1 mg/kg) and acetaminophen (15 mg/kg) plus single boluses of intraoperative dexmedetomidine (0.5 μg/kg) and ketamine (0.5 mg/kg). Pain scores were assessed in the post anesthesia care unit (PACU) using the FLACC (Face, Legs, Activity, Cry, Consolability) scale. Patients with a pain score >4 received fentanyl as needed. PACU time, pain scores, and parent satisfaction were recorded. Postoperatively, patients were instructed to use oral acetaminophen or ibuprofen every 6 hours as needed for pain. The study cohort included 10 patients, 3-8 years of age. All patients had opioid-free anesthetic care. PACU time ranged from 24 to 102 minutes (median: 56 minutes). FLACC pain scores were 0 for all PACU assessments. Nine patients were discharged home and 1 patient had a planned overnight admission. Following hospital discharge, the pain scores were satisfactory during the 72-hour study period and 90% of the patients' guardians were satisfied or highly satisfied with their child's pain control. This opioid-sparing approach provided safe and effective pain control as well as parental satisfaction following adenoidectomy in children. Additional prospective studies are needed to determine whether this regimen is effective in a larger cohort of patients with and for other otolaryngology procedures.


Metabolism of coumarin by human P450s: a molecular modelling study.
The oxidative metabolism of coumarin via several human cytochrome P450 (CYP) enzymes from families CYP1, CYP2 and CYP3 is rationalized in terms of molecular modelling studies carried out on the key interactions with various amino acid residues in the relevant active sites. The findings from modelling by homology with the CYP2C5 crystallographic template are in agreement with the known metabolism of coumarin in human P450s from the CYP1, CYP2 and CYP3 families, which has been published recently, and with independently reported information from site-directed mutagenesis studies.


Transoral Decompression and Stabilization of the Upper Cervical Segments of the Spine Using Custom-Made Implants in Various Pathologic Conditions of the Craniovertebral Junction.
Surgical treatment of patients with atlantoaxial instability caused by pathologic changes of the skull base and craniovertebral junction combined with anterior compression of the brain stem is still associated with substantial technical difficulties and remains a matter of debate. Currently, anterior stabilization of the atlantoaxial junction is a promising approach that allows for the resection of the pathologic lesion of the skull base and craniovertebral junction with subsequent stabilization of C1-C2 or C1-C3 in 1 stage. In this article, we present 5 clinical cases in which transoral decompression and anterior stabilization of the C1-C2 (4 cases) and C1-C3 (1 case of anteroposterior stabilization) segments with custom-made fixation systems was used to treat various pathologic conditions of the craniovertebral junction. In all cases, complete removal of the pathologic lesion and decompression of the upper cervical spinal cord as well as reliable stabilization of the upper spinal segments were achieved. Some degree of movement in the cervical spine was preserved in all patients due to unfixed C0-C1 and C3-C7 segments in 4 cases and C0-C1 and C4-C7 in 1 case. Implant migration or instability was not observed in any of the cases. The follow-up period was from 1 to 4 years after surgery. The first experience of anterior fixation using individually manufactured C1-C2 and C1-C3 systems demonstrated their effectiveness. This approach can be safely used as an alternative or in combination with standard posterior stabilization methods. An innovative surgical technology developed and implemented in our surgical practice allows for optimization of the surgical technique, reduces the number of perioperative complications, eliminates movement restrictions in the cervical spine, improves motor activity, and makes earlier patient rehabilitation possible.


Comparison of ratio-synthetic, sample-size dependent and EBLUP estimators as estimators of food-animal productivity parameters.
A comparison was made of three small-area sampling methods [two traditional design-based methods (ratio-synthetic, sample-size dependent) and one model-based method (EBLUP)] in estimation of some cow and sow population productivity parameters. Performance was evaluated in estimating both farm-specific mean responses and mean animal response over all farms using sample sizes of 100 and 25. Differences in results obtained with the cow and sow data are discussed in terms of the impact of sample size and population size on sampling method. There was a tendency for the model-based method to be the best performer in situations most likely to be operational when the sampling is done as part of a food-animal monitoring scheme. The situations are identified where the sample-size-dependent method performed best.


Co-purification and characterization of UDP-glucose 4-epimerase and UDP-N-acetylglucosamine 4-epimerase from porcine submaxillary glands.
UDP-glucose 4-epimerase and UDP-N-acetylglucosamine 4-epimerase have been co-purified about 9,000-fold from porcine submaxillary glands by affinity chromatography on UDP-hexanolamine-agarose. The homogeneous epimerase has apparent Mr = 88,000 and contains two subunit species with apparent Mr = 37,000 and 35,000, respectively. The two subunits, however, are indistinguishable as judged by peptide mapping. The purified enzyme catalyzes equally well the reversible reactions UDP-glucose in equilibrium UDP-galactose and UDP-N-acetylglucosamine in equilibrium UDP-N-acetylgalactosamine. At saturating substrate concentrations, the ratio of the rate of the former reaction to that of the latter is 1.13 in the forward direction and 0.44 in the backward direction. Both reactions have the same Keq = 0.38 and the same dependence on pH. Moreover, both activities are lost at about the same rate by heat denaturation of the epimerase or reaction with N-ethylmaleimide. Kinetic analysis reveals that the reactants for one reaction are competitive inhibitors of the other reaction, with the Ki values of the inhibitors essentially identical with their Km values as substrates. Taken together, these studies suggest that UDP-glucose 4-epimerase and UDP-N-acetylglucosamine 4-epimerase activities reside in a single enzyme.


MRI guided focal HDR brachytherapy for localized prostate cancer: Toxicity, biochemical outcome and quality of life.
To describe toxicity, biochemical outcome and quality of life after MRI guided focal high dose rate brachytherapy (HDR-BT) in a single fraction of 19 Gy for localized prostate cancer. Between May 2013 and April 2016, 30 patients were treated by MRI-guided focal HDR-BT. Patients with visible tumour on MRI were included. All patients were ≥65 years, T-stage <T3, Gleason ≤7, PSA <10 ng/mL and IPSS <15. Focal irradiation was delivered in a single fraction of 19 Gy to the D95 of the clinical target volume. Toxicity was reported using the Common Terminology Criteria for Adverse Events version 4. Biochemical failure was defined according to the Phoenix criteria and quality of life was measured using validated questionnaires. Median follow up was 24 months. One patient developed a grade 2 and 3 GU toxicity after treatment. In the other 29 patients, no grade 2 or higher perioperative complications occurred. Five patients developed a biochemical recurrence. For all measured time points, there was no statistically significant deterioration in quality of life. Focal MRI guided HDR-BT confers low toxicity rates and maintains quality of life. Biochemical recurrence is rather high, 5 patients developed a biochemical recurrence according to the Phoenix definition. Longer evaluation of these patients is necessary and caution is warranted before implementing focal HDR-BT in patients with localized prostate cancer.


Upper tract urothelial malignancy after cyclophosphamide therapy: a case report and literature review.
We report an unusual case of simultaneous transitional cell carcinoma of the renal pelvis and distal ureter without transitional cell carcinoma of the bladder occurring after chronic cyclophosphamide therapy for nonHodgkin's lymphoma. Other upper tract neoplasms after cyclophosphamide are reviewed.


Asthma in Olympians.
High prevalence of asthma has been reported repeatedly among elite athletes, especially among endurance athletes. So many athletes used asthma drugs that the objective demonstration of bronchial hyperresponsiveness was required to obtain approval for their use in international sports until 2012 when the most used inhaled asthma drugs was allowed for free use, but with a maximum dose for inhaled β2-agonists. Several factors contribute to the development of asthma among the Olympians causing airways inflammation and bronchial hyper-responsiveness.


Single-stranded DNAzyme-based Pb2+ fluorescent sensor that can work well over a wide temperature range.
DNAzymes have become an excellent choice for sensing applications. Based on DNAzymes, three generations of Pb(2+) fluorescent sensors have been reported. In these sensors, two oligonucleotide strands (substrate strand and enzyme strand) were used, which not only increased the complexity of the detection system, but also brought some difficulties for the use of the sensors at elevated temperatures. To overcome this problem, a single-stranded DNAzyme-based Pb(2+) fluorescent sensor was designed by combining the substrate sequence and the enzyme sequence into one oligonucleotide strand. The intramolecular duplex structure of this single-stranded DNAzyme kept the fluorophore and the quencher, labeled at its two ends, in close proximity; thus the background fluorescence was significantly suppressed. Using this fluorescent sensor, Pb(2+) quantitation can be achieved with high sensitivity and high selectivity. In addition, the extraordinary stability of the intramolecular duplex structure could assure a low background fluorescence at high temperature, even if the number of complementary base pairs between the substrate sequence and the enzyme sequence was reduced, allowing the sensor to work well over a wide temperature range. Similar performances of the fluorescent sensor at 4, 25 and 37°C suggested that this sensor has a good ability to resist temperature fluctuations.


The oral microbiome in relation to pancreatic cancer risk in African Americans.
African Americans have the highest pancreatic cancer incidence of any racial/ethnic group in the United States. The oral microbiome was associated with pancreatic cancer risk in a recent study, but no such studies have been conducted in African Americans. Poor oral health, which can be a cause or effect of microbial populations, was associated with an increased risk of pancreatic cancer in a single study of African Americans. We prospectively investigated the oral microbiome in relation to pancreatic cancer risk among 122 African-American pancreatic cancer cases and 354 controls. DNA was extracted from oral wash samples for metagenomic shotgun sequencing. Alpha and beta diversity of the microbial profiles were calculated. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between microbes and pancreatic cancer risk. No associations were observed with alpha or beta diversity, and no individual microbial taxa were differentially abundant between cases and control, after accounting for multiple comparisons. Among never smokers, there were elevated ORs for known oral pathogens: Porphyromonas gingivalis (OR = 1.69, 95% CI: 0.80-3.56), Prevotella intermedia (OR = 1.40, 95% CI: 0.69-2.85), and Tannerella forsythia (OR = 1.36, 95% CI: 0.66-2.77). Previously reported associations between oral taxa and pancreatic cancer were not present in this African-American population overall.


Separation of natural products by countercurrent chromatography.
Countercurrent Chromatography (CCC) provides the natural product chemist with a high-resolution separatory method, which is uniquely applicable to sensitive (unstable) compounds and which allows virtually quantitative recovery of the load sample. Different instruments use different means of retaining a stationary liquid phase. The solvent system (SS) can be chosen to optimize the separatory power and the number of systems available is limitless. Several examples are provided to illustrate the power of the method and to guide the chemist in choice of an appropriate SS.


The occurrence of reinforcing activities in relation to locus of control, success-failure expectancies, and physical attractiveness.
The Pleasant Events Schedule (mimeographed), which measures the retrospective frequency and value of positive reinforcement, was administered to 74 college students; and its relation to subjects' locus of control and success-failure expectancies and to their levels of physical attractiveness was evaluated. While results were less consistent for females than for males, significant relationships were obtained between each of these "person" variables and the various indices derived from the Pleasant Events Schedule. Not only do the findings reflect favorably on the construct validity of the various dimensions as measured, but the data carry implications for a more integrative study of depression.


miR-98 protects endothelial cells against hypoxia/reoxygenation induced-apoptosis by targeting caspase-3.
Endothelial dysfunction is one of the main pathophysiological processes involved in renal ischemia reperfusion injury. Our previous microarray study demonstrated that miR-98 was upregulated in the kidney with ischemia reperfusion injury (IRI). The present study was performed to investigate whether miR-98 was involved in the regulation of endothelial apoptosis under hypoxia and re-oxygenation (H/R) conditions. The dynamic changes of miR-98 in mouse IRI kidney and H/R HUVECs was measured. HUVECs were treated with HIF-1α siRNA to investigate the role of HIF-1α on miR-98 expression. The potential target genes of miR-98 were predicted by bioinformatics analyses. HUVECs were transfected with miR-98 mimics or inhibitor to confirm the role of miR-98 on the expression of target genes and hypoxia-induced apoptosis. The target gene was finally confirmed by dual-luciferase reporter assay. Both of IRI and H/R induced significantly up-regulation of miR-98 in the ischemic kidney and hypoxic HUVECs. HIF-1α siRNA remarkably down-regulated the expression of miR-98 in both normal and hypoxic HUVECs. The putative target genes of miR-98 included IL-6, IL-10 and caspase-3. MiR-98 mimics significantly inhibit caspase-3 expression in HUVECs, while anti-miR-98 significantly up-regulated it. But no change of IL-6 and IL-10 levels was observed after miRNA transfection. miR-98 protected HUVECs against apoptosis induced by hypoxia, while anti-miR-98 had the reverse effect. Furthermore, the dual-luciferase reporter assay confirmed that miR-98 decreased the luciferase activity by targeting the 3' untranslated region of caspase-3. In conclusion, Renal IRI induces up-regulation of miR-98 dependent on HIF-1α, which protects endothelial cells against apoptosis by targeting caspase-3.


CircNFATC3 promotes the proliferation of gastric cancer through binding to IGF2BP3 and restricting its ubiquitination to enhance CCND1 mRNA stability.
Insulin like growth factor II mRNA binding protein 3 (IGF2BP3) is an RNA binding protein with multiple roles in regulation of gene expression at the post-transcriptional level and is implicated in tumorigenesis and progression of numerous cancers including gastric cancer (GC). Circular RNAs (circRNAs) are a diverse endogenous noncoding RNA population that have important regulatory roles in cancer. However, circRNAs that regulate the expression of IGF2BP3 in GC is largely unknown. CircRNAs that bound to IGF2BP3 were screened in GC cells using RNA immunoprecipitation and sequencing (RIP-seq). The identification and localization of circular nuclear factor of activated T cells 3 (circNFATC3) were identified using Sanger sequencing, RNase R assays, qRT-PCR, nuclear-cytoplasmic fractionation and RNA-FISH assays. CircNFATC3 expression in human GC tissues and adjacent normal tissues were measured by qRT-PCR and ISH. The biological role of circNFATC3 in GC was confirmed by in vivo and in vitro experiments. Furthermore, RIP, RNA-FISH/IF, IP and rescue experiments were performed to uncover interactions between circNFATC3, IGF2BP3 and cyclin D1 (CCND1). We identified a GC-associated circRNA, circNFATC3, that interacted with IGF2BP3. CircNFATC3 was significantly overexpressed in GC tissues and was positively associated with tumor volume. Functionally, the proliferation of GC cells decreased significantly after circNFATC3 knockdown in vivo and in vitro. Mechanistically, circNFATC3 bound to IGF2BP3 in the cytoplasm, which enhanced the stability of IGF2BP3 by preventing ubiquitin E3 ligase TRIM25-mediated ubiquitination, thereby enhancing the regulatory axis of IGF2BP3-CCND1 and promoting CCND1 mRNA stability. Our findings demonstrate that circNFATC3 promotes GC proliferation by stabilizing IGF2BP3 protein to enhance CCND1 mRNA stability. Therefore, circNFATC3 is a potential novel target for the treatment of GC.


Antibiotic inhibitors of the peptidyl transferase center. 1. Clindamycin as a composite analogue of the transfer RNA fragments L-Pro-Met and the D-ribosyl ring of adenosine.
Clindamycin's three-dimensional structure is shown via a computer rendered stereomodel to be strikingly similar to L-Pro-Met and the D-ribosyl ring of adenosine. This discovery has important implications for the rational design of new licosamides and for efforts to understand how this and related classes of agents selectively inhibit protein biosynthesis on the prokaryotic ribosome.


Incremental prognostic value of MRI in the staging of early cervical cancer: a prospective study and review of the literature.
This is to evaluate the predictive ability of clinical examination and preoperative magnetic resonance imaging (MRI) for the staging of early cervical cancer. We prospectively evaluated 115 patients with cervical cancer, International Federation of Gynecologic and Obstetrics (FIGO) stage <IIB; receiver operating characteristic (ROC) analysis determined the predictive ability of MRI, clinical assessment, and their combination for tumor staging. Surgery was the standard of reference. MRI was more accurate than clinical examination for tumor estimate, parametrial or internal os involvement. When combined with MRI, the predictive ability of clinical examination for overall staging [area under the curve (AUC)=0.59, P>.05) increased significantly (AUC=0.84, P<.05). Our results support the official incorporation of MRI into FIGO classification system.


The effect of two low-dose propofol infusions on the relationship between six-pulse transcranial electrical stimulation and the evoked lower extremity muscle response.
Transcranial stimulation of the motor cortex using high-voltage electrical stimuli given in train is a method of monitoring the integrity of the motor pathways during thoracoabdominal aortic aneurysm surgery. The purpose of this study was to assess the relationship between the stimulus intensity and the corresponding amplitude of the myogenic motor evoked potential (tcMEP) in response to six-pulse transcranial electrical stimulation during two levels of low-dose propofol infusion and stable fentanyl/nitrous oxide anaesthesia. Nine patients (37-78 yr) scheduled to undergo surgery on the thoracoabdominal aorta were studied. After achieving a stable anaesthetic state the output voltage was decreased with 50 V intervals from 350 V to 200 V during a target propofol infusion aimed at a plasma steady-state concentration of 0.7 microg x ml(-1) and increased with 50 V intervals from 200 V to 450 V during a target propofol infusion aimed at a plasma steady-state concentration of 1.4 microg x ml(-1). TcMEPs were recorded from the right tibialis anterior muscle. Doubling the target propofol infusion to 1.4 microg x ml(-1) resulted in a 30-50% decrease in tcMEP amplitude. The largest tcMEP amplitude using the six-pulse paradigm was found during a propofol infusion aimed at a plasma concentration of 0.7 microg x ml(-1) and demanded a stimulus output of 350 V, corresponding to a charge density of 7.5 microC x cm(-2) per phase. Doubling the target propofol infusion to 1.4 microg x ml(-1) provides less robust, but still recordable tcMEPs in response to six-pulse electrical stimulation. Safety guidelines are discussed.


[Indirect effects of cytomegalovirus infection].
Despite improvements in prevention strategies, cytomegalovirus (CMV) continues to be the main cause of infection in solid organ transplant recipients. In these patients, in addition to direct effects, such as viral syndrome or invasive organ disease, CMV can cause indirect effects resulting from the interaction of the virus with the host's immune system. This interaction may increase immunosuppression, with a consequent rise in opportunistic infections and the risk of malignancies (Epstein-Barr virus-associated posttransplantation lymphoproliferative disease) and graft dysfunction. Currently, a direct causal relation between CMV and most of the indirect effects described cannot be established. However, numerous experimental and clinical studies have found an association between the development of these effects and CMV. Moreover, some of these effects, such as the development of opportunistic infections, have been reduced by CMV prophylaxis.


Cysteine requirements of naturally occurring cysteine auxotrophs of Escherichia coli.
The requirements for cysteine of naturally occurring cysteine auxotrophs of Escherichia coli were determined in a defined liquid medium. Maximal growth was obtained in the presence of cysteine concentrations between 20 and 250 mg/l. At concentrations below 20 mg/l growth of the auxotrophs, but not the prototrophic control, was suboptimal in this system. In the presence of cysteine concentrations in excess of 250 mg/l, growth of both auxotrophic and prototrophic E. coli was inhibited with lower growth yields, a decreased specific growth rate and an extended lag phase being observed. These effects were minimised in the presence of 2 mM L-leucine, L-isoleucine and L-valine.


Validating the New Primary Care Measure in the Medical Expenditure Panel Survey.
The advancement of primary care research requires reliable and validated measures that capture primary care processes embedded within nationally representative datasets. The objective of this study was to assess the validity of a newly developed measure of primary care processes [Medical Expenditure Panel Survey (MEPS)-PC] with preliminary evidence of moderate to excellent reliability. A retrospective cohort study of community-dwelling adults with history of office-based provider visit/s using the MEPS (2013-2014). The 3 MEPS-PC subscales (Relationship, Comprehensiveness, and Health Promotion) were tested for construct validity against known measures of primary care: Usual Source of Care, Known Provider, and Family-Usual Source of Care. Concurrent and predictive logistic regression analyses were calculated and compared with a priori hypotheses for direction and strength of association. For concurrent validity, all odds ratio estimates conformed with hypotheses, with 91% displaying statistical significance. For predictive validity, all estimates were in the direction of hypotheses, with 92% displaying statistically significant results. Although Relationship and Health Promotion subscales conformed uniformly with hypotheses, the Comprehensiveness subscale yielded significant results in 60% of bivariate odds ratio estimates (P<0.05). The MEPS-PC composite measures display modest to strong preliminary evidence of concurrent and predictive validity relative to known indicators of primary care. The MEPS-PC composite measures display preliminary evidence of concurrent and predictive construct validity, and it may be useful to researchers investigating primary care processes and complexities in the health care environment.


Observation and manipulation of different structural variants of individual cation-DNA complexes in the light microscope.
Using different preparation protocols, different structures consisting of individual cation-DNA complexes are obtained. Vigorous mixing provides globular complexes, with different degrees of packing when poly-L-lysine or histone H1 is the cation. When hydrodynamic shearing is minimized by gentle handling, molecular networks or single cable like structures can be obtained. After 4',6-diamidino-2-phenyl indole (DAPI) fluorescence staining as well as with bright-field microscopy, the cables can be directly visualized in the light microscope. Using a pulsed ultraviolet laser coupled into the microscope (a laser microbeam) stretches of complex can be cut out from networks of poly-L-lysine-DNA complexes which may serve as models for highly extended chromosomes.


An open-label comparison of the immunogenicity and tolerability of intranasal and intramuscular formulations of virosomal influenza vaccine in healthy adults.
Many intramuscular inactivated influenza vaccines achieve suboptimal results in the prevention of respiratory disease and influenza complications. This has led to the current interest in developing effective oral or intranasal preparations. This study compared the immunogenicity and tolerability of intranasal and intramuscular formulations of virosomal subunit influenza vaccine in healthy adults. It also assessed the immunogenicity and tolerability of 3 different production lots of the intranasal vaccine containing Escherichia coli heat-labile toxin adjuvant. This was a multicenter, Phase I, randomized, open-label pilot study in which the primary end point was immunogenicity (hemagglutination-inhibition [HI] antibody assay on days 1 and 29). The secondary end point was the frequency of adverse events (AEs). Subjects were assigned to 4 vaccination groups: groups AI, AII, and AIII received intranasal influenza vaccine from batches that differed in the hemagglutinin and neuraminidase strains used, and group B received intramuscular virosomal subunit vaccine. Assessments of health status, hematology, biochemistry, body temperature, heart rate, blood pressure, and incidence of AEs were made on days 1, 8, and 29, and serology was assessed on days 1 and 29. The study enrolled 88 subjects. All 3 production lots of intranasal vaccine induced an immune response to most of the viral strains administered (A/Singapore, A/Texas, A/Wuhan, B/Beijing), with no notable immunogenic differences between lots. After intranasal vaccination, geometric mean titers (GMT) increased 2.7-fold against A/Singapore (group AI); 1.8- and 3.1-fold against A/Texas (groups AII and AIII, respectively); 1.9- to 2.4-fold against A/Wuhan; and 1.5- to 1.7-fold against B/Beijing. After intramuscular vaccination. GMT increased 11.3-, 6.3-, and 2.7-fold against A/Texas, A/Wuhan, and B/Beijing, respectively. Seroprotection (HI antibody titers > or = 1:40 in > 70% of those vaccinated) was achieved against all strains in the group that received intramuscular vaccination, against A/Wuhan in all groups that received intranasal vaccination, and against A/Texas in group AII. Both vaccine formulations were well tolerated. Intranasal vaccination was associated with a low incidence ( < 20%) of nasal AEs. Both the intranasal and intramuscular vaccinations elicited a systemic immune response and were well tolerated. The different batches of intranasal vaccine showed a similar immunogenic profile. Intranasal administration may be preferred to intramuscular administration by some patients.


GDNF promotes hair formation and cutaneous wound healing by targeting bulge stem cells.
Glial-cell-derived neurotrophic factor (GDNF) is a well-studied neuroregenerative factor; however, the degree to which it supports hair formation and skin wound repair is not known. By using a Gfra1 (GDNF family receptor alpha 1) knock-in reporter mouse line, GDNF signaling was found to occur within hair bulge stem cells (BSCs) during the initiation of the hair cycle and early stages of hair formation after depilation. Both recombinant and transgene overexpression of GDNF promoted BSC colony growth, hair formation, and skin repair after wounding through enhanced self-renewal of BSCs and commitment of BSC-derived progenitors into becoming epidermal cells at the injury site. Conditional ablation of Gfra1 among BSCs impaired the onset of the hair cycle, while conditional ablation of the GDNF family member signal transducer, Ret, within BSCs prevented the onset of the hair cycle and depilation-induced anagen development of hair follicles. Our findings reveal that GDNF promotes hair formation and wound repair and that bulge stem cells are critical mediators of both.


Peroxidase activity in human breast carcinomas: correlation with histological and biochemical parameters.
Peroxidase activity was found in 68% of 56 human breast carcinomas. Median activity was higher in ductal carcinomas than in tumors with lobular components. Activity did not correlate with tumor grade or stage, or the presence or absence of axillary node involvement. Activity, however, correlated with tumor cellularity, lymphocyte infiltration levels, and total protein and alkaline phosphatase levels. It is concluded that variation in peroxidase activity in human breast tumors is at least in part due to lymphocyte infiltration. Furthermore, this contamination of breast tumors with lymphocytes may explain the lack of correlation between estradiol receptor levels and peroxidase activity.


Genotoxicity testing: phage T7 inactivation test of various furan and arenofuran derivatives.
The genotoxic activities of 28 furan and arenofuran derivatives were tested by the phage T7-inactivation test. The genotoxic activity of the compounds was characterized quantitatively. All the compounds studied have pronounced genotoxic activities in our system. Empirical rules relating structure to genotoxic activity were found. Data obtained with our system were compared with the results of other biological systems (Salmonella assay, SOS Chromotest, CHO/HGPRT, gene amplification) in the case of some compounds included as references.


Establishment and Characterization of Multi-Drug Resistant p53-Negative Osteosarcoma SaOS-2 Subline.
To establish a p53-negative osteosarcoma (OS) SaOS-2 cellular subline exhibiting resistance to specific chemotherapeutic agents, including topoisomerase II inhibitors, taxanes, and vinca alkaloids. The OS subline exhibiting resistance to the chemotherapeutic agents indicated above was generated by the stepwise treatment of the parental SaOS-2 cell line with increasing concentrations of doxorubicin (Dox) for 5 months. Half-inhibitory concentrations (IC50) for Dox, vinblastine (Vin), and paclitaxel (PTX) were calculated by a colorimetric MTS-based assay. Crystal violet staining was used to assess cellular viability, whereas the proliferation capacities of cancer cells were monitored in real-time by the i-Celligence system. Expression of apoptotic markers (e.g., cleaved PARP and caspase-3), DNA repair proteins (e.g., ATM, DNA-PK, Nbs1, Rad51, MSH2, etc.), and certain ABC transporters (P-glycoprotein, MRP1, ABCG2, etc.) was assessed by western blotting and real-time PCR. Flow cytometry was used to examine the fluorescence intensity of Dox and ABC-transporter substrates (e.g., Calcein AM and CMFDA) and to assess their excretion to define the activity of specific ABC-transporters. To confirm OS resistance to Dox in vivo, xenograft experiments were performed. An OS subline generated by a stepwise treatment of the parental SaOS-2 cell line with increasing concentrations of Dox resulted in an increase in the IC50 for Dox, Vin, and PTX (~6-, 4-, and 30-fold, respectively). The acquisition of chemoresistance in vitro was also evidenced by the lack of apoptotic markers (e.g., cleaved PARP and caspase-3) in resistant OS cells treated with the chemotherapeutic agents indicated above. The development of the multidrug resistance (MDR) phenotype in this OS subline was due to the overexpression of ABCB1 (i.e., P-glycoprotein) and ABCC1 (i.e., multidrug resistance protein-1, MRP-1), which was evidenced on both mRNA and protein levels. Due to increased expression of MDR-related proteins, resistant OS exhibited an excessive efflux of Dox. Moreover, decreased accumulation of calcein AM, a well-known fluorescent substrate for both ABCB1 and ABCC1, was observed for resistant OS cells compared to their parental SaOS-2 cell line. Importantly, tariquidar and cyclosporin, well-known ABC inhibitors, retained the intensity of Dox-induced fluorescence in resistant SAOS-2 cells. Furthermore, in addition to the increased efflux of the chemotherapeutic agents from Dox-resistant OS cells, we found higher expression of several DNA repair proteins (e.g., Rad51 recombinase, Mre11, and Nbs1, activated forms of ATM, DNA-PK, Chk1, and Chk2, etc.), contributing to the chemoresistance due to the excessive DNA repair. Lastly, the in vivo study indicated that Dox has no impact on the SaOS-2 Dox-R xenograft tumor growth in a nude mouse model. An acquired resistance of OS to the chemotherapeutic agents might be due to the several mechanisms undergoing simultaneously on the single-cell level. This reveals the complexity of the mechanisms involved in the secondary resistance of OS to chemotherapies.


Percutaneous trigeminal ganglion balloon compression for treatment of trigeminal neuralgia, part II: results related to compression duration.
The purpose of this study is to find out how different compression time affects the results of percutaneous trigeminal ganglion compression for treatment of trigeminal neuralgia. This study includes 80 patients with intractable third-branch trigeminal (V3) neuralgia who had received percutanious trigeminal ganglion balloon compression. All the patients received some treatment protocol except for the duration of compression. Group 1 patients received 60-second and group 2 patients received 180-second compression. A computerized pressure recording system was used for pressure monitoring and analysis. Both groups had 100% immediate pain relief and all patients experienced mastication weakness immediately after the procedure. The facial numbness was severe in group 2 in the first trigeminal (V1) distribution (p<0.05) but not in the second or third trigeminal (V2,3) distribution (p>0.05) in the immediate period after the operation. The recurrence rate in the first year follow-up was higher in group 1 (5%) than in group 2 (2.5%) but did not reach the statistical difference (p>0.05). At 1 year follow-up after the procedure, group 1 and lower incidence of facial numbness over all trigeminal distribution (V1,2,3) than group 2 (p<0.05) mastication weakness all recovered during the first-year follow up. With accurate monitoring of the balloon pressure during the percutaneous trigeminal ganglion compression, it was found that the shorter duration of compression had less side effect. At one year follow-up, the incidence of recurrrence rate was slightly higher in the patients who received 60-second compressions than in those who received 180-second compressions, but there was no significant statistical difference. Whether patients with first or second branch of trigeminal neuralgia require longer compression duration needs further study.


Modified hemi-double-stapling technique combined with the temporal abdominal-wall-lift method for performing Billroth I anastomosis after laparoscopically assisted distal gastrectomy.
The authors have used a modified hemi-double-stapling (HDS) technique for reconstruction after laparoscopically assisted distal gastrectomy. The stomach is resected from the greater curvature side using a linear stapler inserted into the stomach from that side at a position vertical to the line of the greater curvature. Resection of the stomach is performed by extending the resection line to the lesser curvature using laparoscopic coagulating shears. The resected specimen is examined. After placement of a purse-string suture at the duodenal stump, an anvil is inserted into the stump, and an additional suture with 2-0 silk is placed over the purse-string suture. A curved intraluminal stapler (CDH25) is inserted into the stomach through the opening made on the lesser curvature side, and the center rod of the stapler is passed through the gastric wall on the corner of the resection line at the greater curvature. Ligation with 2-0 silk is added to the center rod by suturing the gastric tissue 5-8 mm from the center rod to encircle it. The authors call this the "one-knot setup HDS," and with this method, a large-caliber anastomosis is secured. In many cases, it is difficult to observe the anastomotic site through the small incisional opening. However, under laparoscopy with the temporal abdominal wall-lift method using the Multi Flap Gate, the anastomotic site can be easily and safely observed. One-knot setup HDS combined with the temporal abdominal wall-lift method is considered a safe and simple method for performing Billroth I anastomosis in laparoscopic distal gastrectomy.


The Negative Regulator CXXC5: Making WNT Look a Little Less Dishevelled.
Wingless-related integration site (WNT)/β-catenin signaling regulates diverse physiological functions including tissue regeneration. Activation of WNT signaling can be inhibited by various agents. Lee et al. investigate the interaction of CXXC-type zinc finger protein 5 (CXXC5) with Dishevelled as one such negative regulator of WNT in hair follicle regeneration.


Properties and mechanisms of drug release from matrix tablets containing poly(ethylene oxide) and poly(acrylic acid) as release retardants.
The interactions between poly(ethylene oxide) (PEO) and poly(acrylic acid) (PAA) in aqueous medium at pH 6.8 were investigated in the current study. We have also studied the effect of interpolymer interactions and various formulation variables, including the molecular weight of PEO, the ratio between PEO and PAA, the crystallinity of PEO, and the presence of an acidifying agent, on the release of theophylline from matrix tablets containing both PEO and PAA as release retardants. At pH 6.8, the synergy in solution viscosity between PEO and PAA as the result of ion-dipole interaction was observed in this study. The release of theophylline from the matrix tablets containing physical mixtures of PEO and PAA was found to be a function of dissolution medium pH because of the pH-dependent interactions between these two polymers. Because of the formation of water insoluble interpolymer complex between PEO and PAA in aqueous medium at pH below 4.0, the release of theophylline was independent of PEO molecular weight and was controlled by Fickian diffusion mechanism in 0.01N hydrochloric acid solution. In comparison, the drug release was a function of PEO molecular weight and followed the anomalous transport mechanism in phosphate buffer pH 6.8. The presence of PAA exerted opposite effects on the release of theophylline in phosphate buffer pH 6.8. In one aspect, theophylline release was accelerated because the erosion of PAA was much faster than that of PEO at pH6.8. On the opposite aspect, theophylline release was slowed down because of the formation of insoluble complex inside the gel layer as the result of the acidic microenvironment induced by PAA, and the increase in the viscosity of the gel layer as the result of the synergy between PEO and PAA. These two opposite effects offset each other. As a result, the release of theophylline remained statistically the same even when 75% PEO in the formulation was replaced with PAA. In phosphate buffer pH 6.8, the release of theophylline was independent of the crystalline form of PEO. The release profile remained identical whether PEO was present as a semicrystalline powder blend with PAA or an amorphous complex with PAA in the matrix tablets. It has also been observed that the presence of citric acid as an acidifying agent had negligible effect on the drug release rate.


Top-down attention based on object representation and incremental memory for knowledge building and inference.
Humans can efficiently perceive arbitrary visual objects based on an incremental learning mechanism with selective attention. This paper proposes a new task specific top-down attention model to locate a target object based on its form and color representation along with a bottom-up saliency based on relativity of primitive visual features and some memory modules. In the proposed model top-down bias signals corresponding to the target form and color features are generated, which draw the preferential attention to the desired object by the proposed selective attention model in concomitance with the bottom-up saliency process. The object form and color representation and memory modules have an incremental learning mechanism together with a proper object feature representation scheme. The proposed model includes a Growing Fuzzy Topology Adaptive Resonance Theory (GFTART) network which plays two important roles in object color and form biased attention; one is to incrementally learn and memorize color and form features of various objects, and the other is to generate a top-down bias signal to localize a target object by focusing on the candidate local areas. Moreover, the GFTART network can be utilized for knowledge inference which enables the perception of new unknown objects on the basis of the object form and color features stored in the memory during training. Experimental results show that the proposed model is successful in focusing on the specified target objects, in addition to the incremental representation and memorization of various objects in natural scenes. In addition, the proposed model properly infers new unknown objects based on the form and color features of previously trained objects.


Unexpected tissue and the biobank that closed: an exploration of value and the momentariness of bio-objectification processes.
Unanticipated situations can arise in biobanking. This paper empirically documents unexpected situations at the anonymous biobank 'Xbank'. Firstly, Xbank received an unexpected and significant quantity of tissue from the historical archive of a hospital network. Secondly, Xbank had its funding withdrawn before the designated end date for the grant, meaning the bank needed to either re-house or destroy its holdings. This paper articulates and uses the theoretical frameworks of bio-objectification and tissue economies to analyse the experiences of Xbank and draw out further implications of the potential precariousness of biobanking practice. The case study allows an inspection of how the value of tissue is configured and reconfigured as institutional contexts shift. We introduce the notion of momentariness as a way of grappling with the related temporariness and perpetualness of biobanking practice in both a theoretical and practical policy context.


Beyond the Economic Gaze: Childbearing During and After Recessions in the Nordic Countries.
During the 2010s, fertility rates fell across the Nordic region. The onset of these declines seems linked to the Great Recession of 2008-2009, but their continuation cannot easily be linked to subsequent economic change. The 1990s, too, brought episodes of economic crises to the Nordic region that were followed by different degrees of fertility decline. In this study, we provide an empirical overview of parity-, age- and education-specific fertility developments in the five Nordic countries in the wake of the economic recessions in 2008 and the early 1990s, respectively. We demonstrate a high degree of heterogeneity in fertility developments across countries after 1990, whereas after 2008, the trends are much more similar across the five countries. Likewise, the educational differences in birth hazards that characterized the developments after 1990 were much smaller in the initial years after 2008-2009. This reversal from heterogeneity to homogeneity in the fertility response to recessions calls for an expansion of theories on the cyclicality of fertility in relation to uncertainty and economic and social change. In our discussion, we consider the role of a set of factors that also incorporates the state, crisis management, and perceptions of economic and welfare uncertainty.


Phytoremediation of the polluted Waigang River and general survey on variation of phytoplankton population.
The Waigang River, a major tributary of the Qinhuai River system, has suffered from long-standing pollution because of lack of management. Restoration was commenced in April 2006 to reduce pollutants and improve water quality. Four ecological areas and ten surface carriers were constructed for the culture of plants (mainly water hyacinth (Eichhornia crassipes) and ryegrass (Lolium perenne L.)) for phytoremediation. Chemical oxygen demand (COD), total suspended solids (TSS), total phosphorus, total nitrogen (TN), ammonia-nitrogen (NH(3)-N), water transparency, and variations in phytoplankton population were investigated to evaluate the effects of restoration. Over 36 months, TSS, COD, TN, and NH(3)-N levels decreased by 91.1, 55.3, 91.5, and 86.5 %, respectively. Transparency increased from 25 cm in 2006 to 165 cm in 2009. Improvements in water quality significantly enhanced the diversity of phytoplankton, which were harmed by pollution stress. Our results show that the water hyacinth and ryegrass cultured in the ecological areas and the surface carriers can be used to restore other heavily polluted rivers with conditions similar to those of the Waigang River, especially in the initial stages of restoration.


Sensitization of glutamate receptor-mediated pain behaviour via nerve growth factor-dependent phosphorylation of transient receptor potential V1 under inflammatory conditions.
Glutamate and metabotropic glutamate (mGlu) receptors on primary sensory neurons are crucial in modulating pain sensitivity. However, it is unclear how inflammation affects mGlu receptor-mediated nociceptive responses. We therefore investigated the effects of mGlu1/5 receptor agonists on pain-related behaviour during persistent inflammation and their underlying mechanisms. Effects of a mGlu1/5 receptor agonist on pain-related behaviour during inflammation was assessed in mice. Intracellular calcium responses, membrane current responses, and protein expression in primary sensory neurons were examined using cultured dorsal root ganglion (DRG) neurons, dissociated from wild-type and gene knockout mice. Persistent inflammation induced by complete Freund's adjuvant increased the duration of mGlu1/5 receptor-mediated pain behaviour, which was antagonized by inhibition of nerve growth factor (NGF)-tropomyosin receptor kinase A (TrkA) signalling. Calcium imaging revealed that NGF treatment increased the number of cultured DRG neurons responding to mGlu1/5 receptor activation. Stimulation of mGlu1/5 receptors in NGF-treated DRG neurons induced inward currents through TRPV1 channels in association with PLC but not with IP3 receptors. NGF treatment also increased the number of neurons responding to a DAG analogue via TRPV1 channel activation. Furthermore, NGF up-regulated expression of TRPV1 and A-kinase anchoring protein 5 (AKAP5), resulting in increased AKAP5-dependent TRPV1 phosphorylation. AKAP5 knockout mice did not exhibit mGlu1/5 receptor-mediated excitation in NGF-treated DRG neurons or pain response facilitation under inflammatory conditions. NGF augments glutamate- and mGlu1/5 receptor-mediated excitation of nociceptive neurons by AKAP5-dependent phosphorylation of TRPV1 channels, potentiating hypersensitivity to glutamate in inflamed tissues.


Alkane-modified low-molecular-weight polyethylenimine with enhanced gene silencing for siRNA delivery.
Small interfering RNA (siRNA) has tremendous potential as a therapeutic agent for diverse diseases; however, due to its susceptibility to degradation and poor cellular uptake, the low efficiency of administration has been the most important limiting factor for clinical applications of siRNA. Herein, we synthesized alkyl chain modified low-molecular-weight polyethylenimines (LMW PEIs) and found that hydrophobically modified PEIs displayed enhanced efficiency in siRNA-mediated knockdown of target genes. To elucidate the mechanism for increased delivery, we characterized the polymers' physicochemical properties and bioactivity via nuclear magnetic resonance (NMR), gel retardation assay, dynamic laser scattering (DLS) analysis, confocal laser scanning microscopy and flow cytometry. The hydrophobic modification reduced siRNA binding affinity but facilitated the formation of nanoparticles in contrast to the original PEI. The PEIs with eight and thirteen alkyl tails were able to self-assemble into nanoparticles and yielded higher cellular uptake, which leaded to even similar efficiencies of 80-90% knockdown as Lipofectamine™ 2000 control. These results suggested that the status of polymers in aqueous solution, which depended on the degree of hydrophobic modification, played an important role in the uptake of siRNA. Therefore, we provided new information on the role of hydrophobic content in the enhanced gene silencing activity.


Endeavour delivers cancer care rewards.
Tony Roger, project manager at building services contractor, Shepherd Engineering Services (SES), describes the successful delivery of the 30 million sterling pounds New Oncology Expansion project at The James Cook University Hospital in Middlesbrough.


Effects of adenosine diphosphate, colchicine and temperature on size of human platelets.
An improved measuring system based on the Coulter principle and developed in our laboratory is used to size human blood platelets. The mean volume of platelets in 24 healthy subjects is found to be 8.45 micron 3 with a standard deviation of 1.07 micron 3; the typical size-distribution curve is unimodal and asymmetrical, with a marked skew to the right. The effects of different reagents on platelet size (shape factor x volume) are evaluated. Platelets increase in size by 23% following suspension in isotonic, phosphate-buffered saline and incubation with 10 microM adenosine diphosphate; no change is observed when the suspending medium is autologous plasma. Cooling the platelets to 0-4 degrees C results in a size increase of 25%; rewarming to 37 degrees C restores them to their initial size within 2 hr. A similar increase occurs when the platelets are incubated with 1-10 mM colchicine. It is proposed that these reagents, which are known to produce changes in the orientation of the marginal bundle of microtubules, cause platelets to undergo disc-sphere transformations. Calculations are made which show that such transformations increase platelet size by 27% as measured electrically, and we conclude that the so-called volume changes reported in the literature reflect shape changes only and that no true volume increase actually takes place.


Bitter compounds in two Tricholoma species, T. aestuans and T. virgatum.
Lascivol was identified as the bitter compound in two Tricholoma species, T. aestuans and T. virgatum, and was previously isolated from the European mushroom T. lascivum. The structure of lascivol was previously solved by X-ray crystallographical analysis but its stereochemistry at C3 remained ambiguous. We thus re-examined the absolute configuration of C3 bearing a hydroxy group using the modified Mosher's method.


Methylene blue: dangerous dye for neonates.
Methylene blue is a basic dye commonly used in histologic microbiologic, and tissue staining. This report describes an instance of methylene blue toxicity in a premature neonate.


Breastfeeding among the Ontario James Bay Cree: a retrospective study.
Although previous unpublished research has demonstrated low breastfeeding rates among the James Bay Cree of Northern Ontario, the reasons for this are not immediately clear. A retrospective medical chart review of women who had given birth at the Weeneebayko General Hospital in Moose Factory, Ontario in the seven-year period 1997 to 2003 was performed. A variety of demographic variables were documented and overall breastfeeding initiation rates and yearly variations were assessed. Univariate chi-square analysis of the data indicated that young maternal age (mean=23; p=0.001), maternal smoking (average rate=52.1%; p=0.03), living location (in a small coastal community; p=0.001); and low education status (not completing high school; p<0.001) were risk factors for a mother choosing not to breastfeed. Regression analysis revealed that only living in small coastal communities and not having post-secondary education were independently associated with not breastfeeding. Absence of a partner nearly reached statistical significance on regression analysis (p=0.056). The overall breastfeeding initiation rates (51.9%, 95% CI: 49.3-54.5) were confirmed to be lower than the national average (78%), and the rate has remained low over the seven years of the study. These results should help clarify why some mothers in the Moose Factory region are at risk of not breastfeeding. This information will be useful in directing future research on the differences in breastfeeding rates among different Aboriginal Peoples' communities, and assist in the development of program policies specific to women who have one or more of the identified risk factors.


T2 relaxation time changes in distal femoral articular cartilage in children with juvenile idiopathic arthritis: a 3-year longitudinal study.
Increased cartilage T2 relaxation time is thought to be an early marker of disease progression in juvenile idiopathic arthritis, because it can identify microstructural changes before damage becomes visible. The purpose of this study was to investigate longitudinal changes in T2 relaxation time mapping (i.e., T2 map) in children with early juvenile idiopathic arthritis and to compare with changes in clinical assessments. Twenty children (age range, 6.4-16 years) with early juvenile idiopathic arthritis completed at least four evaluations with T2 maps and clinical assessments: at enrollment, at 3 months, and at 1, 2, and 3 years. Sagittal T2 maps of distal femoral cartilage were generated, a region of interest was selected, and a T2 relaxation time profile was generated. The area under the curve from the T2 profile (i.e., T2 value) was correlated with patient age and sex and the following clinical assessments: total knee score, Childhood Health Assessment Questionnaire, physician global assessment, parent global assessment, and total number of active joints. There was a significant increase in mean T2 values from 3 months to 2 years (p < 0.05). There was a significant decrease in mean Childhood Health Assessment Questionnaire values between enrollment and 2 years (p < 0.05) and a significant decrease in parent global assessment, physician global assessment, total number of active joints, and total knee score values between enrollment and 1 year (p < 0.05). There were no statistically significant correlations between T2 values and patient age, sex, or clinical assessments. In patients with early juvenile idiopathic arthritis, T2 maps showed increased T2 values from the 3-month to 2-year follow-up, during which time the clinical assessments improved. This increase likely represents progressive microstructural changes, even though clinical symptoms improved with treatment.


An unusually stable DNA binding protein can locate its specific binding site in the presence of high concentrations of urea.
A sequence specific DNA binding protein has been demonstrated in extracts of Drosophila melanogaster third instar larval nuclei which binds close to a chromosome-scaffold associated region. This protein has proven difficult to work with because of its strong tendency to aggregate. Here I show that the protein can be readily maintained in solution in the presence of high concentrations of urea. Surprisingly, the protein turns out to be remarkably resistant to denaturation by urea. It is capable of mediating sequence specific DNA binding in the presence of urea at concentrations up to 8M. When incubated in 4M urea the binding activity appears to slowly degrade, but in 1.3M urea the protein is active, soluble and stable over extended periods of time at room temperature. The molecular basis of this unexpected finding must await the purification of the protein. The ability to keep the protein both soluble and active should now permit its isolation.


Increased production of recombinant hIGFBP-1 in PEG induced autofusion of Chinese hamster ovary (CHO) cells.
A recombinant Chinese hamster ovary (CHO) cell clone, S1, stably expressing human insulin-like growth factor binding protein-1 (hIGFBP-1), was treated with polyethylene glycol (PEG), resulting in cell fusion, in order to further enhance the protein expression by increasing the gene copy number and/or the amount of organelles important to the protein expression/-secretion. Both the fused cell line, Peg1, and its mother cell line, S1, were adapted to serum-free growth in suspension and were characterised with respect to growth and productivity. Peg1 was easier to adapt to the serum-free suspension conditions and had a higher viability during the adaptation period than S1. Furthermore, Peg1 showed a stable productivity of hIGFBP-1 that was twice as high as that for S1 under both adherent and suspension conditions. A considerable difference in the specific productivity (up to 3-4 times) was noticed during the growth phase. PEG fusion experiments have earlier been studied in our laboratory with CHO cells producing recombinant factor VIII and our results correlates very well with the results obtained with the factor VIII producing cells. Surprisingly, it was possible to obtain high producing recombinant cell lines, which were stable for more than 4 months.


Improving the Conversational Skills of a College Student with Peer-Mediated Behavioral Skills Training.
We used a multiple baseline design across behaviors to evaluate peer-mediated behavioral skills training to improve a complex repertoire of conversational skills of an undergraduate student diagnosed with a learning disability NOS. Following treatment, we observed a decrease in interrupting and content specificity and an increase in questioning. Treatment effects maintained with naïve peers during unstructured conversations and outcomes compared favorably with normative data on the conversational skills of three undergraduates without learning disabilities.


Recent advances in improving stability of food emulsion by plant polysaccharides.
Emulsion is considered to be an excellent system for delivering nutraceuticals, but instability limits the application of the emulsion. Adding stabilizers is an effective method to improve the stability of the emulsion. Due to safety concerns, stabilizers from natural resources are attracting more and more attentions in food industry. Plant polysaccharides are natural biopolymers which are widely distributed in the cells of plants. Many plant polysaccharides have been shown good emulsifying and thickening effects, therefore, they are widely used as stabilizers in emulsions. The application of plant polysaccharides in improving emulsion stability was reviewed in this paper. Firstly, the factors affecting the stability of the emulsion were elaborated in detail. On this basis, the methods of improving the stability of the emulsion were discussed. Furthermore, the effects of the plant polysaccharide structures on emulsion stability were explained, such as the molecular weight of the polysaccharide, the hydrophobic group of the polysaccharide, and the protein content of the polysaccharide. Additionally, the application of several common plant polysaccharides and their derivatives in emulsions were introduced. It is hoped that this review can provide sufficient theoretical basis for application of plant polysaccharides in emulsions in the future.


A mobile device app to reduce prehospital medication errors and time to drug preparation and delivery by emergency medical services during simulated pediatric cardiopulmonary resuscitation: study protocol of a multicenter, prospective, randomized controlled trial.
Emergency drug preparation and administration in children is both complex and time-consuming and places this population at a higher risk than adults for medication errors. Moreover, survival and a favorable neurological outcome from cardiopulmonary resuscitation are inversely correlated to drug preparation time. We developed a mobile device application (the pediatric Accurate Medication IN Emergency Situations (PedAMINES) app) as a step-by-step guide for the preparation to delivery of drugs requiring intravenous injection. In a previous multicenter randomized trial, we reported the ability of this app to significantly reduce in-hospital continuous infusion medication error rates and drug preparation time compared to conventional preparation methods during simulation-based pediatric resuscitations. This trial aims to evaluate the effectiveness of this app during pediatric out-of-hospital cardiopulmonary resuscitation. We will conduct a multicenter, prospective, randomized controlled trial to compare the PedAMINES app with conventional calculation methods for the preparation of direct intravenously administered emergency medications during standardized, simulation-based, pediatric out-of-hospital cardiac arrest scenarios using a high-fidelity manikin. One hundred and twenty paramedics will be randomized (1:1) in several emergency medical services located in different regions of Switzerland. Each paramedic will be asked to prepare, sequentially, four intravenously administered emergency medications using either the app or conventional methods. The primary endpoint is the medication error rates. Enrollment will start in mid-2019 and data analysis in late 2019. We anticipate that the intervention will be completed in early 2020 and study results will be submitted in late 2020 for publication (expected in early 2021). This clinical trial will assess the impact of an evidence-based mobile device app to reduce the rate of medication errors, time to drug preparation and time to drug delivery during prehospital pediatric resuscitation. As research in this area is scarce, the results generated from this study will be of great importance and may be sufficient to change and improve prehospital pediatric emergency care practice. ClinicalTrials.gov, ID: NCT03921346. Registered on 18 April 2019.


Zygotic genome activation in the chicken: a comparative review.
Maternal RNAs and proteins in the oocyte contribute to early embryonic development. After fertilization, these maternal factors are cleared and embryonic development is determined by an individual's own RNAs and proteins, in a process called the maternal-to-zygotic transition. Zygotic transcription is initially inactive, but is eventually activated by maternal transcription factors. The timing and molecular mechanisms involved in zygotic genome activation (ZGA) have been well-described in many species. Among birds, a transcriptome-based understanding of ZGA has only been explored in chickens by RNA sequencing of intrauterine embryos. RNA sequencing of chicken intrauterine embryos, including oocytes, zygotes, and Eyal-Giladi and Kochav (EGK) stages I-X has enabled the identification of differentially expressed genes between consecutive stages. These studies have revealed that there are two waves of ZGA: a minor wave at the one-cell stage (shortly after fertilization) and a major wave between EGK.III and EGK.VI (during cellularization). In the chicken, the maternal genome is activated during minor ZGA and the paternal genome is quiescent until major ZGA to avoid transcription from supernumerary sperm nuclei. In this review, we provide a detailed overview of events in intrauterine embryonic development in birds (and particularly in chickens), as well as a transcriptome-based analysis of ZGA.


Effects of pregnancy and lactation on lipolysis of ewe adipocytes induced by beta-adrenergic stimulation.
During pregnancy and lactation, three phases of beta-adrenergic stimulation of lipolysis appeared in adipocytes isolated from omental adipose tissue of ewes: During the first 90 days of pregnancy, there was a fall in the maximal lipolytic effect of isoproterenol. The maximum response to beta-lipolytic stimulus was reduced by 38% on day 90 (815 nmol/2 h/10(6) cells, compared to 1304 for controls) without any change in system sensitivity. Between days 90 and 120 of pregnancy (switch in adipose metabolism), this lipolytic effect increased progressively and became significantly larger (34%) than in non-pregnant ewes around parturition. The system sensitivity was then higher (0.05-0.11 vs. 0.21 microM) and remained so throughout lactation. During the first 3 weeks of lactation, this stimulated rate was twice as great as in controls.


Dynamical system analysis of interacting dark energy in LRS Bianchi type I cosmology.
This paper deals with an interacting dark energy (DE) model in Locally rotationally symmetric (LRS) Bianchi type I cosmological model with scalar field in the form of an exponential potential. We reduce the transformation equations to an independent system of ordinary differential equations by appropriate alteration of the variables to setup the complementary dynamical system and after that we also calculate the critical points of the system. We get six critical points when our coupling parameter is positive. And we get two critical points when our coupling parameter is negative. And dark energy behaves like a perfect fluid for all the critical points. And after that we analyzed all the critical points by calculating the eigenvalues of the Jacobian matrix and we find out that out of these eight critical points, six critical points are stable, which shows that our Universe is accelerating. And two (2) critical points are unstable. We also present the phase plot analysis.


Am I present in imaginary worlds? Intentions, actions, and flow in mediated experiences and fiction.
We support the idea of applying cultural evolution theory to the study of storytelling, and fiction in particular. However, we suggest that a more plausible link between real and imaginary worlds is the feeling of "presence" we can experience in both of them: we feel present when we are able to correctly and intuitively enact our embodied predictions.


Function of CD8+, conventional CD4+, and regulatory CD4+ T cell identification in lung cancer.
Lung cancer is the malignant tumor with the highest mortality rate in the world. There is obvious heterogeneity within the tumor. Single cell sequencing technology enables scholars to obtain information about the cell type, status, subpopulation distribution and communication behavior between cells in the tumor microenvironment from the cellular level. However, due to the problem of sequencing depth, some genes with low expression cannot be detected, which results in that most of the specific genes of immune cells cannot be recognized, and lead to defects in the functional identification of immune cells. In this paper, we used single cell sequencing data of 12346 T cells in 14 treatment-naïve non-small-cell lung cancer patients to identify immune cell-specific genes and infer the function of three types of T cells. The method, named GRAPH-LC, implemented this function by gene interaction network and graph learning methods. Graph learning methods are used to extract genes feature and dense neural network is used to identify immune cell-specific genes. The experiments on 10-cross validation shows that the AUROC and AUPR reached at least 0.802, 0.815 on identifying cell-specific genes of three types of T cells. And we did functional enrichment analysis on the top 15 expressed genes. By functional enrichment analysis, we got 95 GO terms and 39 KEGG pathways that related to three types of T cells. The use of this technology will help to deeply understand the mechanism of the occurrence and development of lung cancer, find new diagnostic markers and therapeutic targets, and provide a theoretical reference for the precise treatment of lung cancer patients in the future.


A case report of traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) in a 21-year-old.
We present an unusual case of a persistent solitary left palatoglossal ulcer with no history of trauma or associated risk factors. A TUGSE lesion, which mimics that of malignancy, must always be noted as a differential even in risk factor absence.


Elevated Hedgehog activity contributes to attenuated DNA damage responses in aged hematopoietic cells.
Accumulation of DNA damage and myeloid-skewed differentiation characterize aging of the hematopoietic system, yet underlying mechanisms remain incompletely understood. Here, we show that aging hematopoietic progenitor cells particularly of the myeloid branch exhibit enhanced resistance to bulky DNA lesions-a relevant type of DNA damage induced by toxins such as cancer drugs or endogenous aldehydes. We identified aging-associated activation of the Hedgehog (Hh) pathway to be connected to this phenotype. Inhibition of Hh signaling reverts DNA damage tolerance and DNA damage-resistant proliferation in aged hematopoietic progenitors. Vice versa, elevating Hh activity in young hematopoietic progenitors is sufficient to impair DNA damage responses. Altogether, these findings provide experimental evidence for aging-associated increases in Hh activity driving DNA damage tolerance in myeloid progenitors and myeloid-skewed differentiation. Modulation of Hh activity could thus be explored as a therapeutic strategy to prevent DNA damage tolerance, myeloid skewing, and disease development in the aging hematopoietic system.


The effect of cannabis on the brain: can it cause brain anomalies that lead to increased risk for schizophrenia?
This review explores what is known about the association of cannabis with schizophrenia, its effects on the brain, and whether the brain changes known to be present in schizophrenia could be caused by cannabis and thus lead to a psychosis. The heavy use of cannabis is known to be associated with some adverse consequences, such as the occurrence of acute psychotic episodes and the development of chronic schizophrenia in some people even after its use has terminated. Recent studies have produced controversy about whether cannabis in heavy use can cause irreversible brain damage, particularly to adolescents, and thus whether a chronic psychosis could be a result of brain changes caused by cannabis. From the evidence that exists, it appears that the above view is unlikely and that cannabis may even have benign effects on brain structure, not producing deleterious damage. Its neurochemical interactions with the dopaminergic pathway, however, may, particularly in genetically vulnerable individuals, have adverse consequences.


Silicon-containing polyoxadiazoles-synthesis and perspectives.
A review is presented on those polymers which contain diphenylsilylene units and 1,3,4-oxadiazole rings either in the main chain or in the pendent groups. The synthesis of silicon-containing monomers as well as of the polyoxadiazoles based on them is described. The properties of these polymers, such as solubility, film forming ability, thermal stability, electrochemical behavior and photoluminescence properties, and their potential applications are discussed.


RNA epigenetics--chemical messages for posttranscriptional gene regulation.
Chemical modifications in cellular RNA are diverse and abundant. Commonly found in ribosomal RNA (rRNA), transfer RNA (tRNA), long-noncoding RNA (lncRNA), and small nuclear (snRNA), these components play various structural and functional roles. Until recently, the roles of chemical modifications within messenger RNA (mRNA) have been understudied. Recent maps of several mRNA modifications have suggested regulatory functions for these marks. This review summarizes recent advances in identifying and understanding biological roles of posttranscriptional mRNA modification, or 'RNA epigenetics', with an emphasis on the most common internal modification of eukaryotic mRNA, N(6)-methyladenosine (m(6)A). We also discuss YTH proteins as direct mediators of m(6)A function and the emerging role of this mark in a new layer of gene expression regulation.


Tuberculous meningitis.
Tuberculous (TB) meningitis is common in resource-poor communities but also occurs in developed countries where the diagnosis is frequently delayed because of unfamiliarity with the disease. TB meningitis develops whenever a small intracranial tuberculoma (Rich focus) ruptures causing predominantly basal meningitis. This results in hydrocephalus, cranial nerve palsies, and ischemic brain injury secondary to tuberculous vasculitis. The primary source of TB is usually the lung. Early diagnosis is difficult because patients tend to present subacutely with nonspecific symptoms such as fever, cough, vomiting, listlessness, and failure to thrive. Lumbar puncture typically shows clear and colorless CSF with a low, predominantly lymphocytic, leukocytosis and raised protein and low glucose levels. Decision to treat is mostly clinical because of difficulty in demonstrating TB bacilli on routine smear and time needed for culture. A positive TB contact, Mantoux skin test, chest radiograph, CT/MRI brain scan, PCR for tuberculosis on CSF, and demonstration of TB bacilli from extraneural sources are invaluable in supporting a diagnosis of TB meningitis. Current World Health Organization guidelines recommend treatment with a four-drug regimen for 2 months, followed by a two-drug regimen for 10 months, the total duration of treatment being 12 months. Corticosteroids reduce mortality without changing neurological morbidity. Outcome relates closely to age and stage of disease.


Plausible subjective experience versus fallible corroborative evidence: The formulation of insanity in Nigerian criminal courts.
Insanity as a defence against criminal conduct has been known since antiquity. Going through significant reformulations across centuries, different jurisdictions across the globe, including Nigeria, have come to adopt various strains of the insanity defence, with the presence of mental disorder being the causative mechanism of the crime as their central theme. A critical ingredient in the Nigerian insanity plea is the presence of 'mental disease' or 'natural mental infirmity' as the basis for the lack of capacity in certain cognitive and behavioural domains resulting in the offence. Mental disorders, which are the biomedical formulations of this critical legal constituent are primarily subjective experiences with variable objective features. Using illustrative cases based on psycho-legal formulation as well as reform-oriented and fundamental legal research, it is shown that Nigerian courts have held that claims of insanity based on the accused person's evidence alone should be regarded as "suspect" and not to be "taken seriously." Thus, Nigerian judicial opinions rely on non-expert accounts of defendants' apparent behavioural abnormalities and reported familial vulnerability to mental illness, amongst other facts while conventionally discountenancing the defendants' plausible phenomenological experiences validated by expert psychiatric opinion in reaching a conclusion of legal insanity. While legal positivism would be supportive of the prevailing judicial attitude in entrenching the validity of the disposition in its tenuous precedential utility, legal realism invites the proponents of justice and fairness to interrogate the merit of such preferential views which are not supported by scientific evidence or philosophical reasoning. This paper argues that disregarding the subjective experience of the defendant, particularly in the presence of sustainable expert opinion when it stands unrebutted is not in the interest of justice. This judicial posturing towards mentally abnormal offenders should be reformed on the basis of current multidisciplinary knowledge. Learning from the South African legislation, formalising the involvement of mental health professionals in insanity plea cases, ensures that courts are guided by professional opinion and offers a model for reform.


[Prevention of thromboembolism and therapy. Introduction].
One-third of all surgical patients develop a deep phlebothrombosis. This frequency of thrombosis after injuries of the lower extremities is estimated at 65%. Most of the thromboses do not become clinically manifest. Ninety-two percent of all fatal pulmonary embolisms originate from a clinically inapparent thrombosis. The ideal prophylaxis should compensate for the undesired effects of an operation or injury on the coagulation system, without subjecting the patient to the danger of elevated tendency to bleed. The discussion of this subject should help to clarify the present successes and risks of thromboembolism prophylaxis and therapy.


Increased heparin cofactor II levels in women taking oral contraceptives.
Heparin cofactor II (HCII) is a thrombin inhibitor present in human plasma whose activity is enhanced by heparin. HCII exhibits important homologies with antithrombin III, the main heparin-enhanced thrombin inhibitor. Cases of recurrent thromboembolism have been recently reported in patients with HCII deficiency. Since the use of oral contraceptives (OC) is associated with an increased risk of thrombosis, the study of the plasma levels of HCII was undertaken in women taking contraceptive pills. Plasma HCII levels were found significantly higher in 62 women taking low-estrogen content OC (1.20 +/- 0.28 U/ml) than in 62 age matched women not taking OC (0.94 +/- 0.16 U/ml) or in 62 men (0.96 +/- 0.19 U/ml). Significant correlations between HCII and fibrinogen levels were reported in the three groups. From the pooled data of the two control groups (men and women not taking OC), the normal range for plasma HCII levels was defined to be between 0.60 and 1.30 U/ml (mean +/- 2 SD). Two cases of low HCII levels (less than 0.60 U/ml) were found in the control groups, but none in the group of women taking OC. It is concluded that the use of oral contraceptives is associated with a rise in HCII levels and that the screening for HCII deficiency has to be performed at distance of any OC therapy.


Cholesteryl ester transfer in hypercholesterolaemia: fasting and postprandial studies with and without pravastatin.
Subjects with hypercholesterolaemia (HC) have increased fasting cholesteryl ester transfer protein (CETP) activity and accelerated cholesteryl ester transfer (CET) from HDL to apo B-containing lipoproteins. The aim of this study was to examine the effects of postprandial lipaemia and pravastatin treatment on plasma triglycerides (TG) and CETP activity and on CET and LDL Stokes' diameter in primary HC (n = 19, total cholesterol > or =6.5, LDL-cholesterol > or =4.5, TG <4.0 mmol/l). Samples were collected fasting and 6 h after an oral fat load (0.88 g/kg body weight) after 6 weeks therapy with placebo or pravastatin 40 mg nocte according to a double-blind randomized cross-over study. Apart from significant reductions in plasma total cholesterol, LDL-cholesterol apo B and TG. pravastatin significantly reduced CETP activity in both the fasting (mean +/- SD, 37.9+/-12.2 to 32.0+/-10.3 nmol/ml plasma per h) and postprandial state (35.5+/-11.3 to 31.3+/-9.5 nmol/ml plasma per h) compared to equivalent placebo phases. CETP activity did not change during postprandial lipaemia despite a significant 45-55% increase in CET to triglyceride-rich lipoproteins (TRL) of d <1.006 g/ml. LDL Stokes' diameter was unchanged postprandially or by pravastatin. The mass of TRL was the strongest contributor to variation in CET in both fasting and postprandial plasma, accounting for at least 77% of the variance of CET. Postprandial TRL-TG was the strongest contributor to variation in fasting LDL Stokes' diameter in untreated HC (54%) whilst HDL-cholesterol was the strongest fasting contributor to variation (45%) for placebo- and pravastatin-treated HC. We conclude that pravastatin may reduce the atherogenicity of the lipoprotein profile in HC by reducing CETP activity. Furthermore, CET is strongly influenced by postprandial lipaemia which may have a cumulative effect on LDL size.


Patient-to-patient transmission of hepatitis C virus through the use of multidose vials during general anesthesia.
A cluster of four patients with hepatitis C virus (HCV) infection was identified in a surgery clinic. Molecular characterization revealed close homology between viruses. This cluster was related to unsafe injection practices through multidose vials and reused materials. Among 796 patients potentially exposed to and screened for HCV, no other cluster was identified.


The impact of the Oncotype Dx breast cancer assay in clinical practice: a systematic review and meta-analysis.
The impact of the Oncotype Dx (ODX) breast cancer assay on adjuvant chemotherapy (ACT) treatment decisions has been evaluated in many previous studies. However, it can be difficult to interpret the collective findings, which were conducted in diverse settings with limited sample sizes. We conducted a systematic review and meta-analysis to synthesize the results and provide insights about ODX utility. Studies, identified from PubMed, Embase, ASCO, and SABCS, were included if patients had ER+, node -, early-stage breast cancer, reported use of ODX to inform actual ACT decisions. Information was summarized and pooled according to: (1) distribution of ODX recurrence scores (RS), (2) impact of ODX on ACT recommendations, (3) impact of ODX on ACT use, and (4) proportion of patients following the treatment suggested by the ODX RS. A total of 23 studies met inclusion criteria. The distribution of RS categories was 48.8 % low, 39.0 % intermediate, and 12.2 % high (21 studies, 4,156 patients). ODX changed the clinical-pathological ACT recommendation in 33.4 % of patients (8 studies, 1,437 patients). In patients receiving ODX, receipt of ACT were: 28.2 % overall, 5.8 % low, 37.4 % intermediate, and 83.4 % high. Low RS patients were significantly more likely to follow the treatment suggested by ODX versus high RS patients RR: 1.07 (1.01–1.14) [corrected].The pooled results are consistent with most individual studies to date. The increased proportion of intermediate scores relative to original estimates may have implications for the clinical utility and cost impacts of testing. In addition, low versus high RS patients were significantly more likely to follow the ODX results, suggesting a tendency toward less aggressive treatment, despite a high ODX RS. Finally, there was a lack of studies on the impact of ODX on ACT use versus standard approaches, suggesting that additional studies are warranted.


Effect of Nebulizer Location and Spontaneous Breathing on Aerosol Delivery During Airway Pressure Release Ventilation in Bench Testing.
Airway pressure release ventilation (APRV) maintains a sustained airway pressure over a large proportion of the respiratory cycle, and has a long inspiratory time at high pressure. The purpose of this study was to determine the influence of the APRV with and without spontaneous breathing on albuterol aerosol delivery with a continuous vibrating-mesh nebulizer (VMN) placed at different positions on an adult lung model of invasive mechanical ventilation. An adult lung model was assembled by connecting a ventilator with a dual-limb circuit to an 8-mm inner diameter endotracheal tube (ETT) and collecting filter attached to a test lung with set compliance of 0.1 L/cmH2O and resistance of 0.5 cmH2O/(L·s). Four ventilator modes were compared: pressure control ventilation (PCV) with no bias flow, PCV with bias flow of 6 L/min (PCVBF6), APRV with no spontaneous breaths (APRV), and APRV with spontaneous breath trigger (APRVs). Peak inspiratory pressure, peak end-expiratory pressure, aerosol dose, and nebulization time were similar for all modes. The VMN was placed (1) between Y-piece and inspiratory limb, (2) at the gas outlet of a heated humidifier, and (3) at the gas inlet of a heated humidifier. Albuterol sulfate (5 mg/2.5 mL) was administered with each run and collected on a filter distal to the ETT. Deposited drug was eluted from each filter (purified water) and analyzed by UV spectrophotometry at 276 nm. Analysis of variance [general linear model (GLM) multivariate] was performed using the linear model of multiple variables, significance at p < 0.05. Albuterol (in micrograms, mean ± standard deviation) delivered was higher with VMN placed at the gas inlet of the humidifier with each mode of ventilation (p < 0.01). APRVs has the highest albuterol delivery followed by PCV, PCVBF6, and APRV (1706.2 ± 60.9 μg vs. 1490.6 ± 61.1 μg vs. 1182.3 ± 61.4 μg vs. 1153.1 ± 99.7 μg, respectively, p < 0.001). The minute volume was positively correlated with the inhaled albuterol dose. Spontaneous breathing increased the albuterol delivery during APRV, compared with APRV alone and PCV modes. Placing the nebulizer proximal to the ventilator was more efficient for all modes tested.