Inhibitory effects of resveratrol on PDGF-BB-induced retinal pigment epithelial cell migration via PDGFRβ, PI3K/Akt and MAPK pathways.
In diseases such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, and age-related macular degeneration, retinal pigment epithelial (RPE) cells proliferate and migrate. Moreover, platelet-derived growth factor (PDGF) has been shown to enhance proliferation and migration of RPE cells in PVR. Even resveratrol can suppress the migration and adhesion of many cell types, its effects on RPE cell migration and adhesion remain unknown. In this study, we investigated the inhibitory effects of resveratrol on RPE cell migration induced by PDGF-BB, an isoform of PDGF, and adhesion to fibronectin, a major ECM component of PVR tissue. The migration of RPE cells was assessed by an electric cell-substrate impedance sensing migration assay and a Transwell migration assay. A cell viability assay was used to determine the viability of resveratrol treated-cells. The cell adhesion to fibronectin was examined by an adhesion assay. The interactions of resveratrol with PDGF-BB were analyzed by a dot binding assay. The PDGF-BB-induced signaling pathways were determined by western blotting and scratch wound healing assay. Resveratrol inhibited PDGF-BB-induced RPE cell migration in a dose-dependent manner, but showed no effects on ARPE19 cell adhesion to fibronectin. The cell viability assay showed no cytotoxicity of resveratrol on RPE cells and the dot binding assay revealed no direct interactions of resveratrol with PDGF-BB. Inhibitory effects of resveratrol on PDGF-BB-induced platelet-derived growth factor receptor β (PDGFRβ) and tyrosine phosphorylation and the underlying pathways of PI3K/Akt, ERK and p38 activation were found; however, resveratrol and PDGF-BB showed no effects on PDGFRα and JNK activation. Scratch wound healing assay demonstrated resveratrol and the specific inhibitors of PDGFR, PI3K, MEK or p38 suppressed PDGF-BB-induced cell migration. These results indicate that resveratrol is an effective inhibitor of PDGF-BB-induced RPE cell migration via PDGFRβ, PI3K/Akt and MAPK pathways, but has no effects on the RPE cell adhesion to fibronectin.


[Involvement of calcineurin A alpha and A beta in neuronal death in a gerbil model of cerebral ischemia].
Treatment with FK506, an inhibitor of Ca2+/calmodulin dependent phosphatase (calcineurin, CaN), within 1 hr after transient ischemia afforded protection from apoptotic death in CA1 pyramidal neurons. To investigate isoform-specific roles of CaN in the neuronal cell death, we localized CaN A alpha and CaN A beta in the gerbil hippocampus using isoform-specific antibodies. In control gerbils, immunoreactions of both isoforms were highly enriched in hippocampal CA1 pyramidal neurons. Four to seven days after the induced ischemia, immunoreactivities of both isoforms were markedly reduced in the CA1 pyramidal cell and lacunosum-molecular layers. The CaN A alpha immunoreactivity was increased in the CA1 radiatum and oriens layers, whereas that of CaN A beta was enhanced in reactive astrocytes in the CA1 region. These findings suggest that CaN A alpha is involved in sprouting of afferent fibers in CA1 and that CaN A beta is involved in the reaction of astrocytes such as assembly of glial fibril acidic protein.


Anti-Depressive Effectiveness of Baicalin In Vitro and In Vivo.
Baicalin (BA), a major polyphenol compound isolated from the extracts of Scutellaria radix, has been previously reported to ameliorate depressive-like behaviors in mice with chronic unpredictable mild stress (CUMS). However, its underlying antidepressant mechanisms remain unclear. This study was designed to confirm the antidepressant-like effects of BA on CUMS induced behavioral abnormalities in mice, and sought to explore the pharmacological mechanisms in vivo and in vitro. The CUMS procedure was carried out to induce depression in mice. Afterwards, the tail suspension test (TST), forced swim test (FST), and open field test (OFT) were performed within 24 h, then sucrose preference test (SPT) was conducted. Additionally, PC12 cells were pretreated with BA for 2 h, then further stimulated with corticosterone for 24 h. The levels of Interleukin-1β (IL-1β), IL-6 and Tumor Necrosis Factor-α (TNF-α) in serum, hippocampus homogenate and cell culture medium were determined using the enzyme-linked immunosorbent assay (ELISA) method. The protein expressions of inhibition of high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathways in hippocampus and PC12 cells were detected. Our results showed that CUMS-treated mice presented notable depressive-like symptoms, such as decreased sucrose consumption, increased FST and TST immobility time. While BA (25, 50 mg/kg) significantly attenuated these changes. Besides, BA treatment considerably inhibited inflammatory cytokinesl (IL-1β, IL-6, TNF-α) levels in serum, hippocampus homogenate and cell culture medium. Western blot analysis indicated that BA inhibited the expressions of HMGB1, TLR4, and p-NF-κBp65 both in vivo and in vitro. In conclusion, the present study confirmed that BA possessed efficient antidepressant effects on depression, which was possibly related to the inhibition of HMGB1/TLR4/NF-κB pathways.


Image guided surgery of paranasal sinuses and anterior skull base--five years experience with the InstaTrak-System.
We report on our experience with navigational tools in paranasal sinus and anterior skull base surgery, especially with electromagnetic guidance systems. During the last five years we operated over 80 selected cases with the InstaTrak system from VTI (Lawrence, MS, USA). Applicability and user friendliness were explored. The InstaTrak 3500 employs a Sun Workstation and is a frameless and free-arm and navigation system. Two different suction devices, used as sensors (receivers), and one transmitter are interconnected to this workstation. The position of the tip of the aspirator is displayed as a pair of crosshairs on the screen in axial, coronal and sagittal planes of the patient's CT-scan on the computerscreen online. Our results showed high accuracy-level, usually better than one millimeter and a setup-time less than ten minutes, on average. No additional personnel is required in the OR. We believe that the system enhances efficacy in selected cases like revision surgery, tumor surgery or difficult anterior skull base surgery. However, one should consider that medicolegal responsibility stays always with the surgeon and not with any navigation system.


Type II achondrogenesis-hypochondrogenesis: morphologic and immunohistopathologic studies.
A 32-wk-gestation female with type II achondrogenesis-hypochondrogenesis has been studied. The clinical features were typical, and radiographs revealed short ribs, hypoplastic ilia, absence of ossification of sacrum, pubis, ischia, tali, calcanei, and many vertebral bodies; the long bones were short with mild metaphyseal flaring. The femoral cylinder index was 6.3. Comparison with previous cases placed the patient toward the mild end of the achondrogenesis-hypochondrogenesis spectrum (Whitley-Gorlin prototype IV). Light microscopy revealed hypercellular cartilage with decreased matrix traversed by numerous fibrous vascular canals. The growth plate was markedly abnormal. Ultrastructural studies revealed prominently dilated rough endoplasmic reticulum containing a fine granular material with occasional fibrils in all chondrocytes. Immunohistologic studies indicated irregular large areas of cartilage matrix staining with monoclonal antibody to human type III collagen. The relative intensity of matrix staining for type II collagen appeared diminished. More striking, however, were intense focal accumulations of type II collagen within small rounded perinuclear structures of most chondrocytes but not other cell types. These results strongly suggest intracellular retention of type II collagen within vacuolar structures, probably within the dilated rough endoplasmic reticulum observed in all chondrocytes by electron microscopy (EM), and imply the presence of an abnormal, poorly secreted type II collagen molecule. Biochemical studies (see companion paper) suggest that this patient had a new dominant lethal disorder caused by a structural abnormality of type II collagen.


Hemodiafiltration in developing countries.
Hemodiafiltration (HDF) is a promising kidney replacement therapy modality for patients with end-stage kidney disease. The principle of uremic toxin clearance by combining convection and diffusion can lead to greater benefits compared to conventional hemodialysis. Evidence is building that supports the advantages of HDF with short-term outcomes such as greater intradialytic hemodynamic stability, improved nutritional status, attenuation of anemia, and reduction of inflammatory cytokines which produce improved key long-term impacts including survival and cardiovascular outcomes. Very little is known about the prevalence of HDF treatments in developing countries due to a shortage of national kidney registries. HDF experience is limited in many countries due to the cost of dialysis treatments, availability of online HDF machines, and reimbursement policies. These obstacles have led to nephrologists developing innovations, for example, convective control HDF (CC-HDF), simple mid-dilution, and simple mixed-dilution methods, which may be as effective as commercially available HDF machines. In this article, we will focus on the experience of HDF practice and barriers to adoption in developing countries. Results can guide clinical practice recommendations for implementing HDF in resource-limited settings.


Transcriptome analysis and discovery of genes involved in immune pathways from hepatopancreas of microbial challenged mitten crab Eriocheir sinensis.
The Chinese mitten crab Eriocheir sinensis is an important economic crustacean and has been seriously attacked by various diseases, which requires more and more information for immune relevant genes on genome background. Recently, high-throughput RNA sequencing (RNA-seq) technology provides a powerful and efficient method for transcript analysis and immune gene discovery. A cDNA library from hepatopancreas of E. sinensis challenged by a mixture of three pathogen strains (Gram-positive bacteria Micrococcus luteus, Gram-negative bacteria Vibrio alginolyticus and fungi Pichia pastoris; 10(8) cfu·mL(-1)) was constructed and randomly sequenced using Illumina technique. Totally 39.76 million clean reads were assembled to 70,300 unigenes. After ruling out short-length and low-quality sequences, 52,074 non-redundant unigenes were compared to public databases for homology searching and 17,617 of them showed high similarity to sequences in NCBI non-redundant protein (Nr) database. For function classification and pathway assignment, 18,734 (36.00%) unigenes were categorized to three Gene Ontology (GO) categories, 12,243 (23.51%) were classified to 25 Clusters of Orthologous Groups (COG), and 8,983 (17.25%) were assigned to six Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Potentially, 24, 14, 47 and 132 unigenes were characterized to be involved in Toll, IMD, JAK-STAT and MAPK pathways, respectively. This is the first systematical transcriptome analysis of components relating to innate immune pathways in E. sinensis. Functional genes and putative pathways identified here will contribute to better understand immune system and prevent various diseases in crab.


Dissociation of suction blister roof epidermis with trypsin and desoxyribonuclease into viable single cells.
Human epidermis, obtained in vivo by the suction blister method, was dissociated with trypsin and desoxyribonuclease into a single-cell suspension. Autoradiographic analysis of the blister roof epidermis and of the epidermal cell suspension was performed to show that neither the suction procedure nor the enzymatic dissociation affected DNA synthesis of the epidermal cells.


[Lung function findings in workers in the rubber industry].
Chronic obstructive lung disease is common in workers in the rubber industry. Because of the close relation between hyperreactivity of the airways (HR) and the annual decline in FEV1 we measured HR in 89 healthy workers of a big rubber plant. Three groups were formed (control, latex production, rubber production). The prevalence of HR was that of a healthy general population (PC 20 FEV1 less than 0.2% Methacholin in 3 cases). In the lower Methacholin range a separation between all groups was possible.


Atrial-esophageal fistula shown by transthoracic echocardiogram.
Nontraumatic atrial-esophageal fistula is a catastrophic problem usually diagnosed postmortem and almost invariably fatal. We report the first case of a patient in whom the diagnosis of atrial-esophageal fistula was made from a transthoracic echocardiography antemortem. Echocardiography showed multiple microbubbles in the left atrium and ventricle emanating from the posterior aspect of the left atrium adjacent to the pulmonary veins. The literature is reviewed and the significance of the case and the echocardiogram is discussed.


Oxidative stress in oral diseases.
Oxidative species, including reactive oxygen species (ROS), are components of normal cellular metabolism and are required for intracellular processes as varied as proliferation, signal transduction, and apoptosis. In the situation of chronic oxidative stress, however, ROS contribute to various pathophysiologies and are involved in multiple stages of carcinogenesis. In head and neck cancers specifically, many common risk factors contribute to carcinogenesis via ROS-based mechanisms, including tobacco, areca quid, alcohol, and viruses. Given their widespread influence on the process of carcinogenesis, ROS and their related pathways are attractive targets for intervention. The effects of radiation therapy, a central component of treatment for nearly all head and neck cancers, can also be altered via interfering with oxidative pathways. These pathways are also relevant to the development of many benign oral diseases. In this review, we outline how ROS contribute to pathophysiology with a focus toward head and neck cancers and benign oral diseases, describing potential targets and pathways for intervention that exploit the role of oxidative species in these pathologic processes.


Rapid colorimetry of zinc in seminal fluid.
This colorimetric method for determination of zinc in seminal liquid is based on the reaction between zinc and 4-(2-pyridylazo)resorcinol in a buffered solution at pH 9.5. It is very simple, fast (approximately equal to 10 min), and economical. It can be used to determine zinc in "whole" semen, seminal plasma, or isolated spermatozoa. We verified its accuracy for sample concentrations up to 0.4 g/L by comparison with a reference method based on atomic absorption spectroscopy of acidic wet-ashed samples. Calcium and magnesium do not interfere, even in concentrations exceeding the physiological values. Between-run precision at a normal concentration of 0.14 g/L is about +/- 7 mg/L; within-run precision at the same concentration is about +/- 2 mg/L.


Management of leakage and stenosis after sleeve gastrectomy.
Sleeve gastrectomy is one of the most commonly performed procedures in obesity and metabolic operation with leakage and stenosis being serious complications. The management of these complications is challenging, with different operative options available. The aim of our study was to evaluate the incidence and management strategies of leakage and stenosis after sleeve gastrectomy at our institution and to compare our outcomes with those previously reported in the literature. We conducted a retrospective analysis of the medical records of 49 patients treated for leakage and/or stenosis after laparoscopic sleeve gastrectomy at our Centre of excellence for bariatric and metabolic operation, including 25 patients referred to our department from other hospitals. Outcomes were evaluated using descriptive statistics. Our study cohort consisted of 49 obese patients, 33 females (66%), with a mean ± standard deviation age of 50 ± 11 years, and body mass index at the time of laparoscopic sleeve gastrectomy, 51 ± 8 kg/m2. Postsleeve gastrectomy leakage was identified in 27 patients (55%), stenosis in 13 (27%), and combined leakage and stenosis in 9 (18%). Leakage, stenosis, and combined leakage/stenosis were managed successfully by interventional methods in 85%, 15%, and 22% of cases, respectively. Conversion into another procedure provided a successful rescue operation for other patients. We had a 0% mortality rate. Most patients with leakage were managed successfully with interventional methods. The majority of patients with stenosis or both leakage and stenosis required rescue operation.


Foliar Exposure of Cu(OH)2 Nanopesticide to Basil ( Ocimum basilicum): Variety-Dependent Copper Translocation and Biochemical Responses.
In this study, low and high anthocyanin basil ( Ocimum basilicum) varieties (LAV and HAV) were sprayed with 4.8 mg Cu/per pot from Cu(OH)2 nanowires, Cu(OH)2 bulk (CuPro), or CuSO4 and cultivated for 45 days. In both varieties, significantly higher Cu was determined in leaves of CuSO4 exposed plants (691 and 672.6 mg/kg for LAV and HAV, respectively); however, only in roots of HAV, Cu was higher, compared to control ( p ≤ 0.05). Nanowires increased n-decanoic, dodecanoic, octanoic, and nonanoic acids in LAV, but reduced n-decanoic, dodecanoic, octanoic, and tetradecanoic acids in HAV, compared with control. In HAV, all compounds reduced eugenol (87%), 2-methylundecanal (71%), and anthocyanin (3%) ( p ≤ 0.05). In addition, in all plant tissues, of both varieties, nanowires and CuSO4 reduced Mn, while CuPro increased chlorophyll contents, compared with controls ( p ≤ 0.05). Results suggest that the effects of Cu(OH)2 pesticides are variety- and compound-dependent.


Ligand-induced down-regulation of the cannabinoid 1 receptor is mediated by the G-protein-coupled receptor-associated sorting protein GASP1.
The cannabinoid 1 receptor (CB1R) is one of the most abundant seven transmembrane (7TM) spanning/G-protein-coupled receptors in the central nervous system and plays an important role in pain transmission, feeding, and the rewarding effects of cannabis. Tolerance to cannabinoids has been widely observed after long-term use, with concomitant receptor desensitization and/or down-regulation depending on the brain region studied. Several CB1R agonists promote receptor internalization after activation, but the postendocytic sorting of the receptor has not been studied in detail. Utilizing human embryonic kidney (HEK293) cells stably expressing the CB1R and primary cultured neurons expressing endogenous CB1R, we show that treatment with cannabinoid agonists results in CB1R degradation after endocytosis and that the G-protein-coupled receptor-associated sorting protein GASP1 plays a major role in the postendocytic sorting process. Thus, these results may identify a molecular mechanism underlying tolerance and receptor down-regulation after long-term use of cannabinoids.


Tissue selectivity and calcium dependence of contractile responses to endothelin.
The tissue selectivity and calcium dependence of endothelin, a potent vasoconstrictor peptide obtained from endothelial cells, were investigated in a number of rat and guinea pig tissues. Endothelin produced a significant dose-dependent contraction of rat tissues with the following rank order of efficacy: aorta greater than portal vein greater than trachea much greater than vas deferens = lung parenchyma much greater than bladder. In the rat atrium and ventricle, endothelin possessed positive inotropic effects at low doses and arrhythmogenic effects at high doses. Endothelin also produced a significant contraction of guinea pig lung parenchyma and induced relaxations of guinea pig taenia coli precontracted with potassium chloride. The aortic ring contractile response to endothelin was characterized by both rapid and slow phases of contraction. The rapid phase of contraction was abolished by removal of extracellular calcium or preincubation of tissues with the dihydropyridine calcium channel antagonist, nifedipine. Removal of the endothelium from aortic rings resulted in an increase of approximately 10-fold in the contractile potency of endothelin. In comparison, the potency of the dihydropyridine calcium channel activator, (-)-S-BAY K 8644, was increased approximately 15-fold by the same treatment. These findings suggest that endothelin, while displaying some selectivity as a vascular smooth muscle spasmogen, is a general smooth and cardiac muscle spasmogen which utilizes both intra- and extracellular sources of calcium to support its contractions.


Predicted versus actual intraocular lens power in silicon-oil-filled eyes undergoing cataract extraction using automated intraoperative retinoscopy.
To compare predicted intraocular lens (IOL) power obtained with adjusted ultrasound biometry versus actual power obtained with automated intraoperative retinoscopy (AIR) in eyes undergoing combined cataract extraction and silicon oil removal in the same session. Fifty eyes with significant cataract; requiring silicon removal were included. Preoperative ultrasonic biometry with adjusted velocity (980 m/s) was recorded. After silicon removal, AIR was done and IOL power was calculated and inserted. Postoperative refraction was recorded up to 3 months. AIR was successfully obtained in all eyes. Significant correlation (p = 0.000, R = 0.91) was detected between mean power of predicted (15.8 ± 8.4) and implanted IOL (11.7 ± 8.5). Mean postoperative refraction was +0.53 ± 0.31 at 1 week, +0.40 ± 0.35 at 1 month and +0.12 ± 0.20 at 3 months. The difference was statistically significant in all time intervals. Myopic shift occurred in 37% of eyes at the third month. AIR in combined cataract extraction and silicon oil removal is easy and provides predictable outcome in all eyes. It represents a bypass to all methods of biometry based on axial length measurement. Future correction formula based on adjusted ultrasound velocity can be a simple alternative and predictable method.


Single-incision versus 3-port laparoscopic cholecystectomy in symptomatic gallstones: A prospective randomized study.
Laparoscopic cholecystectomy is the standard treatment for symptomatic gallbladder disease. Single-incision laparoscopic surgery was developed with the aim of decreasing the invasiveness of conventional laparoscopy. The aim of this study was to compare the clinical outcome of single-incision laparoscopic cholecystectomy with 3-port laparoscopic cholecystectomy. From February 2014 to September 2016, 187 patients with symptomatic cholecystolithiasis were randomized to a single-incision laparoscopic cholecystectomy group (89 patients) or a 3-port laparoscopic cholecystectomy group (98 patients). The primary outcomes were a postoperative pain score (at 6 hours and 1 day) and patients of complications, while the secondary outcomes were operative time, estimated blood loss, opioid requirements, duration of hospital stay, and patient satisfaction with aesthetic effects. When comparing 3-port laparoscopic cholecystectomy and single-incision laparoscopic cholecystectomy, there were differences in the (mean ± standard deviation) operative time (58.9 ± 18.6 minutes vs 45.2 ± 11.8 minutes; P < .001), success rate (93% vs 99%; P < .01), conversion rate (7% vs 1%; P < .001), and aesthetic score (7.9 ± 1.6 vs 6.7 ± 1.4; P = .008). There were no statistically significant differences in estimated blood loss, postoperative pain, opioid requirement, complications, and hospital stay between both groups. Single-incision laparoscopic cholecystectomy is a safe and feasible procedure in selected patients. The main advantage is the superior aesthetic results, while the main disadvantage is a greater operative time with some technical difficulties.


Comparative exploration of free fatty acids in donkey colostrum and mature milk based on a metabolomics approach.
Donkey milk is an ideal substitute for human milk owing to its similar composition. Nevertheless, changes in the composition and related metabolic pathways of free fatty acids (FFA) in donkey milk between colostrum and mature milk have not been studied well. In this study, metabolomic methods based on gas chromatography tandem time-of-flight mass spectrometry (GC-TOF-MS) were used to explore and compare FFA in donkey colostrum (DC) and mature milk (DMM). A total of 24 FFA were characterized and quantified in DC and in DMM. Of these, 11 FFA differed significantly between DC and DMM, and there were 6 key differential metabolic pathways. These results demonstrated that the composition of FFA in donkey milk changed with lactation stage. The interactions and metabolic pathways were further analyzed to explore the mechanisms that altered the milk composition during lactation. Our results provide insights into the changes in milk of the nonruminant mammals during lactation. The results provide practical information for the development of donkey milk products and a foundation for future research on specific milk nutrients.


[Impact of obstructive sleep apnea on the long-term cardiovascular outcomes in patients with acute coronary syndrome].
Objective: To investigate the impact of obstructive sleep apnea (OSA) on long-term cardiovascular outcomes in patients with acute coronary syndrome (ACS). Methods: This is a single-center, prospective cohort study. Between June 2015 to January 2020, consecutive ACS patients hospitalized at Beijing Anzhen Hospital, Capital Medical University were enrolled. All patients underwent portable sleep breathing monitoring, and they were then divided into moderate/severe OSA group (apnea-hypopnea index (AHI)≥15 events/hour) and no/mild OSA group (AHI<15 events/hour). The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, ischemia-driven revascularization and hospital admission for unstable angina or heart failure. MACCE were compared yearly by the log-rank test. Multivariable Cox regression analyses were performed to determine the independent predictors of MACCE. Results: A total of 1 927 patients with ACS were enrolled, including 1 629 males (84.5%), aged (56.4±10.5) years. Moderate/severe OSA was present in 1 014 (52.6%) patients. Compared with no/mild OSA group, moderate/severe OSA group exhibited a higher body mass index (P<0.05). Hypertension, prior PCI were more prevalent in moderate/severe OSA group (both P<0.05). The difference of ACS category between the two groups was statistically significant (P=0.021). The rate of patients who underwent PCI and the number of stents were higher in the moderate/severe OSA group. During a 5-year follow-up (median 2.9 years (IQR 1.5-3.6 years)), the cumulative incidence of MACCE was significantly higher in the moderate/severe OSA group than in the no/mild OSA group (34.0% vs. 24.0%, HR=1.346, 95%CI 1.100-1.646, log-rank P=0.004). The cumulative incidence of MACCE remained statistically higher at 4 and 5 year in the moderate/severe OSA group as compared to the no/mild OSA group (33.3% vs. 22.9%, HR=1.397, 95%CI 1.141-1.710, log-rank P=0.001; 34.0% vs. 24.0%, HR=1.341, 95%CI 1.096-1.640, log-rank P=0.004, respectively). Multivariate analysis showed that moderate/severe OSA (HR=1.312, 95%CI 1.054-1.631, P=0.015) was an independent predictor of long-term MACCE in ACS patients. Conclusions: Moderate/severe OSA is observed in more than 52% ACS patients. Moderate/severe OSA is an independent predictor of long-term MACCE.


PKM2 allosteric converter: A self-assembly peptide for suppressing renal cell carcinoma and sensitizing chemotherapy.
Stronger intrinsic Warburg effect and resistance to chemotherapy are the responses to high mortality of renal cell carcinoma (RCC). Pyruvate kinase M2 (PKM2) plays an important role in this process. Promoting PKM2 conversion from dimer to tetramer is a critical strategy to inhibit Warburg effect and reverse chemotherapy resistance. Herein, a PKM2 allosteric converter (PAC) is constructed based on the "in vivo self-assembly" strategy, which is able to continuously stimulate PKM2 tetramerization. The PAC contains three motifs, a serine site that is protected by enzyme cleavable β-N-acetylglucosamine, a self-assembly peptide and a AIE motif. Once PAC nanoparticles reach tumor site via the EPR effect, the protective and hydrophilic β-N-acetylglucosamine will be removed by over-expressed O-GlcNAcase (OGA), causing self-assembled peptides to transform into nanofibers with large serine (PKM2 tetramer activator) exposure and long-term retention, which promotes PKM2 tetramerization continuously. Our results show that PAC-induced PKM2 tetramerization inhibits aberrant metabolism mediated by Warburg effect in cytoplasm. In this way, tumor proliferation and metastasis behavior could be effectively inhibited. Meanwhile, PAC induced PKM2 tetramerization impedes the nuclear translocation of PKM2 dimer, which restores the sensitivity of cancer cells to first-line anticancer drugs. Collectively, the innovative PAC effectively promotes PKM2 conversion from dimer to tetramer, and it might provide a novel approach for suppressing RCC and enhancing chemotherapy sensitivity.


The activation of the alternative pathway C3 convertase by human plasma kallikrein.
Human plasma kallikrein can replace factor D for the activation of the alternative pathway C3 convertase of human complement. The factor B cleavage patterns by factor D and kallikrein are indistinguishable. The ability of kallikrein to cleave factor B is influenced by the magnesium ion concentration and the C3b concentration. Factor D is about ten-fold more effective on a molar basis, for the alternative pathway C3 convertase activation than is kallikrein. The physiological role of the action of kallikrein on the alternative pathway C3 convertase is discussed.


Obesity is associated with increased arterial stiffness from adolescence until old age.
To our knowledge, only two previous studies have investigated the age dependence of the relationship between the characteristics of large arteries and excessive body weight. We therefore investigated whether the relationship between arterial stiffness and body mass index (BMI) was consistent across an age range from 10 to 86 years. Using a cross-sectional population-based design, we randomly recruited 1306 individuals (median age 43.9 years; 50.5% women). Using a wall-tracking ultrasound system, we measured the properties of the carotid, femoral and brachial arteries and carotid-femoral pulse wave velocity. We analysed men and women separately while adjusting for significant covariates, including age, mean arterial pressure, heart rate, current smoking, alcohol intake and use of antihypertensive drugs. Before and after adjustment, arterial diameter increased with BMI in all territories, with an opposite trend for arterial distensibility. In men and women, the relationships of brachial and femoral properties with BMI were consistent across the whole age range. In men and women, carotid distensibility decreased more with BMI at young than old age. In middle-aged and older women, but not in men of any age, pulse wave velocity increased with higher BMI. Across a wide age range, the diameter and stiffness of muscular arteries increased with higher BMI. In elastic arteries, the relationship between arterial stiffness and BMI was more complex and varied with sex and age. The mechanisms underlying the influence of adiposity on the properties of muscular and elastic arteries and the reversibility of these associations by weight reduction at young age need further clarification.


Campylobacter species in animal, food, and environmental sources, and relevant testing programs in Canada.
Campylobacter species, particularly thermophilic campylobacters, have emerged as a leading cause of human foodborne gastroenteritis worldwide, with Campylobacter jejuni, Campylobacter coli, and Campylobacter lari responsible for the majority of human infections. Although most cases of campylobacteriosis are self-limiting, campylobacteriosis represents a significant public health burden. Human illness caused by infection with campylobacters has been reported across Canada since the early 1970s. Many studies have shown that dietary sources, including food, particularly raw poultry and other meat products, raw milk, and contaminated water, have contributed to outbreaks of campylobacteriosis in Canada. Campylobacter spp. have also been detected in a wide range of animal and environmental sources, including water, in Canada. The purpose of this article is to review (i) the prevalence of Campylobacter spp. in animals, food, and the environment, and (ii) the relevant testing programs in Canada with a focus on the potential links between campylobacters and human health in Canada.


What systems biology can tell us about disease.
A recent debate has touched upon the question of whether diseases can be understood as dysfunctional mechanisms or whether there are "pathological" mechanisms that deserve to be investigated and explained independently (Nervi 2010; Moghaddam-Taaheri 2011). Here I suggest that both views tell us something important about disease but that in many instances only a systemic view can shed light on the relationship between physiology and pathology. I provide examples from the literature in systems biology in support of my position. As a result of my analysis, I conclude that a perspective narrowly focusing on mechanisms is insufficient if the goal is to get a comprehensive picture of disease.


Corneal donation within palliative care: a review of the literature.
Corneal donation occurs infrequently within palliative care, even though the majority of the public say they are in favour of donating organs and tissue after death. One of the roles of the health professional is to provide patients with the necessary information to make choices, and this should include the option of donating their corneas should they so wish. This literature review explores how the subject can be raised in a systematic manner within palliative care. It looks at the potential benefits and dangers of involving the patient in such discussions, and the effects on the families. Practical issues, such as when to raise the issue, are also considered. Finally, the review discusses the implications for nursing practice and research.


Sensorineural hearing loss of noise in members of aviation club of Larissa (Greece).
To evaluate the clinical and audiometric characteristics of noise by an one-engine Cessna (1300-1750 RPM), by ultra light aircrafts and different types of air modeling products which induce hearing loss in air modeling members of Aviation club of Larissa in Greece. During the past 2 years members in the aviation club were referred for clinical and audiological examination in the ENT Department of hearing and speech and underwent a personal interview with a specific questionnaire. No one of the examined members was using individual protection systems during aviation activities. From all members examined, a 30% had an audiogram with a slope in high frequencies, not attributed to presbyacousis and had experienced at least one symptom associated with hearing disturbance. Air modeling members in aviation club that are exposed to noise during aviation activities without protection are at high risk of noise induced hearing loss.


It's a Man's World? Gender Spillover Effects on Performance in a Male-Dominated Industry.
Getting more women into male-dominated industries has become the nucleus of public debate in many industrialized countries. However, it is still not clear how growing female representation impacts the individual performance of workers in these sectors. The research setting of this study is the Norwegian oil industry as a typically male-dominated sector. Using a fixed-effects regression model, the present paper investigates two different constellations: 1) how growing female representation impacts the individual performance of workers at the same hierarchical level (within-ranks); 2) how growing female representation at the next highest rank impacts the performance of subordinated workers (downward-flowing). Consistent with prevailing theory, the within-ranks analysis reveals that the performance of men in relation to a higher share of female peers follows a cubic pattern. This shows that men's performance is the highest in gender-balanced teams. For women, this relationship cannot be confirmed. In terms of downward-flowing effects, female supervisors in this particular industry are estimated to have a negative effect on the performance of both, men and women. This result on negative downward-flowing effects requires a deeper analysis on the corporate cultural background.


Monogalactosyldiacylglycerols as Host Recognition Cues for Western Corn Rootworm Larvae (Coleoptera: Chrysomelidae).
Monogalactosyldiacylglycerol (MGDG) was identified as a host recognition cue for larvae of the western corn rootworm Diabrotica virgifera virgifera LeConte. An active glycolipid fraction obtained from an extract of germinating maize roots was isolated with thin layer chromatography using a bioassay-driven approach. When analyzed with LC-MS (positive ion scanning), the assay-active spot was found to contain four different MGDG species: 18:3-18:3 (1,2-dilinolenoyl), 18:2-18:3 (1-linoleoyl, 2-linolenoyl), 18:2-18:2 (1,2-dilinoleoyl), and 18:2-16:0 (1-linoleoyl, 2-palmitoyl). A polar fraction was also needed for activity. When combined with a polar fraction containing a blend of sugars (glucose:fructose:sucrose:myoinositol), the isolated MGDG elicited a unique tight-turning behavior by neonate western corn rootworm larvae that is indicative of host recognition. In behavioral bioassays where disks treated with the active blend were exposed to successive sets of rootworm larvae, the activity of MGDG increased over four exposures, suggesting that larvae may be responding to compounds produced after enzymatic breakdown of MGDG. In subsequent tests with synthetic blends composed of theoretical MGDG-breakdown products, larval responses to four synthetic blends were not significantly different (P<0.5) than the response to isolated MGDG. GC-MS analysis showed modest increases in the amounts of the 16:0, 18:0, and 18:3 free fatty acids released from MGDG after a 30-min exposure to rootworm larvae, which is consistent with the enzymatic breakdown hypothesis.


Tumor-associated autoantibody signature for the early detection of gastric cancer.
Autoantibodies against tumor-associated antigens are very attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer because of their specificity and stability in the sera. In our study, we applied T7 phage display-based serological analysis of recombinant cDNA expression libraries technique to identify a representative set of antigens eliciting humoral responses in patients with gastric cancer (GC), produced phage-antigen microarrays and exploited them for the survey of autoantibody repertoire in patients with GC and inflammatory diseases. We developed procedures for data normalization and cutoff determination to define sero-positive signals and ranked them by the signal intensity and frequency of reactivity. To identify autoantibodies with the highest diagnostic value, a 1,150-feature microarray was tested with sera from 100 patients with GC and 100 cancer-free controls, and then the top-ranked 86 antigens were used for the production of focused array that was tested with an independent validation set comprising serum samples from 235 patients with GC, 154 patients with peptic ulcer and gastritis and 213 healthy controls. The receiver operating characteristic curve analysis showed that 45-autoantibody signature could discriminate GC and healthy controls with area under the curve (AUC) of 0.79 (59% sensitivity and 90% specificity), GC and peptic ulcer with AUC of 0.76 and GC and gastritis with AUC of 0.64. Moreover, it could detect early GC with equal sensitivity than advanced GC. Interestingly, the autoantibody production did not correlate with histological type, H. pylori status, grade, localization and size of the primary tumor, whereas it appeared to be associated with the metastatic disease.


mRNA expression pattern of multiple members of connexin gene family in normal and abnormal fetal gonads in mouse.
Gap junctions are made of connexin (Cx) molecules and provide communications between adjacent cells through which small molecules (<1kDa) move between cytoplasms. The connexin gene family consists of at least 17 members. Gap junctions play important roles in ovarian and testicular function. Connexin 43 (Cx43) knockout mouse is a model for developmentally impaired fetal gonads. The aim of the current study was twofold: (a) to analyze mRNA expression pattern of multiple members of connexin gene family in normal fetal gonads; (b) to investigate any alteration of mRNA expression of connexins in developmentally impaired fetal gonads. The study was conducted in normal gonads obtained from 17.5 dpc wildtype (Cx43+/+) and heterozygote (Cx43+/-) fetuses and in developmentally impaired gonads obtained from 17.5 dpc knockout (Cx43-/-) fetuses. The mRNA expression pattern of connexins (Cx26, Cx30.3, Cx31, Cx31.1, Cx32, Cx37, Cx40, Cx43, Cx45, Cx46 and Cx50) was analyzed by RT-PCR. The mRNA transcripts for Cx32 and Cx50 were absent in fetal testis of all the genotypes, and the transcripts for Cx26, Cx30.3, Cx31.1, Cx32, Cx40, Cx46 and Cx50 were absent in fetal ovary of all the genotypes. The transcripts for Cx43 showed expression in Cx43+/+ and Cx43+/- gonads and were absent in Cx43-/- gonads, as expected. Additionally, the mRNA transcripts for 8 more connexins (Cx26, Cx30.3, Cx31, Cx31.1, Cx37, Cx40, Cx45 and Cx46) showed expression in Cx43+/+ and Cx43+/- fetal testes, but the transcripts for only 4 connexins (Cx26, Cx37, Cx40 and Cx45) showed expression in Cx43-/- fetal testis. In fetal ovary, the mRNA transcripts for 3 more connexins (Cx31, Cx37 and Cx45) were expressed in all the genotypes. In summary, from the mRNA expression analysis of 11 members of connexin, gene family in 17.5 dpc fetal gonads, besides the expression of Cx43, 8 additional connexins were expressed in normal fetal testis but only 4 connexins were expressed in developmentally impaired testis. The fetal ovary showed the expression of 3 additional connexins besides the expression of Cx43. In developmentally impaired fetal ovary, only Cx43 was not expressed as expected but other three connexins were expresed. The study may be useful in interpreting human testis defects in infertility cases.


An epidemiological survey of occlusal anomalies among secondary school children in Ibadan, Nigeria.
To assess the prevalence of some of the occlusal anomalies in Ibadan, Nigeria, an epidemiological survey of 644 secondary school children aged 12-18 years (mean age, 14.73 +/- 1.17 S.D.) was done. The sample consisting of 341(53%) males and 303(47%) females was randomly selected. About 66% were from the middle social class while 34% belonged to the working class. Scissors bite recorded the highest prevalence (6.7%) and cross bite was next with 2.2%. No statistically significant associations were found between the occlusal anomalies and socio-economic class (p > 0.05). No statistically significant gender differences were found in relation to the anomalies (p > 0.05). The prevalences of the occlusal anomalies studied were generally lower than those among northern Nigerian children.


Comparison of the efficacy of small and large-bore thoracostomy tubes for pleural space evacuation in canine cadavers.
To determine if there is a difference in the amounts of air (A), low-viscosity fluid (LV), or high-viscosity fluid (HV) that can be aspirated from the pleural cavity of canine cadavers using small-bore (SB) or large-bore (LB) thoracostomy tubes. Prospective experimental ex vivo study. University teaching hospital. Thirty-six canine cadavers. Each cadaver was randomly assigned to 1 of 6 groups (SB-A, LB-A, SB-LV, LB-LV, SB-HV, LB-HV). In each cadaver bilateral thoracostomy tubes (either SB or LB) were placed and 20 mL/kg of air, LV fluid, or HV fluid was instilled via 1 thoracostomy tube. Both tubes were aspirated and the volume aspirated was recorded and analyzed as a percentage of instilled air or fluid volume. The procedure was repeated on the contralateral hemithorax. There was no significant difference in air or fluid recovery when SB and LB groups were compared. Median (range) air recovery volumes in the SB-A and LB-A groups were 101.5% (94.4-115.8%) and 102.8% (94.1-107.8%), respectively (P = 0.898). Recovery of LV fluid was 93.5% (79.2-99.0%) for SB-LV and 85.8% (77.1-101.8%) for LB-LV cadavers (P = 0.305) and recovery percentages of HV fluid were 92.6% (86.1-96.2%) and 91.4% (74.2-96.4%) for SB-HV and LB-HV groups, respectively (P > 0.999). There was no significant difference between SB and LB groups when all substances were combined (94.1% [79.2-115.8%] and 93.5% [74.2-107.8%], respectively, P = 0.557). SB and LB thoracostomy tubes demonstrated similar efficacy in removing known amounts of air, LV fluid, and HV fluid from the pleural space of canine cadavers. Further study is necessary to determine if SB and LB thoracostomy tubes demonstrate similar efficacy in clinical veterinary patients.


[Determination of IgG toxoplasma antibodies using ELISA with uniform serum dilutions].
The ELISA reaction with uniform serum dilution (1:400) for assessment of toxoplasmatic antibodies class IgG agreed in 100% when compared with commercial kits (VIRELISA and GULL Lab.). Both these tests disagreed with the standard complement fixation reaction in 7.5% of the specimens. This qualitative disagreement was confirmed also in a group of 400 sera where 7.14% of CFR negative specimens reacted positively in the described ELISA reaction. Quantitative correlation of results of CFR and ELISA IgG displays the usual scatter of values. Therefore individual CFR titres cannot be matched unequivocally with titres of optic density and thus it is not possible to assess empirically the stage of infection. To assess the stage of infection it is therefore necessary to make a supplementary assessment of IgM antibodies. In cases detected in time the decision can be based on a rise of IgG values in paired serum specimens examined in one reaction. Dynamics of formation of IgG antibodies and their chronological sequence with IgM antibodies displayed a typical course in patients with clinical toxoplasmosis. The described reaction is the basis of commercially manufactured kits ELISA IgG Toxo Micro II.


Differential developmental effects of acute hypoxia on the rabbit atrioventricular conduction axis.
The differential developmental effects of hypoxia on antegrade fast and slow and retrograde conduction through the atrioventricular junction are unknown. This study describes the effects of hypoxia on fast and slow antegrade atrioventricular node, infra-Hisian and retrograde conduction in immature and mature hearts during premature pacing protocols in excise, perfused adult and neonatal rabbits. The results are: (1) antegrade conduction delay through the atrioventricular node is the same developmentally, but delay through the His-Purkinje system is greater in adults; (2) hypoxia reduces the extra delay in the His-Purkinje system in adults; (3) fast atrioventricular node conduction is more sensitive to hypoxia in neonates than in adults, and slow atrioventricular node conduction is more sensitive to hypoxia in adults than in neonates, and (4) retrograde atrioventricular node conduction is more resistant to hypoxia in neonates than in adults.


A stochastic model to simulate the growth of anchorage dependent cells on flat surfaces.
A stochastic model is proposed to simulate the growth of anchorage dependent cells on a flat surface. The model, based on representing the cell shapes on the surface as external irregular polygons with the nuclei distributed as a set of Poisson points (producing a modified Voronoi tessellation of 2 space) and incorporating a distribution function to describe cell division of the perimeter cells of the colony, provides data not only on population dynamics but also on the patterns produced by clusters of cells in the colony. These patterns produced by the model are qualitatively similar to observations reported for some cell cultures. The periods of induction, rapid growth, and decreasing growth asymptoting to zero as confluence is reached are predicted by the model. Quantitative comparison with published experimental data for this is good. The specific growth rate computed for the period of rapid growth predicted by the model is dependent on the distribution function describing the cell division time. As the standard deviation of this increases, the specific growth rate decreases as with a consequent increase in time to achieve confluence. The removal of cells from the colony by shear forces or death is considered in the model. As the probability for removal increases, the cell density at confluence and specific growth rate decrease. The clusters of cells, patterns, in the colony are very sensitive to cell removal. By analyzing these patterns in experiments, an estimate of cell removal can be made. The areas covered by cells on a substrate are fractal patterns. The fractal dimension is always greater than 1 and is a function of the removal probability.


Predictive Structure and Topology of Peroxisomal ATP-Binding Cassette (ABC) Transporters.
The peroxisomal ATP-binding Cassette (ABC) transporters, which are called ABCD1, ABCD2 and ABCD3, are transmembrane proteins involved in the transport of various lipids that allow their degradation inside the organelle. Defective ABCD1 leads to the accumulation of very long-chain fatty acids and is associated with a complex and severe neurodegenerative disorder called X-linked adrenoleukodystrophy (X-ALD). Although the nucleotide-binding domain is highly conserved and characterized within the ABC transporters family, solid data are missing for the transmembrane domain (TMD) of ABCD proteins. The lack of a clear consensus on the secondary and tertiary structure of the TMDs weakens any structure-function hypothesis based on the very diverse ABCD1 mutations found in X-ALD patients. Therefore, we first reinvestigated thoroughly the structure-function data available and performed refined alignments of ABCD protein sequences. Based on the 2.85 Å resolution crystal structure of the mitochondrial ABC transporter ABCB10, here we propose a structural model of peroxisomal ABCD proteins that specifies the position of the transmembrane and coupling helices, and highlight functional motifs and putative important amino acid residues.


Double administration of self-complementary AAV9NDUFS4 prevents Leigh disease in Ndufs4-/- mice.
Leigh disease, or subacute necrotizing encephalomyelopathy, a genetically heterogeneous condition consistently characterized by defective mitochondrial bioenergetics, is the most common oxidative-phosphorylation related disease in infancy. Both neurological signs and pathological lesions of Leigh disease are mimicked by the ablation of the mouse mitochondrial respiratory chain subunit Ndufs4-/-, which is part of, and crucial for, normal Complex I activity and assembly, particularly in the brains of both children and mice. We previously conveyed the human NDUFS4 gene to the mouse brain using either single-stranded adeno-associated viral 9 recombinant vectors or the PHP.B adeno-associated viral vector. Both these approaches significantly prolonged the lifespan of the Ndufs4-/- mouse model but the extension of the survival was limited to a few weeks by the former approach, whereas the latter was applicable to a limited number of mouse strains, but not to primates. Here, we exploited the recent development of new, self-complementary adeno-associated viral 9 vectors, in which the transcription rate of the recombinant gene is markedly increased compared with the single-stranded adeno-associated viral 9 and can be applied to all mammals, including humans. Either single intra-vascular or double intra-vascular and intra-cerebro-ventricular injections were performed at post-natal Day 1. The first strategy ubiquitously conveyed the human NDUFS4 gene product in Ndufs4-/- mice, doubling the lifespan from 45 to ≈100 days after birth, when the mice developed rapidly progressive neurological failure. However, the double, contemporary intra-vascular and intra-cerebroventricular administration of self-complementary-adeno-associated viral NDUFS4 prolonged healthy lifespan up to 9 months of age. These mice were well and active at euthanization, at 6, 7, 8 and 9 months of age, to investigate the brain and other organs post-mortem. Robust expression of hNDUFS4 was detected in different cerebral areas preserving normal morphology and restoring Complex I activity and assembly. Our results warrant further investigation on the translatability of self-complementary-adeno-associated viral 9 NDUFS4-based therapy in the prodromal phase of the disease in mice and eventually humans.


Serological and molecular studies of a novel virus isolate causing yellow mosaic of Patchouli [Pogostemon cablin (Blanco) Benth].
Here we have identified and characterized a devastating virus capable of inducing yellow mosaic on the leaves of Patchouli [Pogostemon cablin (Blanco) Benth]. The diagnostic tools used were host range, transmission studies, cytopathology, electron microscopy, serology and partial coat protein (CP) gene sequencing. Evidence from biological, serological and sequence data suggested that the causal virus belonged to genus Potyvirus, family Potyviridae. The isolate, designated as Patchouli Yellow Mosaic Virus (PaYMV), was transmitted through grafting, sap and the insect Myzus persicae (Sulz.). Flexuous rod shaped particles with a mean length of 800 nm were consistently observed in leaf-dip preparations from natural as well as alternate hosts, and in purified preparation. Cytoplasmic cylindrical inclusions, pinwheels and laminar aggregates were observed in ultra-thin sections of infected patchouli leaves. The purified capsid protein has a relative mass of 43 kDa. Polyclonal antibodies were raised in rabbits against the coat protein separated on SDS - PAGE; which were used in ELISA and western blotting. Using specific antibodies in ELISA, PaYMV was frequently detected at patchouli plantations at Lucknow and Bengaluru. Potyvirus-specific degenerate primer pair (U335 and D335) had consistently amplified partial CP gene from crude preparations of infected tissues by reverse transcription polymerase chain reaction (RT-PCR). Comparison of the PCR product sequence (290 bp) with the corresponding regions of established potyviruses showed 78-82% and 91-95% sequence similarity at the nucleotide and amino acid levels, respectively. The results clearly established that the virus under study has close homology with watermelon mosaic virus (WMV) in the coat protein region and therefore could share a common ancestor family. Further studies are required to authenticate the identity of PaYMV as a distinct virus or as an isolate of WMV.


Nursing undergraduates' experiences of a simulation-centred educational program in hospice care in Macao: A qualitative research.
The study aimed to explore the experiences of nursing undergraduates participating in a simulation-centred educational program in hospice care in Macao, China. This descriptive qualitative study was based on the data collected through semi-structured individual interviews. Seventeen nursing undergraduates in Macao, China who attended the simulation-centred program in hospice care participated in this qualitative from November to December 2020. This program included three parts: introduction to hospice care (2 h), management of terminal symptoms (10 h), and hospice situation simulations (6 h). The interview data were analyzed using qualitative content analysis. This study revealed two themes and six sub-themes. Theme 1 was developing competencies in caring for dying patients and their families, which included four subcategories of sensitivity to patients' needs, knowledge of hospice care, skills of symptom control and comfort supply, and communication skills. Theme 2 was improving the ability to self-care and support colleagues, which included two subcategories of reflection on life and death and sharing and supporting among colleagues. This program improved the competency of nursing undergraduates in hospice care and participants' learning experience was good.


A combined proteomic and transcriptomic analysis of slime secreted by the southern bottletail squid, Sepiadarium austrinum (Cephalopoda).
Sepiadarium austrinum, the southern bottletail squid, is a small squid that inhabits soft sediments along Australia's south-east coast. When provoked, it rapidly secretes large volumes of slime, presumably as a form of chemical defense. We analyzed the proteomic composition of this slime using tandem mass spectrometry and transcriptomics and found that it was remarkably complex with 1735 identified protein groups (FDR:0.01). To investigate the chemical defense hypothesis we performed an Artemia toxicity assay and used sequence analysis to search for toxin-like molecules. Although the slime did not appear to be toxic to Artemia we found 13 proteins in slime with the hallmarks of toxins, namely cysteine richness, short length, a signal peptide and/or homology to known toxins. These included three short (80-130AA) cysteine rich secreted proteins with no homology to proteins on the NCBI or UniProt databases. Other protein families found included, CAP, phospholipase-B, ShKT-like peptides, peptidase S10, Kunitz BPTI and DNase II. Quantitative analysis using intensity based absolute quantification (iBAQ via MaxQuant) revealed 20 highly abundant proteins, accounting for 67% of iBAQ signal, and three of these were toxin-like. No mucin homologues were found suggesting that the structure of the slime gel may be formed by an unknown mechanism. This study is the first known instance of a slime secretion from a cephalopod to be analyzed by proteomics methods and is the first investigation of a member of the family Sepiadariidae using proteomic methods. 1735 proteins were identified with 13 of these fitting criteria established for the identification of putative toxins. The slime is dominated by 20 highly abundant proteins with secreted, cysteine rich proteins. The study highlights the importance of 'omics approaches in understanding novel organisms.


Discovery of a novel linear-in-k spin splitting for holes in the 2D GaAs/AlAs system.
The spin-orbit interaction generally leads to spin splitting (SS) of electron and hole energy states in solids, a splitting that is characterized by a scaling with the wave vector k. Whereas for 3D bulk zinc blende solids the electron (heavy-hole) SS exhibits a cubic (linear) scaling with k, in 2D quantum wells, the electron (heavy-hole) SS is currently believed to have a mostly linear (cubic) scaling. Such expectations are based on using a small 3D envelope function basis set to describe 2D physics. By treating instead the 2D system explicitly as a system in its own right, we discover a large linear scaling of hole states in 2D. This scaling emerges from coupling of hole bands that would be unsuspected by the standard model that judges coupling by energy proximity. This discovery of a linear Dresselhaus k scaling for holes in 2D implies a different understanding of hole physics in low dimensions.


Conceptual evolution of renin research.
Research on renin in the last 90 years has undergone numerous conceptual evolution since its discovery by Tigerstedt and Bergman in 1898. This paper briefly reviews the evolutionary steps leading up to the recently discovered intracellular function of renin and generation of angiotensin II in renin containing cells and molecular biological studies approaching the regulation of renin expression in various tissues.


Timing is everything: consequences of transient and sustained AhR activity.
The aryl hydrocarbon receptor (AhR) was implicated as a mediator of xenobiotic toxicity over three decades ago. Although a complete picture continues to elude us, investigations by many laboratories during the ensuing period have revealed much about AhR biology in normal physiological processes, as well as the toxicities induced by the dioxins and related polychlorinated aromatic hydrocarbons. The findings are captured in numerous excellent reviews. This commentary attempts to inject a new perspective on some new as well as frequently overlooked observations in the context of established receptor properties. Specifically, we examine the impact of transient versus sustained receptor activation on AhR biology, and explore the potential role for cytochrome P450 expression in regulating AhR activity amongst various tissues. The growing recognition that AhR action functions through multiple mechanisms serves to further highlight the importance of limiting prolonged receptor activation.


Ontogeny of ocular serotonin N-acetyltransferase activity daily rhythm in four anuran species.
The profile of daily ocular serotonin N-acetyltransferase (NAT) rhythm has been examined during the development of four anuran amphibians in different environments and of varying phylogenetic origins: Xenopus laevis, Discoglossus pictus, Rana perezi, and Bufo calamita. A significant day/night rhythm of ocular NAT with the acrophase at midnight was first detected at stages 43/44 and 25 in X. laevis and R. perezi, respectively. Total enzymatic activity increased with body weight throughout development, although both mean levels and amplitudes of NAT activity per milligram of protein significantly decreased; this attentuation of rhythm was more significant in postmetamorphic froglets, and the acrophase was delayed about 1 hr. There were no significant differences in daily NAT profiles before and after metamorphosis in D. pictus and B. calamita. The amplitude of the NAT rhythm was maximal (> 10-fold nocturnal values) in Xenopus compared with other species (2- to 3-fold).


Sequestering of As(III) and As(V) from wastewater using a novel neem leaves/MnFe2O4 composite biosorbent.
An arsenic biosorbent comprising neem leaves (NL) and MnFe2O4 particles was developed and its removal potential was investigated. Physicochemical analysis of the NL/MnFe2O4 composite (MNL) was performed for the Brunauer, Emmett and Teller surface area, Fourier transform infrared spectra (FT-IR), and scanning electron microscopy-Energy-dispersive X-ray (EDX). The following parameters were optimized: pH, biosorbent dose, contact time, temperature, and initial arsenic concentration. The optimum pH values achieved for biosorption of As(III) and As(V) were 7.0 and 4.0, respectively, when the equilibrium time was 110 minutes for both. MNL was found to be efficient with 85.217% and 88.154% biosorption efficiency at a concentration of 50 mg/L of As(III) or As(V) solution, respectively. This was also proved by the FT-IR study of arsenic-loaded biosorbent. For establishing the best suitable correlation for the equilibrium curves exploiting the procedure of the nonlinear regression for curve fitting analysis, isotherm studies were conducted for As(III) and As(V) using 30 isotherm models. The pattern of biosorption fitted well with Brouers-Sotolongo isotherm model for As(III) and Langmuir-Freundlich as well as Sips isotherm models for As(V). Dubinin-Radushkevich (D-R) isotherm studies specified that ion exchange might play a significant role. The influence of various co-existing ions at different concentrations was examined. Desorption study was performed using various concentrations of NaOH solution.


Study of the synthesis, antiproliferative properties, and interaction with DNA and polynucleotides of cisplatin-like Pt(II) complexes containing carcinogenic polyaromatic amines.
The chemical and biological features of two newly synthesized [PtCl2(L)(2-aminonaphthalene)] complexes (L is NH3 or 2-aminonaphthalene) were compared with those of two already reported enantiomeric complexes of formula [PtCl2(DABN)] [DABN is (R)-1,1'-binaphthyl-2,2'-diamine or (S)-1,1'-binaphthyl-2,2'-diamine]. Solution behavior, lipophilicity, cytotoxicity with regard to one colorectal (HCT116) and two ovarian (A2780 and A2780Cp8) human carcinoma cell lines, and in vitro DNA- and G-quadruplex-binding properties were evaluated. In particular, the cytotoxicity of [PtCl2(NH3)(2-aminonaphthalene)] was better than that of cisplatin for all cell lines, and rather resembled that of oxaliplatin. The solution behavior of the whole series of complexes and the absence of an evident relationship between lipophilicity and cytotoxicity seem to suggest that all these experimental parameters are probably smoothed out during the 3-day cytotoxicity experiments and do not strongly affect the half-maximal inhibitory concentrations. The results of electrophoretic studies indicate that different kinds of interaction with DNA can be involved in the mode of action of these complexes, with intercalation in double-stranded DNA and stacking on G-quadruplex DNA being strongly implicated in particular for [PtCl2(NH3)(2-aminonaphthalene)].


Radiotherapy treatment verification using radiological thickness measured with an amorphous silicon electronic portal imaging device: Monte Carlo simulation and experiment.
This work validates the use of an amorphous-silicon, flat-panel electronic portal imaging device (a-Si EPID) for use as a gauge of patient or phantom radiological thickness, as an alternative to dosimetry. The response of the a-Si EPID is calibrated by adapting a technique previously applied to scanning liquid ion chamber EPIDs, and the stability, accuracy and reliability of this calibration are explored in detail. We find that the stability of this calibration, between different linacs at the same centre, is sufficient to justify calibrating only one of the EPIDs every month and using the calibration data thus obtained to perform measurements on all of the other linacs. Radiological thickness is shown to provide a reliable means of relating experimental measurements to the results of BEAMnrc Monte Carlo simulations of the linac-phantom-EPID system. For these reasons we suggest that radiological thickness can be used to verify radiotherapy treatment delivery and identify changes in the treatment field, patient position and target location, as well as patient physical thickness.


Optimization of L-malic acid production by Aspergillus flavus in a stirred fermentor.
Effects of various nutritional and environmental factors on the accumulation of organic acids (mainly L-malic acid) by the filamentous fungus Aspergillus flavus were studied in a 16-L stirred fermentor. Improvement of the molar yield (moles acid produced per moles glucose consumed) of L-malic acid was obtained mainly by increasing the agitation rate (to 350 rpm) and the Fe(z+) ion concentration (to 12 mg/L) and by lowering the nitrogen (to 271 mg/L) and phosphate concentrations (to 1.5 mM) in the medium. These changes resulted in molar yields for L-malic acid and total C(4) acids (L-malic, succinic, and fumaric acids) of 128 and 155%, respectively. The high molar yields obtained (above 100%) are additional evidence for the operation of part of the reductive branch of the tricarboxylic acid cycle in L-malic acid accumulation by A. flavus. The fermentation conditions developed using the above mentioned factors and 9% CaCO(3) in the medium resulted in a high concentration (113 g/L L-malic acid from 120 g/L glucose utilized) and a high overall productivity (0.59 g/L h) of L-malic acid. These changes in acid accumulation coincide with increases in the activities of NAD(+)-malate dehydrogenase, fumarase, and citrate synthase.


Pentoxifylline in treatment of sarcoidosis.
The optimal therapy for sarcoidosis remains unclear. Most patients show a short-term response to corticosteroid therapy, but they have to face the risk of significant side effects. Because tumor necrosis factor alpha (TNF) plays a critical role in granuloma formation and sustenance as well as in the progression of sarcoidosis, we investigated pentoxifylline (POF), which exerts TNF-inhibitory activity, as a therapeutic agent in active pulmonary sarcoidosis. Twenty-three previously untreated patients with documented disease progression during the preceding 3 mo were treated with POF (25 mg/kg daily) and followed for 6 mo of therapy. Two patients were lost to follow-up, and three patients discontinued POF therapy because of gastrointestinal side effects; 18 patients were thus evaluated. Eleven patients improved, seven remained stable and, most importantly, none deteriorated. Lung function tests-DL(CO), Pa(O2) and Pa(O2)[exercise]-were significantly improved in the patient group as a whole and increased in a highly significant manner in those who improved. Three patients with corticosteroid-resistant disease progression were additionally treated with a combination of corticosteroids with POF. In all three patients the combination therapy resulted in an immediate complete decrease of disease activity, even after tapering prednisone to 7.5 mg daily or tapering off corticosteroids. These promising results suggest that POF may improve therapeutic regimens in pulmonary sarcoidosis either by sparing or replacing corticosteroids.


Antibacterial activity and biofilm inhibition by surface modified titanium alloy medical implants following application of silver, titanium dioxide and hydroxyapatite nanocoatings.
One of the most common causes of implant failure is peri-implantitis, which is caused by bacterial biofilm formation on the surfaces of dental implants. Modification of the surface nanotopography has been suggested to affect bacterial adherence to implants. Silver nanoparticles are also known for their antibacterial properties. In this study, titanium alloy implants were surface modified following silver plating, anodisation and sintering techniques to create a combination of silver, titanium dioxide and hydroxyapatite (HA) nanocoatings. Their antibacterial performance was quantitatively assessed by measuring the growth of Streptococcus sanguinis, proportion of live/dead cells and lactate production by the microbes over 24 h. Application of a dual layered silver-HA nanocoating to the surface of implants successfully inhibited bacterial growth in the surrounding media (100% mortality), whereas the formation of bacterial biofilm on the implant surfaces was reduced by 97.5%. Uncoated controls and titanium dioxide nanocoatings showed no antibacterial effect. Both silver and HA nanocoatings were found to be very stable in biological fluids with material loss, as a result of dissolution, to be less than 0.07% for the silver nanocoatings after 24 h in a modified Krebs-Ringer bicarbonate buffer. No dissolution was detected for the HA nanocoatings. Thus, application of a dual layered silver-HA nanocoating to titanium alloy implants creates a surface with antibiofilm properties without compromising the HA biocompatibility required for successful osseointegration and accelerated bone healing.


Vascular thoracic outlet in a competitive swimmer: a case report.
Thoracic outlet syndrome (TOS) is a well-described condition resulting from compression of the brachial plexus, subclavian artery and/or vein. Though symptoms of pain, numbness, tingling and signs of muscular weakness associated with this condition usually begin insidiously, on rare occasions the presentation is of acute onset and may represent an acute vascular compression. An unusual form of "effort" thrombosis of the subclavian vein may require emergency care in order to ensure controlled clot lysis and thrombus dissolution. Confirmation of subclavian thrombus is obtained by venography and makes use of real time videography to assess for venous flow impairment. Definitive treatment for the underlying cause of this form of TOS is first rib resection and scalenectomy. This case report presents a competitive swimmer who developed an acute onset of limb cyanosis and turgidity during swim training. Awareness of the possibility of acute thrombosis obstructing venous return and producing such signs and symptoms should lead the astute clinician to consider recommending contrast venography to assess the lesion and lead to appropriate medical intervention.


Differences in response of the proximal esophagus to wet swallows in patients of Chagas' disease and idiopathic achalasia.
Chagas' disease and idiopathic achalasia have similar esophageal manifestations such as absent or incomplete lower esophageal sphincter relaxation and aperistalsis in the esophageal body (alterations seen mainly in the distal esophageal body). Our aim in this paper was to study the response of the proximal esophageal body to wet swallows in patients with Chagas' disease and patients with idiopathic achalasia. We retrospectively analyzed the time interval between the onset of the pharyngeal contractions 1 cm proximal to the upper esophageal sphincter, as well as 5 cm distal to the pharyngeal measurement. Amplitude, duration and area under the curve of contractions in the proximal esophagus were also determined in 42 patients with Chagas' disease (15 with associated esophageal dilatation), 21 patients with idiopathic achalasia (14 with concomitant esophageal dilatation) and 31 control subjects. The time between the onset of pharyngeal and proximal esophageal contractions was longer in patients with Chagas' disease and in those with esophageal dilatation (1.39 +/- 0.16 s) than in control subjects (0.86 +/- 0.04 s, P < 0.01). The amplitude of proximal esophageal contractions was lower in patients with idiopathic achalasia and esophageal dilatation (60.9 +/- 16.3 mmHg) than in control subjects (89.7 +/- 6.9 mmHg, P = 0.06). The authors conclude that in patients with advanced esophageal disease, the proximal esophageal contractions in Chagas' disease have a delayed response to wet swallows when compared with controls, and that the amplitude of proximal esophageal contractions was lower than expected in patients with idiopathic achalasia.


Water Transport Mediated by Other Membrane Proteins.
Water transport through membrane is so intricate that there are still some debates. (Aquaporins) AQPs are entirely accepted to allow water transmembrane movement depending on osmotic gradient. Cotransporters and uniporters , however, are also concerned in water homeotatsis. Urea transporter B (UT-B) has a single-channel water permeability that is similar to AQP1. Cystic fibrosis transmembrane conductance regulator (CFTR ) was initially thought as a water channel but now not believed to transport water directly. By cotranporters, water is transported by water osmosis coupling with substrates, which explains how water is transported across the isolated small intestine. This chapter provides information about water transport mediated by other membrane proteins except AQPs .


A tale of two approaches: complementary mechanisms of cytotoxic and targeted therapy resistance may inform next-generation cancer treatments.
Chemotherapy and molecularly targeted approaches represent two very different modes of cancer treatment and each is associated with unique benefits and limitations. Both types of therapy share the overarching limitation of the emergence of drug resistance, which prevents these drugs from eliciting lasting clinical benefit. This review will provide an overview of the various mechanisms of resistance to each of these classes of drugs and examples of drug combinations that have been tested clinically. This analysis supports the contention that understanding modes of resistance to both chemotherapy and molecularly targeted therapies may be very useful in selecting those drugs of each class that will have complementing mechanisms of sensitivity and thereby represent reasonable combination therapies.


Isolation and characterization of aminopeptidase (Jc-peptidase) from Japanese cedar pollen (Cryptomeria japonica).
An aminopeptidase, Jc-peptidase, was purified from Japanese cedar pollen by seven steps, including precipitation with ammonium sulfate, ion-exchange chromatography, gel filtration, hydrophobic interaction chromatography on phenyl-agarose, and high-performance liquid chromatography. Purified Jc-peptidease has a molecular weight of 42 kDa and hydrolyzes the synthetic substrates of L-phenylalanyl-4-methylcoumaryl-7-amide (Phe-MCA) with Km = 5 x 10(-5) M, Tyr-MCA with Km = 7 x 10(-4) M, Leu-MCA with Km = 1 x 10(-3) M, and Met-MCA with Km = 1 x 10(-3) M. Other MCA analogues such as Arg-MCA or Glu-MCA failed to serve as its substrates. The activity was inhibited in the presence of phebestin, [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-valyl]-L-phenylalanine, with Ki = 4.7 x 10(-5) M, or bestatin, [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, with Ki = 1.1 x 10(-4) M. According to amino acid sequence analysis, the N-terminal amino group seems to be blocked. The physiological function of the aminopeptidase (Jc-peptidase) has not been clarified in vivo.


Dirac semimetal-assisted near-field radiative thermal rectifier and thermostat based on phase transition of vanadium dioxide.
The near-field thermal radiation has broad application prospects in micro-nano-scale thermal management technology. In this paper, we report the Dirac semimetal-assisted (AlCuFe quasicrystal) near-field radiative thermal rectifier (DSTR) and thermostat (DST), respectively. The DSTR is made of a Dirac semimetal-covered vanadium dioxide (VO2) plate and silicon dioxide (SiO2) plate separated by a vacuum gap. The left and right sides of DST are consisted of the SiO2 covered with Dirac semimetal, and the intermediate plate is the VO2. The strong coupling of the surface electromagnetic modes between the Dirac semimetal, SiO2, and insulating VO2 leads to enhance near-field radiative transfer. In the DSTR, the net radiative heat flux of VO2 in the insulating state is much larger than that in metallic state. When the vacuum gap distance d=100 nm, Fermi level EF=0.20 eV, and film thickness t=12 nm, the global rectification factor of DSTR is 3.5, which is 50% higher than that of structure without Dirac semimetal. In the DST, the equilibrium temperature of the VO2 can be controlled accurately to achieve the switching between the metallic and insulating state of VO2. When the vacuum gap distance d=60 nm, intermediate plate thickness δ=30 nm, and film thickness t=2 nm, with the modulation of Fermi level between 0.05-0.15 eV, the equilibrium temperature of VO2 can be controlled between 325-371 K. In brief, when the crystalline state of VO2 changes between the insulating and metallic state with temperature, the active regulation of near-field thermal radiation can be realized in both two-body and three-body parallel plate structure. This work will pave a way to further improve performance of near-field radiative thermal management and modulation.


Clinical and epidemiological characteristics of pyogenic liver abscess in people 65 years or older versus people under 65: a retrospective study.
To analyse the clinical, epidemiological, microbiological and prognostic differences of pyogenic liver abscess (PLA) in older (≥ 65 years of age) versus younger patients (< 65 years). Multicentre, retrospective cohort study in all patients with PLA admitted to two Spanish hospitals from January 2000 to January 2014. Cases were divided into two age groups (< 65 years and ≥65 years) for comparison of clinical, epidemiological and microbiological characteristics as well as treatment. Of 98 patients analysed, 40 patients were younger than 65, and 58 were aged 65 or older. Significant associations in the older group were found with female sex (adjusted odds ratio [ORa] 9.0; 95% CI 1.4, 56), non-cryptogenic origin (ORa 14.5; 95% CI 1.6, 129), absence of chronic liver disease (ORa 14; 95% CI 1.3, 155), Escherichia coli infection (ORa 7.7; 95% CI 1.03, 58), and incidence of complications (ORa 2.3; 95% CI 1.04, 5.4). Mortality was 8.2% overall, although all deaths occurred in the older group (8/58; 13.8%) (p = 0.02). Our results are in consonance with other published studies. Older patients with PLA tend to present more anomalies in the biliary tract (Kai et. al, World J Gastroenterol 18: 2948-295, 2012, Rahimian et. al, Clin Infect Dis 39:1654-9, 2004, Seeto, Medicine (Baltimore) 75:99-113, 1996, Kao et.al, Aliment Pharmacol Ther 36:467-76, 2012, Lai et. al, Gastroenterology 146:129-37, 2014), while younger patients are more often male and present more commonly with previous liver disease (especially related to alcohol) and cryptogenic PLA. In patients aged 65 or older, PLA was more common in women and in those with a history of biliary disease, and E. coli was the most frequent bacterium. Mortality was also higher in the older group.


Long-lived excited states of zwitterionic copper(I) complexes for photoinduced cross-dehydrogenative coupling reactions.
Four heteroleptic copper(I) complexes containing phenanthroline and monoanionic nido-carborane-diphosphine ligands have been prepared and structurally characterized by various spectroscopic techniques and X-ray diffraction. These complexes exhibit intense absorptions in the visible range and excited-state lifetimes on the microsecond scale. Their application in visible-light-induced cross-dehydrogenative coupling reactions was investigated. Preliminary studies showed that one of the four copper(I) complexes is an efficient catalyst for photoinduced oxidative C-H functionalization using oxygen as oxidant. Furthermore, α-functionalized tertiary amines were obtained in good-to-excellent yields by light irradiation (λ>420 nm) of a mixture of our Cu(I) complex, tertiary amines, and a variety of nucleophiles (nitroalkane, acetone, or indoles) under aerobic conditions. Electron paramagnetic resonance measurements provided evidence for the formation of superoxide radical anions (O2(-⋅)) rather than singlet oxygen ((1)O2) during these photocatalytic reactions.


[Connections between the mast cell system of a focus of inflammation and the zona fasciculata of the adrenal cortex].
At aseptic inflammation developing around a solid foreign body and proceeding both under common conditions and on the background of disturbed inactivation of free amines as a result of monoaminoxidase blockade with vetrasin or devastation of amine tissue depots with reserpine it has been stated that indices of the adrenal cortex activity (hyperemia, contents of ascorbic acid and corticoids) and those of the mast cells system in the inflammatory focus (amount of the cells, their size, contents of glycosaminoglycans, RNA, tryptophan and histidine) are subjected to certain fluctuations during inflammation. Increasing activity of the adrenal cortex fascicular zone and renewal of the mast cell population in the inflammatory focus are directly proportional to the degree of a disturbed deposition of free amines in the organism. Certain positive correlations prevail in cooperation of the adrenal cortex activity, decomposition rate of large (mature) mast cells and migration into the inflammatory focus of small (immature) forms of these cells.


Modulo-addition operation enables terahertz programmable metasurface for high-resolution two-dimensional beam steering.
Electrically controlled terahertz (THz) beamforming antennas are essential for various applications such as wireless communications, security checks, and radar to improve coverage and information capacity. The emerging programmable metasurface provides a flexible, cost-effective platform for THz beam steering. However, scaling such arrays to achieve high-gain beam steering faces several technical challenges. Here, we propose a pixelated liquid crystal THz metasurface with a crossbar structure, thereby increasing the array scale to more than 3000. The coding pattern on the programmable device is generated by the modulo-addition of the coding sequences on the top and bottom layers. We experimentally demonstrate the programmable liquid crystal metasurface capable of active beam deflection in the upper half-space. This scale-up of programmable devices opens exciting opportunities in pencil beamforming, high-speed information processing, and optical computing.


Is Sp1 binding site polymorphism within COL1A1 gene associated with tennis elbow?
Tennis elbow defines a condition of pain and tenderness over the lateral epicondyle of the humerus. The exact aetiology of the injury is not yet fully understood. The major constituent of tendons is type 1 collagen which is encoded by COL1A1 gene. The aim of the study was to determine whether Sp1 binding site polymorphism (SNP rs1800012; 1546G/T) within the intronic region of COL1A1 gene is associated with tennis elbow. One hundred and three tennis elbow patients and one hundred and three healthy subjects without any history of previous ligament or tendon injuries were recruited for this genetic association study. All participants were genotyped for the COL1A1 Sp1 binding site polymorphism by using PCR-RFLP method. There were no observed statistical differences in the genotype (p=0.17) or allele (p=0.11) distributions between the groups. G allele frequency in patients and controls was 82.5% and 76.21%, and T allele frequency was 17.5% and 23.79% respectively. This study has shown that there is no association between this polymorphism and tennis elbow within the population studied.


Solubilisation and cytotoxicity of albendazole encapsulated in cucurbit[n]uril.
The aqueous solubilities of albendazole encapsulated in cucurbit[6, 7 and 8]urils (Q[6], Q[7] and Q[8]) have been determined by (1)H NMR spectroscopy, and the effect of encapsulation on their cytotoxicities evaluated. Encapsulation in Q[6] and Q[7] increased the aqueous solubility of albendazole by 2000-fold, from 3 microM to 6 mM at pH 6.6, while Q[8]-encapsulation increased the solubility to over 2 mM. Encapsulation in Q[7] and Q[8] induced significant upfield shifts for the albendazole propyl and benzimidazole resonances, compared to those observed for Q[6]-binding and what would normally be expected for the respective functional groups. The upfield shifts indicate that the albendazole propyl and benzimidazole protons are located within the Q[7] and Q[8] cavity upon encapsulation. Alternatively, encapsulation in Q[6] only induced a large upfield shift for the albendazole carbamate methyl resonance, indicating that the drug associates with Q[6] at its portals, with only the carbamate group within the cavity. Simple molecular models based on the observed relative changes in chemical shift could be constructed that were consistent with the conclusions from the NMR experiments. Cytotoxicity assays against human colorectal cells (HT-29), human ovarian cancer cells (1A9) and the human T-cell acute lymphoblastic leukaemia cells (CEM) indicated that encapsulation in Q[7] did not significantly reduce the in vitro anti-cancer activity of albendazole.


2-Hydroxyestradiol modulates a facilitative action of catecholamines on porcine granulosa cells.
Recent studies have disclosed a novel intraovarian paracrine system whereby catecholestrogens [e.g. 2-hydroxyestradiol (2-OH-E2)], synthesized locally from estradiol (E2) can stimulate progesterone secretion by granulosa cells (GC). Since these studies suggested that effects of 2-OH-E2 were discrete from those of E2, the present studies were undertaken to determine if the effects of 2-OH-E2 could be mediated through or interact with the catecholamine response system of GC. First, the effects of 2-OH-E2 were compared with those of E2 and epinephrine (EPI) using undifferentiated porcine GC. After 4 days of treatment, saturating concentrations of EPI (1 microgram/ml), 2-OH-E2 (4 micrograms/ml), and E2 (1 microgram/ml) stimulated progesterone production per cell 2-, 9-, and 10-fold, respectively. Saturating doses of EPI plus 2-OH-E2 or EPI plus E2 caused further significant increases in progesterone production above the effects of any single treatment, and the effects of EPI plus 2-OH-E2 were significantly greater than that of EPI plus E2. Isoproterenol mimicked the effect of EPI. Neither propranolol (a beta-antagonist) nor phentolamine (an alpha-antagonist) blocked the effects of 2-OH-E2, suggesting that effects of 2-OH-E2 were not mediated through alpha- or beta-adrenergic receptors. Collectively, these data suggest that 2-OH-E2, beta-adrenergic agonists, and E2 use separate response systems. To further evaluate the interaction between catecholamines and 2-OH-E2, GC were treated with increasing doses of 2-OH-E2 with or without EPI or isoproterenol. EPI and isoproterenol caused a synergistic increase in progesterone production above that induced by all doses of 2-OH-E2 along (average 3.8 +/- 0.7- and 3.2 +/- 0.4-fold enhancement for EPI and isoproterenol, respectively). This synergistic effect was blocked with addition of propranolol, indicating a beta-adrenergic mediation for the catecholamine portion of this effect. Studies using the catechol-O-methyltransferase inhibitor, U-0521, and the O-methyl derivative of EPI, metanephrine, suggested that catechol-O-methyltransferase present in GC dramatically reduces the potency of EPI, but is not involved in the synergism between EPI and 2-OH-E2. In conclusion, 2-OH-E2 is a more efficacious stimulator of progesterone secretion than catecholamines and synergizes with beta-adrenergic agonists to further stimulate progesterone production by GC. The mechanism by which catecholamines and 2-OH-E2 interact within GC is unknown.4+owever, this catecholamine/2-OH-E2 interaction


Preparation of High Stability Pd/Ceramic/Ti-Al Alloy Composite Membranes by Electroless Plating.
High stability Pd/ceramic/Ti-Al alloy composite membranes were prepared by electroless plating. Ceramic membranes fabricated by an in situ oxidation method were used as an inter-diffusion barrier between the Pd layer and the Ti-Al alloy support of the membranes to prevent intermetallic diffusion. The stabilities of the ceramic membranes at high temperatures in an H2 atmosphere were investigated. The permeation performances and stabilities of the Pd/ceramic/Ti-Al alloy composite membranes were also studied. The results showed that the thickness, pore size, and microstructure of the ceramic membranes did not change significantly after the treatment in an H2 atmosphere at high temperatures, indicating that the ceramic membranes prepared by the in situ oxidation method were stable in an H2 atmosphere at high temperatures. The thickness of the Pd layer was ~13 μm. The hydrogen permeability and H2/N2 selectivity of the Pd composite membranes at 773 K were 2.13 × 10-3 mol m-2 s-1 Pa-0.5 and 600, respectively. In addition, the H2 flux, N2 flux, and H2/N2 selectivity of the composite membranes remained nearly constant over three heat cycles (under the same conditions), indicating that the structures of the Pd/ceramic/Ti-Al alloy composite membranes were stable.


Intracranial aneurysms at higher clinical risk for rupture demonstrate increased wall enhancement and thinning on multicontrast 3D vessel wall MRI.
Identification of aneurysms at risk for rupture is important and challenging. We sought to evaluate if intracranial vessel wall (IVW) imaging characteristics of unruptured aneurysms correlate with clinical risk factors for rupture. Patients with unruptured intracranial aneurysms were prospectively recruited and underwent a multi contrast 3D IVW protocol between April 6, 2016 and August 29, 2017. Two independent raters, blinded to aneurysm vulnerability, evaluated each aneurysm for wall enhancement, extent of enhancement in terms of the numbers of quadrants enhancing circumferentially, intensity of enhancement, and qualitative wall thinning. PHASES score was calculated for each aneurysm. Univariate logistic regression analysis was used to compare IVW characteristics between aneurysms at higher clinical risk for rupture (PHASES score > 3) and lower clinical risk for rupture (PHASES score ≤ 3). 45 patients with 65 unruptured aneurysms were analyzed; 38 aneurysms with PHASES score > 3 (58%) and 27 aneurysms with PHASES score ≤ 3 (42%). Aneurysms with PHASES score > 3 were more likely to demonstrate enhancement (42.1% vs 14.8%, p = 0.022), greater extent of enhancement (mean: 2.9 vs 2.2 quadrants, p = 0.063), and wall thinning (9.2% vs 0%, p = 0.044). Inter-reader agreement was moderate-to-good for the presence (κ = 0.64), extent (κ = 0.64), and intensity of enhancement (κ = 0.60) but relatively low for wall thinning (κ = 0.25). Aneurysms at higher risk of rupture by PHASES score are more likely to demonstrate wall enhancement, more diffuse enhancement, and wall thinning on IVW. This study prospectively compares IVW-detected wall enhancement and thinning between unruptured aneurysms stratified into high and low risk groups by clinical scores (PHASES) of vulnerability.


Coverage of overdose prevention programs for opiate users and injectors: a cross-sectional study.
The use of opiates, particularly heroin, remains an important cause of morbidity and mortality. Half of the deaths among heroin consumers are attributed to overdose. In response to this problem, overdose prevention programs (OPPs) were designed. The objective of our study was to assess coverage of OPPs among the target population in a specific Spanish region (Catalonia) and to identify characteristics related to attendance. A cross-sectional survey recruited individuals from outpatient treatment centers (OTCs), therapeutic communities (ThCs), and harm reduction facilities (HRFs) in Catalonia. From 513 participants, 306 opiate users and/or injectors were selected for this study. Coverage was calculated as the proportion of subjects who declared having participated in an OPP. A Poisson regression with robust variance was used to assess factors (socio-demographic aspects and psychoactive substance use patterns) associated to OPP participation, taking into account recruitment strategy. Average age of the 306 subjects was 39.7 years (s.d.: 7.7); 79% were male; 79.2% lived in urban areas and 56.3% were unemployed or had never worked. Overall OPP coverage was 43.5% (95% CI: 37%-49%). Training was received mostly in HRF (60%), followed by OTC (24.4%), prison (19%), and ThC (16%). OPP sessions were attended by 41% of Spanish-born study participants and by 63.3% of foreigners; 92.2% of the participants lived in urban areas. The Poisson regression analysis adjusted by age, sex, and type of recruitment center showed that OPP participation rates were higher for individuals with foreign nationality (PR = 1.3; 95% CI: 1.04-1.72), for those living in municipalities with more than 100,000 inhabitants (PR = 2.0; 95% CI: 1.37-2.81) or the Barcelona conurbation (PR = 2.5; 95% CI: 1.68-3.77), and for those having ever been in prison (PR = 1.6; 95% CI: 1.41-1.81) and had first consumption when they were less than 12 years old (PR = 1.2; 95% CI: 1.06-1.45). Coverage as a whole can be considered high. However, in Catalonia, new strategies ought to be developed in order to attract opiate users and injectors not currently participating, by expanding OPP offer to services and regions where coverage is poor.


UV tanning advertisements in national high school newspapers.
Many young adults have utilized indoor ultraviolet(UV) tanning, putting them at higher risk for development of skin cancers. Prior to the increased regulations on indoor tanning for minors, indoor tanning businesses marketed to teens through modalities such as advertisements in high school newspapers. The purpose of this study was to quantify tanning advertisements in high school newspapers published across the United States between August 2014 and July 2015. Online versions of the newspaper issues were available on issuu.com. Tanning advertisements appeared in 3 of 23 high school newspapers with advertisements of any kind(13%). Among all newspapers with advertisements, 10% were indoor tanning advertisements. One newspaper in Colorado contained advertisements of any kind and had 0 tanning advertisements. A prior study of Colorado high schools showed 11 of 23 schools (48%) to contain tanning advertisements. This suggests that there may be a decrease in indoor UV tanning advertisements owing to increased tanning regulation by state legislatures, national attention to UV tanning, or a general decrease in high school tanning advertisements.


Glioma formation, cancer stem cells, and akt signaling.
Several recent reports have provided evidence that cancer is initiated by a rare fraction of cells called "cancer stem cells" which are multipotent, self-renewing subset of the tumor. However, several issues regarding the biology and techniques of isolating these cells from solid tumors remain to be clarified. In addition, experimental data supports two possibilities for glioma cell of origin. First, that stem cells or early progenitors are transformed and show variable differentiation of their progeny during tumor development. Second, that more differentiated glia are transformed by genetic events that lead to a loss of differentiation maintenance. In human gliomas, these two theories are not mutually exclusive. In this review we will summarize both theories, and highlight outstanding issues that remain to be resolved.


Relationship between Water Activity and Moisture Content in Floral Honey.
The water activity (Aw) and moisture content (MC) data of floral honey at five temperatures were determined using the Aw method and it was found that temperature significantly affected the Aw/MC data. The linear equation could be used to express the relationship between Aw and MC of honeys. The empirical regression equations between parameters and temperature were established. To evaluate the factors affecting the Aw/MC data, we used categorical tests of regression analysis to assess the effect of the correlation between Aw and MC of honey and examined the factors affecting the regression parameters. Six datasets from five countries were selected from the literature. The significance of the levels of qualitative categories was tested by t-test. The slope of the relationship between Aw and MC was affected by the state of honey (liquid and crystallized). The intercepts were significantly affected by honey type (flower or honeydew), harvesting year, geographical collection site, botanical source and other factors. The outliers in the datasets significantly affected the results. With modern regression analysis, useful information on the correlation between Aw and MC could be found. The results indicated that no universal linear equation for Aw and MC could be used. The Aw value could be used as a criterion for the honey industry; then, the MC of honey could be calculated by the specific linear equation between Aw and MC.