[Radiomics strategy based on cardiac magnetic resonance imaging cine sequence for assessing the severity of mitral value regurgitation].
To assess the performance of radiomics model based on cardiac magnetic resonance imaging (CMR) cine sequence for assessing the severity of mitral regurgitation. Methods: A total of 80 patients who underwent CMR and echocardiography examination were retrospectively enrolled, including 67 patients with no or slight mitral regurgitation and 13 patients with moderate or severe mitral regurgitation. The relative difference in average filtered gradient (RDAFG) of CMR cine sequence were generated, which were combined with minimum output sum of squared error tracker (MOSSE) to extract 25 radiomics features. After reducing feature dimensionality by principal component analysis (PCA) and oversampling the minority samples, the radiomics model was established using support vector machine (SVM). The performance of the model was assessed by receiver operating characteristic (ROC) curve. Results: There were significant differences (both P<0.01) of the 2-dimension radiomics features between the two groups. The best performance (area under the ROC curve) of the established radiomics model was 0.971, with sensitivity and specificity at 85.7% and 94.1%, respectively. Conclusion: The performance of the machine learning-based radiomics model derived from CMR cine sequence for assessing the severity of mitral regurgitation was excellent, which can facilitate the computer-aided diagnosis and treatment in the era of artificial intelligence.


The effects of cheese snacks on caries in desalivated rats.
Rats that had had their submandibular/sublingual glands removed surgically, and their parotid ducts tied, developed fewer and less severe caries lesions on coronal and root surfaces when fed cheese snacks in addition to a cariogenic diet than when fed additional cariogenic snacks or no additional snacks. The effects of cheese snacks were particularly dramatic on root-surface caries. These observations may be relevant for elderly humans who are most likely to develop root surface caries. Populations of Streptococcus mutans did not differ among the groups. Actinomyces viscosus was not detected at the end of the experiment in any of the groups. The results of this study demonstrate that cheese exerts a protective effect against coronal and root-surface caries in rats with a severely limited salivary function.


Separation and quantification of milk casein from different buffalo breeds.
Understanding the milk protein expression profile in different buffalo breeds plays an important role in improving hybrid selection and determining the effects on milk protein synthesis. The aim of this research is to compare the differences in milk protein content, composition and distribution between River buffalo and their crossbreeds for hybrid screening. Four groups of milk samples that included Nili-Ravi (N), Murrah (M), a Nili-Ravi-Murrah crossbreed (M-N), and a crossbreed of river buffalo with local swamp buffalo (C) were collected. The protein composition of the buffalo milk was determined by RP-HPLC. A gel-based proteomic approach consisting of two-dimensional gel electrophoresis coupled with mass spectrometry was utilised for the detailed protein characterisation of milk from different breeds. The results of this analysis showed that the river/swamp buffalo crossbreed (C) displayed the highest content of total protein (4·46%) and κ-casein (11·14%) but the lowest content of α-lactalbumin (6·79%). By selecting 23 different protein spots among the four types of milk that contained the most spots corresponding to κ-casein, β-casein and αs1-casein, correlations between the crossbreeds, protein polymorphism and phosphorylation could be made. The results of this study indicate that crossbreeding a swamp buffalo with a river buffalo has a notable effect on the protein content and composition that may be exploited for producing high-quality raw milk in food technology applications and dairy food production.


Regulation of light-induced chloroplast transcription and translation in eight-day-old dark-grown barley seedlings.
Plastid transcription and translation are light-activated in 8-day-old dark-grown barley (Hordeum vulgare L.) seedlings. Pretreatment of dark-grown seedlings with cycloheximide (inhibitor of cytoplasmic protein synthesis) abolished the activation of rbcL, psbA, and psaA-B transcription by light. In contrast, inhibition of plastid protein synthesis by chloramphenicol stimulated light-activated transcription of rbcL, psbA, and psaA-B. Light-induced transcription of the plastid genome occurred normally in the chlorophyll-deficient mutant xan-J(64). These results suggest that although the light-induced activation of plastid transcription is modulated by cytoplasmic and organellar protein synthesis, transcriptional activation is not dependent on the absorption of light by protochlorophyllide or the attainment of photosynthetic competence. In addition, plastid translation increased dramatically when 8-day-old dark-grown seedlings were illuminated and activation was dependent on cytoplasmic protein synthesis. Blockage of light-activated plastid transcription by Tagetin treatment (inhibitor of plastid RNA polymerase) did not attenuate the activation of plastid translation by light. These results suggest that while light simultaneously activates plastid transcription and translation, the rapid burst in plastid protein synthesis is due mainly to cytoplasmic-derived changes that regulate the rate of translation of pre-existing mRNAs.


A Novel Method for Lower Blepharoplasty: Repositioning of the Orbital Septum Using Inverted T-Shaped Plication.
Numerous techniques have been used for lower blepharoplasty. The techniques can be classified into four principles: excision of excess fat, septal reset, orbital fat repositioning, and reinforcement of the attenuated orbital septum. We modified the conventional approach of septal reinforcement to utilize an inverted T-shaped plication with preservation of the orbital fat, repositioning the septum below the arcus marginalis to refine tear-trough deformity. From April 2010 to September 2015, 93 individuals underwent bilateral lower blepharoplasty. Retrospective chart reviews were performed, and the results and complications during the follow-up period were recorded and photographed. The patients comprised 76 women and 17 men. Thirteen, 33, and 47 patients exhibited mild, moderate, and severe fat herniation, respectively, accompanied by tear-trough deformity. A total of 70 and 23 patients underwent lower blepharoplasty via subciliary and transconjunctival approaches, respectively. We performed inverted T-shaped plication of the orbital septum in mild and moderate cases and X-shaped plication in severe cases, and in moderate and severe cases, we performed septal repositioning simultaneously. The mean follow-up period was 25 months. When immediate mild lid retraction or lid malposition was observed, it recovered without specific treatment within 1 to 2 weeks. No permanent lid malposition or ectropion was observed in any of the patients. Septal plication with inverted T-shape or X-shape can minimize the downward forces that affect postoperative eyelid malposition and ectropion. Further, these procedures provide sufficiently strong reinforcement of the orbital septum to restore infraorbital fat herniation.


Hypersensitivity reaction after inhalation of a lactose-containing dry powder inhaler.
Milk protein allergy-induced reactions from lactose-containing dry powder inhalers (DPIs) have not been widely described in the literature. Lactose is a common inactive ingredient in many pharmaceutical products that is used to enhance the stability of active substances in medicinal products, including asthma medications. Contamination of lactose with milk proteins has been identified in reports of inhaled corticosteroid product lot testing. Serious respiratory sequelae may follow after the inhalation of a DPI corticosteroid in a patient with milk protein allergy because DPIs that contain lactose may be contaminated with milk proteins. Lactose-containing DPIs are contraindicated in patients with milk protein allergy. Although manufacturers identify this contraindication in product package inserts, some drug references may not include this information and health care professionals may lack awareness. Clinicians should consider reviewing multiple medication resources for warnings and contraindications of medications to prevent complications. We describe a refractory asthma exacerbation secondary to a hypersensitivity reaction following administration of a lactose-containing DPI corticosteroid and long-acting β2 agonist combination in a child with a milk protein allergy.


Supplementing cultured human myotubes with hibernating bear serum results in increased protein content by modulating Akt/FOXO3a signaling.
Hibernating bears remain in their dens for 5-7 months during winter and survive without eating or drinking while staying inactive. However, they maintain their physical functions with minimal skeletal muscle atrophy and metabolic dysfunction. In bears, resistance to skeletal muscle atrophy during hibernation is likely mediated by seasonally altered systemic factors that are independent of neuromuscular activity. To determine whether there are components in bear serum that regulate protein and energy metabolism, differentiated human skeletal muscle cells were treated with bear serum (5% in DMEM/Ham's F-12, 24 h) collected during active summer (July) and hibernating winter (February) periods. The serum samples were collected from the same individual bears (Ursus thibetanus japonicus, n = 7 in each season). Total protein content in cultured skeletal muscle cells was significantly increased following a 24 h treatment with hibernating bear serum. Although the protein synthesis rate was not altered, the expression of MuRF1 protein, a muscle-specific E3 ubiquitin ligase was significantly decreased along with a concomitant activation of Akt/FOXO3a signaling. Increased levels of insulin-like growth factor-1 (IGF-1) were also observed in hibernating bear serum. These observations suggest that protein metabolism in cultured human myotubes may be altered when incubated with hibernating bear serum, with a significant increase in serum IGF-1 and diminished MuRF1 expression, a potential target of Akt/FOXO3a signaling. A protein sparing phenotype in cultured muscle cells by treatment with hibernating bear serum holds potential for the development of methods to prevent human muscle atrophy and related disorders.


Spheroid-Based Tissue Engineering Strategies for Regeneration of the Intervertebral Disc.
Degenerative disc disease, a painful pathology of the intervertebral disc (IVD), often causes disability and reduces quality of life. Although regenerative cell-based strategies have shown promise in clinical trials, none have been widely adopted clinically. Recent developments demonstrated that spheroid-based approaches might help overcome challenges associated with cell-based IVD therapies. Spheroids are three-dimensional multicellular aggregates with architecture that enables the cells to differentiate and synthesize endogenous ECM, promotes cell-ECM interactions, enhances adhesion, and protects cells from harsh conditions. Spheroids could be applied in the IVD both in scaffold-free and scaffold-based configurations, possibly providing advantages over cell suspensions. This review highlights areas of future research in spheroid-based regeneration of nucleus pulposus (NP) and annulus fibrosus (AF). We also discuss cell sources and methods for spheroid fabrication and characterization, mechanisms related to spheroid fusion, as well as enhancement of spheroid performance in the context of the IVD microenvironment.


[Effect of total flavonoids in Scutellaria barbata in mediating autophagy in tumor cells via PI3K/AKT/mTOR pathway].
To investigate the effect of the total flavonoids in Scutellaria barbata(TF-SB) against autophagy in tumor cells in vivo, and further determine whether the mechanism is correlated with the PI3K/AKT/mTOR pathway, which lead to autophagy-induced tumor cell death. Melanoma-bearing mice were prepared and divided into control group, rapamycin group (Rap 1.5 mg•kg⁻¹), and high, middle and low-dose TF-SB (200, 100, 50 mg•kg⁻¹) groups. The groups were given drugs once a day for successively 11 days. The inhibitory effect of TF-SB on the growth of melanoma was determined by measuring tumor volume and tumor inhibition rate. TUNEL method was used to detect the apoptosis of tumor cells to further verify the antitumor activity of TF-SB. The protein expressions of LC3-Ⅰ and LC3-Ⅱ were detected by Western blot, and the relative expression of LC3-Ⅱ was calculated based on LC3-Ⅱ/LC3-Ⅰ. In addition, the effect of TF-SB on autophagy of tumor cells, the underlying molecular mechanism of TF-SB in inducing autophagy and PI3K/AKT/mTOR pathway marker protein phosphorylation were also studied. According to the results, TF-SB effectively inhibited melanoma growth in mice, reduced tumor volume, increased the tumor inhibition rate, and significantly increased tumor cell apoptosis index and the ratio of LC3-Ⅱ/LC3-I (P<0.05, P<0.01 or P<0.001). The protein expressions of p-PI3K, p-AKT and p-mTOR were also suppressed dramatically compared with those in control group (P<0.05, P<0.01 or P<0.001). In conclusion, the total flavonoids in S. barbata could inhibit the growth of melanoma in vivo by inducing autophagy and apoptosis of tumor cells, which may be correlated with suppression of PI3K/AKT/mTOR pathway.


[Bronchiolitis associated with ulcerative colitis].
Inflammatory bowel disease (IBD) only occasionally affects the lung. Noteworthy among the various pulmonary entities related to IBD are chronic bronchitis and bronchiectasis, though reports of bronchiolitis, obliterants bronchiolitis with organizing pneumonia and other interstitial diseases have also been published. Given the rarity of such pneumopathy, we report a case of bronchiolitis in a patient with a prior diagnosis of ulcerative colitis. We discuss the radiological findings and the results of lung function testing, emphasizin the utility of corticosteroid treatment, which usually leads to a good outcome in pneumopathy secondary to IBD.


Nutritional value and intestinal effects of dipeptides and tripeptides. Comparison with their issuing bovine plasma protein in rats.
A hydrolysate containing 75% di- and tripeptides (DTP) was prepared from bovine plasma proteins (BP) and the original protein and hydrolysate were compared for nutritional value. Food intake, protein efficiency ratio (PER), nitrogen balance and digestibility and plasma amino acid concentrations were measured in young rats receiving the diets over 17 days. Moreover, intestinal adaptation was evaluated in duodenum, jejunum and ileum, with the aid of light microscopy and enzyme analyses; tritiated thymidine incorporation was also measured. In DTP- and BP-fed rats, food intake, body weight gain, nitrogen balance and digestibility as well as PER were similar. Plasma amino acid concentration analyses showed an increased concentration of threonine and valine in the BP-fed group. Measurements of mucosal enzyme activities suggest adaptation to the diets especially in the ileum as indicated by increasing aminopeptidase N and dipeptidyl peptidase IV specific activities in the BP-fed group. This group also displayed substantial 3H-thymidine incorporation. It is concluded that the hydrolysate containing di- and tripeptides is efficiently utilized in healthy growing rats, though the efficacy is not higher than with the BP diet except for the difference in 3H-thymidine incorporation.


Effects of doxazosin and propranolol on A2A adenosine receptors in essential hypertension.
A2A adenosine receptors inhibit neutrophil adhesion and superoxide anion generation. The aim of the present study was to evaluate the effect of antihypertensive treatment with doxazosin or propranolol on the binding and functional parameters of A2A adenosine receptors of lymphocytes and neutrophils in essential hypertensive patients. Two groups of previously untreated, essential hypertensive patients were studied. The mean affinity (K(d)) and density (B(max)) of adenosine receptors, by the A2A selective radioligand [3H]-ZM-241385 binding assays, and EC50, by cAMP assays, were obtained first on no medication and a second time after treatment for up to 13 weeks with doxazosin (13 patients) or propranolol (8 patients). A third group of 15 healthy normotensive volunteers matched by age, sex, and body mass index was used as a control. Binding and functional parameters of the A2A adenosine receptors were significantly higher in the 2 hypertensive groups than in controls (P always <0.0001), both in lymphocyte and neutrophil membranes. After treatment with propranolol, the binding parameters did not change significantly, whereas after treatment with doxazosin, K(d), B(max), and EC50 values returned to control levels. In never-treated essential hypertensive patients, lower affinity, higher density, and impaired function of A2A adenosine receptors are present. The binding and functional parameters of A2A adenosine receptors appear to be normalized after treatment with doxazosin but not with propranolol.


Diseasome and comorbidities complexities of SARS-CoV-2 infection with common malignant diseases.
With the increasing number of immunoinflammatory complexities, cancer patients have a higher risk of serious disease outcomes and mortality with SARS-CoV-2 infection which is still not clear. In this study, we aimed to identify infectome, diseasome and comorbidities between COVID-19 and cancer via comprehensive bioinformatics analysis to identify the synergistic severity of the cancer patient for SARS-CoV-2 infection. We utilized transcriptomic datasets of SARS-CoV-2 and different cancers from Gene Expression Omnibus and Array Express Database to develop a bioinformatics pipeline and software tools to analyze a large set of transcriptomic data and identify the pathobiological relationships between the disease conditions. Our bioinformatics approach revealed commonly dysregulated genes (MARCO, VCAN, ACTB, LGALS1, HMOX1, TIMP1, OAS2, GAPDH, MSH3, FN1, NPC2, JUND, CHI3L1, GPNMB, SYTL2, CASP1, S100A8, MYO10, IGFBP3, APCDD1, COL6A3, FABP5, PRDX3, CLEC1B, DDIT4, CXCL10 and CXCL8), common gene ontology (GO), molecular pathways between SARS-CoV-2 infections and cancers. This work also shows the synergistic complexities of SARS-CoV-2 infections for cancer patients through the gene set enrichment and semantic similarity. These results highlighted the immune systems, cell activation and cytokine production GO pathways that were observed in SARS-CoV-2 infections as well as breast, lungs, colon, kidney and thyroid cancers. This work also revealed ribosome biogenesis, wnt signaling pathway, ribosome, chemokine and cytokine pathways that are commonly deregulated in cancers and COVID-19. Thus, our bioinformatics approach and tools revealed interconnections in terms of significant genes, GO, pathways between SARS-CoV-2 infections and malignant tumors.


Radon concentrations in water in the region of Tokat city in Turkey.
The aim of this study is to measure the radon ((222)Rn) concentrations in drinking water and river water in the region of Tokat city in Turkey. The measurements were performed by analysing the water samples collected from tap water, spring water and Yesilırmak river water flowing through the centre of the city of Tokat. The obtained radon concentrations ranged from 0.48 ± 0.22 to 1.30 ± 0.27 Bq l(-1) in tap water, from 0.13 ± 0.17 to 1.20 ± 0.29 Bq l(-1) in spring water and from 0.09 ± 0.12 to 0.83 ± 0.17 Bq l(-1) in the Yesilirmak river water. The results are presented and compared with other studies. From these data, the average effective dose equivalent from radon in tap water and in spring water has been estimated as 5.0 and 3.0 µSv y(-1), respectively.


Diagnostic utility of ventilation/perfusion lung scans in acute pulmonary embolism is not diminished by pre-existing cardiac or pulmonary disease.
The purpose of this study was to assess the impact of prior cardiac or pulmonary disease upon the utility of ventilation/perfusion (V/Q) scans in the diagnosis of acute pulmonary embolism (PE). Ventilation/perfusion scans were evaluated among 365 patients with no prior cardiac or pulmonary disease and compared to V/Q scans in 526 patients with prior cardiac or pulmonary disease. Among patients with no prior cardiac or pulmonary disease, PE was present in 117 and PE was excluded in 248. Among patients with prior cardiac or pulmonary disease, PE was present in 140 and excluded in 386. The positive predictive value for PE of high probability V/Q scans among patients with prior cardiac or pulmonary disease, 55 of 66 (83 percent), was not significantly lower than among patients without prior cardiac or pulmonary disease, 50 of 54 (93 percent) (NS). The positive predictive value of low probability V/Q scans was similar with prior cardiac or pulmonary disease, 25 of 182 (14 percent), and without prior cardiac or pulmonary disease, 17 of 113 (15 percent) (NS), as was the predictive value of near normal/normal V/Q scans, 2 of 51 (4 percent), vs 3 of 79 (4 percent) (NS). The sensitivity of high probability V/Q scans, with pre-existing cardiac or pulmonary disease and without, 55 of 140 (39 percent) vs 50 of 117 (43 percent), did not differ significantly. The specificity of high probability V/Q scans with prior cardiac or pulmonary disease and without, 375 of 386 (97 percent) vs 244 of 248 (98 percent) was also similar (NS). In conclusion, the diagnostic utility of V/Q scans for acute PE was not impaired by the presence of pre-existing cardiac or pulmonary disease. Fewer patients, however, with no prior cardiac or pulmonary disease, had intermediate (indeterminate) V/Q scans.


Increased expression of soluble inducible costimulator ligand (ICOSL) in patients with systemic lupus erythematosus.
To investigate the level of costimulating molecules in systemic lupus erythematosus (SLE), we assessed the plasma concentrations of soluble forms of costimulatory molecules such as programmed death-1 (PD-1), B7-H1 (also called PD-L1 or CD274) and inducible costimulator ligand (ICOSL) in patients with SLE. Plasma concentrations of soluble PD-1, B7-H1 and ICOSL were measured by ELISA using plasma samples from 57 SLE patients with or without the active disease, 21 rheumatoid arthritis (RA) patients and 35 healthy subjects. We also evaluated surface ICOSL expression on B cells using flow cytometry to gain a better understanding of ICOSL expression. To compare the level of ICOSL mRNA expression, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using total RNA from peripheral blood mononuclear cells (PBMCs) isolated from eight healthy subjects and 11 patients with SLE. The concentration of plasma ICOSL was significantly higher in patients with SLE compared with healthy subjects (P = 0.005). Plasma ICOSL concentrations in patients with active SLE were also significantly higher than those of either patients with inactive SLE or patients with RA (P = 0.001, P = 0.015, respectively). Plasma ICOSL concentrations in patients with SLE correlated modestly with the SLE disease activity index score (r = 0.298, P = 0.024). We also found a significant inverse correlation between the soluble ICOSL expression and the surface ICOSL expression on B cells (r = -0.690, P = 0.001). However, ICOSL mRNA levels of patients with SLE were comparable with those of the control subjects. There was also no significant difference in plasma B7-H1 concentrations between groups, and plasma PD-1 was not detectable in any of the groups. The plasma concentration of soluble ICOSL might be correlated to the disease severity of lupus. The increased levels of ICOSL in active lupus suggest that this pathway is involved in the pathogenesis of SLE. The mechanism and physiological role of soluble ICOSL in the pathogenesis of SLE, however, remains to be investigated.


Purification and characterization of the 7S vicilin from Korean pine (Pinus koraiensis).
Pine nuts are economically important as a source of human food. They are also of medical importance because numerous pine nut allergy cases have been recently reported. However, little is known about the proteins in pine nuts. The purpose of this study was to purify and characterize pine nut storage proteins. Reported here is the first detailed purification protocol of the 7S vicilin-type globulin from Korean pine (Pinus koraiensis) by gel filtration, anion exchange, and hydrophobic interaction chromatography. Reducing SDS-PAGE analysis indicated that purified vicilin consists of four major bands, reminiscent of post-translational protease cleavage of storage proteins during protein body packing in other species. The N-terminal ends of vicilin peptides were sequenced by Edman degradation. Circular dichroism (CD) and differential scanning calorimetry (DSC) analyses revealed that pine nut vicilin is stable up to 80 degrees C and its folding-unfolding equilibrium monitored by intrinsic fluorescence can be interpreted in terms of a two-state model.


Three-dimensional structure of the zinc-containing phosphotriesterase with the bound substrate analog diethyl 4-methylbenzylphosphonate.
Phosphotriesterase from Pseudomonas diminuta catalyzes the hydrolysis of paraoxon and related acetylcholinesterase inhibitors with rate enhancements that approach 10(12). The enzyme requires a binuclear metal center for activity and as isolated contains 2 equiv of zinc per subunit. Here we describe the three-dimensional structure of the Zn2+/Zn2+-substituted enzyme complexed with the substrate analog diethyl 4-methylbenzylphosphonate. Crystals employed in the investigation belonged to the space group C2 with unit cell dimensions of a = 129.6 A, b = 91.4 A, c = 69.4 A, beta = 91.9 degrees, and two subunits in the asymmetric unit. The model was refined by least-squares analysis to a nominal resolution of 2.1 A and a crystallographic R-factor of 15.4% for all measured X-ray data. As in the previously reported structure of the cadmium-containing enzyme, the bridging ligands are a carbamylated lysine residue (Lys 169) and a hydroxide. The zinc ions are separated by 3.3 A. The more buried zinc ion is surrounded by His 55, His 57, Lys 169, Asp 301, and the bridging hydroxide in a trigonal bipyramidal arrangement as described for the cadmium-substituted enzyme. Unlike the octahedral coordination observed for the more solvent-exposed cadmium ion, however, the second zinc is tetrahedrally ligated to Lys 169, His 201, His 230, and the bridging hydroxide. The diethyl 4-methylbenzylphosphonate occupies a site near the binuclear metal center with the phosphoryl oxygen of the substrate analog situated at 3.5 A from the more solvent-exposed zinc ion. The aromatic portion of the inhibitor binds in a fairly hydrophobic pocket. A striking feature of the active site pocket is the lack of direct electrostatic interactions between the inhibitor and the protein. This most likely explains the broad substrate specificity exhibited by phosphotriesterase. The position of the inhibitor within the active site suggests that the nucleophile for the hydrolysis reaction is the metal-bound hydroxide.


Functional luteolysis in response to hydrogen peroxide in human luteal cells.
To evaluate the effect of reactive oxygen species in human corpus luteum function, we investigated whether hydrogen peroxide (H2O2) affects the in vitro luteal cell production of steroids. H2O2 treatment (1.0-100 microM) of mid and late luteal cell cultures elicited a dose-dependent decrease in basal progesterone production. However, treatment of mid luteal cells with a low concentration of H2O2 (0.01 microM) significantly stimulated progesterone secretion (P < 0.05). In addition, H2O2 (100 microM) markedly inhibited human chorionic gonadotropin (hCG)-stimulated progesterone and estradiol secretion. cAMP production was enhanced (2.4-fold, P < 0.05) by hCG treatment of luteal cells. The addition of H2O2 (0.1-100 microM) to hCG-stimulated luteal cell cultures elicited a decrease in cAMP concentration (P < 0.05) and in the specific binding of radiolabeled hCG by luteal cells. Progesterone and estradiol production stimulated by dibutyryl cAMP were significantly inhibited by H2O2 (P < 0.05). These findings suggest that H2O2 interferes with basal steroid production and, in hCG-stimulated conditions, it may inactivate the gonadotropin-receptor complex. The anti-steroidogenic action of H2O2 therefore raises the possibility of a modulatory role of H2O2 in human luteal steroidogenesis.


COVID-19 ARDS: Points to Be Considered in Mechanical Ventilation and Weaning.
The COVID-19 disease can cause hypoxemic respiratory failure due to ARDS, requiring invasive mechanical ventilation. Although early studies reported that COVID-19-associated ARDS has distinctive features from ARDS of other causes, recent observational studies have demonstrated that ARDS related to COVID-19 shares common clinical characteristics and respiratory system mechanics with ARDS of other origins. Therefore, mechanical ventilation in these patients should be based on strategies aiming to mitigate ventilator-induced lung injury. Assisted mechanical ventilation should be applied early in the course of mechanical ventilation by considering evaluation and minimizing factors associated with patient-inflicted lung injury. Extracorporeal membrane oxygenation should be considered in selected patients with refractory hypoxia not responding to conventional ventilation strategies. This review highlights the current and evolving practice in managing mechanically ventilated patients with ARDS related to COVID-19.


A glycosaminoglycan inhibitor of thrombin: a new mechanism for abnormal hemostatic assays in cancer.
The isolation and partial characterization of a novel anticoagulant from the plasma of a patient with metastatic prostate cancer is described. The patient had a prolonged activated partial thromboplastic time, prothrombin time and thrombin time which did not correct by mixing with normal plasma. The reptilase time was normal and the prolonged thrombin time was corrected with protamine sulfate suggesting a heparin-like anticoagulant. A glycosaminoglycan anticoagulant (GAC) was isolated from the patient's plasma. The inhibitory activity of the GAC was destroyed by treatment with chondroitinase ABC. The GAC migrated on agarose gel electrophoresis between keratin sulfate and heparan sulfate. Purified GAC possessed only 2% (W/W) of the antithrombin III cofactor activity of porcine heparin. In assays using purified fibrinogen, the GAC was shown to directly inhibit fibrinogen proteolysis by thrombin. It is concluded that this glycosaminoglycan anticoagulant directly inhibits thrombin clotting of fibrinogen and is a new mechanism for abnormal hemostatic assays in cancer.


Ravenic acid, a new tetramic acid isolated from a cultured microfungus, Penicillium sp.
A new antibiotic polyene tetramic acid, ravenic acid (2), has been isolated from the mycelia of a cultured fungus, Penicillium sp. The structure of ravenic acid was determined by detailed spectroscopic analysis and the major isomer identified as possessing (3Z, 7E, 9E, 11E, 13E) stereochemistry.


Wettability Switching of Electrode for Signal Amplification: Conversion of Conformational Change of Stimuli-Responsive Polymer into Enhanced Electrochemical Chiral Analysis.
Signal amplification of chiral interaction is a much needed task for sensing of enantiomers due to nearly identical chemical and physical properties of the chiral isomers. In this article, we established an electrochemical chiral sensing method with high sensitivity and selectivity for monosacharrides based on the stimuli-responsive copolymer/graphene hybrid-modified screen-printed carbon electrodes. The hybrid synthesized by the "grafting from" atom transfer radical polymerization (ATRP) process not only acted as a chiral recognition element but also provided a chiral signal amplification strategy. This occurs due to high sensitivity of conformational transition of copolymer on graphene to the weak chiral interactions that greatly facilitating the diffusion of electroactive probes and monosaccharides to the electrode surface. The described method can quantify monosaccharides, even the concentration of one enantiomer is as low as 1 nM. Apart from the demonstrated chiral distinguish ability, good selectivity toward monosaccharides in comparison to potential interference molecules was also observed. The electrodes with significant analytical performance were successfully applied for discriminating glucose enantiomers in live cells and studying their different transport mechanism. Together, the results show that the coupling of amplification-by-wettability switching concept with electrochemical method offers great promises in providing a sensitive, facile, and cost-effective solution for chiral recognition of molecules in biological process.


[Enhanced chemotherapeutic drug delivery to tumor tissue by high intensity focused ultrasound].
Cancer is the first leading cause of death in Korea. Systemic chemotherapy is currently the standard treatment for a wide variety of cancers; however, in the majority of cases, cure is not achieved, and the attendant side effects of the treatment are considerable. The effectiveness of chemotherapy in cancers depends on the adequate delivery of the chemotherapeutic agent to cancer cells. The achievement of uniform drug delivery of chemotherapeutic agents throughout tumors is limited by the anomalous vascularization and blood vessel permeability. Ultrasound has an ever-increasing role in the delivery of therapeutic agents including chemotherapeutic agents, proteins, and genetic materials. Ultrasound technology allows for the use of focused ultrasound energy for therapeutic purposes by delivering high-intensity focused ultrasound for applications such as tissue ablation, and enhanced drug delivery. We reviewed recent work in the emerging field of ultrasound-based therapeutics, with particular emphasis on the delivery of drugs to tumor tissue.


[The tertiary effect of psychotropic drugs. Results of an anthropologic study conducted in southwestern France among elderly consumers].
This article presents part of the results of a research conducted in the South-west of France on consumption by elderlies of psychotropic drugs. Two institutions have been chosen. The author was seeking to measure the consumption of psychotropic drugs before and after institutionalization, based on a medical questionnaire distributed to doctors working in these institutions. The author then examines the impact of this consumption on social relations, at home and within institutions, from an anthropologic perspective. Elderlies, members of their families, as well as doctors and other parties concerned by this consumption have been questioned during semi-directed interviews. Other than the general consumption of psychotropic drugs in the two institutions which the author attempts to understand the extent, only modifications in family relationships after the taking of drugs at home are exposed in this article.


[Population health protection at territories contaminated after the Chernobyl accident].
A concept of preserving population health at territories contaminated after the Chernobyl accident is proposed, which is based on the results of multifactorial evaluation of relationships and prognostic evaluations of the basic medical demographic parameters.


Source/Sink relations of abscising and nonabscising soybean flowers.
The partitioning of recently fixed (14)C to setting and abscising flowers within the axillary raceme of ;Clark' isoline E1t soybeans (Glycine max L. Merr) was examined as a function of time after anthesis of individual flowers. In such racemes, the first four flowers showed a 17% abscission while the next four flowers showed 47% abscission.Source/sink relations of flowers I-IV (normally setting) were compared to those of flowers V-VIII (normally abscising) by pulse labeling source leaves with (14)CO(2) and determining the radioactivity of individual flowers after a 4-hour chase period. The relative specific activity (RSA;% disintegrations per minute per% dry weight), sink strength (% disintegrations per minute), and its components, sink size (milligrams dry weight) and sink intensity (% disintegrations per milligram dry weight) were then calculated as a function of days after anthesis.Sink intensity (i.e. the competitive ability to accumulate photoassimilate per unit mass) was very high prior to anthesis of both setting and abscising flowers. Sink intensity then became very low for the first 3 days following anthesis after which it recovered in normally setting flowers, but failed to recover in normally abscising flowers. It is concluded that soybean reproductive abscission is determined at or very near the day of anthesis.


Longitudinal smooth muscle of the mammalian intestine. A model for Ca2+ signaling by cADPR.
Ca2+ mobilization in muscle cells from the circular muscle layer of the mammalian intestine is mediated by IP3-dependent Ca2+ release. Ca2+ mobilization in muscle from the adjacent longitudinal muscle layer involves a distinct, phosphoinositide-independent pathway. Receptors for contractile agonists in longitudinal muscle cells are coupled via a pertussis toxin-sensitive G protein to activation of PLA2 and formation of arachidonic acid (AA). The latter activates Cl- channels resulting in depolarization of the plasma membrane and opening of voltage-sensitive Ca2+ channels. Ca2+ influx via these channels induces Ca2+ release by activating sarcoplasmic ryanodine receptor/Ca2+ channels. The increase in [Ca2+]i activates membrane-bound ADP ribosyl cyclase, and the resultant formation of cADPR enhances Ca(2+)-induced Ca2+ release.


Vitamin C: an experimental and theoretical study on the gas-phase structure and ion energetics of protonated ascorbic acid.
In order to investigate the gas-phase mechanisms of the acid catalyzed degradation of ascorbic acid (AA) to furan, we undertook a mass spectrometric (ESI/TQ/MS) and theoretical investigation at the B3LYP/6-31 + G(d,p) level of theory. The gaseous reactant species, the protonated AA, [C6 H8 O6 ]H+ , were generated by electrospray ionization of a 10-3 M H2 O/CH3 OH (1 : 1) AA solution. In order to structurally characterize the gaseous [C6 H8 O6 ]H+ ionic reactants, we estimated the proton affinity and the gas-phase basicity of AA by the extended Cooks's kinetic method and by computational methods at the B3LYP/6-31 + G(d,p) level of theory. As expected, computational results identify the carbonyl oxygen atom (O2) of AA as the preferred protonation site. From the experimental proton affinity of 875.0 ± 12 kJ mol-1 and protonation entropy ΔSp 108.9 ± 2 J mol-1 K-1 , a gas-phase basicity value of AA of 842.5 ± 12 kJ mol-1 at 298 K was obtained, which is in agreement with the value issuing from quantum mechanical computations. Copyright © 2016 John Wiley & Sons, Ltd.


Treatment of indolent non-Hodgkin's lymphoma localized in the head and neck.
A total of 25 patients with indolent non-Hodgkin's lymphoma localized in the head and neck region was analyzed. Of these, 21 patients were classified as clinical Stage I, and 4 as Stage II. In 22 patients the extranodal site was involved, and it was a remarkable characteristic of this series of patients. Overall treatment results were as follows: survival rate 100% at 5 years, and relapse-free survival rate 81% at 2 and 5 years. There was only 1 death at 6 years and 2 months after treatment, and 4 relapses occurred by 2 years after treatment. Relapse was observed in 3 of 8 patients with follicular mixed/follicular medium type, which was in contrast to the other indolent histologies (SL, DSCl, ILL) with very few relapses.


Characterization of a new HLA-B*38 allele (B*3803) in a Spanish Caucasian individual which is closely related to the Oriental B*38021 and B*39021 alleles.
The broad HLA-B16 serologic specificity is divided into B38 and B39 splits associated to Bw4 and Bw6, respectively. Differential serologic variants have been defined for several molecular subtypes of B39 and for B38. We found a Spanish Caucasian individual carrying a B16 Bw4-associated antigen which was not recognized by reagents against B16 splits. Sequencing analysis showed a new B16 subtype termed B*3803. HLA class I sequence-based typing (SBT) analysis demonstrated that B*3803 co-segregates with A*2608 and Cw*1203, forming a common Caucasian haplotype. Sequence comparison with B*38 and B*39 subtypes evidences that although B*3803 is close related to B*3802, it only differs from B*39021 by six clustered nucleotide position in the Bw4/Bw6 motif, and strongly suggests that B*3803 could have evolved from, or be the ancestral gene of the Oriental-associated B*3802 and B*39021 alleles. However, more complex patterns of genetic events should be considered due to the Caucasian background of the B*3803 individual an its associated haplotype.


Assessing the utility of testing aluminum levels in dialysis patients.
Plasma aluminum (Al) is routinely tested in many dialysis patients. Aluminum exposure may lead to acute toxicity and levels in excess of ∼2.2 μmol/L (60 μg/L) should be avoided. Historically, toxicity has been caused by excessive dialyzate Al but modern reverse osmosis (RO) water should be Al free. Nevertheless, many units continue to perform routine Al levels on dialysis patients. This single-center study retrospectively analyzed Al levels in plasma, raw water feed, and RO product between 2010 and 2013 using our database (Nephworks 6) with the aim of determining the utility of these measurements. Two thousand fifty-eight plasma Al tests in 755 patients (61.9% male, mean age 64.7 years) were reviewed showing mean ± SD of 0.41 ± 0.30 μmol/L. One hundred eleven (5.4%) tests from 61 patients had Al levels >0.74 μmol/L and 45 (73.8%) of these patients were or had been prescribed Al hydroxide (Al(OH)(3)) as a phosphate binder. Seven patients had Al concentrations >2.2 μmol/L with no source of Al identified in 1 patient. One hundred sixty-six patients taking Al(OH)(3) (78.7% of all patients on Al(OH)(3)) had levels ≤0.74 μmol/L, the odds ratio of plasma Al > 0.74 μmol/L on Al(OH)3 was 9. The cost of plasma Al assay is $A30.60; thus, costs were $A62,974.80 over the study period. Despite RO feed water Al levels as high as 48 μmol/L, Al output from the RO was almost always undetectable (<0.1 μmol/L) with dialyzate Al levels > 2.2 μmol/L only 3 times since 2010, and never in the last 3 years. Routine unselected testing of plasma Al appears unnecessary and expensive and more selective testing in dialysis patients should be considered.


The prediction of imminent aggression in patients with mental illness and/or intellectual disability using the Dynamic Appraisal of Situational Aggression instrument.
Objective: The aim of this paper was to determine whether imminent aggression in psychiatric inpatients can be accurately predicted using a structured risk assessment instrument, the Dynamic Appraisal of Situational Aggression (DASA). Methods: This prospective validation study involved 10 013 DASA risk assessments of patients residing in a psychiatric hospital. Twenty-four hours after the risk assessment, psychiatric nurses documented whether patients had behaved aggressively towards others or whether they had deliberately damaged property. They also noted the target of aggression, whether towards staff, patients or property. Results: The predictive validity of the DASA varied according to the type and target of aggression. The prediction of any aggressive behaviour, irrespective of type of aggression or target, was significantly greater than chance (AUC = 0.69). The strongest predictive accuracy (AUC = 0.80) was for physical aggression towards staff. Conclusions: These results suggest that imminent aggression in psychiatric hospitals may be able to be accurately predicted by psychiatric nurses using a structured risk assessment instrument.


Toward an organ based dose prescription method for the improved accuracy of murine dose in orthovoltage x-ray irradiators.
Accurate dosimetry is essential when irradiating mice to ensure that functional and molecular endpoints are well understood for the radiation dose delivered. Conventional methods of prescribing dose in mice involve the use of a single dose rate measurement and assume a uniform average dose throughout all organs of the entire mouse. Here, the authors report the individual average organ dose values for the irradiation of a 12, 23, and 33 g mouse on a 320 kVp x-ray irradiator and calculate the resulting error from using conventional dose prescription methods. Organ doses were simulated in the Geant4 application for tomographic emission toolkit using the MOBY mouse whole-body phantom. Dosimetry was performed for three beams utilizing filters A (1.65 mm Al), B (2.0 mm Al), and C (0.1 mm Cu + 2.5 mm Al), respectively. In addition, simulated x-ray spectra were validated with physical half-value layer measurements. Average doses in soft-tissue organs were found to vary by as much as 23%-32% depending on the filter. Compared to filters A and B, filter C provided the hardest beam and had the lowest variation in soft-tissue average organ doses across all mouse sizes, with a difference of 23% for the median mouse size of 23 g. This work suggests a new dose prescription method in small animal dosimetry: it presents a departure from the conventional approach of assigninga single dose value for irradiation of mice to a more comprehensive approach of characterizing individual organ doses to minimize the error and uncertainty. In human radiation therapy, clinical treatment planning establishes the target dose as well as the dose distribution, however, this has generally not been done in small animal research. These results suggest that organ dose errors will be minimized by calibrating the dose rates for all filters, and using different dose rates for different organs.


An estimate of rapid cytoplasmic calcium buffering in a single smooth muscle cell.
Cytoplasmic calcium increments in the absence of sarco (endo) plasmic reticulum function were measured with a low-affinity fluorophore Indo-1FF in single isolated smooth muscle cells from guinea-pig urinary bladder. To evaluate the Ca(2+)-buffering properties of the myoplasm, Ca2+ influx, measured as time integral of the Ica (integral of Ica), was compared with corresponding free Ca2+ increments (delta [Ca2+]i) in the cytoplasm. The ratio between integral of ICa and delta [Ca2+]i (integral Ica/delta [Ca2+]i), reflecting the Ca2+ buffering properties of the cytosol, was in the range of 4.9-9.3 pC/microM (mean 6.2 +/- 1.2, n = 12). It remained approximately constant (6.4 +/- 1.4 pC/microM, n = 8) during recordings lasting up to 25 min, suggesting that cytoplasmic Ca2+ binding does not change markedly during cell dialysis and that the endogenous Ca2+ buffer is not significantly washed out of the cell through the patch pipette. Wash-in or wash-out of BAPTA, a mobile high-affinity Ca2+ buffer, into or from the cell markedly changed the relationship between Ca2+ influx through Ca2+ channels and delta [Ca2+]i within minutes. Changes in integral of ICa/delta [Ca2+]i during the sequence of depolarizing steps, which increased free [Ca2+]i up to 5 microM, suggested lower limits for the apparent affinity of a rapid Ca2+ buffer (16 microM) and for the total buffer concentration (530 microM). Introduction of 4 mM DPTA (Kd for Ca2+ = 81 microM) into the cell more than doubled the total cytoplasmic Ca2+ buffer capacity. These results suggest that cytoplasmic Ca2+ buffer in smooth muscle cells has a low affinity for free Ca2+. The Ca(2+)-binding ratio of the cytoplasm in most cells was estimated to be between 30 and 40. The Ca(2+)-binding ratio did not differ markedly between cells isolated from neonatal (< or = 5 days) and adult animals.


A basic residue, Lys 782, composes part of the ATP-binding site on the epidermal growth factor receptor tyrosine kinase.
To identify amino acids specific for tyrosine kinase activity, the role of several conserved basic residues in kinase function was tested. Modeling of the epidermal growth factor receptor tyrosine kinase domain based on the crystal structure of cyclic AMP-dependent protein kinase and insulin receptor revealed several basic residues present on the surface of epidermal growth factor receptor. Using the molecular modeling program, GRASP, the basic residues Arg 779, Lys 782, and Lys 855 were shown to provide an area of positive charge to the surface of the molecule. To deduce the role of these residues in ATP and substrate binding, site-directed mutants were prepared and kinetic constants were measured. Mutation of Lys 855 to Ala destabilized the enzyme and caused partial inactivation. Mutation of either Arg 779 or Lys 782 had little effect on the Km value for peptide substrate. However, alteration of Lys 782 increased the Km value for ATP 28-fold, indicating a role for Lys 782 in binding ATP. Because residues similar to Lys 782 in the sequences of mitogen-activated protein kinase and insulin receptor make contact with a ribose hydroxyl of ATP, it is proposed that Lys 782 may be one of the residues composing the ribose-binding site of epidermal growth factor receptor.


[Adenocarcinoma of the ileal segment with transitional cell carcinoma of the bladder following ileocytoplasty: a case report].
A 67 year-old woman visited our hospital complaining of pollakisuria. She had undergone left nephrectomy and augmentation ileocystoplasty for tuberculous bladder atrophy 40 years previously. She underwent a total cystectomy and tubeless ureterocutaneostomy with a preoperative diagnosis of muscle-invading transitional cell carcinoma of the bladder. The pathological diagnosis was adenocarcinoma of the ileal segment and transitional cell carcinoma of the original bladder. This is the first case report of adenocarcinoma of the ileal segment and transitional cell carcinoma of the original bladder among 22 patients suffering from bladder cancer after ileocystoplasty.


Using the Tools and Resources of the RCSB Protein Data Bank.
The Protein Data Bank (PDB) archive is the worldwide repository of experimentally determined three-dimensional structures of large biological molecules found in all three kingdoms of life. Atomic-level structures of these proteins, nucleic acids, and complex assemblies thereof are central to research and education in molecular, cellular, and organismal biology, biochemistry, biophysics, materials science, bioengineering, ecology, and medicine. Several types of information are associated with each PDB archival entry, including atomic coordinates, primary experimental data, polymer sequence(s), and summary metadata. The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) serves as the U.S. data center for the PDB, distributing archival data and supporting both simple and complex queries that return results. These data can be freely downloaded, analyzed, and visualized using RCSB PDB tools and resources to gain a deeper understanding of fundamental biological processes, molecular evolution, human health and disease, and drug discovery. © 2016 by John Wiley & Sons, Inc.


Imaging studies in dyspepsia.
Patients with functional dyspepsia have discomfort centred in the upper abdomen in the absence of oesophagitis, ulcer, cancer or other pathology which could have explained the dyspepsia. It is generally accepted that neither endoscopy, nor other imaging modalities give any positive findings supporting the diagnosis. However, recent investigations have shown that both endoscopic and ultrasonographic imaging show changes: erosive prepyloric changes (EPC) and accommodation abnormalities, respectively, in a high percentage of the patients. The diagnostic sensitivity and specificity of the changes are not yet known, but the fact that they are also seen in several other conditions characterised by dyspepsia, for instance in gallstone disease, may simply indicate that they are linked to epigastric discomfort in general, and not to a specific dyspeptic condition. Ultrasonographic imaging is a non-invasive, widely available, convenient, and reliable method for evaluation of gastric emptying, gastric motility, transpyloric flow and accommodation disturbances, which may play a crucial role in the pathogenesis of dyspepsia.


[Allergy to the bites of blood-sucking insects: clinical manifestations].
Blood-sucking insects and other arthropods may occur allergic reactions when stinging. Usually, inflammatory symptoms are mild with a locoregional extension. Pruritus may be painful and sometimes patients experienced a functional impotency. Systemic reactions are possible. Anaphylaxis is rare and rather observed with ticks (Ixodes and Argas) and kissing-bugs. The circumstances and mechanisms of the sting related to the knowledge of the insect biology elicit the clinical symptoms. Skin prick-tests are usually not practicable. Indeed, the diagnosis remains based upon anamnestic and entomological data because the poor sensibility of in vitro tests. However, some immunological investigations gave signs of interest for prospective studies. Symptomatic drugs and prevention advices must be purchased for exposed patients.


Bilateral optic neuritis as the presenting sign of post SARS-CoV-2 acute disseminated encephalomyelitis.
to report a case of Acute Disseminated EncephaloMyelitis (ADEM) occurring after documented SARS-Cov2 infection and flu-like disease. A 59-years-old woman presented with progressive visual loss and right leg paresthesia started 6 days earlier when CT scan excluded abnormalities. Visual acuity was OU hand motion with bilateral slow pupillary response and unremarkable ocular extrinsic motility while visual field testing showed diffuse bilateral sensitivity reduction. The patient had also right leg paresthesia and reported a 2-weeks flu-like syndrome 15 days earlier, with nausea, diarrhea, anosmia, ageusia, cough. Brain Magnetic Resonance Imaging revealed bilateral optic nerve enhancement, multiple brain and spine lesions. SARS-CoV-2 PCR tested negative on nasal swab and positive on cerebrospinal fluid. Patient's serum tested positive for anti-SARS-CoV-2 IgG, negative for anti-aquaporin-4 and anti-myelin oligodendrocyte glycoprotein antibodies. A diagnosis of suspect ADEM post SARS-CoV-2 infection was made and treatment with high dose intravenous methylprednisolone (with subsequent prednisone tapering) and immunoglobulins started. Ten days later vision improved to 20/30 RE and 20/25 LE and 3 months later to 20/20. ADEM may ensue after SARS-CoV-2 virus infection. High suspicious index and prompt aggressive treatment may result in complete vision restauration.


Role of insulin in the anti-apoptotic effect of glucose-insulin-potassium in rabbits with acute myocardial ischemia and reperfusion.
To study the effects of glucose-insulin-potassium (GIK) cocktail on cardiac myocyte apoptosis and cardiac functional recovery following myocardial ischemia/reperfusion (MI/R), and to further determine the role of insulin in the GIK-induced cardioprotective effect in vivo . Forty eight male rabbits were subjected to 40 min MI followed by R for 3 h and were randomly received one of the following treatments: saline, GIK (glucose: 150 g/L, insulin: 60 U/L and KCl: 80 mmol/L), or insulin (n = 16 in each group) at 1 ml x kg(-1) x h(-1), beginning 30 min before MI and continuing throughout the 3 h-reperfusion. Blood glucose, electrolytes, arterial blood pressure and left ventricular pressure (LVP) were monitored throughout the experiment. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activity were measured spectrophotometrically. Myocardial infarction and myocardial apoptosis (both DNA laddering and TUNEL analysis) were determined in a blinded manner. MI/R caused significant cardiac dysfunction and myocardial apoptosis (both strong DNA ladder formation and TUNEL-positive staining). Compared with vehicle, GIK-treated rabbits showed protection against MI/R as evidenced by reduced myocardial infarction (19.7% +/- 2.6% vs . 26.8% +/- 3.3% of vehicle, n = 10, P < 0.05), marked decrease in DNA fragmentation and apoptotic index (11.0% +/- 2.1% vs . 20.1% +/- 3.1% of vehicle, n = 6, P < 0.01), significant decrease of plasma CK and LDH and improved recovery of cardiac systolic/diastolic function at the end of R. Treatment with insulin alone decreased blood glucose significantly but still exerted cardioprotective effects comparable with that of GIK. GIK exerts cardioprotective effects against postischemic myocardial injury and improves cardiac functional recovery in vivo . Insulin, mainly through the anti-apoptotic effect, plays a key role in the GIK-elicited myocardial protection in MI/R.


[Rhodnius prolixus in Nicaragua: geographical distribution, control, and surveillance, 1998-2009].
Present an overview of the control of Rhodnius prolixus, the principal vector in the transmission of Chagas' disease in Central America, during the period 1998-2009 in Nicaragua. Describe the vector control carried out and the geographical distribution of the infested localities. The available information in Nicaragua's Ministry of Health was studied and analyzed. The geographical distribution of R. prolixus was visualized using the Quantum GIS 1.5.0 map visualization program. It was determined that 59 localities in 14 municipalities of 8 departments had a history of R. prolixus infestation between 1998 and 2009. The altitude of the infested localities ranges between 160 and 1 414 meters above sea level. A total of 56 localities have been treated with more than two cycles of chemical control. The presence of the vector was detected in the second spraying cycle, but it was not found in any locality during the third cycle. The greatest geographical concentration of R. prolixus was found in two departments in the northern region: Madriz and Nueva Segovia. There were fewer infested localities in Nicaragua than in other Central American countries. Chemical control has been successful in the localities treated, but the institutional and community surveillance system needs to be strengthened to monitor R. prolixus reinfestation and expand vector control coverage.


Dimensional Accuracy and Clinical Value of 3D Printed Models in Congenital Heart Disease: A Systematic Review and Meta-Analysis.
The aim of this paper is to summarize and evaluate results from existing studies on accuracy and clinical value of three-dimensional printed heart models (3DPHM) for determining whether 3D printing can significantly improve on how the congenital heart disease (CHD) is managed in current clinical practice. Proquest, Google Scholar, Scopus, PubMed, and Medline were searched for relevant studies until April 2019. Two independent reviewers performed manual data extraction and assessed the risk of bias of the studies using the tools published on National Institutes of Health (NIH) website. The following data were extracted from the studies: author, year of publication, study design, imaging modality, segmentation software, utility of 3DPHM, CHD types, and dimensional accuracy. R software was used for the meta-analysis. Twenty-four articles met the inclusion criteria and were included in the systematic review. However, only 7 studies met the statistical requirements and were eligible for meta-analysis. Cochran's Q test demonstrated significant variation among the studies for both of the meta-analyses of accuracy of 3DPHM and the utility of 3DPHM in medical education. Analysis of all included studies reported the mean deviation between the 3DPHM and the medical images is not significant, implying that 3DPHM are highly accurate. As for the utility of the 3DPHM, it is reported in all relevant studies that the 3DPHM improve the learning experience and satisfaction among the users, and play a critical role in facilitating surgical planning of complex CHD cases. 3DPHM have the potential to enhance communication in medical practice, however their clinical value remains debatable. More studies are required to yield a more meaningful meta-analysis.


Behavior of pigment cells closely correlates the manner of gastrulation in sea urchin embryos.
To know whether behavior of pigment cells correlates the process of gastrulation or not, gastrulating embryos of several species of regular echinoids (Anthocidaris crassispina, Mespilia globulus and Toxopneustes pileolus) and irregular echinoids (Clypeaster japonicus and Astriclypeus manni) were examined. In M. globulus and A. crassispina, the archenteron elongated stepwise like in well-known sea urchins. In the embryos of both species, fluorescent pigment cells left the archenteron tip and migrated into the blastocoel during gastrulation. In T. pileolus, C. japonicus and A. manni, on the other hand, the archenteron elongated at a constant rate throughout gastrulation. In these species, no pigment cell was observed at the archenteron tip during invagination processes; pigment cells began to migrate in the ectoderm from the vegetal pole side toward the apical plate without entering the blastocoel. These results clearly indicate that the behavior of pigment cells closely correlated the manner of gastrulation. Further, it was examined whether the archenteron cells are rearranged during invagination, by comparing the number of cells observed on cross sections of the archenteron at the early and late gastrula stages. The rearrangement was not conspicuous in A. crassispina and M. globulus, in which archenteron elongated stepwise. In contrast, the archenteron cells were remarkably rearranged in C. japonicus, alothough the archenteron elongated continuously. Thus, neither the behavior of pigment cells nor the manner of gastrulation matches the current taxonomic classification of echinoids.


Decreased renal perfusion during acute kidney injury in critical COVID-19 assessed by magnetic resonance imaging: a prospective case control study.
Renal hypoperfusion has been suggested to contribute to the development of acute kidney injury (AKI) in critical COVID-19. However, limited data exist to support this. We aim to investigate the differences in renal perfusion, oxygenation and water diffusion using multiparametric magnetic resonance imaging in critically ill COVID-19 patients with and without AKI. A prospective case-control study where patients without prior kidney disease treated in intensive care for respiratory failure due to COVID-19 were examined. Kidney Disease: Improving Global Outcomes Creatinine criteria were used for group allocation. Main comparisons were tested using Mann-Whitney U test. Nineteen patients were examined, ten with AKI and nine without AKI. Patients with AKI were examined in median 1 [0-2] day after criteria fulfillment. Age and baseline Plasma-Creatinine were similar in both groups. Total renal blood flow was lower in patients with AKI compared with patients without (median 645 quartile range [423-753] vs. 859 [746-920] ml/min, p = 0.037). Regional perfusion was reduced in both cortex (76 [51-112] vs. 146 [123-169] ml/100 g/min, p = 0.015) and medulla (28 [18-47] vs. 47 [38-73] ml/100 g/min, p = 0.03). Renal venous saturation was similar in both groups (72% [64-75] vs. 72% [63-84], ns.), as was regional oxygenation (R2*) in cortex (17 [16-19] vs. 17 [16-18] 1/s, ns.) and medulla (29 [24-39] vs. 27 [23-29] 1/s, ns.). In critically ill COVID-19 patients with AKI, the total, cortical and medullary renal blood flows were reduced compared with similar patients without AKI, whereas no differences in renal oxygenation were demonstrable in this setting. Trial registration ClinicalTrials ID: NCT02765191 , registered May 6 2014 and updated May 7 2020.


Comparative Study of Ex Vivo Transmucosal Permeation of Pioglitazone Nanoparticles for the Treatment of Alzheimer's Disease.
Pioglitazone has been reported in the literature to have a substantial role in the improvement of overall cognition in a mouse model. With this in mind, the aim of this study was to determine the most efficacious route for the administration of Pioglitazone nanoparticles (PGZ-NPs) in order to promote drug delivery to the brain for the treatment of Alzheimer's disease. PGZ-loaded NPs were developed by the solvent displacement method. Parameters such as mean size, polydispersity index, zeta potential, encapsulation efficacy, rheological behavior, and short-term stability were evaluated. Ex vivo permeation studies were then carried out using buccal, sublingual, nasal, and intestinal mucosa. PGZ-NPs with a size around of 160 nm showed high permeability in all mucosae. However, the permeation and prediction parameters revealed that lag-time and vehicle/tissue partition coefficient of nasal mucosa were significantly lower than other studied mucosae, while the diffusion coefficient and theoretical steady-state plasma concentration of the drug were higher, providing biopharmaceutical results that reveal more favorable PGZ permeation through the nasal mucosa. The results suggest that nasal mucosa represents an attractive and non-invasive pathway for PGZ-NPs administration to the brain since the drug permeation was demonstrated to be more favorable in this tissue.


Use of fenoldopam for prevention of radiocontrast nephropathy in the cardiac catheterization laboratory: a case series.
Many of the longstanding challenges in interventional cardiology, such as restenosis and thrombosis, have been met. However, radiocontrast-induced nephropathy (RCN) continues to be problematic, particularly as the population of patients who are diagnosed and treated for vascular occlusions in the cardiac catheterization laboratory have become increasingly older and more complex. Introduction of nonionic contrast media has not eliminated this problem. We present the cases of four high risk patients whom we treated with a newly available renal vasodilator, fenoldopam, as a strategy to prevent RCN and its associated morbidity and mortality.


DOCK11 and DENND2A play pivotal roles in the maintenance of hepatitis B virus in host cells.
Human hepatitis B virus (HBV) infection remains a serious health problem worldwide. However, the mechanism for the maintenance of HBV in a latent state within host cells remains unclear. Here, using single-cell RNA sequencing analysis, we identified four genes linked to the maintenance of HBV in a liver cell line expressing HBV RNA at a low frequency. These genes included DOCK11 and DENND2A, which encode small GTPase regulators. In primary human hepatocytes infected with HBV, knockdown of these two genes decreased the amount of both HBV DNA and covalently closed circular DNA to below the limit of detection. Our findings reveal a role for DOCK11 and DENND2A in the maintenance of HBV.


Proposed 131-cm f/3.5 Achromatic Schmidt Telescope.
An achromatic Schmidt design is proposed for use in twin instruments at Kitt Peak and Cerro Tololo (Chile). The use of an achromatic plate, rather than the conventional Schmidt plate, allows extended spectral coverage by virtue of improved aberration correction. The improvement in geometrical blur diameter appears to be on the order of three times or an improved light concentration of nine times. Some schemes to convert the Schmidt to a Cassegrainian telescope during bright moon periods are evaluated; the choice would be determined on the basis of acceptable mechanical assemblies and economic factors.


Does diagnostic coronary angiography induce significant coronary microembolization in stable, ischemic patients? A prospective study.
Although microembolization during percutaneous coronary interventions is a frequent event, the extent of possible microembolization during diagnostic coronary angiography is unknown. The aim of the study was to investigate whether diagnostic coronary angiography results in coronary microembolization and consequent subtle, subclinical myocardial necrosis with enzyme elevations. Fifty-three consecutive patients underwent diagnostic coronary angiography due to inducible ischemia. Creatine kinase MB isoenzyme (CK MB) and cardiac troponin I (cTnI) were used as sensitive surrogate markers of myocardial necrosis. Serial measurements, before, and 6 and 24 hours following a diagnostic procedure, were performed. Baseline cTnI was below the limits of detection in all patients (<0.20 ng/mL), except for one patient with 1.31 ng/mL. Baseline median CK-MB was 1.05 ng/mL (interquartile range, 0.80-1.56 ng/mL) (Fig. 1). Both at 6 and 24 hours, no patients had any increase in cTnI, with the exception of a minor increase to 0.22 ng/mL at 24 hours in one patient. At 6 hours, 25 patients had decreases in CK MB, while 22 had increases (exact P = 0.77). At 24 hours, 26 patients had decreases in CK MB and 19 patients had increases. Detectable embolization with subsequent subclinical myonecrosis is an unlikely event.


An essential component in steroid synthesis, the steroidogenic acute regulatory protein, is expressed in discrete regions of the brain.
Recent data implicate locally produced steroids, termed neurosteroids, as regulators of neuronal function. Adrenal and gonadal steroidogenesis is controlled by changes in the steroidogenic acute regulatory protein (StAR); however, little is known about the regulation of neurosteroid production. We now demonstrate unequivocally that StAR mRNA and protein are expressed within glia and neurons in discrete regions of the mouse brain, and that glial StAR expression is inducible. Consistent with a role in de novo neurosteroidogenesis, StAR colocalizes with the cholesterol side-chain cleavage enzyme P450(scc) in both mouse and human brains. These data support a role for StAR in the production of neurosteroids and identify potential sites of active de novo steroid synthesis in the brain.


Molecular phylogeny and evolutionary relationships of Cryptosporidium parasites at the actin locus.
To further validate previous observations in the taxonomy of Cryptosporidium parasites, the phylogenetic relationship was analyzed among various Cryptosporidium parasites at the actin locus. Nucleotide sequences of the actin gene were obtained from 9 putative Cryptosporidium species (C. parvum, C. andersoni, C. baileyi, C. felis, C. meleagridis, C. muris, C. saurophilum, C. serpentis, and C. wrairi) and various C. parvum genotypes. After multiple alignment of the obtained actin sequences, genetic distances were measured, and phylogenetic trees were constructed. Results of the analysis confirmed the presence of genetically distinct species within Cryptosporidium and various distinct genotypes within C. parvum. The phylogenetic tree constructed on the basis of the actin sequences was largely in agreement with previous results based on small subunit rRNA, 70-kDa heat shock protein, and Cryptosporidium oocyst wall protein genes. The Cryptosporidium species formed 2 major clades; isolates of C. andersoni, C. muris, and C. serpentis formed the first major group, whereas isolates of all other species, as well as various C. parvum genotypes, formed the second major group. Intragenotype variations were low or absent at this locus.


What happens when hospital-based skilled nursing facilities close? A propensity score analysis.
To assess the effects of hospital-based skilled nursing facility (HBSNF) closures on health care utilization, spending, and outcomes among Medicare fee-for-service beneficiaries. One hundred percent Medicare fee-for-service claims files for 1997-2002 were merged with Medicare Provider of Services files and beneficiary-level enrollment records. Medicare spending, the use of postacute care, and health outcomes, were compared among hospitals that did and did not close their HBSNFs between 1997 and 2001. Hospitals were stratified according to propensity scores (i.e., predicted probability of closure from a logistic regression) and analyses were conducted within these strata. HBSNF closures were associated with increased utilization of alternative postacute care settings, and longer acute care hospital stays. Because of increased use of alternative settings, HBSNF closures were associated with a slight increase in total Medicare spending. There are no statistically robust associations between HBSNF closures and changes in either mortality or rehospitalization. HBSNF closures altered utilization patterns, but there is no indication that closures adversely affect beneficiaries' health outcomes.


Ferrocyanide carbon-13 NMR line broadening as a probe of electron transfer reactions.
The electron transfer reaction between ferrocyanide ion and the blue copper protein, stellacyanin, has been investigated by means of 13C NMR line broadening of the inorganic oxidant. The temperature dependence of the ferrocyanide line broadening gives an activation energy for the electron transfer reaction of 17 +/- 3 kJ. The apparent rate constant decreases with increasing concentration of K4Fe(CN)6, a result which can be explained either by formation of a strong precursor ferrocyanide--stellacyanin [Cu(II)] complex or by increased formation of KFe(CN)3-6 ion pairs. The direct electron transfer between ferrocyanide and ferricyanide has also been studied by 13C NMR line broadening of the former species. The ferricyanide concentration dependence of the exchange line broadening yields a value for the apparent second-order rate constant at 25 degrees C of k = 1.65 . 10(3) M-1 . s-1, in agreement with previously reported values derived from 14N NMR and isotope exchange studies. This rate constant shows a linear dependence on the K+ concentration, independent of ionic strength, a result which confirms the importance of ion pair species such as KFe(CN)3-6 and KFe(CN)2-6 in the direct electron transfer mechanism. The general applications of the method are discussed, including the considerations which suggest that a wide range of electron transfer rates, from about 1 s-1 to 4 . 10(3) s-1, are, in principle, accessible to this technique. The potential utility of ferrocyanide 13C spin--lattice relaxation time measurements is decreasing the lower limit of this range is also discussed.


Does the Dutch Safety Management Program predict adverse outcomes for older patients in the emergency department?
Frailty screening in the emergency department may identify frail patients at risk for adverse outcomes. This study investigated if the Dutch Safety Management Program (VMS) screener predicts outcomes in older patients in the emergency department. In this prospective cohort study, patients aged 70 years or older presenting to the emergency department were recruited on workdays between 10:00 AM and 7:00 PM from May 2017 until August 2017. Patients were screened in four domains: activities of daily living, malnutrition, risk of delirium, and risk of falling. After 90 days of follow up, mortality, functional decline, living situation, falls, readmission to the emergency department, and readmission to the hospital were recorded. VMS was studied using the total VMS score as a predictor with ROC curve analysis, and using a cut-off point to divide patients into frail and non-frail groups to calculate positive predictive value (PPV) and negative predictive value (NPV). A total of 249 patients were included. Higher VMS score was associated with 90-day mortality (AUC 0.65, 95% CI 0.54-0.76) and falling (AUC 0.67, 95% CI 0.56-0.78). VMS frailty predicted mortality (PPV 0.15, NPV 0.94, p = 0.05) and falling (PPV 0.22, NPV 0.92, p = 0.02), but none of the other outcomes. In this selected group of patients, higher VMS score was associated with 90-day mortality and falls. The low positive predictive value shows that the VMS screener is unsuitable for identifying high-risk patients in the ED. The high negative predictive value indicates that the screener can identify patients not at risk for adverse medical outcomes. This could be useful to determine which patients should undergo additional screening.


Dendrimer Heparan Sulfate Glycomimetics: Potent Heparanase Inhibitors for Anticancer Therapy.
Heparanase is a mammalian endoglycosidase that cleaves heparan sulfate (HS) polysaccharides and contributes to remodelling of the extracellular matrix and regulation of HS-binding protein bioavailabilities. Heparanase is upregulated in malignant cancers and inflammation, aiding cell migration and the release of signaling molecules. It is established as a highly druggable extracellular target for anticancer therapy, but current compounds have limitations, because of cost, production complexity, or off-target effects. Here, we report the synthesis of a novel, targeted library of single-entity glycomimetic clusters capped with simple sulfated saccharides. Several dendrimer HS glycomimetics display low nM IC50 potency for heparanase inhibition equivalent to comparator compounds in clinical development, and potently inhibit metastasis and growth of human myeloma tumor cells in a mouse xenograft model. Importantly, they lack anticoagulant activity and cytotoxicity, and also inhibit angiogenesis. They provide a new candidate class for anticancer and wider therapeutic applications, which could benefit from targeted heparanase inhibition.


Signaling Induced by Chronic Viral Hepatitis: Dependence and Consequences.
Chronic viral hepatitis is a main cause of liver disease and hepatocellular carcinoma. There are striking similarities in the pathological impact of hepatitis B, C, and D, although these diseases are caused by very different viruses. Paired with the conventional study of protein-host interactions, the rapid technological development of -omics and bioinformatics has allowed highlighting the important role of signaling networks in viral pathogenesis. In this review, we provide an integrated look on the three major viruses associated with chronic viral hepatitis in patients, summarizing similarities and differences in virus-induced cellular signaling relevant to the viral life cycles and liver disease progression.


Alternative techniques for a continent urinary reservoir.
A modification of the Gilchrist procedure is used to create a continent urinary reservoir that provides reliable continence and antireflux mechanisms. The tubular form of the cecum is altered by a patch or reconfiguration to prevent bolus contractions of the reservoir. The procedure offers a choice of locations of the reservoir and stoma in most patients. Each step of the procedure uses techniques already familiar to urologists.


Bypass by an alternate 'carrier' of acquired unresponsiveness to hCG upon repeated immunization with tetanus-conjugated vaccine.
We report here the use of an alternative carrier diphtheria toxoid (DT) in human subjects to overcome antigen-specific unresponsiveness upon immunization with a hapten/ligand-carrier conjugate. In the phase I clinical trial of a birth control vaccine using gonadotrophin subunits linked to tetanus toxoid, some of the subjects failed to evoke a booster antibody response to human chorionic gonadotrophin (hCG). Presentation of the ligand on DT instead in subsequent immunizations restored anti-hCG response.


Quality of life in children with well-controlled epilepsy.
In our pediatric neurology clinic, we noticed that some of the children and adolescents with well-controlled epilepsy seemed to have difficulty in school, social and family life situations. We postulated that having epilepsy and needing to take daily antiepileptic drugs caused occasional problems in these areas. A questionnaire assessing self concept, home life, school life, social activities and medication issues was developed to explore this issue. Sixty patients with mild epilepsy from our pediatric neurology clinic were surveyed. With an age range of 8-18 years, the mean age of the participants was 12.38 years (SD = 2.93). Thirty-five were females and 25 were males. Twenty had generalized tonic-clonic, 7 absence, 30 partial with motor symptoms, 2 partial with sensory symptoms and 1 unspecified type. Preliminary data indicate statistically significant correlations (p < .05) between children's concerns about seizure activity and self-perceived academic and social difficulties. A simple tool like this questionnaire can be used to help nurses assess quality of life issues in children and adolescents with epilepsy.


Effectiveness of personalized written asthma action plans in the management of children with partly controlled asthma in Trinidad: a randomized controlled trial.
The provision of written asthma action plans (WAAPs) is regarded by regional and international guidelines as an essential component of patient education and self-management. However, the evidence for this practice in children is deficient. To evaluate the effectiveness of adding a personalized WAAP in the treatment of children with partly controlled asthma. Children with partly controlled asthma were randomized to receive a personalized WAAP or no plan, in addition to standard care including education. They were followed up with serial measurement of outcome variables. The primary outcome measured was the number of emergency room (ER) revisits. Ninety-one children participated, 45 in the intervention group and 46 in the control group. Comparison with pretrial data revealed significantly improved outcomes with respect to the numbers of ER visits ( p = 0.005 and 0.0002) and acute asthmatic attacks ( p = 0.0064 and 0.0006) in both arms of the study. Children in receipt of a personalized WAAP had fewer ER visits ( p = 0.78), asthma attacks ( p = 0.84), missed school days ( p = 0.28), night-time awakenings ( p = 0.48) and unscheduled doctor visits ( p = 0.69) than those who did not receive a plan. The results of this study suggest that the provision of personalized WAAPs may play a useful role in the management of children with partly controlled asthma but is no better than standard care. Asthma education is a critical component in the prevention of exacerbations in children with partly controlled asthma.


Renal tubular damage: an extraintestinal manifestation of chronic inflammatory bowel disease.
To investigate whether treatment of inflammatory bowel disease (IBD) with 5-aminosalicylate or sulphasalazine in IBD may induce renal tubular damage. The urinary enzymes beta-N-acetyl-D-glucosaminidase ( beta-NAG), dipeptidylpeptidase 4 (DPP4) and alanine aminopeptidase (AAP) were measured as markers of renal tubular damage in 104 consecutive patients with Crohn's disease and in 43 consecutive patients with ulcerative colitis (all with normal serum creatinine values). Control values were gained from 65 healthy persons. The normal values (mean +/- SD) for the urinary enzymes investigated (U/g creatinine in the urine) were: DPP4 4.5 +/- 2.2, beta-NAG 1.6 +/- 1.4, AAP 11.4 +/- 6.5. In 28% of the patients with ulcerative colitis elevated beta-NAG levels of more than the mean + 2 x SD were measured. This pathological enzymuria was nearly exclusively found in patients with active disease (CAI > 6): DPP4 15.6 +/- 25.3, beta-NAG 8.3 +/- 10.1, AAP 24.7 +/- 50.1 (all three enzymes were significantly elevated). The highest values were measured in patients with active ulcerative colitis before start of therapy. Nineteen per cent of the patients with Crohn's disease had elevated beta-NAG levels of more than the mean + 2 x SD. There was no significant difference in enzymuria between patients with active (CDAI > 150) and patients with inactive Crohn's disease (CDAI < or = 150). DPP4 and AAP were normal in both groups. A correlation between the enzymuria and the cumulative doses of 5-aminosalicylic acid, sulphasalazine or prednisolone could not be found. The courses of enzymuria in three patients who presented with the first severe manifestation of IBD are described. They were treated with either corticosteroids and 5-aminosalicylic acid or corticosteroids and sulphasalazine. Before onset of therapy, very high urine enzyme values were measured. They almost normalized in the course of successful medical therapy despite increasing cumulative doses of 5-aminosalicylic acid or sulphasalazine. Renal tubular damage can frequently be observed in IBD. Our results suggest that this is an extraintestinal manifestation of the disease and not a toxic side-effect of anti-inflammatory therapy using 5-aminosalicylic acid or sulphasalazine.


Association of hepatitis C infection and risk of kidney cancer: A systematic review and meta-analysis of observational studies.
Although some epidemiological studies have investigated the association between Hepatitis C virus (HCV) infection and the development of kidney cancer, the results are far from consistent. We conducted a systematic review and meta-analysis of observational studies to determine the association. PubMed, EMBASE and Cochrane database were searched from 1 January 1975 to 7 January 2020. Study selection, data extraction and bias assessment (using the Newcastle-Ottawa scale) were performed independently by 2 authors. Pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated using a random-effects model. In all, 16 studies (11 cohort studies and 5 case-control studies) involving a total of 391,071 HCV patients and 38,333,839 non-HCV controls were included. The overall analysis showed a 47% higher risk to develop kidney cancer among the patients with HCV infection (pooled OR 1.47; 95% CI 1.14-1.91), despite significant heterogeneity (I2 = 87.6%). The multivariable meta-regression showed that study design, age, sample size and HIV co-infection were significant sources of variance, and totally accounted for 82% of the I2 . The risk of KC in HCV patients was further increased in studies without HCV/HBV- and HCV/HIV- co-infection (pooled OR 1.66; 95%CI 1.23-2.24). Multiple sensitivity analyses did not change the significant association. The present meta-analysis indicated that HCV-infected patients have a significantly higher risk of developing kidney cancer. Our results highlighted the rationale for improved renal surveillance in HCV patients for the early diagnosis of kidney cancer. Further investigations for the mechanisms underlying HCV-induced kidney cancer are warranted.


Spinal cord blood flow and evoked potential responses after treatment with nimodipine or methylprednisolone in spinal cord-injured rats.
This study examined the effect of nimodipine or methylprednisolone on spinal cord blood flow (SCBF) and electrophysiological function after spinal cord injury in rats. Three groups of male rats (n = 10 per group) were injured by compression of the cord at T1 for 1 minute with a 52-g clip. The hydrogen clearance technique was used to measure SCBF at the T1 segment. Motor and somatosensory evoked potentials were recorded. SCBF and evoked potentials were measured before injury and again at approximately 1 and 2.5 hours after injury. The methylprednisolone group received a bolus of methylprednisolone (30 mg/kg) at 5 minutes after injury and then at 15 minutes after injury, the group received an infusion of methylprednisolone at 5.4 mg/kg per hour. The nimodipine group received placebo at 5 minutes and then received an infusion of nimodipine at 0.02 mg/kg per hour at 15 minutes. The placebo group received placebo at both times. Physiological parameters were closely monitored and maintained within the normal range. Albumin was administered after injury to maintain mean arterial blood pressure at or above 80 mm Hg. The infusions were continued for approximately 3 hours after spinal cord injury. SCBF was not significantly different between the experimental groups at either 1 or 2.5 hours postinjury (P = 0.16 and 0.71, respectively), and evoked potential responses did not return in any rat at any time after injury. Thus, this experiment failed to demonstrate an improvement in SCBF or electrophysiological function with either drug.(ABSTRACT TRUNCATED AT 250 WORDS)


Microstructure and Properties of Nano-Hydroxyapatite Reinforced WE43 Alloy Fabricated by Friction Stir Processing.
This research mainly focuses on the successful fabrication of nano-hydroxyapatite (nHA) reinforced WE43 alloy by two-pass friction stir processing (FSP). Microstructure evolution, mechanical properties, and in vitro corrosion behavior of FSPed WE43/nHA composite and FSPed WE43 alloy were studied. The results show that nHA particles are effectively dispersed in the processing zone, and the well-dispersed nHA particles can enhance the grain refine effect of FSP. The average grain sizes of FSPed WE43 alloy and WE43/nHA composite are 5.7 and 3.3 μm, respectively. However, a slight deterioration in tensile strength and yield strength is observed on the WE43/nHA composite, compared to the FSPed WE43 alloy, which is attributed to the locally agglomerated nHA particles and the poor quality of interfacial bonding between nHA particles and matrix. The electrochemical test and in vitro immersion test results reveal that the corrosion resistance of the WE43 alloy is greatly improved after FSP. With the addition of nHA particles, the corrosion resistance of the WE43/nHA composite shows an even greater improvement.


Experimental assessment of vehicle performance and injury risk for cutaway buses using tilt table and modified dolly rollover tests.
Rollover crashes of buses occur less frequently than do those involving passenger cars; however, they are associated with higher fatality rates. During rollover crashes, a vehicle experiences multidirectional acceleration and multiple impacts, yielding a complex interaction between structural components and its occupants. A better understanding of vehicle and occupant's motion, structural deformation, and vehicle and road interactions are necessary to improve the safety of the occupants during this event. One of the key factors in rollover crashworthiness assessment is to investigate the relationship between the strength of the vehicle's structure and the risk of injury outcomes. However, rollover crashes involving buses have received less research attention than have those involving passenger cars. Experimental studies in bus rollover safety have mainly focused on the structural integrity of the passenger compartment without considering the occupant responses. The main goal of this research is to evaluate the rollover mechanism and associated injury risk during two experimental rollover tests for a paratransit cutaway bus that is commonly used by transit agencies. The modified dolly rollover (MDR) and tilt table (TT) tests were conducted using a similar bus and anthropomorphic test device (ATD) configurations. In each test, a 2-point and 3-point belted Hybrid III 50th percent male ATDs were used to quantify the kinematics of the occupants. The deformation index (DI), accelerations and angular velocities of the bus's CG were measured as vehicle responses. The collected data were then calibrated and filtered to assess the effects of the test procedure on kinematic responses of the vehicle and occupants. Next, the effectiveness of the 2-point vs 3-point seatbelt to reduce or prevent the injuries, the vulnerable body regions and corresponded injury risk were evaluated. The residual space remained intact (DI < 1) during both rollover tests, however, the ATD responses were quite different. The results of the injury assessment indicate that the risk of the injuries in the MDR test was significantly higher than the TT test. The highest risk of injuries was identified for the head, neck, and shoulder of 2-point belted ATD during the MDR test. Also, the main source of injuries during the MDR test was partial ejection due to the shattered side window, whereas for the TT test impacts between the ATDs and the side window and/or window frame were the injury causes. From the vehicle point of view, the total energy produced in the MDR was 3.5 times higher than the TT test, but the overall structural deformation in the TT test was higher than MDR test. Overall, the tilt table test provides a more severe scenario compared to the MDR test for the assessment of structural strength. Considering the limited real-world injury data in rollover crashes of buses, the MDR test presented the more realistic occupant responses.


Pharmacologic targeting of endothelial progenitor cells.
The endothelium entered the field of regenerative medicine with the discovery of endothelial progenitor cells (EPCs). These cells participate in endothelial homeostasis and are actively involved in physiological and pathological neovascularization. Despite the unresolved discussion about the very phenotype of these cells, great efforts have been devoted to study the role of EPCs in cardiovascular diseases. EPCs are very rare in peripheral circulation and are further reduced in association with cardiovascular diseases. Therefore, finding therapies to improve EPCs could unleash the way to promising cell-based therapies. Ex-vivo expansion of EPCs is a critical step to augment EPCs number, but it still needs several improvements. An alternative strategy to partially overcome these limitations is to target EPCs with available drugs. In this review we will discuss how disparate pharmacological compounds have been used to improve EPCs number and functions.


KLHL14: A Novel Prognostic Biomarker and Therapeutic Target for Ovarian Cancer.
Ovarian cancer (OV) is a gynaecological malignancy that poses a serious risk to the health status of women. To date, effective molecular markers are unavailable for the diagnosis and management of ovarian malignancies. In this study, we aimed to investigate the molecular markers associated with the development of this cancer. We used bioinformatic analysis to determine the molecules and genes related to ovarian cancer using the gene expression profiling interactive analysis (GEPIA) and the cancer genome Atlas (TCGA) databases. In addition, we examined the genes and mechanisms underlying ovarian cancer. Our results showed that the KLHL14 gene is overexpressed in some cancers. An increase in the KLHL14 expression indicates a poor prognosis in patients with ovarian cancer. Results of immune cell infiltration analysis and half-maximal inhibitory concentration (IC50) analysis provide novel insights into the treatment of ovarian cancer. KLHL14 is anticipated to emerge as a novel molecular marker specifically for ovarian carcinoma.


Risk Factors for Hepatic Toxicity of High-dose Methotrexate in Patients With Osteosarcoma.
High-dose methotrexate (HD-MTX) is widely used to treat osteosarcoma. However, some patients develop hepatic toxicity, leading to dose modification and delays in the scheduled chemotherapy. The present study aimed to identify the risk factors of hepatotoxicity in patients with osteosarcoma. We conducted a retrospective study of patients with osteosarcoma treated with HD-MTX between January 2014 and June 2020 at the National Cancer Center Hospital, Japan. The risk factors for MTX-induced hepatotoxicity (≥grade 3) were identified using multivariate logistic regression analysis. The final analysis included 88 courses of 36 patients. Hepatotoxicity occurred in 51 (58.0%) of the 88 courses. Female sex, MTX dose (>10.2 g/m2), and serum calcium concentration (>9.3 mg/dl) were identified as risk factors for HD-MTX-induced hepatotoxicity. Identifying the risk factors of HD-MTX-induced hepatotoxicity may contribute to improvements in the safety and management of HD-MTX therapy.


Adsorptive stripping voltammetry of bleomycin.
In 0.05 M H2SO4 solution, two reductive peaks, P1 and P2, of bleomycin were obtained. The peak potentials E(P1) and E(P2) were -0.83 and -1.09 V (versus Ag/AgCl), respectively. The sensitivity of P2 was much higher than that of P1. The peak current of P2 was proportional to the concentration of bleomycin over the range 1.0 x 10(-9)-1.0 x 10(-7) M with a detection limit of 5.0 x 10(-10) M using adsorptive voltammetry at an accumulation time of 120 s (Ei = -0.80 V). The behaviour of the reduction wave was studied and applied to the determination of bleomycin in mouse serum. The reduction process of P1 was irreversible with adsorptive characteristics and the adsorption behavior obeyed the Frumkin adsorptive isotherm. The adsorptive coefficient beta was 8.9 x 10(5), the interaction factor alpha was 0.94 and the Gibbs energy of adsorption delta G degree was -33.93 kJ mol-1. P2 was an irreversible adsorption peak with catalytic hydrogen properties.


Active brainwave pattern generation for brain-to-machine communication.
Over the years of research, Electroencephalogram (EEG) signal study has grown to give promising outcomes. A lot of research has been done on implementing brain-computer-interfaces, and the brain-computer interface (BCI) algorithm as well as the study of the effects of different stimuli on brain signals. This paper intends to make progress toward that goal by developing a responsive real-time EEG-based brain-to-machine communication system by generating distinct EEG signals at will and identification of the explicit pattern that they reflect for the presented self-induced internal visual and auditory stimuli. The brain-to-machine communication system delivers the real-time capture, analysis, and visualization of the brain signal patterns that can be used for smart medical applications such as rehabilitation robotic control, smart wheelchair, etc.