Vitreous inflammatory reaction. Vitreous inflammation in rabbits, induced by saline, air, or sodium salt of hyaluronic acid.
Inflammation of the vitreous body of rabbits after the injection of normal saline, sterile air, or SSHA was studied over a period of 30 days. The course of the inflammation follows a definite pattern: it shows an exacerbation 24 h after injection, an abrupt regression 48 h after injection, a new peak on the 8th day and subsequently a gradual regression until the 30th day. Although the course of the inflammation is approximately the same for the three vitreous substitutes, the reaction they provoke varies in intensity. The inflammation is most intense after the injection of SSHA and mildest after saline injection, while the intensity of the reaction caused by air lies between the two. The reaction was assessed by measuring the number and types of vitreous cells and the changes in the percentual proportions of globulin and albumin in the vitreous body, as well as by ascertaining the alterations of the vitreous structure.


The regulatory kinetic properties of porcine hepatic glucokinase.
Porcine hepatic glucokinase (ATP: D-hexose 6-phosphotransferase EC 184.108.40.206) has been purified by a modification of the procedure for its purification from rats. However, difficulties were encountered with endogenous proteases and the reliability of a source for porcine livers. The molecular weight has been determined to be 60,400 +/- 1,400 by sodium dodecyl sulfate, polyacrylamide gel electrophoresis. The enzyme has been characterized kinetically. The parameter values, S0.5 (glucose) and Hill coefficient (nH) are 2.4 mM and 1.9 respectively under sulfhydryl-reducing conditions. The enzyme undergoes the two sulfhydryl-related decays of its activity previously observed in the enzyme isolated from rat (Tippett PS, Neet KE: Arch Biochem Biophys 222:285-298, 1983). The enzyme is inhibited by palmitoyl-CoA, Ki (apparent) = 1.0 microM, nH = 1.8; this concentration of inhibitor is significantly below its critical micelle concentration. Physically and kinetically glucokinase isolated from pig is similar to the enzyme isolated from rat. The porcine system provides a second source for isolation and further characterization of this important and unusual enzyme.


A combined method for synthesis of superconducting Cu doped Bi2Se3.
We present a two-step technique for the synthesis of superconducting CuxBi2Se3. Cu0.15Bi2Se3 single crystals were synthesized using the melt-growth method. Although these samples are non-superconducting, they can be employed to generate high quality superconducting samples if used as precursors in the following electrochemical synthesis step. Samples made from Cu0.15Bi2Se3 reliably exhibit zero-resistance even under the non-optimal quenching condition, while samples made from pristine Bi2Se3 require fine tuning of the quenching conditions to achieve similar performance. Moreover, under the optimal quenching condition, the average superconducting shielding fraction was still lower in the samples made from pristine Bi2Se3 than in the samples made from Cu0.15Bi2Se3. These results suggest that the pre-doped Cu atoms facilitate the formation of a superconducting percolation network. We also discuss the useful clues that we gathered about the locations of Cu dopants that are responsible for superconductivity.


Comparison between Percutaneous Gastrostomy and Self-Expandable Metal Stent Insertion for the Treatment of Malignant Esophageal Obstruction, after Propensity Score Matching.
The outcomes of the two procedures; self-expandable metal stent (SEMS) insertion and percutaneous gastrostomy (PG) feeding procedures, used in patients with malignant esophageal obstruction, are still controversial. We aimed to compare the outcomes between the two procedures, following propensity score (PS) matching. We retrospectively reviewed 568 esophageal cancer patients who underwent SEMS insertion (stent group) or PG (gastrostomy group) at the Samsung Medical Center between January 1996 and December 2018. Procedures for reasons other than malignant obstruction were excluded. We analyzed the datasets after PS matching. Primary outcomes were the post-procedural nutritional status, and need for additional intervention (AI). The secondary outcome was overall survival (OS). In a matched cohort, the gastrostomy group showed less decrease in albumin level after the procedure (-0.15 ± 0.57 vs. stent group; 0.41 ± 0.59, p = 0.021). The gastrostomy group required less need for, and number of, AIs (2.1% vs. stent group; 23.4%, p < 0.001 and 0.04 ± 0.25 vs. stent group; 0.31 ± 0.61, p < 0.001). After matching, there was no significant difference between the two groups in OS. However, PG was associated with OS based on multivariable analysis of the matched cohort (vs. stent group, hazard ratio 0.69, 95% confidence interval 0.5-0.95). PG tends to provide better post-procedure nutritional status than SEMS insertion in patients with malignant esophageal obstruction.


The feasibility of colorectal cancer detection using dual-energy computed tomography with iodine mapping.
To assess the feasibility of colorectal cancer detection using dual-energy computed tomography with iodine mapping and without bowel preparation or bowel distension. Consecutive patients scheduled for preoperative staging computed tomography (CT) because of diagnosed or high suspicion for colorectal cancer were prospectively included in the study. A single contrast-enhanced abdominal CT acquisition using dual-source mode (100 kV/140 kV) was performed without bowel preparation. Weighted average 120 kV images and iodine maps were created with post-processing. Two observers performed a blinded read for colorectal lesions after being trained on three colorectal cancer patients. One observer performed an unblinded read for lesion detectability and placed a region of interest (ROI) within each lesion. In total 21 patients were included and 18 had a colorectal cancer at the time of the CT acquisition. Median cancer size was 43 mm [interquartile range (IQR) 27-60 mm] and all 18 colorectal cancers were visible on the 120 kV images and iodine map during the unblinded read. During the blinded read, observers found 90% (27/30) of the cancers with 120 kV images only and 96.7% (29/30) after viewing the iodine map in addition (p = 0.5). Median enhancement of colorectal cancers was 29.9 HU (IQR 23.1-34.6). The largest benign lesions (70 and 25 mm) were visible on the 120 kV images and iodine map, whereas four smaller benign lesions (7-15 mm) were not. Colorectal cancers are visible on the contrast-enhanced dual-energy CT without bowel preparation or insufflation. Because of the patient-friendly nature of this approach, further studies should explore its use for colorectal cancer detection in frail and elderly patients.


Synthesis of oxazoles through copper-mediated aerobic oxidative dehydrogenative annulation and oxygenation of aldehydes and amines.
A fragment-assembling strategy is used to form oxazoles from aryl acetaldehydes, amines, and molecular oxygen under mild conditions. The transformation is highly efficient with the removal of six hydrogen atoms, including the cleavage of four C(sp(3))-H bonds.


Putative Alginate Assimilation Process of the Marine Bacterium Saccharophagus degradans 2-40 Based on Quantitative Proteomic Analysis.
Quantitative proteomic analysis was conducted to assess the assimilation processes of Saccharophagus degradans cultured with glucose, pectin, and alginate as carbon sources. A liquid chromatography-tandem mass spectrometry approach was used, employing our unique, long monolithic silica capillary column. In an attempt to select candidate proteins that correlated to alginate assimilation, the production of 23 alginate-specific proteins was identified by statistical analyses of the quantitative proteomic data. Based on the analysis, we propose that S. degradans has an alginate-specific gene cluster for efficient alginate utilization. The alginate-specific proteins of S. degradans were comprised of alginate lyases, enzymes related to carbohydrate metabolism, membrane transporters, and transcription factors. Among them, the short-chain dehydrogenase/reductase Sde_3281 annotated in the alginate-specific cluster showed 4-deoxy-L-erythro-5-hexoseulose uronic acid reductase (DehR) activity. Furthermore, we found two different genes (Sde_3280 and Sde_0939) encoding 2-keto-3-deoxy-D-gluconic acid (KDG) kinases (KdgK) that metabolize the KDG derived from alginate and pectin in S. degradans. S. degradans used Sde_3280 to phosphorylate the KDG derived from alginate and Sde_0939 to phosphorylate the KDG derived from pectin. The distinct selection of KdgKs provides an important clue toward the elucidation of how S. degradans recognizes and processes polysaccharides.


Performance evaluation of poly (l-lactide-co-D, l-lactide)/poly (acrylic acid) blends and their nanofibers for tissue engineering applications.
Poly (l-lactide-co-D, l-lactide) (PLDLLA) is a biodegradable polymer predominantly used in biomedical applications. Despite unprecedented characteristics of PLDLLA, its wettability, mechanical properties, degradation, and cell attachment are main issues to improve. In this work, different blend films based on PLDLLA/poly (acrylic acid) (PAAc) are prepared to evaluate their miscibility, hydrophilicity, hydrolytic degradation and mechanical properties. For this purpose, a series of experiments such as DSC alongside SEM, water contact angle (WCA)/water up-take, weight measurements in phosphate buffer saline (PBS) and NaOH as well as tensile test are carried out. The DSC and SEM results show a miscibility for the blends, and hence by increasing PAAc, the WCA values and degradation rates are decreased and increased, respectively. Moreover, the degradation mechanisms of the blend samples follow surface/bulk erosion and bulk process in the alkaline and PBS environments, respectively. Subsequently, PLDLLA and its blends are electrospun to prepare nanofibrous samples, thereby assessing their cytotoxicity and cell viability by the use of thiazolyl blue assay and acridine orange/ethidium bromide staining, respectively. The in vitro SNL 76/7 fibroblast cells cultivation onto the surface of the blend with 10% wt. of PAAc revealed that this sample is a promising candidate for tissue engineering applications.


Fracture of the tibial tubercle does not affect clinical outcomes in medial opening wedge high tibial osteotomy with distal tibial tubercle osteotomy.
To investigate whether tibial tubercle fracture affected clinical outcomes and bony union in medial opening wedge high tibial osteotomy with distal tibial tubercle osteotomy (DTO) and to determine the anatomical risk factors for tibial tubercle fracture. All patients who underwent DTO were retrospectively reviewed, and 104 successive patients were included. The Knee Society Score and complications including tibial tubercle fracture were recorded. On radiographs and computed tomography scans, the length, thickness, width, height, and bony union of the osteotomized tibial tubercle and the posterior tibial slope were statistically analysed. Fracture of the tibial tubercle occurred intraoperatively in 11 patients (10.6%) and in the postoperative period in 1 (1.0%). The case of postoperative fracture showed non-union. There was no significant difference in the Knee Society Score between the non-fracture and fracture groups. There were significant differences in the posterior tibial slope and the height of the tibial tubercle between the groups (p < 0.0001 for each comparison). The logistic regression analysis showed that the height of the tibial tubercle was associated with a higher risk of the fracture of the tibial tubercle (p < 0.01; OR, 1.548; 95% CI, 1.149-2.085). However, there were no significant differences in the bony union rate of the tibial tubercle at 6 months after surgery between the groups. Tibial tubercle fracture did not affect the clinical outcome and bony union in spite of the relatively high occurrence rate. Anatomical risk factors for the fractures was a lower tibial tubercle position. Level IV.


Utility of radiology, laser fluorescence, and transillumination.
This article provides readers with an overview of the latest developments in caries detection using radiology, laser fluorescence, and transillumination. Different imaging techniques, methods to assess diagnostic accuracy, and factors affecting the diagnostic accuracy of imaging in film and digital receptors are discussed. In addition, the DIAGNOdent and DIFOTI devices are introduced as possible supplemental techniques for detecting incipient and hidden carious lesions.


Renal risk scores: progress and prospects.
Worldwide adoption of the Kidney Disease Outcomes Quality Initiative classification for chronic kidney disease (CKD) and widespread use of the estimated glomerular filtration rate to assess renal function have identified large numbers of patients with previously undiagnosed CKD. It is clear, however, that this is a heterogeneous group and that only a small minority of such patients ever progress to end-stage renal disease. There is thus an urgent need for a simple method of risk assessment that can be applied to all patients with CKD to identify those few at greatest risk. The magnitude of baseline proteinuria has long been recognized as an important predictor of renal prognosis. Furthermore, several studies have found that change in proteinuria after initiation of antihypertensive treatment as well as achieved level of proteinuria correlate with prognosis. Thus, proteinuria has emerged as the single most important marker of renal risk. Many other factors have been identified as risk factors for CKD progression. Several attempts have been made to combine a relatively small number of risk factors into a risk score to predict renal outcomes in specific groups of patients. Validation of these risk scores as well as further studies are now required to develop a renal risk score applicable to a more general population of patients with CKD. Similar methodology could be applied to assess the important issue of the cardiovascular risk associated with CKD.


Identification of molecular mechanisms causing skin lesions of cutaneous leishmaniasis using weighted gene coexpression network analysis (WGCNA).
Leishmaniasis is an infectious disease, caused by a protozoan parasite. Its most common form is cutaneous leishmaniasis, which leaves scars on exposed body parts from bites by infected female phlebotomine sandflies. Approximately 50% of cases of cutaneous leishmaniasis fail to respond to standard treatments, creating slow-healing wounds which cause permanent scars on the skin. We performed a joint bioinformatics analysis to identify differentially expressed genes (DEGs) in healthy skin biopsies and Leishmania cutaneous wounds. DEGs and WGCNA modules were analyzed based on the Gene Ontology function, and the Cytoscape software. Among almost 16,600 genes that had significant expression changes on the skin surrounding Leishmania wounds, WGCNA determined that one of the modules, with 456 genes, has the strongest correlation with the size of the wounds. Functional enrichment analysis indicated that this module includes three gene groups with significant expression changes. These produce tissue-damaging cytokines or disrupt the production and activation of collagen, fibrin proteins, and the extracellular matrix, causing skin wounds or preventing them from healing. The hub genes of these groups are OAS1, SERPINH1, and FBLN1 respectively. This information can provide new ways to deal with unwanted and harmful effects of cutaneous leishmaniasis.


Effectiveness and side effects of closed and open suctioning: an experimental evaluation.
To compare the effectiveness of closed system suctioning (CSS) and open system suctioning (OSS) and the side effects on gas exchange and haemodynamics, during pressure-controlled ventilation (PCV) or continuous positive airway pressure (CPAP). Bench test and porcine lung injury model. Twelve bronchoalveolar saline-lavaged pigs. Research laboratory in a university hospital. In a mechanical lung, the efficacy of OSS and CSS with 12 and 14 Fr catheters were compared during volume-control ventilation, PCV, CPAP 0 or 10 cmH(2)O by weighing the suction system before and after aspirating gel in a transparent trachea. Side effects were evaluated in the animals with the same ventilator settings during suctioning of 5, 10 or 20 s duration. Suctioning with 12 and 14 Fr catheters was significantly more efficient with OSS (1.9+/-0.1, 2.8+/-0.9 g) and with CSS during CPAP 0 cmH(2)O (1.8+/-0.2, 4.2+/-0.5 g) as compared to CSS during PCV (0.2+/-0.2, 0.8+/-0.3 g) or CPAP 10 cmH(2)O (0.0+/-0.1, 0.7+/-0.4 g), p<0.01 (means +/- SD). OSS and CSS at CPAP 0 cmH(2)O resulted in a marked decrease in SpO(2), mixed venous oxygen saturation and tracheal pressure, p<0.001, but the side effects were considerably fewer during CSS with PCV and CPAP 10 cmH(2)O, p<0.05. Irrespective of catheter size, OSS and CSS during CPAP 0 cmH(2)O were markedly more effective than CSS during PCV and CPAP 10 cmH(2)O but had worse side effects. However, the side effects lasted less than 5 min in this animal model. Suctioning should be performed effectively when absolutely indicated and the side effects handled adequately.


Preventing occludin tight-junction disruption via inhibition of microRNA-193b-5p attenuates viral load and influenza-induced lung injury.
Virus-induced lung injury is associated with loss of pulmonary epithelial-endothelial tight junction integrity. While the alveolar-capillary membrane may be an indirect target of injury, viruses may interact directly and/or indirectly with miRs to augment their replication potential and evade the host antiviral defense system. Here, we expose how the influenza virus (H1N1) capitalizes on host-derived interferon-induced, microRNA (miR)-193b-5p to target occludin and compromise antiviral defenses. Lung biopsies from patients infected with H1N1 revealed increased miR-193b-5p levels, marked reduction in occludin protein, and disruption of the alveolar-capillary barrier. In C57BL/6 mice, the expression of miR-193b-5p increased, and occludin decreased, 5-6 days post-infection with influenza (PR8). Inhibition of miR-193b-5p in primary human bronchial, pulmonary microvascular, and nasal epithelial cells enhanced antiviral responses. miR-193b-deficient mice were resistant to PR8. Knockdown of occludin, both in vitro and in vivo, and overexpression of miR-193b-5p reconstituted susceptibility to viral infection. miR-193b-5p inhibitor mitigated loss of occludin, improved viral clearance, reduced lung edema, and augmented survival in infected mice. Our results elucidate how the innate immune system may be exploited by the influenza virus and how strategies that prevent loss of occludin and preserve tight junction function may limit susceptibility to virus-induced lung injury.


Suprazygomatic maxillary nerve block: an ultrasound and cadaveric study to identify correct sonoanatomical landmarks.
PURPOSE: Suprazygomatic maxillary nerve blocks (SMB) are used in adult and pediatric patients to provide analgesia for midface surgery and chronic maxillofacial pain syndromes. The ultrasound-guided SMB technique ensures visualisation of the needle tip, avoidance of the maxillary artery and confirmation of local anesthetic spread. The goal of this study was to correctly identify SMB sonoanatomical landmarks to ensure the nerve block is performed safely and effectively. Following an ultrasound-guided SMB with dye injection on 2 embalmed cadavers, pre-tragal face-lift style incision with a full thickness flap dissection was performed allowing accurate visualization of the bony landmarks being used for sonography and identification of the location of the injected dye. This study identifies the correct sonoanatomic landmarks as the maxilla and the coronoid process of the mandible which suggests that the block needle tip and local anesthetic injection are within the infratemporal fossa as opposed to the previously reported pterygopalatine fossa. An improved understanding of the sonoanatomy will aid clinicians who are learning, performing and teaching the ultrasound-guided suprazygomatic approach to the maxillary nerve block.


Anti-inflammatory activity of D-002: an active product isolated from beeswax.
D-002 is a natural mixture of high molecular weight alcohols isolated and purified from beeswax, which contains triacontanol among its main components. This study was undertaken to investigate the anti-inflammatory effects of D-002 administered by the oral route in two animal models commonly used in the pharmacological screening of anti-inflammatory drugs. D-002 administered orally to rats (100 and 200 mg/kg) produced a mild but significant reduction of exudate volume in carrageenan-induced pleuritic inflammation that was accompanied by a marked and significant decrease of leukotriene B4 (LTB4) levels in the exudate. D-002 (25, 50 and 200 mg/kg) also significantly diminished the granuloma weight in the cotton pellet granuloma in rats. In both cases, D-002 was less effective than indomethacin, which was used as an established anti-inflammatory reference drug. On the other hand, D-002 administered from 25-1000 mg/kg did not induce erosions or gastromucosal lesions in rats, which differs from results usually obtained with non steroidal anti-inflammatory drugs. These results indicate that D-002 is a mild anti-inflammatory agent without any ulcerogenic effect associated. The results suggest that these effects are probably not mediated through an inhibition of cyclooxygenase, but a reduction in LTB4 levels induced by D-002 could explain these results.


Mutation-specific dual potentiators maximize rescue of CFTR gating mutants.
The potentiator ivacaftor (VX-770) has been approved for therapy of 38 cystic fibrosis (CF) mutations (∼10% of the patient population) associated with a gating defect of the CF transmembrane conductance regulator (CFTR). Despite the success of VX-770 treatment of patients carrying at least one allele of the most common gating mutation G551D-CFTR, some lung function decline and P. aeruginosa colonization persist. This study aims at identifying potentiator combinations that can considerably enhance the limited channel activity of a panel of CFTR gating mutants over monotherapy. The functional response of 13 CFTR mutants to single potentiators or systematic potentiator combinations was determined in the human bronchial epithelial cell line CFBE41o- and a subset of them was confirmed in primary human nasal epithelia (HNE). In six out of thirteen CFTR missense mutants the fractional plasma membrane (PM) activity, a surrogate measure of CFTR channel gating, reached only ∼10-50% of WT channel activity upon VX-770 treatment, indicating incomplete gating correction. Combinatorial potentiator profiling and cluster analysis of mutant responses to 24 diverse investigational potentiators identified several compound pairs that improved the gating activity of R352Q-, S549R-, S549N-, G551D-, and G1244E-CFTR to ∼70-120% of the WT. Similarly, the potentiator combinations were able to confer WT-like function to G551D-CFTR in patient-derived human nasal epithelia. This study suggests that half of CF patients with missense mutations approved for VX-770 administration, could benefit from the development of dual potentiator therapy.


A metagenomic assessment of microbial communities in anaerobic bioreactors and sediments: Taxonomic and functional relationships.
The present study used metagenomic sequencing, metagenome assembly and physical-chemical analysis to describe taxonomically and functionally 3 anaerobic bioreactors treating manure (LI), brewery (BR) and cornmeal (CO) wastes, and an anaerobic estuarine sediment (ES). Proteobacteria, Firmicutes, Euryarchaeota and Bacteroidetes were the most abundant Phyla in all metagenomes. A bacteria/archaea ratio of 3.4 was found in the industrial full-scale anaerobic bioreactors BR and CO, while ratios greater than 10 were found for LI and ES. Canonical correspondence analysis showed that environmental variables such as chemical oxygen demand, lipid content, and ammonium nitrogen influenced the ordination of taxonomic groups. Mesotoga prima was linked to high-temperature conditions, particularly in the BR bioreactor, along with the presence of heat shock proteins genes. Likewise, the hydrogenotrophic methanogen, Methanoregula formicica, was associated with high ammonium concentration in LI bioreactor. The interactions of microbes with specific methanogenic pathways were identified using Clusters of Orthologous Groups (COG) functions, while metagenome-assembled genomes (MAGs) further confirmed relationships between taxa and functions. Our results provide valuable information to understand microbial processes in anaerobic environments.


Predictors of in-hospital mortality in 1333 patients with acute myocardial infarction complicated by cardiogenic shock treated with primary percutaneous coronary intervention (PCI); Results of the primary PCI registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK).
Aims Acute myocardial infarction complicated by cardiogenic shock is associated with an exceedingly high mortality, even if patients are treated with early reperfusion therapy. The aim of this study was to evaluate predictors of in-hospital mortality of a large cohort of consecutive patients with cardiogenic shock treated with primary percutaneous coronary intervention (PCI). Methods and results Between July 1994 and March 2001 all interventions performed in 80 centres in Germany were prospectively entered into the primary PCI registry of the ALKK. A total of 9422 procedures were registered, of these 1333 (14.2%) were performed in patients with cardiogenic shock. Total in-hospital mortality was 46.1% and was dependent on TIMI flow grade after PCI, with mortality rates of 78.2%, 66.1% and 37.4% in patients with TIMI 0/1, TIMI 2 and TIMI 3 flow, respectively. In a multivariate analysis left main disease, TIMI <3 flow after PCI, older age, three-vessel disease and longer time-intervals between symptom onset and PCI were significant independent predictors of mortality. The relative number of PCIs performed in patients with cardiogenic shock did not change significantly from 1995-2000. There was a significant decrease in mortality over the years (P for trend 0.02). Conclusions In-hospital mortality in patients with acute myocardial infarction complicated by cardiogenic shock remains high, even with early interventional therapy. However, our data demonstrate that the PCI in these high-risk patients is feasible in a wide spectrum of community hospitals with acceptable success rates. Our results seen in connection with the results of the randomized SHOCK study advocate an early invasive approach in younger patients with cardiogenic shock, while the best strategy in elderly patients is still a matter of debate.


Subtyping of haptoglobin--presentation of a new method.
A method is described for large scale routine phenotyping of haptoglobin (Hp) which allows complete subtyping without prior purification of the Hp molecule. The procedure includes polyacrylamide gel isoelectric focusing of reduced, neuraminidase treated serum or plasma samples, and nitrocellulose blots developed with the immunoperoxidase technique. Different variables including sample treatment, electrofocusing, blotting procedures, and immunoperoxidase visualization are discussed. Characteristic alpha-chain patterns allow identification of the common allotypes 2FS, 2SS, 2FF, IS, IF, and Johnson. Isoelectric variations in the beta-chain may also be recognized. For comparison, two-dimensional Hp-patterns are presented. The results from concurrent typing of 600 samples by ordinary starch gel electrophoresis and by the described isofocusing technique, are evaluated.


[Expression of C-erb B-2 and its relation to angiogenesis in nasopharyngeal carcinoma].
To investigate the association of C-erb B-2 expression with angiogenesis in nasopharygeal carcinoma. Seventy-seven specimens of nasopharygeal carcinoma were examined immunohistochemically for protein expressions of C-erb B-2 and vascular endothelial growth factor (VEGF), and the microvessel density (MVD) was determined by immunostaining of the endothelial cells for factor VIII-related antigen (F8). Positive C-erb B-2 immunostaining was observed in 36.36% (28/77) of the nasopharygeal carcinoma tissues, which had a VEGF positivity rate of 32.48% (25/77). High positivity rate of C-erg B-2 was associated with high positivity rate of VEGF and high MVD (P<0.05). The expression of C-erb B-2 may contribute to angiogenesis in nasopharygeal carcinoma.


Enhanced delivery of α-glucosidase for Pompe disease by ICAM-1-targeted nanocarriers: comparative performance of a strategy for three distinct lysosomal storage disorders.
Enzyme replacement therapies for lysosomal storage disorders are often hindered by suboptimal biodistribution of recombinant enzymes after systemic injection. This is the case for Pompe disease caused by acid α-glucosidase (GAA) deficiency, leading to excess glycogen storage throughout the body, mainly the liver and striated muscle. Targeting intercellular adhesion molecule-1 (ICAM-1), a protein involved in inflammation and overexpressed on most cells under pathological conditions, provides broad biodistribution and lysosomal transport of therapeutic cargoes. To improve its delivery, we coupled GAA to polymer nanocarriers (NCs; ∼180 nm) coated with an antibody specific to ICAM-1. Fluorescence microscopy showed specific targeting of anti-ICAM/GAA NCs to cells, with efficient internalization and lysosomal transport, enhancing glycogen degradation over nontargeted GAA. Radioisotope tracing in mice demonstrated enhanced GAA accumulation in all organs, including Pompe targets. Along with improved delivery of Niemann-Pick and Fabry enzymes, previously described, these results indicate that ICAM-1 targeting holds promise as a broad platform for lysosomal enzyme delivery. In this study, ICAM-1 targeted nanocarriers were used to deliver GAA (acid alpha glucosidase) into cells to address the specific enzyme deficiency in Pompe's disease. The results unequivocally demonstrate enhanced enzyme delivery over nontargeted GAA in a mice model.


Lessons learned in developing family medicine residency training programs in Japan.
While family medicine is not well established as a discipline in Japan, a growing number of Japanese medical schools and training hospitals have recently started sougoushinryoubu (general medicine departments). Some of these departments are incorporating a family medicine approach to residency training. We sought to learn from family medicine pioneers of these programs lessons for developing residency training. This qualitative project utilized a long interview research design. Questions focused on four topics: 1) circumstances when becoming chair/faculty member; 2) approach to starting the program; 3) how Western ideas of family medicine were incorporated; and 4) future directions. We analyzed the data using immersion/crystallization to identify recurring themes. From the transcribed data, we selected representative quotations to illustrate them. We verified the findings by emailing the participants and obtaining feedback. Participants included: five chairpersons, two program directors, and three faculty members. We identified five lessons: 1) few people understand the basic concepts of family medicine; 2) developing a core curriculum is difficult; 3) start with undergraduates; 4) emphasize clinical skills; and 5) train in the community. While organizational change is difficult, the identified lessons suggest issues that merit consideration when developing a family medicine training program. Lessons from complexity science could inform application of these insights in other countries and settings newly developing residency training.


Minimally invasive use of coloured composite resin in aesthetic restoration of periodontially involved teeth: Case report.
Gingival recession causes not only aesthetic problems, but problems with oral hygiene, plaque accumulation, speech, and tooth sensitivity. Replacing the missing gingival tissue with composite resin, when indicated, can be a time- and cost-effective solution. Here we report the case of a 25-year-old female who presented with generalized gingival recession. Black triangles were present between the maxillary and mandibular anterior teeth due to loss of interdental tissues, caused by recent periodontal surgery. She also had slightly malposed maxillary anterior teeth. The patient elected to replace gingival tissue with pink composite resin and to alter the midline with composite resin veneers. The first treatment phase involved placement of pink gingival composite to restore the appearance of interdental papilla to her upper (16, 15, 14, 13, 12, 11, 21, 22, 23, and 24) and lower (34, 33, 32, 31, 41, 42, 43, and 44) teeth. Phase two was to place direct composite resin bonded veneers on her upper (16, 15, 14, 13, 12, 11, 21, 22, 23, and 24) teeth to alter the midline and achieve desired colour. The third treatment phase was to level the lower incisal edge shape by enameloplasty (31, 32, 41, and 42) to produce a more youthful and attractive smile. This case report and brief review attempt to describe the clinical obstacles and the current treatment options along with a suggested protocol. Use of contemporary materials such as gingival coloured composite to restore lost gingival tissue and improve aesthetics can be a simple and cost-effective way to manage patients affected by generalized aggressive periodontitis (AgP).


The relationship between regional cerebral blood flow and response to methylphenidate in children with attention-deficit hyperactivity disorder: comparison between non-responders to methylphenidate and responders.
In a sample of children with attention-deficit hyperactivity disorder (ADHD), a voxel based investigation of regional cerebral blood flow (rCBF) during resting state was conducted to identify functional differences between non-responders to methylphenidate (MPH) and responders. Thirty-four children with ADHD were examined by technetium-99m-hexamethylporphylenamine oxime (HMPAO) SPECT. According to clinical response after 8 weeks of treatment with MPH, they were classified as non-responders to MPH and responders. Using SPM analysis, we compared the SPECT images of non-responders to MPH with those of responders. Non-responders to MPH had higher rCBF in the left anterior cingulate cortex, the left claustrum, the right anterior cingulate cortex, and the right putamen relative to responders. In addition, lower rCBF was found in the right superior parietal lobule in non-responders to MPH relative to responders. Further stepwise discriminant analysis revealed that 88.2% could be correctly classified as either non-responders to MPH or responders when considering the extracted rCBF values in the left anterior cingulate cortex, the left claustrum, and the right superior parietal lobule. The current findings suggest that non-responders to MPH may have different patterns of rCBF in brain regions, which have been known as a part of frontal-striatal circuitry and posterior attentional system, respectively.


Label-free identification of microplastics in human cells: dark-field microscopy and deep learning study.
The development of an automatic method of identifying microplastic particles within live cells and organisms is crucial for high-throughput analysis of their biodistribution in toxicity studies. State-of-the-art technique in the data analysis tasks is the application of deep learning algorithms. Here, we propose the approach of polystyrene microparticle classification differing only in pigmentation using enhanced dark-field microscopy and a residual neural network (ResNet). The dataset consisting of 11,528 particle images has been collected to train and evaluate the neural network model. Human skin fibroblasts treated with microplastics were used as a model to study the ability of ResNet for classifying particles in a realistic biological experiment. As a result, the accuracy of the obtained classification algorithm achieved up to 93% in cell samples, indicating that the technique proposed will be a potent alternative to time-consuming spectral-based methods in microplastic toxicity research.


An algorithm for source signal extraction from the peripheral nerve.
Extracting physiological signals to control external devices such as prosthetics is a field of research that offers great hope for patients suffering from disabilities. In this paper, a novel source signal extraction algorithm, based on the source localization method Champagne, is presented. The algorithm constructs spatial filters that not only maximizes the signal to noise ratio (SNR > 13 dB) of the source activities but also minimizes the cross-talk interference between the sources 10log((P(source of interest)/P(interference sources)) > 14 dB.


Clinical parameters predicting pathologic tumor response after preoperative chemoradiotherapy for rectal cancer.
To identify pretreatment clinical parameters that could predict pathologic tumor response to preoperative chemoradiotherapy (CRT) for rectal cancer. The study involved 351 patients who underwent preoperative CRT followed by surgery between October 2001 and July 2006. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and tumor regression. Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Tumor downstaging (defined as ypT2 or less) was observed in 167 patients (47.6%), whereas tumor regression (defined as Dworak's Regression Grades 3 or 4) was observed in 103 patients (29.3%) and complete regression in 51 patients (14.5%). Multivariate analysis found that predictors of downstaging were pretreatment hemoglobin level (p = 0.045), cN0 classification (p < 0.001), and serum carcinoembryonic antigen (CEA) level (p < 0.001), that predictors of tumor regression were cN0 classification (p = 0.044) and CEA level (p < 0.001), and that the predictor of complete regression was CEA level (p = 0.004). The data suggest that pretreatment CEA level is the most important clinical predictor of pathologic tumor response. It may be of benefit in the selection of treatment options as well as the assessment of individual prognosis.


Novel leucine ureido derivatives as aminopeptidase N inhibitors. Design, synthesis and activity evaluation.
Aminopeptidase N (APN/CD13) over-expressed on tumor cells and tumor microenvironment, plays critical roles in tumor invasion, metastasis and angiogenesis. Here we described the design, synthesis and preliminary activity studies of novel leucine ureido derivatives as aminopeptidase N (APN/CD13) inhibitors. The results showed that compound 7a had the most potent inhibitory activity against APN with the IC50 value of 20 nM, which could be used for further anticancer agent research.


Preliminary safety assessment of a new Bacteroides fragilis isolate.
The novel commensal strain of Bacteroides fragilis HCK-B3 isolated from a healthy Chinese donor was discovered beneficial effects of attenuating lipopolysaccharides-induced inflammation. In order to contribute to the development of natural next-generation probiotic strains, the safety assessment was carried out with in vitro investigations of its morphology, potential virulence genes and antimicrobial resistance, and an in vivo acute toxicity study based on both healthy and immunosuppressed mice by cyclophosphamide injection. Consequently, the potential virulence genes in the genome of B. fragilis HCK-B3 have yet been identified as toxicity-associated. The absence of plasmids prevents the possibility of transferring antibiotic resistance features to other intestinal commensals. No intracorporal pathogenic properties were observed according to the body weight, hematological and liver parameters, cytokine secretions and tissue integrity. In addition, B. fragilis HCK-B3 performed alleviations on part of the side effects caused by the cyclophosphamide treatment. Thus, the novel strain of B. fragilis HCK-B3 was confirmed to be non-toxigenic and did not display adverse effects in both healthy and immune-deficient mice at a routinely applicable dose.


Normal electrophysiological findings in a patient with symptomatic intermittent advanced atrioventricular block.
This report describes an otherwise healthy young woman who presented with syncope during episodes of advanced atrioventricular (AV) block. The His bundle recordings during normal sinus rhythm and atrial and ventricular pacing were normal. Carotid sinus massage produced no abnormality. Subsequently, the patient received a permanent pacemaker and has been free of symptoms. Intermittent advanced AV block has been observed on follow-up electrocardiograms. This unique case demonstrates a potential limitation of routine electrophysiologic investigation.


Septicemia due to Pasteurella pneumotropica: 16S rRNA sequencing for diagnosis confirmation.
Bacteremia due to Pasteurella pneumotropica occurs infrequently. We report a case of septicemia in a 72-year-old woman who had no underlying illness. The microorganism was isolated from 10 blood cultures and identified by conventional and molecular methods. This is the first reported case of P. pneumotropica septicemia in an immunocompetent patient. The history of P. pneumotropica diseases in animals and humans and their varied clinical features are reviewed.


Variable appearances of fat necrosis on breast MRI.
The purpose of this article is to illustrate the varying appearances of fat necrosis on MRI. Fat necrosis may mimic malignancy with varying appearances on MRI. Suspicious morphologic and kinetic features may be present, necessitating biopsy to exclude new or recurrent breast cancer.


Percutaneous absorption and anti-inflammatory effect of a substance P receptor antagonist: spantide II.
There is accumulating evidence that neurogenic mediators such as substance P (SP) and alpha-melanocyte stimulating hormone (alpha-MSH) contribute to inflammation following chemical and thermal injuries or in disease conditions such as psoriasis and contact dermatitis. Spantide II is a peptide with a molecular weight of 1670.2 which binds to neurokinin-1 receptor (NKR-1) and blocks proinflammatory activities associated with SP. The aim of this study was to investigate in vitro permeation and distribution of spantide II through hairless rat skin and the anti-inflammatory effect of topically delivered spantide II in an allergic contact dermatitis (ACD) mouse model. The in vitro permeation and distribution of spantide II with or without cysteine HCl (CH) as a penetration enhancer through hairless rat skin was studied using Franz diffusion cells. The anti-inflammatory effect of spantide II was studied by measuring the reduction of ACD in C57BL/6 mice after application of spantide II as a topical solution. The skin permeation experiments with or without cysteine HCl (as penetration enhancer) showed no detectable levels of spantide II permeation across rat skin over a period of 48 h. Cysteine HCl significantly increased the distribution of spantide II in skin layers; also, the reduction in ACD response was significantly higher with the formulation containing cysteine HCl (p < 0.05). Spantide II at different concentrations showed a dose-dependent reduction of ACD response in mice. The current study demonstrates that spantide II can effectively be delivered to epidermis and dermis to exert a significant anti-inflammatory activity on the reduction of inflammation in a mouse model of ACD.


Determination of selected perfluorinated compounds and polyfluoroalkyl phosphate surfactants in human milk.
Polyfluoroalkyl phosphate surfactants (PAPS) are used on food contact paper to impart oil/grease resistance and have been shown to be able to migrate into food. The biotransformation of the congeners belonging to this class of compounds is considered to be a potential source of perfluorinated carboxylic acids (PFCAs). In this study, two methods were developed for the determination of seven perfluorinated compounds (PFCs) and eight polyfluorinated disubstituted phosphate surfactants (diPAPS) in human milk. PFCs were extracted from milk using an ion-pairing technique; while the diPAPs extraction involved a sample clean up using solid phase extraction. Analyses of all compounds in this study were performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Of the seven PFCs analyzed in human milk, only perfluorooctanoic acid (PFOA) was detected in eleven out of thirteen (85%) individual human milk samples analyzed, with a concentration range of <0.072 to 0.52 ng mL(-1). Four diPAPS were detected and quantified in human milk samples. Eight out of thirteen samples contained 4:2 diPAP with a concentration range of <0.01-0.26 ng mL(-1); 6:2 diPAP was detected in five samples with a concentration range of <0.01-0.14 ng mL(-1); 8:2 diPAP was detected in only three samples with concentrations of 0.21, 0.27, and 0.30 ng mL(-1). The 10:2 diPAP was quantified in seven milk samples, with concentration range of <0.01-0.83 ng mL(-1). No correlation was established between PFCAs and PAPS levels in this small sample size. To the best of the authors' knowledge, this is the first study to report the presence of PAPS in human milk.


An inapparent infection with a probable picornavirus in several stocks of laboratory reared and naturally occurring populations of Dacus oleae Gmel. pupae in Greece.
Pupae from several stocks of wild and laboratory reared olive fruit fly, Dacus oleae, were fractionated by a series of steps designed to identify occluded and nonoccluded viruses. Two different size of particles were isolated, the smaller of which contained a single-stranded RNA molecule of about 2.8 x 10(6). This small RNA virus was found to inapparently infect a Ceratitis capitata continuous cell line.


A method for preparation of hydrogel microcapsules for stem cell bioprocessing and stem cell therapy.
A method for the preparation of suspension culture microcapsules used in the bioprocessing of human mesenchymal stem cells (hMSCs) is reported. The microcapsules are prepared from a semi-synthetic hydrogel comprising Pluronic®F127 conjugated to denatured fibrinogen. The Pluronic-fibrinogen adducts display a lower critical solubility temperature (LCST) at ∼30 °C, thus enabling mild, cell-compatible physical crosslinking of the microcapsules in a warm gelation bath. Cell-laden microgels were prepared from a solution of Pluronic-fibrinogen hydrogel precursor and hMSCs; these were cultivated for up to 15 days in laboratory-scale suspension bioreactors and harvested by reducing the temperature of the microcapsules to disassemble the physical polymer network. The viability, proliferation and cell recovery yields of the hMSCs were shown to be better than photo-chemically crosslinked microcapsules made from a similar material. The cell culture yields, which exceeded 300% after 15 days in suspension culture, were comparable to other microcarrier systems used for the mass production of hMSCs. The simplicity of this methodology, both in terms of the cell inoculation and mild recovery conditions, represent distinct advantages for stem cell bioprocessing with suspension culture bioreactors.


Bis[1,1'-(1,3-phenyl-enedimethyl-ene)di(1H-imidazol-3-ium)] β-octa-molybdate.
In the title compound, (C(14)H(16)N(4))(2)[Mo(8)O(26)], the β-octa-molybdate anion is centrosymmetric. N-H⋯O hydrogen bonds link the diimidazolium cations and the polyoxidoanions into a chain structure along [100]. π-π inter-actions between the imidazole rings and between the imidazole and benzene rings [centroid-centroid distances = 3.611 (2) and 3.689 (3) Å, respectively] connect the chains.


Headspace analyses of ²H labeling of acetone: enabling studies of fatty acid oxidation in vivo.
We demonstrate that one can measure low levels of ²H labeling (e.g., <0.025% excess ²H) by exchanging hydrogen (deuterium) in water with acetone and subjecting samples to gas chromatography-pyrolysis-isotope ratio mass spectrometry. This analytical method circumvents the need to use typical off-line reduction methods that convert water to hydrogen gas prior to isotope ratio mass spectrometry or the need to purchase extra peripheral devices that would permit the direct analysis of water labeling. This method enables routine measurements of fatty acid oxidation in rodents; that is, one administers a ²H-labeled fatty acid(s) and then quantifies the production of ²H-labeled water.


The flesh ethanolic extract of Hylocereus polyrhizus exerts anti-inflammatory effects and prevents murine colitis.
IBD is a chronic disorder of the gastrointestinal tract characterized by mucosal inflammation and epithelial damage. Biologic therapy has significantly improved the course of the disease but there are still a high percentage of patients that do not respond to current therapies. We aim to determine the effects of the flesh ethanolic extract of Hylocereus polyrhizus (EH) in a mice model of colitis induced by TNBS. Balb/c mice received TNBS (175 mg/kg, 100 μl, i.r.) and six and thirty hours later were administered with EH (1 g/kg, i.p.). Mice were weighted daily and after sacrificing (2 and 4 days after TNBS) we analyzed mucosal histology, myeloperoxidase activity (MPO), the expression of pro-inflammatory molecules (qPCR) and NF-κB and Iκβ-α protein levels. The chemical characterization of the EH was determined by LC-MS/MS. The administration of EH to TNBS-treated mice prevented (P < 0.05) the loss of body weight and significantly reduced in the colon: a) histological damage score, b) MPO enzymatic activity c) the expression of pro-inflammatory molecules and d) Iκβ-α degradation and nuclear NF-κβ protein levels. The LC-MS analysis detected metabolites such as polyphenols and fatty acids. Systemic administration of the ethanolic extract of H. polyrhizus exerts an anti-inflammatory effect and prevents murine colitis induced by TNBS.


Conformational changes in mutant lysozymes detected with monoclonal antibody.
A monoclonal antibody (mAb) against hen egg white lysozyme (HEWL) with the exquisitely sensitive specificity to native conformation was prepared to detect the conformational changes in mutant lysozymes constructed by genetic modification in a yeast expression system. The binding of mAb with lysozyme was decreased both by denaturation with heat and guanidine-HCl, corresponding to the denaturation curves of lysozyme. These results demonstrate that mAb is a powerful probe to monitor the conformational changes in the lysozyme molecule. By using this probe, the conformational change of various mutant lysozymes was detected. A good correlation was observed between the binding with mAb and the delta G (Gibbs free energy change), reflecting the conformational stability of wild-type and seven mutant lysozymes. This result suggests that a monoclonal antibody with the specificity for native conformation can be used as a powerful probe of protein conformation.


F, N neutralizing effect induced Co-P-O cleaving endows CoP nanosheets with superior HER and OER performances.
Electrochemical water splitting, the most direct and clean method used for the production of hydrogen, requires highly efficient bifunctional electrocatalysts that can accelerate hydrogen evolution reactions (HER) and oxygen evolution reactions (OER) by overcoming their kinetics barriers. Herein, self-supported F, N codoping CoP nanosheets (denoted as FN-CoP NS) are prepared as efficient and stable bifunctional electrocatalysts. Codoping of F and N neutralizes the electronegativity of surface P-O by cleaving the Co-P-O of non-metallic P sites on the surface (O derived from the surface oxidation). This contributes to an increased Co2+ content with considerable adjustable electronegativity and also optimizes HER and OER processes. As a result, FN-CoP NS requires 66 and 241 mV overpotentials to deliver the current density of 10 mA cm-2 during HER and OER, respectively. A full water electrolyzer equipped FN-CoP NS as both cathode and anode only require 1.57 V to drive the current density of 10 mA cm-2 and to sustain 50 mA cm-2 for 48 h. This work adjusts the electronic structure of metal phosphides by a double anion codoping strategy, which provides a reference value for the rational design of efficient bifunctional electrocatalysts.


Ultrasound scanning techniques.
Ultrasound is an essential tool for the hepatobiliary and pancreatic surgeon. This review focuses on transabdominal, open intraoperative, and laparoscopic ultrasonography of the liver, biliary tract, and pancreas. The goal is to obtain optimal ultrasound images through an understanding of the equipment setup, transducer (probe) selection, terminology, and general scanning principles. Outlined is a structured, standardized approach necessary to obtain complete information when doing intraoperative ultrasound. When done by the surgeon, the goal of the examination typically is to answer a question or questions through a focused rather than a comprehensive diagnostic examination. Finally, presented are the details of techniques specific to scanning each of the major organs. A structured, standardized ultrasound scanning approach provides for optimal image acquisition. It allows one to develop standardized views of common structures resulting in "pattern recognition," making learning and interpreting images easier. A standardized approach ensures a complete ultrasound examination, and it minimizes the chance of missed findings. The general principles for transabdominal, open intraoperative, and laparoscopic ultrasonography scanning are similar. One can gather considerable information using these modalities during a clinical examination, procedure, or operation. For success, it is critical to develop a standardized approach to scanning and use it every time. This facilitates familiarity when viewing images, making it easier for the novice to learn and gain experience. Using a systematic approach ensures that the experienced ultrasonographer obtains all the essential information needed at the time of surgery.


Rotaviral nonstructural protein 5 (NSP5) promotes proteasomal degradation of up-frameshift protein 1 (UPF1), a principal mediator of nonsense-mediated mRNA decay (NMD) pathway, to facilitate infection.
Nonsense-mediated mRNA decay (NMD), a cellular RNA quality system, has been shown to be an ancestral form of cellular antiviral response that can restrict viral infection by targeting viral RNA for degradation or other various mechanisms. In support to this hypothesis, emerging evidences unraveled that viruses have evolved numerous mechanisms to circumvent or modulate the NMD pathway to ensure unhindered replication within the host cell. In this study, we investigated the potential interplay between the cellular NMD pathway and rotavirus (RV). Our data suggested that rotavirus infection resulted in global inhibition of NMD pathway by downregulating the expression of UPF1 in a strain independent manner. UPF1 expression was found to be regulated at the post-transcriptional level by ubiquitin-proteasome mediated degradation pathway. Subsequent studies revealed rotaviral non-structural protein 5 (NSP5) associates with UPF1 and promotes its cullin-dependent proteasome mediated degradation. Furthermore, ectopic expression of UPF1 during RV infection resulted in reduced expression of viral proteins and viral RNAs leading to diminished production of infective rotavirus particles, suggesting the anti-rotaviral role of UPF1. Finally, the delayed degradation kinetics of transfected rotaviral RNA in UPF1 and UPF2 depleted cells and the association of UPF1 and UPF2 with viral RNAs suggested that NMD targets rotaviral RNAs for degradation. Collectively, the present study demonstrates the antiviral role of NMD pathway during rotavirus infection and also reveals the underlying mechanism by which rotavirus overwhelms NMD pathway to establish successful replication.


Mechanism of pyruvate dehydrogenase activation by increased cardiac work.
The effects of increased cardiac work, pyruvate and insulin on the state of pyruvate dehydrogenase (PDH) activation and rate of pyruvate decarboxylation was studied in the isolated perfused rat heart. At low levels of cardiac work, 61% of PDH was present in the active form when glucose was the only substrate provided. The actual rate of pyruvate decarboxylation was only 5% of the available capacity calculated from the percent of active PDH. Under this condition, the rate of pyruvate decarboxylation was restricted by the slow rate of pyruvate production from glycolysis. Increasing cardiac work accelerated glycolysis, but production of pyruvate remained rate limiting for pyruvate oxidation and only 40% of the maximal active PDH capacity was used. Addition of insulin along with glucose reduced the percent of active PDH to 16% of the total at low cardiac work. This effect of insulin was associated with increased mitochondria NADH/NAD and acetyl CoA/CoA ratios. With both glucose and insulin the calculated maximum capacity of active PDH was about the same as measured rates of pyruvate oxidation indicating that pyruvate oxidation was limited by the activation state of PDH. In this case, raising the level of cardiac work increased the active PDH to 85% and although pyruvate oxidation was accelerated, measured flux through PDH was only 73% of the maximal activity of active PDH. With pyruvate as added exogenous substrate, PDH was 82% of active at low cardiac work probably due to pyruvate inhibition of PDH kinase. In this case, the measured rate of pyruvate oxidation was 64% of the capacity of active PDH. However, increased cardiac work still caused further activation of PDH to 96% active. Thus, actual rates of pyruvate oxidation in the intact tissue were determined by (1) the supply of pyruvate in hearts receiving glucose alone, (2) by the percent of active PDH in hearts receiving both glucose and insulin at low work and (3) by end-product inhibition in hearts receiving glucose and insulin at high work or at all levels of work with pyruvate as substrate. The increase in active PDH with higher levels of cardia work was associated most closely with reduced mitochondrial NADH/NAD ratios and with decreased acetyl CoA/CoA ratios when insulin or pyruvate were present.


Physical and mental health outcomes of women in nonviolent, unilaterally violent, and mutually violent relationships.
Despite equivocal findings on whether men or women are more violent, the negative impact of violence is greatest for women. To determine how gender asymmetry in perpetration affects women's health status, we conducted a study in two phases with 835 African American, Euro-American, and Mexican American low-income women in Project Health Outcomes of Women. In Phase 1, we used severity and frequency of women's and male partners' violence to create six groups: nonviolent (NV), uni-directional male (UM) perpetrator, uni-directional female (UF) perpetrator and, when both partners were violent, symmetrical (SYM), male primary perpetrator (MPP), and female primary perpetrator (FPP). The MPP group sustained the most threats, violence, sexual aggression, and psychological abuse. They also reported the most fear. Injury was highest in the MPP and FPP groups. In Phase 2, we examined group differences in women's health status over time for 535 participants, who completed five annual interviews. Surprisingly, women's health in the MPP and FPP violence groups was similar and generally worse than if violence was uni-directional.


Mushroom lectin enhanced immunogenicity of HBV DNA vaccine in C57BL/6 and HBsAg-transgenic mice.
DNA vaccination is a promising strategy for activating immune responses against hepatitis B virus (HBV) infection. However, the accumulated data have shown that DNA vaccination alone generates weak immune responses. To enhance the immunogenicity of HBV DNA vaccine, lectin purified from pleurotus ostreatus (POL) was used as adjuvant of HBV DNA vaccine for C57BL/6 and HBV surface antigen transgenic (HBVsAg-Tg) mice. Our data demonstrate that low dose of POL (1 μg/mouse) in conjunction with HBV DNA vaccine stimulated stronger HBV-specific delayed-type hypersensitivity (DTH) responses and higher HBV-specific IgG level than that in high dose of POL groups (5 μg/mouse and 10 μg/mouse). POL activated strong Th2 and Tc1 cell responses in immunized C57BL/6 and HBVsAg-Tg mice. POL as adjuvant of HBV DNA vaccine effectively enhanced HBV surface protein antibody (HBVsAb) and decreased HBVsAg level for HBV Tg mice treatment. Furthermore, POL infiltrated more lymphocytes excluding Th1, Th2 and Tc1 cell subtypes to liver of HBVsAg-Tg mice. Together, these results suggest that POL as adjuvant enhanced immunogenicity of HBV DNA vaccination and effectively stimulated immune reaponse for HBsAg-Tg mice treatment. Our findings implicate the potential of mushroom lectin as adjuvant of HBV DNA vaccine.


Bladder exstrophy in the newborn: a snapshot of contemporary practice patterns.
To use a large nationwide database to investigate and describe practice patterns in the contemporary management of bladder exstrophy. The Healthcare Cost and Utilization Project Nationwide Inpatient Sample (1988 to 2000) was queried to identify infants with bladder exstrophy hospitalized during the first week after birth. Admission and disposition patterns, resource utilization and length of stay, surgical repair trends, and factors associated with in-hospital death were analyzed. We identified 426 hospital admissions of newborns with exstrophy. Most patients (75%) were transferred in from, or out to, other facilities; this was a fundamental feature of early exstrophy care. Racial differences were evident, with Hispanics less likely to be transferred (19% versus 60%, P = 0.001). Among newborns who were not transferred, many (46%) were discharged without bladder surgery. Surgical repair was usually done in a hospital other than the birth hospital; the mean hospital charges for surgery were 75,742 dollars. Of the 5 patients who died after repair, all had undergone surgery at "low-volume" hospitals. The length of stay did not change significantly during the study period, helping to keep resource utilization high in this population. The results of this study provide a "snapshot" of bladder exstrophy practice patterns during the newborn period between 1988 and 2000. Additional research should investigate whether newborns with exstrophy are receiving optimal care, including appropriate timing of surgery, equitable transfers to tertiary centers, and reconstruction at centers with adequate volume and experience.


Chromatographic behaviour of phenols on thin layers of cation and anion exchangers. II. Dowex 50-X4 and Rexyn 102.
The chromatographic characteristics of 58 phenols on Rexyn 102 and Dowex 50-X4 thin layers in both the acidic and sodium salt forms have been studied, using elution with water, water-alcohol mixtures and aqueous salt solutions at different pH values. The influence of the percentage of alcohol, the pH and the ionic strength on the chromatographic behaviour of these phenols was investigated. The validity of the relationships among the RF values, the pH of the eluent and the pKa of the phenol has been verified on Dowex 50-X4 (Na+) thin layers. It has been shown that from the RFac, RFalk and pKa values of the different phenols, it is possible to predict their behaviour over the whole pH range and therefore to select the best conditions for their chromatographic separation.


SR-135, a peroxynitrite decomposing catalyst, enhances β-cell function and survival in B6D2F1 mice fed a high fat diet.
Peroxynitrite has been implicated in β-cell dysfunction and insulin resistance in obesity. Chemical catalysts that destroy peroxynitrite, therefore, may have therapeutic value for treating type 2 diabetes. To this end, we have recently demonstrated that Mn(III) bis(hydroxyphenyl)-dipyrromethene complexes, SR-135 and its analogs, can effectively catalyze the decomposition of peroxynitrite in vitro and in vivo through a 2-electron mechanism (Rausaria et al., 2011). To study the effects of SR-135 on glucose homeostasis in obesity, B6D2F1 mice were fed with a high fat-diet (HFD) for 12 weeks and treated with vehicle, SR-135 (5mg/kg), or a control drug SRB for 2 weeks. SR-135 significantly reduced fasting blood glucose and insulin levels, and enhanced glucose tolerance as compared to HFD control, vehicle or SRB. SR-135 also enhanced glucose-stimulated insulin secretion based on ex vivo studies. Moreover, SR-135 increased insulin content, restored islet architecture, decreased islet size, and reduced tyrosine nitration and apoptosis. These results suggest that a peroxynitrite decomposing catalyst enhances β-cell function and survival under nutrient overload.


The Pilot Study of the Effect of Meditation to the Serum Brain-Derived Neurotrophic Factor (BDNF) of Medical Students, Srinakharinvirot University.
Mindfulness meditation is a method to decrease stress and increase memory. So, mindfulness meditation should increase serum brain-derived neurotrophic factor (BDNF). To study the effect of mindfulness meditation on the serum BDNF of medical students. The study group consisted of 30 male and female second-year medical students that volunteered to participate in the study, aged 19.1 ± 0.55 year olds (range 18-20) from Srinakharinwirot University. Their blood was drawn to measure BDNF before and after a four-day mindfulness meditation programme. The comparison of serum BDNF levels before and after meditation were analysed by paired t-test. The subjects were 66.77%female and 33.33% male. The average serum BDNF level before the meditation was 17.67 ng/ml (SD 3.58). After meditation, there was a decrease in serum BDNF to 17.34 ng/ml, which was however not statistically significant (SD 4.04, p > 0.05). The levels of blood BDNF decreases slightly after practising meditation. We plan to investigate the reason in the future.


Serum levels of leptin and adiponectin are not associated with disease activity or treatment response in multiple sclerosis.
Adipokines secreted by fatty tissue have inflammatory properties and are suggested biomarkers of MS disease activity. To assess this, 88 MS patients were followed with nine repeated measurements of leptin and adiponectin and 12 magnetic resonance imaging (MRI) scans for two years; six months without any immunomodulatory treatment followed by 18 months during interferon-beta (IFNB) treatment. Serum levels of leptin dropped and adiponectin increased upon initiation of IFNB-therapy, but were not associated with clinical or MRI disease activity or with treatment response. Our findings indicate that leptin and adiponectin are not useful as biomarkers of MS disease activity.


First report on the phylogenetic relationship, genetic variation of Echinococcus shiquicus isolates in Tibet Autonomous Region, China.
Cystic or alveolar echinococcosis caused by the larval stages of Echinococcus spp. is a very severe zoonotic helminth infection. Echinococcus shiquicus is a newly discovered species that has only been reported in the Qinghai and Sichuan provinces of the Qinghai-Tibet plateau, China where, to date, it has only been confirmed in Tibetan foxes and wild small mammal populations of the Tibetan plateau. Information on its genetic and evolutionary diversity is scanty. The aim of this study was to investigate the prevalence of E. shiquicus in plateau pikas (Ochotona curzoniae), a known intermediate host, and to determine the genetic variation and phylogenetic relationship of the E. shiquicus population in the Tibet region of China based on mitochondrial DNA. Echinococcus shiquicus samples were collected from Damxung and Nyêmo counties (located in Tibet Autonomous Region, China). The mitochondrial cox1 and nad1 gene sequences were analyzed, and the genetic diversity and epidemiology of E. shiquicus in the region were discussed based on the results. The prevalence of E. shiquicus in pikas in Damxung and Nyêmo counties was 3.95% (6/152) and 6.98% (9/129), respectively. In combination with previous public sequence data, the haplotype analysis revealed 12 haplotypes (H) characterized by two distinct clusters (I and II), and a sequence distance of 99.1-99.9% from the reference haplotype (H1). The diversity and neutrality indices for the entire E. shiquicus populations were: haplotype diversity (Hd) ± standard deviation (SD) 0.862 ± 0.035; nucleotide diversity (Hd ± SD) 0.0056 ± 0.0003; Tajima's D 0.876 (P > 0.05); and Fu's F 6.000 (P > 0.05). This was the first analysis of the newly discovered E. shiquicus in plateau pikas in the Tibet Autonomous Region of China. The neutrality indices suggest a deficiency of alleles, indicative of a recent population bottleneck.


A genomics-based approach to assessment of vaccine safety and immunogenicity in children.
Immune responses to vaccines in infants and young children are typically Th2-biased, giving rise to concerns regarding potential atopy-like side effects, and antagonism of Th1-associated sterilising immunity. Conventional immunological methodology has limited capacity to effectively address these problems because of the inherent complexity of the immune responses involved. In the present study, we sought to develop an unbiased systems biology approach to elucidate superficially similar Th2-associated responses to paediatric vaccines and allergens, and to differentiate between them via gene coexpression network analysis. We demonstrate below that in immune responses to the diptheria/acellular pertussis/tetanus and pneumococcal polysaccharide conjugate vaccines, potentially antagonistic Th1-/IFN-associated and Th2-associated gene networks coexist in an apparent state of dynamic equilibrium, whereas in Th2-dominant allergen-specific responses of atopics the Th1 and IFN networks are respectively disrupted and downregulated. Capacity to detect and interpret these covert differences between responses to vaccines and allergens relies on the use of sophisticated algorithms that underpin coexpression network analysis, which identify genes that function co-ordinately in complex pathways. This methodology has significant potential to identify covert interactions between inflammatory pathways triggered by vaccination, and as such may be a useful tool in prediction of vaccine safety/efficacy.


Atrial electrical activity and its suppression during cardioplegic arrest in pigs.
Right atrial electrical activity and myocardial temperatures of all four chambers were monitored during a 1 hour period of cardioplegic arrest in 20 pigs subjected to different methods of venous cannulation and cardiac cooling. Myocardial protection was provided by systemic hypothermia (28 degrees C) and intermittent intra-aortic administration of cold (4 degrees C) hyperkalemic (20 mEq/L) crystalloid cardioplegia. The use of a single right atrial cannula for venous drainage was associated with sustained atrial activity (50 +/- 5.5 minutes) during cardioplegic arrest and the warmest right atrial (27 degrees +/- 0.2 degrees C) and right ventricular (20.5 degrees +/- 0.4 degrees C) temperatures. Separate caval cannulation with snaring and right atrial venting decreased right atrial and ventricular temperatures marginally (25.3 degrees +/- 0.5 degrees C and 19.1 degrees +/- 0.4 degrees C, respectively, p less than 0.05) but did not significantly alter the duration of atrial electrical activity (42.2 +/- 2.5 minutes, p greater than 0.05). Addition of an extracavitary right atrial drip of cold (4 degrees C) saline, 750 ml for the 1 hour aortic clamping period, reduced right atrial temperature (22.8 degrees +/- 0.4 degrees C) and activity (24.8 +/- 6.3 minutes) to a significant extent. Intracavitary irrigation of the right atrium with cold saline, in the presence of snared double caval cannulas, decreased right atrial and ventricular temperatures most dramatically (17.0 degrees +/- 0.5 degrees C and 17.5 degrees +/- 0.3 degrees C, respectively, p less than 0.05), reduced the duration of atrial electrical activity by 84% (to 8 +/- 3.9 minutes, p less than 0.01), and diminished the total number of atrial contractions per hour of aortic clamping by 88%. It is concluded that intracavitary right atrial cooling with separate snared caval cannulation is the most effective method of ensuring atrial inactivity and prolonged right heart hypothermia during cardioplegic arrest.


Inhibition of adsorption of human T-cell-leukemia virus type 1 by a plant lectin, wheat-germ agglutinin.
Thirty-six lectins that recognize various sugar chains were examined for inhibitory activities against infection with human T-cell leukemia virus type I (HTLV-I). Wheat-germ agglutinin (WGA) was the most inhibitory among them: plating of the pseudotype of vesicular-stomatitis virus (VSV) bearing envelope antigens of HTLV-I was markedly inhibited by treatment of indicator cells with WGA just before adsorption, but not by treatment after virus adsorption. Treatment with WGA before adsorption, however, could not inhibit the plating of VSV, VSV pseudotypes of bovine leukemia virus, Moloney murine leukemia virus and human immunodeficiency virus type I. Syncytium formation induced by HTLV-I was also inhibited by WGA upon co-cultivation of U-251 MG human glioma cells or MOLT-4 human T-cells with HTLV-I-producing C91/PL cells. Formation of proviral DNA detected one day after infection was also inhibited when indicator cells had been treated with WGA before adsorption of HTLV-I, but not after its adsorption. These findings indicated that WGA specifically inhibits plating of HTLV-I when added to culture just before adsorption and suggested that a substance(s) containing sugar chains recognized by WGA might be involved in an adsorption step of HTLV-I.


Crystallization and some properties of chondroitinase from Arthrobacter aurescens.
A strain of Arthrobacter aurescens which secretes a large amount of chondroitinase into a culture broth, was isolated from soil. The chondroitinase was purified 380-fold over culture broth in 24% yield and crystallized. Some properties of the purified enzyme were studied and described: thermal stability (below 45 degrees), pH stability (pH 4.9 to 7.4), optimum temperature (50 degrees), and optimum pH (pH 6.0). Chrondroitin sulfate A and C, chondroitin, and hyaluronic acid were split by the enzyme but dermatan sulfate could not be. The initial rates of enzymic degradation of chondroitin sulfate C, chondroitin, and hyaluronic acid were 1.1, 1.95, and 3.2, respectively, compared to that of chondroitin sulfate A. When the enzyme was allowed to act on chondroitin sulfate A and C, the reducing power and the ultraviolet absorption at 232 nm increased proportionally to the decrease in viscosity of the substrate solution. Finally these substrates were degraded to the extent of 100% to disaccharides. By the enzyme action the main products from chondroitin sulfate A and C were deta 4,5-unsaturated disaccharides, which were identified as 2-acetamido-2-deoxy-3-O-(Beta-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose and 2-acet-amido-2-deoxy-3-O-(Beta-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose by paper chromatography, ultraviolet absorption spectroscophy, and infrared spectroscopy. Thus it is suggested that the chondroitinase is a chondroitin sulfate A and C lyase, one of the hyaluronate lyases (EC 18.104.22.168).


Tailor-made polyfluoroacrylate and its block copolymer by RAFT polymerization in miniemulsion; improved hydrophobicity in the core-shell block copolymer.
Controlled/living radical polymerization (CRP) of a fluoroacrylate was successfully carried out in miniemulsion by Reversible Addition Fragmentation chain Transfer (RAFT) process. In this case, 2,2,3,3,4,4,4-heptafluorobutyl acrylate (HFBA) was polymerized using 2-cyanopropyl dodecyl trithiocarbonate (CPDTC) as RAFT agent, Triton X-405 and sodium dodecyl sulfonate (SDS) as surfactant, and potassium persulphate (KPS) or 2,2'-azobis isobutyronitrile (AIBN) as initiator. Being compatible with hydrophobic fluoroacrylate, this RAFT agent offered very high conversion and good control over the molecular weight of the polymer. The miniemulsion was stable without any costabilizer. The long chain dodecyl group (-C12H25) (Z-group in the RAFT agent) had beneficial effect in stabilizing the miniemulsion. When 2-cyano 2-propyl benzodithioate (CPBD) (Z=-C6H5) was used as RAFT agent, the conversion was less and particle size distribution was very broad. Block copolymerization with butyl acrylate (BA) using PHFBA as macro-RAFT agent showed core-shell morphology with the aggregation of PHFBA segment in the shell. GPC as well as DSC analysis confirmed the formation of block copolymer. The core-shell morphology was confirmed by TEM analysis. The block copolymers (PHFBA-b-PBA) showed significantly higher water contact angle (WCA) showing much better hydrophobicity compared to PHFBA alone.


Interleukin-34 contributes to poor prognosis in triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is a subtype characterized by the absence of therapeutic targets. It shows rapid progression, higher relapse, and poor prognosis, so the establishment of an effective therapeutic target is required. We focused on interleukin-34 (IL-34) that is a novel cytokine relating to inflammation and tumorigenesis. It has been reported that IL-34 correlates with poor prognosis of various cancers. In this study, we evaluated the relationship of IL-34 and prognosis in TNBC using human clinical information and mice model. We found that IL-34 was highly expressed in TNBC, and the survival rate in TNBC was significantly lower in patients with high IL-34 expression. Furthermore, multivariate analysis revealed that IL-34 independently affects prognosis. In murine TNBC model, IL-34 deficiency in tumor cells decreased in vivo tumor growth and increased inflammatory cytokine production from macrophages. These results suggest that tumor-derived IL-34 creates a favorable environment for TNBC cells. Thus, we showed a novel pathological role of IL-34 in TNBC and the potential of IL-34 as a therapeutic target for it.


Lectin binding studies with FITC-marked WGA and UEA I and flowcytometric measurements on isolated rat pancreatic acinar cells.
Lectin binding to the glycocalyx of isolated rat pancreatic acinar cells was studied by flowcytometric measurements. The pancreatic exocrine cells were prepared after collagenase digestion and cleaned in a density gradient. The fluorescence of cells was measured in a FACScan after binding of FITC marked WGA or UEA I. The binding of lectins was inhibited by preabsorption of WGA-FITC with N-acetyl-glucosamine, sialic acid or chitinous and by preabsorption of UEA-FITC with alpha-L-fucose, respectively. Furthermore, we were able to measure a decreased WGA-FITC and UEA-FITC binding after a short preincubation of isolated cells with the peptide hormone cholecystokinin and its agonists (caerulein, pentagastrin).


Selective localization of alpha-fetoprotein and serum albumin within the sensory ganglia cells of developing chicken.
The presence of alpha-fetoprotein (AFP) and serum albumin (SA) has been described within developing brain cells of mammals and chicken. In order to avoid the influence of the choroid plexuses in the transport, via the cerebrospinal fluid, of these proteins to brain cells, we studied the presence of AFP and SA within chicken sensory ganglion cells during ontogeny using the indirect immunoperoxidase technique. Our results show that before day 9 of egg incubation, both AFP and SA can be detected within the trigeminal and spinal ganglia cells. Henceforth, the labeling for AFP starts decreasing in the spinal ganglia but not in the trigeminal ganglion. The labeling for SA remains constant in both structures. Differences between AFP and SA staining in the spinal ganglia are maximal on day 11 of incubation, when AFP is no longer detected. It is concluded that at this time, the uptake of AFP by spinal ganglia cells is switched-off while SA is still taken up. As the blood concentration of both proteins is similar at this time, the finding reported here gives support to the advanced hypothesis suggesting the presence of specific receptors for AFP and/or SA in embryonic neural cells.


Spain: government orders distribution of clean needles in prisons.
In a previous issue of the Review we published an article about the positive results of the evaluation of the first needle exchange programs in Spanish prisons. Recently it was reported that Spain's Ministry of the Interior has ordered that sterile needles be distributed in prisons.


Interfacial film formation: influence on oil spreading rates in lab basin tests and dispersant effectiveness testing in a wave tank.
Test facilities such as lab basins and wave tanks are essential when evaluating the use of chemical dispersants to treat oil spills at sea. However, these test facilities have boundaries (walls) that provide an ideal environment for surface (interfacial) film formation on seawater. Surface films may form from surfactants naturally present in crude oil as well as dispersant drift/overspray when applied to an oil spill. The objective of this study was to examine the impact of surface film formation on oil spreading rates in a small scale lab basin and on dispersant effectiveness conducted in a large scale wave tank. The process of crude oil spreading on the surface of the basin seawater was influenced in the presence of a surface film as shown using a 1st order kinetic model. In addition, interfacial film formation can greatly influence chemically dispersed crude oil in a large scale dynamic wave tank.


Skin inhibits cartilage proliferation and calcification. Tissue culture of fetal mice bones.
In an in vitro study, fetal mice metatarsal bones were cultured with skin or muscle fragments at some distance. We found that skin fragments inhibit growth in length and progress of calcification. Muscle fragments had no significant effects. Apparently, skin cells may produce factors that inhibit the development of metatarsal bones.


Isotypic antibody responses in cattle infected with Haemophilus somnus.
Bovine antibody responses to Haemophilus somnus were compared on the basis of clinical and bacteriological findings. Serum IgG1 and IgM antibody titres were significantly increased in clinically normal cattle that were bacteriologically positive for H somnus from the nasal or vaginal mucosae compared with clinically normal, negative cows. IgG2 titres did not differ significantly between these two groups. However, IgG2 antibody was significantly higher in animals with H somnus disease (pneumonia or abortion) than in clinically normal cattle (whether bacteriologically positive or negative), while IgG1 and IgM titres did not differ between diseased and bacteriologically positive, clinically normal cattle. These antibody trends were duplicated in experimental H somnus abortion or pneumonia, with the greatest response occurring within the IgG2 subclass. Cattle vaccinated systemically with killed whole H somnus produced a predominant IgG2 response with minimal IgG1 and IgM responses. These results demonstrate that IgG2 antibody is consistently elevated in H somnus disease, and suggest that this response may be useful in discriminating diseased from asymptomatic cattle.


Feasibility of quantitative susceptibility mapping (QSM) of the human kidney.
To evaluate the feasibility of in-vivo quantitative susceptibility mapping (QSM) of the human kidney. An axial single-breath-hold 3D multi-echo sequence (acquisition time 33 s) was completed on a 3 T-MRI-scanner (Magnetom Prisma, Siemens Healthineers, Erlangen, Germany) in 19 healthy volunteers. Graph-cut-based unwrapping combined with the T2*-IDEAL approach was performed to remove the chemical shift of fat and to quantify QSM of the upper abdomen. Mean susceptibility values of the entire, renal cortex and medulla in both kidneys and the liver were determined and compared. Five subjects were measured twice to examine the reproducibility. One patient with severe renal fibrosis was included in the study to evaluate the potential clinical relevance of QSM. QSM was successful in 17 volunteers and the patient with renal fibrosis. Anatomical structures in the abdomen were clearly distinguishable by QSM and the susceptibility values obtained in the liver were comparable to those found in the literature. The results showed a good reproducibility. Besides, the mean renal QSM values obtained in healthy volunteers (0.04 ± 0.07 ppm for the right and - 0.06 ± 0.19 ppm for the left kidney) were substantially higher than that measured in the investigated fibrotic kidney (- 0.43 ± - 0.02 ppm). QSM of the human kidney could be a promising approach for the assessment of information about microscopic renal tissue structure. Therefore, it might further improve functional renal MR imaging.


Update on Radiation Therapy for Central Nervous System Tumors.
Radiation therapy has long been a critical modality of treatment of patients with central nervous system tumors, including primary brain tumors, brain metastases, and meningiomas. Advances in radiation technology and delivery have allowed for more precise treatment to optimize patient outcomes and minimize toxicities. Improved understanding of the molecular underpinnings of brain tumors and normal brain tissue response to radiation will allow for continued refinement of radiation treatment approaches to improve clinical outcomes for brain tumor patients. With continued advances in precision and delivery, radiation therapy will continue to be an important modality to achieve optimal outcomes of brain tumor patients.


Luteolin 8-C-β-fucopyranoside downregulates IL-6 expression by inhibiting MAPKs and the NF-κB signaling pathway in human monocytic cells.
Numerous studies have been suggested that derivatives can improve the effects of original substances. Therefore, we made luteolin derivative luteolin 8-C-β-fucopyranoside (LU8C-FP) for better anti-inflammatory and anti-cancer effects. In a previous study, we demonstrated that LU8C-FP inhibits invasion of human breast cancer cells via suppression of matrix metalloproteinase 9 and IL-8, which play major roles in tumor progression and cancer cell invasion. Various stimuli trigger inflammatory responses by inducing pro-inflammatory cytokines and chemokines in THP-1 cells. IL-6 induces inflammation via inducing various cytokines and appears to be a potential mediator of inflammatory diseases. Here, we investigated the precise mechanism by which LU8C-FP inhibited phorbol 12-myristate 13-acetate-induced IL-6 mRNA and protein expression. We showed LU8C-FP downregulated IL-6 expression by inhibiting mitogen-activated protein kinases and the nuclear factor-kappaB signaling pathway in human monocytic cells. Furthermore, LU8C-FP exerts less cytotoxicity than luteolin and also it has specific inhibitory effect on IL-6 expression. However, luteolin has a variety of inhibitory effects on pro-inflammatory cytokines and chemokines. Our in vitro studies may provide valuable information leading to the use of LU8C-FP to treat inflammatory diseases caused by IL-6.


X-ray crystal structure of cytochrome P450 monooxygenase CYP101J2 from Sphingobium yanoikuyae strain B2.
The cytochrome P450 monooxygenases (P450s) catalyze a vast array of oxygenation reactions that can be useful in biocatalytic applications. CYP101J2 from Sphingobium yanoikuyae is a P450 that catalyzes the hydroxylation of 1,8-cineole. Here we report the crystallization and X-ray structure elucidation of recombinant CYP101J2 to 1.8 Å resolution. The CYP101J2 structure shows the canonical P450-fold and has an open conformation in the absence of substrate. Analysis of the structure revealed that CYP101J2, in the absence of substrate, forms a well-ordered substrate-binding channel that suggests a unique form of substrate guidance in comparison to other bacterial 1,8-cineole-hydroxylating P450 enzymes. Proteins 2017; 85:945-950. © 2016 Wiley Periodicals, Inc.


A novel variant of C12orf4 linked to autosomal recessive intellectual disability type 66 with phenotype expansion.
Intellectual disability (ID) is a hallmark of many rare disorders that are highly heterogeneous and complex. A large number of specific genes are involved in development of this heterogeneity, and each of these genes is only found in a small number of patients. This weakens the definition of the predominant genotype and the phenotypic characteristics associated with that gene. Autosomal recessive ID type 66 (OMIM #618221) is one of these very rare diseases created by defects in the C12orf4 gene. The present study included two patients from an Iranian family with initial diagnosis of non-syndromic ID, aiming to identify the possible genetic cause(s), and whole-exome sequencing (WES) was performed for the proband. The obtained variant was confirmed by Sanger sequencing and co-segregated in the family. The patients carried a novel pathogenic splicing variant called c.1441-1G>A in exon 12 of the C12orf4 gene (NM_001304811). They predominantly manifested ID, behavioral problems, speech impairment and dysmorphic facial features, some of which had not been reported in previous studies. A novel pathogenic splicing variant was identified named c.1441-1G>A in the C12orf4 gene. To date, only seven families have been reported with defects in this gene. Previous studies have not highlighted the exact clinical manifestations of these patients; thus, the present study could contribute to a better delineation of the genotype-phenotype correlation and interpretation of very rare variants of the gene.


Role of ESAT-6 in pathogenicity of Beijing and non-Beijing Mycobacterium tuberculosis isolates.
Mycobacterium tuberculosis Beijing genotype was associated with tuberculosis outbreaks and increased transmissibility. To understand the variation in virulence between Beijing and non-Beijing clinical isolates of M.tuberculosis genotypes, the esat-6 gene sequencing, and its expression was compared in the macrophage environment. Among 64 nonrepetitive, culture-positive M.tuberculosis, DNA extraction of 24 and 40 pure confirmed Beijing and non-Beijing isolates was accompanied by the boiling method. esat-6 gene PCR amplification and their sequencing were carried out by specific primers and its expression was performed on human macrophage cell line U937 after 6, 12, and 18 h of exposure to bacilli. The esat-6 mRNA transcription and expression in M. tuberculosis treated macrophage by Real-Time PCR and Western blot method. Data analysis based on sequencing of the east-6 gene PCR product showed that this gene exists in all isolates and there are no changes or single nucleotide variation between the Beijing and non-Beijing isolates. In Beijing strains, the esat-6 expression was increased during the study times, but it was constant in non-Beijing isolates. esat-6 gene expression in Beijing isolates reached to about 44.9 times more than non-Beijing isolates after 18 h incubation on the macrophages cell line. esat-6 is a conserved gene both in Beijing and non-Beijing isolates of M.tuberculosis. More expression of the east-6 gene in the macrophage model may indicate that this gene is likely to play a more important role in increasing the pathogenicity of Beijing strains.


The eyes know what you are thinking: eye movements as an objective measure of mind wandering.
Paralleling the recent work by Reichle, Reineberg, and Schooler (2010), we explore the use of eye movements as an objective measure of mind wandering while participants performed a reading task. Participants were placed in a self-classified probe-caught mind wandering paradigm while their eye movements were recorded. They were randomly probed every 2-3 min and were required to indicate whether their mind had been wandering. The results show that eye movements were generally less complex when participants reported mind wandering episodes, with both duration and frequency of within-word regressions, for example, becoming significantly reduced. This is consistent with the theoretical claim that the cognitive processes that normally influence eye movements to enhance semantic processing during reading exert less control during mind wandering episodes.


Open Surgical Approaches for Pulmonary Metastasectomy.
Surgeons differ in the approach to resection of pulmonary metastases from nonpulmonary primary malignancies, with some favoring procedures that minimize trauma to the patient, and others performing open procedures with the goal of maximizing likelihood of resection of all detectable sites of disease. This article reviews how pulmonary metastasectomy emerged as a therapy for metastatic disease. Discussed is how surgical approaches used for this procedure have evolved, the available literature addressing whether open procedures lead to more complete resections, and if so whether resection by open procedures increases the likelihood of cure following resection. The technical aspects of the various thoracotomy techniques are also reviewed.


Erratum: Application of circulating tumour DNA in terms of prognosis prediction in chinese follicular lymphoma patients.
[This corrects the article DOI: 10.3389/fgene.2023.1066808.].


Quantitation of 6-(pyridin-3-yl)quinolin-2(1H)-one, a cardiac stimulant, and its N-oxide metabolite in dog plasma by high-performance liquid chromatography.
A method is described for the determination of UK-57,400 (I), a 6-substituted quinoline cardiotonic, and its pyridyl-N-oxide in dog plasma. The analytes are selectively retained from plasma (1 ml) on a solid-phase extraction column and eluted with 1 ml of methanol. After evaporation to dryness, the residue is reconstituted in 100 microliters of the mobile phase. Chromatography is carried out on a Spherisorb 5 microns phenyl high-performance liquid chromatography column, with ultraviolet detection. Calibration curves are linear for concentrations from 10 to 100 ng ml-1. For I, the coefficients of variation at highest and lowest concentrations are 1 and 14%, respectively, while the corresponding figures for the pyridyl-N-oxide metabolite are 4 and 10%, respectively. Sample recovery from extraction is greater than 90%. The limit of detection is 4 ng ml-1 for both analytes.


Anticancer, antiobesity, and anti-inflammatory activity of Artemisia species in vitro.
To investigate the anticancer, anti-inflammatory, and antiobesity activity of methanol extracts of eight distinct species: Artemisia Stolonifera (AST), Artemisia Selengensis (ASE), Artemisia Japonica, Artemisia Montana, Artemisia Capillaris (ACA), Artemisia Sylvatica (ASY), Artemisia Keiskeana (AKE), and Artemisia Scoparia (ASC) in vitro. Antiproliferative activity was investigated in human breast cancer estrogen receptor-a positive T47D and negative HS578T cell lines exposed to the extracts at various concentrations (5-200 mg/ mL) for 24, 48, and 72 h. For evaluating the anti-inflammatory activity of the extracts, inhibition of nitrite synthesis was investigated in lipopolysaccharide (LPS)-stimulated cultures of macrophages cells exposed to 10, 50, 100, and 200 mg/mL for 24 h. The antiobesity activity of the extracts was determined as triglyceride content and by a lipolysis assay in differentiated 3T3-L1 cells exposed to the extracts for 72 h at the same concentrations described above. All extracts showed similar antiproliferative activity in a dose- and time-dependent manner in HS578T cells. Although extracts at lower concentrations and shorter times stimulated growth of T47D cells, the antiproliferative effects of the extracts on T47D cells at higher concentrations (> 100 mg/ mL) for 72 h were significantly greater than those of HS578T cells. In case of anti-inflammatory activity, some extracts (AST, ASE, ACA, and AKE) significantly reduced nitric oxide production at higher concentrations in the presence of LPS compared with that in control cells. Antiobesity activity was showed with reducing lipid accumulation significantly (> 50%) at concentrations above 100 mg/mL in most extracts (except AST and ACA). Additionally, AKE and ASC increased lipolysis by 11%-24% compared with that in the control. Artemisia spp. demonstrates potential as bioactive food supplements.


Novel injectable bioartificial tissue facilitates targeted, less invasive, large-scale tissue restoration on the beating heart after myocardial injury.
Implantation of bioartificial patches distorts myocardial geometry, and functional improvement of the recipient heart is usually attributed to reactive angiogenesis around the graft. With the liquid bioartificial tissue compound used in this study, we achieved targeted large-scale support of the infarcted left ventricular wall and improvement of heart function. A liquid compound consisting of growth factor-free Matrigel and 10(6) green fluorescent protein (GFP)-positive mouse (129sv) embryonic stem cells (ESCs) was generated and injected into the area of ischemia after ligation of the left anterior descending artery in BALB/c mice (group I). Left anterior descending artery-ligated mice (group II) and mice with Matrigel (group III) or ESC treatment alone (group IV) were used as the control groups (n=5 in all groups). The hearts were harvested for histology 2 weeks later after echocardiographic assessment with a 15-MHz probe. The liquid injectable tissue solidified at body temperature and retained the geometry of the infarcted lateral wall. Immunofluorescence stains revealed voluminous GFP grafts. The quality of restoration (graft/infarct area ratio) was 45.5+/-10.8% in group I and 29.1+/-6.7% in group IV (P=0.034). ESCs expressed connexin 43 at intercellular contact sites. The mice treated with the compound had a superior heart function compared with the controls (P<0.0001 by ANOVA/Bonferroni test; group I: 27.1+/-5.4, group II:11.9+/-2.4, group III:16.2+/-2.8, group IV: 19.1+/-2.7). Injectable bioartificial tissue restores the heart's geometry and function in a targeted and nondistorting fashion. This new method paves the way for novel interventional approaches to myocardial repair, using both stem cells and matrices.