Distribution of human polyomaviruses, adenoviruses, and hepatitis E virus in the environment and in a drinking-water treatment plant.
Large numbers of viruses are excreted in human feces and urine, which even at low concentrations may cause illness when ingested. Some of these viruses have not been traditionally monitored in terms of waterborne diseases and are considered emergent viruses, such as hepatitis E virus (HEV) and JC and BK polyomavirus (JCPyV and BKPyV). The high prevalence of human adenoviruses (HAdV) and polyomaviruses, which both show DNA genomes, in sewage from widely divergent areas has suggested the relevance of evaluating these viruses as possible indicators of viral contamination. The concentration of these viruses was analyzed in sewage and river water and after treatment in a drinking-water treatment plant including chlorination, flocculation, ozonation, and granulate active carbon (GAC) filtration. Samples of GAC-filtered water were collected before a second chlorination treatment. The river used as a source of fresh water presented an average concentration of 2.6 x 10(1) JCPyV and 4 x 10(2) HAdV GC (genome copies)/L. A removal of 2 logarithms (99%) of HAdV and JCPyV was observed in the drinking-water treatment plant. All the GAC-filtered water samples studied contained HAdV, with a mean value of 4.3 HAdV GC/L. HEV strains belonging to genotype 3 were frequently detected in low concentrations in urban sewage and in biosolids or sewage containing swine feces but not in the river water samples studied. The detection of viruses by molecular techniques is useful for genetically describe emergent viruses in community wastewaters and water supplies. Quantification of JCPyV and HAdV using quantitative real-time PCR (QPCR) may be useful for evaluating virus removal efficiency in water treatment plants and as an index of the virological quality of water and of the potential presence of human viruses.


[Ultrasonic examination in cholecystitis and biliourolithiasis].
Results of the ultrasonic examination (USE) in 511 patients with cholecystitis and biliurolithiasis are described. The authors point to possible use of USE on urgent indications for differential diagnosis of acute cholecystitis. The diagnostic signs of biliary and urinary stones are divided into the absolute and relative ones.


Tropane alkaloids production in transgenic Hyoscyamus niger hairy root cultures over-expressing putrescine N-methyltransferase is methyl jasmonate-dependent.
The cDNA from Nicotiana tabacum encoding Putrescine N-methyltransferase (PMT), which catalyzes the first committed step in the biosynthesis of tropane alkaloids, has been introduced into the genome of a scopolamine-producing Hyoscyamus niger mediated by the disarmed Agrobacterium tumefaciens strain C58C1, which also carries Agrobacterium rhizogenes Ri plasmid pRiA4, and expressed under the control of the CaMV 35S promoter. Hairy root lines transformed with pmt presented fivefold higher PMT activity than the control, and the methylputrescine (MPUT) levels of the resulting engineered hairy roots increased four to fivefold compared to the control and wild-type roots, but there was no significant increase in tropane alkaloids. However, after methyl jasmonate (MeJA) treatment, a considerable increase of PMTase and endogenous H6Hase as well as an increase in scopolamine content was found either in the transgenic hairy roots or the control. The results indicate that hairy root lines over-expressing pmt have a high capacity to synthesize MPUT, whereas their ability to convert hyoscyamine into scopolamine is very limited. Exposure to MeJA strongly stimulated both polyamine and tropane biosynthesis pathways and elicitation led to more or less enhanced production simultaneously.


Synthesis of the macrocyclic core of leiodermatolide.
The macrocyclic core (2) of the marine macrolide leiodermatolide (1) has been synthesized in 19 steps through a convergent strategy exploiting boron aldol methodology to install the requisite stereochemistry and a selective Stille coupling reaction for controlled fragment assembly, followed by a Yamaguchi macrolactonization and carbamate introduction at the C9-OH.


[Usefulness of selected serum cytokines for monitoring compliance with a gluten-free diet in celiac patients].
In celiac disease in response to gluten, the immune reaction develops both in the small intestine and in cells of peripheral blood. The profile of cytokines produced by the cells differs between patients in compliance and not, with regard to gluten-free diet. The aim of the study was to evaluate the usefulness of serum profile determination for chosen cytokines in monitoring of gluten-free diet in celiac patients. The investigation comprised a group of 110 patients with celiac disease, who were divided into two groups: with active form of celiac disease (EmA(+), n=56) and with a non-active form of the disease (EmA (-), n = 54). The chosen cytokine IL-2, IL-4, IL-6, IL-IO and IFN-y levels were determined in patients and soluble receptor For IL-2 (sIL-2R). For determination of the selected cytokines, brand sets of ELISA microplates (Bender Med. Systems) were used according to recommendations of the producer. The obtained results were analysed with statistical methods. Comparison of mean values of chosen cytokines levels in particular groups showed, that in case of sIL-2R and IL-6, they were significantly statistically higher in the group of patients complying to gluten-free diet. Statistical analysis revealed negative correlation between sIL-2R levels and the length of diet compliance in patients with non-active celiac disease and positive correlation between concentrations of sIL-2R and the titre of endomysial antibodies in the group of patients with active form of the disease. The determination of sIL-2R levels in serum together with endomysial antibodies assessment can be used as a method for monitoring the compliance to gluten-free diet in patients with celiac disease.


Synaptic proteome changes in mouse brain regions upon auditory discrimination learning.
Changes in synaptic efficacy underlying learning and memory processes are assumed to be associated with alterations of the protein composition of synapses. Here, we performed a quantitative proteomic screen to monitor changes in the synaptic proteome of four brain areas (auditory cortex, frontal cortex, hippocampus striatum) during auditory learning. Mice were trained in a shuttle box GO/NO-GO paradigm to discriminate between rising and falling frequency modulated tones to avoid mild electric foot shock. Control-treated mice received corresponding numbers of either the tones or the foot shocks. Six hours and 24 h later, the composition of a fraction enriched in synaptic cytomatrix-associated proteins was compared to that obtained from naïve mice by quantitative mass spectrometry. In the synaptic protein fraction obtained from trained mice, the average percentage (±SEM) of downregulated proteins (59.9 ± 0.5%) exceeded that of upregulated proteins (23.5 ± 0.8%) in the brain regions studied. This effect was significantly smaller in foot shock (42.7 ± 0.6% down, 40.7 ± 1.0% up) and tone controls (43.9 ± 1.0% down, 39.7 ± 0.9% up). These data suggest that learning processes initially induce removal and/or degradation of proteins from presynaptic and postsynaptic cytoskeletal matrices before these structures can acquire a new, postlearning organisation. In silico analysis points to a general role of insulin-like signalling in this process.


Real-world treatment pattern and outcomes among patients who took tapentadol IR or oxycodone IR.
To evaluate differences in patient characteristics, healthcare resource utilization, and healthcare costs among patients receiving immediate release (IR) formulations of tapentadol (TAP IR) or oxycodone (OXY IR). Patients (≥18 years) who took TAP IR or OXY IR (6/1/2009-7/31/2011) were selected from the OptumInsight Clinformatics Data Mart claims database. Patients were assigned to the TAP IR or OXY IR cohort based on initial drug usage (index event). Continuous health plan coverage 60 days before (baseline period) and after (follow-up period) the index event was required. TAP IR patients were matched to OXY IR patients (1:1) using exact match of key patient characteristics and propensity score matching with patient demographics and clinical characteristics as covariates. T-test and chi-squared test were utilized to evaluate differences in patient characteristics, healthcare utilization and charges among cohorts. Patient profiles during the baseline period significantly differed among TAP IR users (n = 17,539) and OXY IR users (n = 85,821) in the overall study population. The matched sample of TAP IR and OXY IR patients (n = 10,185 in both cohorts) had similar patient characteristics. During the 60-day follow-up period, patients who took TAP IR had a shorter mean hospital LOS (0.21 vs 0.35 days, p < 0.0001), a lower mean number of hospitalizations (0.07 vs 0.10, p < 0.0001), and lower mean inpatient ($2900 vs $4382, p < 0.001) and outpatient healthcare charges ($10,550 vs $11,084, p = 0.047). The higher index opioid prescription charge of TAP IR ($190 vs $150, p < 0.0001) was offset by other lower healthcare charges. The characteristics of patients who took TAP IR were different from patients who took OXY IR in many respects. In the sub-set of patients matched on demographic and clinical characteristics, those who took TAP IR used healthcare resources to a lesser extent, which was reflected in their lower healthcare charges, relative to OXY IR users.


Cbl promotes clustering of endocytic adaptor proteins.
The ubiquitin ligases c-Cbl and Cbl-b play a crucial role in receptor downregulation by mediating multiple monoubiquitination of receptors and promoting their sorting for lysosomal degradation. Their function is modulated through interactions with regulatory proteins including CIN85 and PIX, which recognize a proline-arginine motif in Cbl and thus promote or inhibit receptor endocytosis. We report the structures of SH3 domains of CIN85 and beta-PIX in complex with a proline-arginine peptide from Cbl-b. Both structures reveal a heterotrimeric complex containing two SH3 domains held together by a single peptide. Trimerization also occurs in solution and is facilitated by the pseudo-symmetrical peptide sequence. Moreover, ternary complexes of CIN85 and Cbl are formed in vivo and are important for the ability of Cbl to promote epidermal growth factor receptor (EGFR) downregulation. These results provide molecular explanations for a novel mechanism by which Cbl controls receptor downregulation.


Early Experiences of Contact Laser Vaporization of the Prostate using the 980 nm High Power Diode Laser for Benign Prostatic Hyperplasia.
We report early experiences of contact laser vaporization of the prostate for symptomatic benign prostatic hyperplasia (BPH). A total of 80 patients recruited at four institutions in Japan from April 2013 through September 2014 underwent contact laser vaporization of the prostate using 980 nm high power diode laser with an end-firing fiber in the contact mode. Patients were followed prospectively at 1 day, 2, 4, 8, 12, and 24 weeks, postoperatively per protocol, and at 1 and 2 years post-protocol. Of 76 eligible patients, 64 (84.2%) achieved more than 50% decrease in International Prostate Symptom Score at 24 weeks (95% confidence interval: 74.0-91.6%), clearing the pre-fixed non-inferiority efficacy level to transurethral resection of the prostate (65%). Symptom scores, maximum flow rate, post-void residual urine, and prostate volume showed significant improvements at 12 and 24 weeks after the surgery. Perioperative complications included transient urinary retention (n = 20), retrograde ejaculation (5), bladder neck contracture (4), urethral stricture (3), stone in prostatic bed (3), bladder stone (2), bladder perforation (1), bladder deformity (1), and transient urgency incontinence (1). Urinary retention and bladder neck contracture occurred almost exclusively at one institution. Improved symptom scores, maximum flow rate, and post-void residual urine observed at 24 weeks remained virtually unchanged at 1 and 2 years. Early experience of contact laser vaporization in Japan showed efficacy comparable to transurethral resection of the prostate as a surgical procedure for BPH at 24 weeks. Long-term efficacy of the procedure remains uncertain.


A repetitive electron beam driver based on 6-stage linear transformer driver cavities.
A repetitive electron beam driver based on 6-stage Linear Transformer Driver (LTD) cavities is presented. Each cavity consists of two Blumlein pulse forming networks (BPFNs) sharing a laser trigger switch. Voltage adding is obtained by means of Linear Transformer (LT) technology. The LTD cavity consists of two BPFNs connected in parallel, an LT with a ratio of 1:1, and a laser-triggered spark switch. The energy efficiency of a single LTD was investigated. The results show that the energy efficiency of an L-type BPFN and an LT was 94.3% and 92.8%, respectively. An electron beam driver consisting of 6 such cavities was developed with an output voltage of 740 kV, a current of 12.3 kA, and a power of 9.1 GW. The repetition frequency operation results show that the electron beam driver can operate stably for 20 s at 25 Hz with a jitter of approximately 1.7 ns.


Perventricular device closure of residual muscular ventricular septal defects after repair of complex congenital heart defects in pediatric patients.
Residual muscular ventricular septal defects are surgical challenges, especially after the repair of complex congenital heart defects. We investigated perventricular device closure as a salvage technique in pediatric patients who had postoperative residual muscular ventricular septal defects. From February 2009 through June 2011, 14 pediatric patients at our hospital had residual muscular ventricular septal defects after undergoing surgical repair of complex congenital heart defects. Ten patients met our criteria for perventricular device closure of the residual defects: significant left-to-right shunting (Qp/Qs >1.5) or substantial hemodynamic instability (a defect ≥2 mm in size). The patients' mean age was 20.4 ± 13.5 months, and their mean body weight was 10 ± 3.1 kg. The median diameter of the residual defects was 4.2 mm (range, 2.5-5.1 mm). We deployed a total of 11 SQFDQ-II Muscular VSD Occluders (Shanghai Shape Memory Alloy Co., Ltd.; Shanghai, China) in the 10 patients, in accord with conventional techniques of perventricular device closure. The mean procedural duration was 31.1 ±9.1 min. We recorded the closure and complication rates perioperatively and during a 12-month follow-up period. Complete closure was achieved in 8 patients; 2 patients had persistent trivial residual shunts. No deaths, conduction block, device embolism, or other complications occurred throughout the study period. We conclude that perventricular device closure is a safe, effective salvage treatment for postoperative residual muscular ventricular septal defects in pediatric patients. Long-term studies with larger cohorts might further confirm this method's feasibility.


Soft tissue concentrations of plutonium and americium in occupationally-exposed humans.
Human tissues, obtained at autopsy from 82 volunteer donors with a history of occupational exposure, were analyzed for 238Pu, 239 + 240Pu, and 241Am by chemical separation and subsequent alpha spectrometry. Concentrations of these actinide nuclides in soft tissues (testes, thyroid gland, spleen, kidneys, heart, and skeletal muscle) were compared to those of the livers in the same subjects. Tissue:liver concentration ratios were essentially constant over a wide range of liver concentrations. The spleen had consistently high actinide concentrations relative to liver; however, the heart had the greatest concentration ratio for 241Am. Testes had relatively high concentration ratios of the plutonium nuclides but low concentrations of 241Am. Skeletal muscle had low concentrations of plutonium relative to liver but high concentrations of 241Am. In the tissues studied, concentration ratios of 241Am were greater than those of the plutonium nuclides, most likely a result of more rapid excretion of that nuclide than the plutonium nuclides by the liver.


Unveiling the Fundamental Role of Temperature in RRAM Switching Mechanism by Multiscale Simulations.
Even though resistance switching memories (RRAMs) can be potentially employed in a broad variety of fields, such as electronics and brain science, they are still affected by issues that prevent their application in circuitry. These problems are a consequence of the lack of detailed knowledge about the physical processes occurring in the device. In this work, we propose multiscale simulations, combining kinetic Monte Carlo and finite difference methods, to shed light on the yet-unclear switching process occurring in the valence change RRAMs, which are believed to work as a consequence of the drift and diffusion of crystalline defects that act as dopants. Results show that the height of the defect diffusion barrier influences the switching process, the retention, and the switching time. In particular, nonvolatile switching can be achieved only by means of the fundamental role of temperature variations induced by Joule heating if the diffusion barriers of the defects are larger than ∼1 eV. High barriers prevent defects from hopping when no voltage is applied. During the transition from the high-resistance to the low-resistance state of the device, a heating stage of the material precedes the defect drift because the applied electric field by itself is not enough to lead to a drift velocity such that switching is achieved within microseconds. The temperature increase has, therefore, the double effect of activating the motion of the defects and enhancing their drift velocity. The switching process can occur only if a sufficiently high temperature is reached thanks to the Joule effect. On the basis of these findings, the RRAM design could aim at a better temperature management to achieve at the same time reproducibility and reliability.


Drug-eluting scaffold to deliver chemotherapeutic medication for management of pancreatic cancer after surgery.
Traditional post-surgical chemotherapy for pancreatic cancer is notorious for its devastating side effects due to the high dosage required. On the other hand, legitimate concerns have been raised about nanoparticle-mediated drug delivery because of its potential cytotoxicity. Therefore, we explored the local delivery of a reduced dosage of FOLFIRINOX, a four-drug regimen comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil, for pancreatic cancer using a biocompatible drug-eluting scaffold as a novel chemotherapy strategy after palliative surgery. In vitro assays showed that FOLFIRINOX in the scaffold caused massive apoptosis and thereby a decrease in the viability of pancreatic cancer cells, confirming the chemotherapeutic capability of the drug-eluting scaffold. In vivo studies in an orthotopic murine xenograft model demonstrated that the FOLFIRINOX in the scaffold had antitumorigenic and antimetastatic effects comparable with those achieved by intraperitoneal injection, despite the dose released by the scaffold being roughly two thirds lower. A mechanistic study attributed our results to the excellent ability of the FOLFIRINOX in the scaffold to destroy the CD133(+)CXCR4(+) cell population responsible for pancreatic tumorigenesis and metastasis. This clinically oriented study gives rise to a promising alternative strategy for postsurgical management of pancreatic cancer, featuring a local chemotherapeutic effect with considerable attenuation of side effects.


Understanding emotions from standardized facial expressions in autism and normal development.
The study investigated the recognition of standardized facial expressions of emotion (anger, fear, disgust, happiness, sadness, surprise) at a perceptual level (experiment 1) and at a semantic level (experiments 2 and 3) in children with autism (N = 20) and normally developing children (N = 20). Results revealed that children with autism were as able as controls to recognize all six emotions with different intensity levels, and that they made the same type of errors. These negative findings are discussed in relation to (1) previous data showing specific impairment in autism in recognizing the belief-based expression of surprise, (2) previous data showing specific impairment in autism in recognizing fear, and (3) the convergence of findings that individuals with autism, like patients with amygdala damage, pass a basic emotions recognition test but fail to recognize more complex stimuli involving the perception of faces or part of faces.


Investigation of the thermal quenching of two emission centers in Sr9MnLi(PO4)7:Eu2+ using time-resolved technique.
The thermal stability of the phosphors in phosphor-converted light-emitting diodes (LEDs) plays an important role in the practical application of lighting. Herein, the Mn2+-based red-emitting phosphors of pure and Eu2+-doped Sr9MnLi(PO4)7 (SMPO) samples were prepared using the high temperature solid-state reaction method. The crystal field environment around the Mn2+ ions was analyzed by combining the results of photoluminescence excitation spectroscopy and Tanabe-Sugano diagrams. By comparing the results of X-ray photoelectron spectroscopy, two additional bands centered at about 129.8 eV and 130.7 eV were found in the Eu2+-doped sample, which corresponded to the chemical states of P 2p3/2 and P 2p1/2. Two different sets of emission spectra were observed for Sr9MnLi(PO4)7:5%Eu2+ (SMPO:Eu2+) on employing the time-resolved technique. The emission peaks centered at 615 nm and 661 nm were attributed to Mn2+ and Eu2+ ions, respectively. The thermal quenching behaviors of Eu2+ and Mn2+ were investigated in the temperature range of 300-620 K and the thermal quenching mechanisms are given in this work. Systematic research on the luminescent properties of Eu2+ and Mn2+ ions in the SMPO:Eu2+ phosphor contributes to the understanding of the thermal stability and aids in the development of Mn2+-based red-emitting phosphors.


New dispenser types for integrated pest management of agriculturally significant insect pests: an algorithm with specialized searching capacity in electronic data bases.
Pheromone effects discovered some 130 years, but scientifically defined just half a century ago, are a great bonus for basic and applied biology. Specifically, pest management efforts have been advanced in many insect orders, either for purposes or monitoring, mass trapping, or for mating disruption. Finding and applying a new search algorithm, nearly 20,000 entries in the pheromone literature have been counted, a number much higher than originally anticipated. This compilation contains identified and thus synthesizable structures for all major orders of insects. Among them are hundreds of agriculturally significant insect pests whose aggregated damages and costly control measures range in the multibillions of dollars annually. Unfortunately, and despite a lot of effort within the international entomological scene, the number of efficient and cheap engineering solutions for dispensing pheromones under variable field conditions is uncomfortably lagging behind. Some innovative approaches are cited from the relevant literature in an attempt to rectify this situation. Recently, specifically designed electrospun organic nanofibers offer a lot of promise. With their use, the mating communication of vineyard insects like Lobesia botrana (Lep.: Tortricidae) can be disrupted for periods of seven weeks.


[Age-dependency of isotope drainage in diuretic renograms].
The aim of the study was to establish normal values of the isotope drainage in diuretic scintigrams for children of different age-groups. Isotope drainage was determined 30 minutes after the application of technetium- (99m)MAG 3 as well as 15 minutes after the following application of furosemide. We analysed the data from 274 investigations in sonographically normal renal units (RU) contralateral to kidneys with ureteropelvic junction obstruction or non-refluxing primary megaureters. There was a significant age-dependency of isotope drainage during the first weeks of life. In 79 RU the results of the first diuretic renogramm were compared with the follow-up examinations. The reliability of the measurements was lowest in children initially investigated during the first six weeks of life. If both the investigations were performed thereafter, no significant difference was found between the results. The isotope drainage of the sonographically normal contralateral RU seems to be a sufficient marker for the meaningfulness of the diuretic renogram. In urinary tract dilatation, mistakes regarding the interpretation of isotope drainage may be minimized by taking the measurements in the normal contralateral RU in account and by comparing them with age-referred normal values.


[Prevalance of conjunctival concretions].
To establish prevalence of conjunctival concretions in a random cohort of patients visiting the general outpatients' department of the Department of Ophthalmology of the Faculty Hospital and 1st Medical faculty, Charles University in Prague, Czech Republic. COHORT OF PATIENTS AND METHODS: The cohort consisted of 500 consecutive patients, 190 males and 310 females visiting the general outpatients' department with various problems. The mean age was 46.8 years (13-103 years). The complete eye examination, including detailed check-up of tarsal conjunctiva and conjunctiva of the fornices at the slit lamp was performed. The presence of conjunctival concretions, frequency of the foreign body sensation in patients with concretions, localization of the concretions and their structure, dependence of the concretions' presentation on the patient's age, the dysfunction of the Meibomian glands, and chronic meibomitis were established. The presence of the conjunctival concretions was found in 198 patients (39.6%), symptomatic were 6% of patients with deposits only. No significant difference was found between the localization on the upper and lower eye lid, nor right or left eye. Superficial deposits (85.8%) were more common than the deep ones, hard deposits (79.8%) more common than the gelatinous ones, and single deposits (77.8%) more common than the confluent ones. Deposits were found in patients as early as at the age of 20 years, with the maximum of occurrence between 30-80 years of age. In 30.3% of patients with conjunctival concretions, the dysfunction of Meibomian glands, or chronic meibomitis were detected. Frequent presence of conjunctival deposits in random cohort of patients was established, and occurrence in younger groups of patients was noticed. Symptomatic deposits were found in 6% of patients only.


Spore Germination of the Obligate Biotroph Spongospora subterranea: Transcriptome Analysis Reveals Germination Associated Genes.
For soilborne pathogens, germination of the resting or dormant propagule that enables persistence within the soil environment is a key point in pathogenesis. Spongospora subterranea is an obligate soilborne protozoan that infects the roots and tubers of potato causing root and powdery scab disease for which there are currently no effective controls. A better understanding of the molecular basis of resting spore germination of S. subterranea could be important for development of novel disease interventions. However, as an obligate biotroph and soil dwelling organism, the application of new omics techniques for the study of the pre-infection process in S. subterranea has been problematic. Here, RNA sequencing was used to analyse the reprogramming of S. subterranea resting spores during the transition to zoospores in an in-vitro model. More than 63 million mean high-quality reads per sample were generated from the resting and germinating spores. By using a combination of reference-based and de novo transcriptome assembly, 6,664 unigenes were identified. The identified unigenes were subsequently annotated based on known proteins using BLAST search. Of 5,448 annotated genes, 570 genes were identified to be differentially expressed during the germination of S. subterranea resting spores, with most of the significant genes belonging to transcription and translation, amino acids biosynthesis, transport, energy metabolic processes, fatty acid metabolism, stress response and DNA repair. The datasets generated in this study provide a basic knowledge of the physiological processes associated with spore germination and will facilitate functional predictions of novel genes in S. subterranea and other plasmodiophorids. We introduce several candidate genes related to the germination of an obligate biotrophic soilborne pathogen which could be applied to the development of antimicrobial agents for soil inoculum management.


Fabrication of microfluidic reactors and mixing studies for luciferase detection.
We report the detection of luciferase by implementing a bioluminescent assay in microfluidic reactors. The reactors were fabricated in poly(methyl methacrylate) by hot embossing using a mold master with the reactor layouts made by high-precision micromilling. The overall fabrication process was simple to implement and had a quick turnaround time with low cost. Two reactors, one with smooth channels (called reactor I) and the other with staggered herringbone mixers (called reactor II), were studied for the bioluminescent assay. The assay was implemented by introducing a sample and an assay solution into the reactors and then mixing took place to achieve the enzymatic reactions. We found that the mixing efficiency in reactor II was 17.8 times higher than reactor I. Theoretical analysis of the experimental results indicated that the required channel length of mixing was linearly proportional to the flow rate. A calibration curve for luciferase was obtained for both reactors. We found that the detection sensitivity of reactor II was 3 times higher than reactor I. The limit of detection in reactor II was determined to be 0.14 microg/mL luciferase. The device was further exploited to determine the concentration of luciferase samples obtained from in vitro protein expression.


Inhibition and Reading Comprehension in Adolescents with and without Histories of Language Difficulties.
This study sought to determine if the inhibitory construct of executive function (EF) and self-regulation (SR) contributes unique variance to reading comprehension (RC) beyond word recognition/decoding (WR/D) and language comprehension (LC), and if the contribution differs according to language history. Thirty-two sixth, seventh, and eighth grade students participated in this study. Seventeen students had language difficulties (LD) and fifteen students had typical language histories (LH). Participants were given a battery of RC, LC, WR/D, and inhibition (attentional control and interference) measures. Hierarchical multiple regression analyses and tests for moderation effects were used to explore the contribution of each variable to RC. Inhibition contributed significant variance to RC in addition to the variance accounted for by LC and WR/D in adolescent learners. Inhibition contributed a greater proportion of variance to RC for students with typical LH than for students with LD. Advancing the understanding of the role of inhibition in EF, SR, and RC may support early identification efforts and drive the development of interventions that effectively target RC deficits.


Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
In obesity, white adipose tissue (WAT) inflammation is linked to insulin resistance. Increased adipocyte chemokine (C-C motif) ligand 2 (CCL2) secretion may initiate adipose inflammation by attracting the migration of inflammatory cells into the tissue. Using an unbiased approach, we identified adipose microRNAs (miRNAs) that are dysregulated in human obesity and assessed their possible role in controlling CCL2 production. In subcutaneous WAT obtained from 56 subjects, 11 miRNAs were present in all subjects and downregulated in obesity. Of these, 10 affected adipocyte CCL2 secretion in vitro and for 2 miRNAs (miR-126 and miR-193b), regulatory circuits were defined. While miR-126 bound directly to the 3'-untranslated region of CCL2 mRNA, miR-193b regulated CCL2 production indirectly through a network of transcription factors, many of which have been identified in other inflammatory conditions. In addition, overexpression of miR-193b and miR-126 in a human monocyte/macrophage cell line attenuated CCL2 production. The levels of the two miRNAs in subcutaneous WAT were significantly associated with CCL2 secretion (miR-193b) and expression of integrin, α-X, an inflammatory macrophage marker (miR-193b and miR-126). Taken together, our data suggest that miRNAs may be important regulators of adipose inflammation through their effects on CCL2 release from human adipocytes and macrophages.


Break CDK2/Cyclin E1 interface allosterically with small peptides.
Most inhibitors of Cyclin-dependent kinase 2 (CDK2) target its ATP-binding pocket. It is difficult, however, to use this pocket to design very specific inhibitors because this catalytic pocket is highly conserved in the protein family of CDKs. Here we report some short peptides targeting a noncatalytic pocket near the interface of the CDK2/Cyclin complex. Docking and molecular dynamics simulations were used to select the peptides, and detailed dynamical network analysis revealed that these peptides weaken the complex formation via allosteric interactions. Our experiments showed that upon binding to the noncatalytic pocket, these peptides break the CDK2/Cyclin complex partially and diminish its kinase activity in vitro. The binding affinity of these peptides measured by Surface Plasmon Resonance can reach as low as 0.5 µM.


An Anti-HER2 Monoclonal Antibody H2Mab-41 Exerts Antitumor Activities in Mouse Xenograft Model Using Dog HER2-Overexpressed Cells.
Overexpression of human epidermal growth factor receptor 2 (HER2) has been reported in a variety of cancer types, including breast, lung, gastric, pancreatic, and colorectal cancers. Trastuzumab, a humanized anti-HER2 monoclonal antibody (mAb), has been shown to provide significant survival benefits in HER2-overexpressing breast cancer and gastric cancer patients. Previously, an anti-HER2 mAb, H2Mab-41 (IgG2b, kappa), was developed in our laboratory and its antitumor activity was demonstrated in mouse xenograft models of human colon cancer. The present study aimed to investigate the ability of H2Mab-41 to induce antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in dog HER2 (dHER2)-overexpressed cell lines, and thus exert its antitumor activity against dHER2-overexpressed tumors in vivo. Flow cytometry results demonstrated the cross-reactivity of H2Mab-41 with dHER2. Further evaluation of interaction between H2Mab-41 and dHER2-overexpressed CHO-K1 (CHO/dHER2) cells indicated moderate binding affinity of H2Mab-41 toward dHER2, with a dissociation constant (KD) of 2.6 × 10-8 M. In vitro analysis revealed that the administration of H2Mab-41 induced high levels of ADCC and CDC in CHO/dHER2 cells. Furthermore, intraperitoneal administration of H2Mab-41 in mouse xenograft models of CHO/dHER2 resulted in significant inhibition of tumor development compared to the control mouse IgG. Thus, the findings of the present study demonstrated the in vivo safety and efficacy of H2Mab-41, highlighting its suitability to be included as a part of a therapeutic regimen for dHER2-expressing canine cancers.


SRCAP mutations drive clonal hematopoiesis through epigenetic and DNA repair dysregulation.
Somatic mutations accumulate in all cells with age and can confer a selective advantage, leading to clonal expansion over time. In hematopoietic cells, mutations in a subset of genes regulating DNA repair or epigenetics frequently lead to clonal hematopoiesis (CH). Here, we describe the context and mechanisms that lead to enrichment of hematopoietic stem cells (HSCs) with mutations in SRCAP, which encodes a chromatin remodeler that also influences DNA repair. We show that SRCAP mutations confer a selective advantage in human cells and in mice upon treatment with the anthracycline-class chemotherapeutic doxorubicin and bone marrow transplantation. Furthermore, Srcap mutations lead to a lymphoid-biased expansion, driven by loss of SRCAP-regulated H2A.Z deposition and increased DNA repair. Altogether, we demonstrate that SRCAP operates at the intersection of multiple pathways in stem and progenitor cells, offering a new perspective on the functional impact of genetic variants that promote stem cell competition in the hematopoietic system.


Conjoint corpora cavernosa and its role in erection.
The two penile corpora cavernosa (CC) remain as separate structures along the penile shaft. During our study of 28 cadavers, we came across three cadavers in which the two CCs were fused together forming a single tubular structure; this article discusses these three cadaveric specimens. The cadavers were aged 52, 36, and 12 years. After penile degloving, the dorsal groove on the penile shaft was absent. In two of the cadavers, multiple transverse cut-sections in the penile shaft showed that the two CCs were united into one single tubular structure that extended from the symphysis pubis to the glans penis. The cut section was kidney-shaped, with the corpus spongiosum lying under cover of the concave surface. No intercavernosal septum was identified. The transverse cut-section of the third cadaveric specimen revealed an incomplete fusion of the two CCs. An intercavernosal septum was present in its upper part, but absent in its lower part where the two CCs were fused together. In all three cadaveric specimens, the CCs showed a normal histologic pattern and the corpus spongiosum was morphologically normal. Based on biomechanical principles, we theorize that the blood volume occupying the two CCs would be greater, the penile rigidity stronger, and the penetration force more powerful in the two separate CCs as normal than in the two CCs if fused. However, further studies involving large number of cases are needed.


Eggshell quality as influenced by sodium bicarbonate, calcium source, and photoperiod.
The effects of Ca source (limestone or a mixture of one-third limestone and two-thirds oyster shell), NaHCO3 (0 or .5%) and feeding photoperiod (16 or 24 hr) were studied in a 16-week experiment involving 240 Hy-Line W-36 Leghorn hens, 25 weeks of age. Neither egg production (percent hen-day and egg mass, kg egg/bird per 16 weeks) nor feed conversion ratio (kg feed per kg egg) were significantly (P greater than .05) affected by dietary treatment or photoperiod. However, extending the photoperiod to 24 hr significantly (P less than .05) increased feed consumption with a consequent increase in egg weight (P less than .01). Feeding oyster shell in combination with limestone significantly (P less than .05) improved specific gravity of eggs, whereas dietary NaHCO3 significantly (P less than .01) improved elasticity of the egg shell as measured by deformation. Eggshell quality was improved by increasing the photoperiod to 24 hr and was most pronounced when hens were fed diets supplemented with .5% NaHCO3 and limestone as the only source of Ca.


The Stress and Coping Context of Type 1 Diabetes Management Among Latino and Non-Latino White Early Adolescents and Their Mothers.
Examine ethnic differences in diabetes-related stress and coping among adolescents with type 1 diabetes and their mothers. Early adolescents with type 1 diabetes ( N = 118, ages 10-15 years; 54% female; 47% Latino and 53% non-Latino White) and mothers described the adolescent's diabetes-related stressors and coping strategies, and rated stressor severity and controllability and coping competence. Surveys measured adherence; glycemic control (HbA1c) was indexed from medical records. Few ethnic differences in stress and coping emerged among adolescents. However, Latina mothers reported fewer diabetes-related stressors, had lower congruence with their adolescent on reports of diabetes-related stress, and appraised their adolescent as less competent in coping than non-Latino Whites. Lower dyadic stressor congruence and lower appraisals of coping competence were associated with poorer HbA1c. Mother-adolescent congruence in perceptions of diabetes stress, and appraisals of early adolescents' coping, may be important for understanding diabetes management in ethnically diverse samples.


Recombinant Activated Protein C (rhAPC) Affects Lipopolysaccharide-Induced Mechanical Compliance Changes and Beat Frequency of mESC-Derived Cardiomyocyte Monolayers.
Septic cardiomyopathy increases mortality by 70% to 90% and results in mechanical dysfunction of cells. Here, we created a LPS-induced in-vitro sepsis model with mouse embryonic stem cell-derived cardiomyocytes (mESC-CM) using the CellDrum technology which simultaneously measures mechanical compliance and beat frequency of mESCs. Visualization of reactive oxygen species (ROS), actin stress fibers, and mRNA quantification of endothelial protein C receptor (EPCR) and protease-activated receptor 1 (PAR1) before/after LPS incubation were used for method validation. Since activated protein C (APC) has cardioprotective effects, samples were treated with human recombinant APC (rhAPC) with/-out LPS predamage to demonstrate the application in therapeutic studies. Twelve hours LPS treatment (5 μg/mL) increased ROS and decreased actin stress fiber density and significantly downregulated EPCR and PAR1 compared to control samples (0.26, 0.39-fold respectively). rhAPC application (5 μg/mL, 12 h) decreased ROS and recovered actin density, EPCR, and PAR1 levels were significantly upregulated compared to LPS predamaged samples (4.79, 3.49-fold respectively). The beat frequencies were significantly decreased after 6- (86%) and 12 h (73%) of LPS application. Mechanical compliance of monolayers significantly increased in a time-dependent manner, up to eight times upon 12-h LPS incubation compared to controls. rhAPC incubation increased the beat frequency by 127% (6h-LPS) and 123% (12h-LPS) and decreased mechanical compliance by 68% (12h-LPS) compared to LPS predamaged samples. LPS-induced contraction dysfunction and the reversal effects of rhAPC were successfully assessed by the mechanical properties of mESC-CMs. The CellDrum technology proved a decent tool to simulate sepsis in-vitro.


Expression of messenger RNA for GM-CSF by blood mononuclear cells after allogeneic bone marrow transplantation.
We examined blood mononuclear cells from six recipients of HLA-identical sibling marrow transplants for their ability to express messenger (m) RNA for granulocyte-macrophage colony stimulating factor (GM-CSF). Cells were cultured for 48 hours with the stimulus of ionomycin and phorbol myristate acetate. mRNA specific for GM-CSF was detectable in stimulated cell cultures from all six patients. In two patients at days 31 and 40 post transplant respectively, mRNA for GM-CSF was just detectable; in a third at day 38 post transplant it was readily detectable, and in the three others at days 42, 165 and 185 respectively, it was easily detectable. These results indicate that maintenance of haemopoiesis post transplant may, at least in part, be due to the elaboration of GM-CSF by blood mononuclear cells.


Nitric oxide and macrophage function.
At the interface between the innate and adaptive immune systems lies the high-output isoform of nitric oxide synthase (NOS2 or iNOS). This remarkable molecular machine requires at least 17 binding reactions to assemble a functional dimer. Sustained catalysis results from the ability of NOS2 to attach calmodulin without dependence on elevated Ca2+. Expression of NOS2 in macrophages is controlled by cytokines and microbial products, primarily by transcriptional induction. NOS2 has been documented in macrophages from human, horse, cow, goat, sheep, rat, mouse, and chicken. Human NOS2 is most readily observed in monocytes or macrophages from patients with infectious or inflammatory diseases. Sustained production of NO endows macrophages with cytostatic or cytotoxic activity against viruses, bacteria, fungi, protozoa, helminths, and tumor cells. The antimicrobial and cytotoxic actions of NO are enhanced by other macrophage products such as acid, glutathione, cysteine, hydrogen peroxide, or superoxide. Although the high-output NO pathway probably evolved to protect the host from infection, suppressive effects on lymphocyte proliferation and damage to other normal host cells confer upon NOS2 the same protective/destructive duality inherent in every other major component of the immune response.


Meditation as an intervention for chronic pain: an integrative review.
Chronic pain is a complex phenomenon that causes a significant disruption in the lives of those affected. Chronic pain is difficult to treat and challenges healthcare professionals' abilities to implement effective treatments. Therefore, chronic pain sufferers often seek complementary alternative medicine therapies such as meditation. Literature reviews have examined studies using mindfulness-based stress reduction program as an intervention for a variety of health problems. However, no reviews exist looking at a specific patient population's utilization of meditation-based programs. Therefore, the purpose of this integrative review is to examine studies that have investigated meditation as an intervention for chronic pain, identify gaps in the literature, and make recommendations for further research.


Sealant effectiveness for children receiving a combination of preventive methods in a fluoridated community: two-year results.
A series of preventive methods in combination have been used to reduce dental caries in children including dental health education, prophylaxes, pit and fissure sealants, topical application of fluoride and restorative care. Prophylaxes, sealant, and fluoride procedures are repeated every six months. Two-year results show reductions of occlusal caries increments of 74.3% for first graders and 77.1% for sixth graders. Sealant loss, as defined in this study, varied from 33% to 90% with the highest loss occurring in the newly erupted permanent molars during the first six months of the project. These high sealant loss rates are thought to be related to the age of the population which was designed to include children at the ages of peak eruption of permanent molar teeth (ages six and twelve). These teeth were often only minimally erupted and maintaining the dry field required for sealant retention was extremely difficult. However, in spite of these high rates of sealant loss, caries reduction on occlusal surfaces was highly significant in comparision to that of children who did not receive sealants.


Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension.
Inhalation of iloprost, a stable prostacyclin analog, is an effective therapy for pulmonary hypertension with few side effects. This approach may, however, be handicapped by limitations of currently available nebulization devices. We assessed whether the physical characterization of a device is sufficient to predict drug deposition and pharmacologic effects. We investigated the effects of a standardized iloprost aerosol dose (5 micro g; inhaled within approximately 10 min) in 12 patients with severe pulmonary hypertension in a crossover design employing three well-characterized nebulizers. The nebulizers use different techniques to increase efficiency and alveolar targeting (Ilo-Neb/Aerotrap [Nebu-Tec; Elsenfeld, Germany], Ventstream [MedicAid; Bognor Regis, UK], and HaloLite [Profile Therapeutics; Bognor Regis, UK]). Measurements were performed using a Swan-Ganz catheter and determination of arterial iloprost plasma levels. During inhalation of iloprost, the pulmonary vascular resistance decreased substantially (baseline, approximately 1,250 dyne.s.cm(-5); decrease, - 35.5 to - 38.0%) and pulmonary artery pressure decreased substantially (baseline, approximately 58 mm Hg; decline, - 18.4 to -21.8%), whereas the systemic arterial pressure was largely unaffected. Cardiac output and mixed venous and arterial oxygen saturation displayed a marked increase. The pharmacodynamic profiles with the three devices were superimposable. Moreover, rapid entry of iloprost into the systemic circulation was noted, peaking immediately after termination of the inhalation maneuver, with very similar maximum serum concentrations (158 pg/mL, 155 pg/mL, and 157 pg/mL), and half-lives of serum levels (6.5 min, 9.4 min, and 7.7 min) for the three nebulizers, respectively. Interestingly, the "half-life" of the pharmacodynamic effects in the pulmonary vasculature (eg, decrease in pulmonary vascular resistance, ranging between 21 and 25 min) clearly outlasted this serum level-based pharmacokinetic half-life. A standardized dose of aerosolized iloprost delivered by different nebulizer types induces comparable pharmacodynamic and pharmacokinetic responses. Pulmonary vasodilation, persisting after disappearance of the drug from the systemic circulation, supports the hypothesis that local drug deposition largely contributes to the preferential pulmonary vasodilation in response to inhaled iloprost.


[10 years results after repair of recurrent problem inguinal hernia with prolene mesh].
The repair of multiple recurrences of inguinal hernias remains a surgical challenge. In 38 patients with a problematic recurrent inguinal hernia we implanted a polypropylene mesh (Prolene) in order to reinforce the transversalis fascia and to repair the inguinal hernia. 20 of these were medial and 14 lateral hernias; 4 patients had a combination of both types. All patients were prospectively included into this study and were seen in median follow-up periods of 3 and 6 months, as well as 4 and 9 years. As early complications hematoma of the wound (n = 3), scrotal edema (n = 1), temporary pain at the wound site (n = 12) and paresthesia (n = 13) occurred. Two patients (n = 2) developed a femoral hernia and one patient suffered from a persisting nerve injury of the ilioinguinal nerve. Due to the low complication and recurrency rate the tension free repair with polypropylene mesh is a effective method for treatment of problematic recurrent hernias.


Severe perioperative hyperglycemia attenuates postoperative monocytic function, basophil count and T cell activation.
Hyperglycemia in hospitalized patients is associated with increased morbidity and mortality. Postoperative infections are particularly common in the setting of perioperative hyperglycemia; however, the relationship between perioperative glucose levels and the innate immune system remains unclear. Immune cells, monocytic respectively T cell function and T cell subspecies of 32 patients after esophageal or pancreatic resection were analyzed preoperatively and on the first day after surgery (POD 1). Perioperative blood glucose was measured hourly via arterial blood gas analyses. Groups were classified by maximum perioperative glucose levels: <180 mg/dL versus at least one episode of ≥180 mg/dL. The suppression of immune cells and cytokines was defined as the difference between pre- and postoperative values. In perioperative hyperglycemic patients, preoperative CD4+/CD8+ ratio (P=0.039), count of CD4+ T cells (P=0.039) and release of IFN-γ (P=0.013) and TNF-α (P=0.045) after ex-vivo T cell stimulation of whole blood were significantly higher. Furthermore, the postoperative count of basophils was significantly lower (P=0.011), HLA-DR expressing CD8- T cells were tendentially lower (P=0.058) and more suppressed (P=0.035). The suppression of IFN-γ (P=0.003) and TNF-α (P=0.006) was significantly higher in these patients after ex-vivo T cell stimulation but absolute values were similar between the groups. IL-10 release of lipopolysaccharide-stimulated whole blood was tendentially more suppressed after perioperative hyperglycemia (P=0.084). Severe perioperative hyperglycemia attenuated postoperative basophil count, T cell activation and monocytic function. These patients were also at preoperative higher immune activation.


A cell proteomic approach for the detection of secretable biomarkers of invasiveness in oral squamous cell carcinoma.
To identify potential biomarkers of invasiveness in oral squamous cell carcinoma. A pilot proteomic study for the identification of secreted and cleaved proteins that can serve as potential biomarkers for head and neck carcinoma invasiveness. Two primary cell lines and their variants were established from 2 oral squamous cell carcinoma human tissue samples with distinct invasive phenotypes. The cell lines were confirmed to maintain the invasive capacity of the original cancer when implanted into the tongues of immunocompromised RAG-2/gamma(c) mice. Invasiveness was assessed by the capacity of cells to invade through a matrigel matrix using the Boyden chamber assay and correlated with the invasiveness seen clinically and histologically in patients. In parallel, cell lines were grown in serum-free conditioned medium, which was then used to identify secreted and/or cleaved proteins that emanate from cancer cells, using 2-dimensional gel electrophoresis and matrix-assisted laser desorption-ionization combined with tandem mass spectrometry. The invasion assays revealed a correlation between cell migration capacity through matrigel matrix and the aggressive phenotype seen in the clinical and histopathological assessments. More than 50 proteins were identified as being differentially secreted in media between the least and the more aggressive cell lines (P < .05). These include proteins that regulate cell metabolism, cell structure, cell adhesion, and cell motility, as well as proteins with undefined function. We report a sensitive and clinically relevant approach to screen for secreted biomarkers of oral squamous cell carcinoma invasiveness using proteomic technology. Both high- and low-abundant secreted proteins were identified and can represent potential biomarkers for oral cancer.


Mastocarcinoma therapy synergistically promoted by lysosome dependent apoptosis specifically evoked by 5-Fu@nanogel system with passive targeting and pH activatable dual function.
This manuscript describes a synergistic therapy for mastocarcinoma by pH and temperature dual-sensitive nanogel, and effects of microstructure, composition and properties of nanogel on the cellular response mechanism. The extracellular internalization of nanogels was obviously enhanced, due to the passive targeting function at T>VPTT. Interestingly, the increased cytotoxicity was further synergistically enhanced by an unexpected apoptosis as evoked by the 5-fluorouracil loaded nanogel (FLNG). The systemically evaluation of the effectors generated from different sub-cellular organelles including endosome, lysosome, autophagosome confirmed that it was a lysomal dependent apoptosis. Such specific apoptosis was mainly attributed to its activatable protonated PEI at low pH, which caused lysosomal membrane destruction and lysosomal enzyme cathepsin B (Cat B) leakage. This Cat B was then translocated to the mitochondria resulting in mitochondrial membrane permeability increase and mitochondrial membrane potential (MMP) decrease, followed by cytochrome c (Cyt C) release. Cyt C was the main molecule that evoked apoptosis as reflected by overexpression of caspase 9. Additionally, such lysosome dependent, apoptosis was further enhanced by the passive cellular targeting at T>VPTT. Thus, the tumor growth inhibition was synergistically enhanced by the extracellular temperature dependent passive targeting and intracellular pH activatable lysosomal dependent apoptosis.


Survival of children with rare structural congenital anomalies: a multi-registry cohort study.
Congenital anomalies are the leading cause of perinatal, neonatal and infant mortality in developed countries. Large long-term follow-up studies investigating survival beyond the first year of life in children with rare congenital anomalies are costly and sufficiently large standardized cohorts are difficult to obtain due to the rarity of some anomalies. This study aimed to investigate the survival up to 10 years of age of children born with a rare structural congenital anomaly in the period 1995-2014 in Western Europe. Live births from thirteen EUROCAT (European network for the epidemiological surveillance of congenital anomalies) population-based registries were linked to mortality records. Survival for 12,685 live births with one of the 31 investigated rare structural congenital anomalies (CAs) was estimated at 1 week, 4 weeks and 1, 5 and 10 years of age within each registry and combined across Europe using random effects meta-analyses. Differences between registries were evaluated for the eight rare CAs with at least 500 live births. Amongst the investigated CAs, arhinencephaly/holoprosencephaly had the lowest survival at all ages (58.1%, 95% Confidence Interval (CI): 44.3-76.2% at 1 week; 47.4%, CI: 36.4-61.6% at 1 year; 35.6%, CI: 22.2-56.9% at 10 years). Overall, children with rare CAs of the digestive system had the highest survival (> 95% at 1 week, > 84% at 10 years). Most deaths occurred within the first four weeks of life, resulting in a 10-year survival conditional on surviving 4 weeks of over 95% for 17 out of 31 rare CAs. A moderate variability in survival between participating registries was observed for the eight selected rare CAs. Pooling standardised data across 13 European CA registries and the linkage to mortality data enabled reliable survival estimates to be obtained at five ages up to ten years. Such estimates are useful for clinical practice and parental counselling.


[Antiepileptics].
Despite introduction of new antiepileptic drugs the established drugs phenytoin, carbamazepine and valproate still provide the treatment of choice in most forms of epilepsy, being efficacious in approximately two-thirds of all newly referred patients. In 20-60% of patients resistant to treatment with the older drugs, a 50% reduction of seizure frequency can be achieved by adding ethosuximide, clobazam, vigabatrine, oxcarbazepine, lamotrigine, felbamate, tiagabine or topiramate to the classic treatment. The majority of the new drugs are free of the problematic enzyme induction of the older compounds, making monotherapy as well as combination therapy much easier. To what extent the new antiepileptic drugs are going to be used for the treatment of patients with epilepsy will depend on the analysis of cost and benefits. This will be based on efficacy, side effects, interactions and teratogenicity of these new compounds.


Mapping small inland wetlands in the South-Kivu province by integrating optical and SAR data with statistical models for accurate distribution assessment.
There are several techniques for mapping wetlands. In this study, we examined four statistical models to assess the potential distribution of wetlands in the South-Kivu province by combining optical and SAR images. The approach involved integrating topographic, hydrological, and vegetation indices into the four most used classifiers, namely Artificial Neural Network (ANN), Random Forest (RF), Boosted Regression Tree (BRT), and Maximum Entropy (MaxEnt). A wetland distribution map was generated and classified into 'wetland' and 'non-wetland.' The results showed variations in predictions among the different models. RF exhibited the most accurate predictions, achieving an overall classification accuracy of 95.67% and AUC and TSS values of 82.4%. Integrating SAR data improved accuracy and precision, particularly for mapping small inland wetlands. Our estimations indicate that wetlands cover approximately 13.5% (898,690 ha) of the entire province. BRT estimated wetland areas to be ~ 16% (1,106,080 ha), while ANN estimated ~ 14% (967,820 ha), MaxEnt ~ 15% (1,036,950 ha), and RF approximately ~ 10% (691,300 ha). The distribution of these areas varied across different territories, with higher values observed in Mwenga, Shabunda, and Fizi. Many of these areas are permanently flooded, while others experience seasonal inundation. Through digitization, the delineation process revealed variations in wetland areas, ranging from tens to thousands of hectares. The geographical distribution of wetlands generated in this study will serve as an essential reference for future investigations and pave the way for further research on characterizing and categorizing these areas.


Experiences of family-staff relationships in the care of people with dementia in residential aged care: a qualitative systematic review protocol.
The objective of this systematic review is to identify, critically appraise and synthesize the best available literature regarding experiences and perceptions of family-staff relationships in the care of people with dementia living in residential aged care facilities.More specifically, the objectives are to identify family caregiver and healthcare staff experiences and perceptions of their own and each other's roles and responsibilities and the characteristics that facilitate or hinder a constructive family-staff relationship.


Viral hepatitis: how to manage type C and D infections.
Hepatitis C and D are relative newcomers to the study of viral hepatitis. Their transmission is mainly parenteral. The 0.5 to 2.2% prevalence of hepatitis C in the United States does not vary by patient age. Often, hepatitis C is asymptomatic. In older patients, symptomatic infection has a cholesteatic appearance, and progress to chronic hepatitis and cirrhosis is more rapid than in younger adults. Hepatitis D virus is a defective single-stranded RNA that presents as a co-infection or superinfection of hepatitis B. Prevalence varies by geographic region. The rate of progression to chronic disease and cirrhosis is high in superinfection.


DNA sequence analysis of spontaneous mutations at the aprt locus of hamster cells.
To determine the nature of spontaneous mutational events in cellular genes in hamster cells, mutant adenine phosphoribosyltransferase (aprt) genes were cloned and the regions to which we mapped alterations were sequenced. A variety of nucleotide changes were found to occur in the 12 mutant genes analyzed. Most mutations were simple base-pair substitutions-transitions (both G X C----A X T and A X T----G X C) and transversions. The only multiple mutation was a simple transition next to a single-base-pair insertion. Of the 12 mutations, 4 were more complex, involving small deletions or duplications. Two of these were similar to previously described deletions in that they occurred between short direct sequence repeats. No hot spots were detected. Three independent mutations were characterized at one restriction endonuclease site, although no other mutations were detected in the nucleotides surrounding this site in other mutant strains. At a functional level, sequence changes were either in exons (resulting in missense and, in one instance, nonsense mutations) or at splicing sites.


Multiple cranial nerve palsy revealing hypertrophic pachymeningitis with positive myeloperoxidase-antineutrophil cytoplasmic antibody.
Pachymeningitis is a progressive disease resulting in a diffuse thickening of dura mater due to inflammation, tumor or autoimmune diseases, but most cases are idiopathic. Here, we report the case of a 60-year old man who had a progressive sensorineural hearing loss, visual disturbance and others cranial nerve involvement with an accompanying headache over several months. Brain magnetic resonance imaging showed diffusely thickened dura mater, highly enhanced after gadolinium administration, which was consistent with pachymeningitis. It was assumed to be related to autoimmune pathogenesis on the basis of elevated serum myeloperoxidase-antineutrophil cytoplasmic antibody titers. After empirical steroid and cyclophosphamide therapy, the neurological problems were partially improved. Therefore, in the case of atypical sensorineural hearing loss accompanied by cranial nerve palsy or headache, pachymeningitis should be considered in the differential diagnosis.


Anti-respiratory syncytial virus prenylated dihydroquinolone derivatives from the gorgonian-derived fungus Aspergillus sp. XS-20090B15.
Two new prenylated dihydroquinolone derivatives, 22-O-(N-Me-l-valyl)aflaquinolone B (1) and 22-O-(N-Me-l-valyl)-21-epi-aflaquinolone B (2), and two known analogues, aflaquinolones A (3) and D (or a diastereomer of D, 4), were isolated from the mycelia of a gorgonian-derived Aspergillus sp. fungus. The structures of the new compounds were elucidated by spectroscopic methods, ECD spectra, Marfey's method, and chemical conversion. Compounds 1 and 2 display an unusual esterification of N-Me-l-Val to the side-chain prenyl group. Compound 2 exhibited outstanding anti-RSV activity with an IC50 value of 42 nM, approximately 500-fold stronger than that of the positive control ribavirin (IC50 = 20 μM), and showed a comparatively higher therapeutic ratio (TC50/IC50 = 520).


Charts for the early stopping of pilot studies.
Cooperative oncology groups usually run pilot studies of new agents or combinations concurrently with their major randomized clinical trials. A primary objective of these studies is to determine whether the new regimen should be tested further in a group-wide clinical trial. The accrual goals of such pilot studies are typically fixed in advance at between 30 and 40 patients, on the grounds that this number provides a reasonably tight confidence interval on the true response rate. Nevertheless early termination of pilot studies is often desirable either because the regimen appears inactive or because early results indicate extreme activity and justify immediate testing in a randomized study. Statistical charts are provided for early termination in both these situations. The charts are read by specifying the number of evaluable patients already accrued, the number of responses observed and the minimum true response rate, theta 0, at which the regimen would be considered active. The charts provide the posterior probability that the true response rate exceeds theta 0, that is, that the regimen is active. An additional chart that computes a 90% probability interval for the true response rate, based on the observed rate and sample size, is also provided. The use of the chart is illustrated with two examples from the Eastern Cooperative Oncology Group.


Exclusive triplet electron transfer leading to long-lived radical ion-pair formation in an electron rich platinum porphyrin covalently linked to fullerene dyad.
The formation of a high-energy, long-lived radical ion-pair by electron transfer exclusively from the triplet excited state, is demonstrated in a newly synthesized platinum porphyrin-fullerene dyad, in which the porphyrin ring is modified with three electron rich triphenylamine entities. The spin selectivity of the electron transfer leading to the formation of the radical ion-pair is demonstrated using time-resolved optical and EPR spectroscopic techniques.


Permselectivity: relation between foot process simplification and macromolecular configuration.
The simplification of the foot processes of the glomerular epithelial cells is the structural hallmark of proteinuria in nephrotic man and animals. The increased shear force in a filtrate funnelled within the lamina densa to simplified slit pores may decrease the friction of macromolecules which are prolate ellipsoids (cigar-shaped). The permeability of rigid long narrow proteins such as albumin, transferrin and immunoglobulin G may selectively increase when the slit pore is converted from a wide serpentine to a straight narrow space.


Pattern formation in diffusive-advective coupled map lattices.
We investigate pattern formation and evolution in coupled map lattices when advection is incorporated, in addition to the usual diffusive term. All patterns may be suitably grouped into five classes: three periodic, supporting static patterns and traveling waves, and two nonperiodic. Relative frequencies are determined as a function of all model parameters: diffusion, advection, local nonlinearity, and lattice size. Advection plays an important role in coupled map lattices, being capable of considerably altering pattern evolution. For instance, advection may induce synchronization, making chaotic patterns evolve periodically. As a byproduct we describe a practical algorithm for classifying generic pattern evolutions and for measuring velocities of traveling waves.


Impact of Surface Charge on Cerium Oxide Nanoparticle Uptake and Translocation by Wheat (Triticum aestivum).
Nanoparticle (NP) physiochemical properties, including surface charge, affect cellular uptake, translocation, and tissue localization. To evaluate the influence of surface charge on NP uptake by plants, wheat seedlings were hydroponically exposed to 20 mg/L of ∼4 nm CeO2 NPs functionalized with positively charged, negatively charged, and neutral dextran coatings. Fresh, hydrated roots and leaves were analyzed at various time points over 34 h using fluorescence X-ray absorption near-edge spectroscopy to provide laterally resolved spatial distribution and speciation of Ce. A 15-20% reduction from Ce(IV) to Ce(III) was observed in both roots and leaves, independent of NP surface charge. Because of its higher affinity with negatively charged cell walls, CeO2(+) NPs adhered to the plant roots the strongest. After 34 h, CeO2(-), and CeO2(0) NP exposed plants had higher Ce leaf concentrations than the plants exposed to CeO2(+) NPs. Whereas Ce was found mostly in the leaf veins of the CeO2(-) NP exposed plant, Ce was found in clusters in the nonvascular leaf tissue of the CeO2(0) NP exposed plant. These results provide important information for understanding mechanisms responsible for plant uptake, transformation, and translocation of NPs, and suggest that NP coatings can be designed to target NPs to specific parts of plants.


High-voltage testing of a 500-kV dc photocathode electron gun.
A high-voltage dc photocathode electron gun was successfully conditioned up to a voltage of 550 kV and a long-time holding test for 8 h was demonstrated at an acceleration voltage of 500 kV. The dc photocathode electron gun is designed for future light sources based on energy-recovery linac and consists of a Cockcroft-Walton generator, a segmented cylindrical ceramic insulator, guard-ring electrodes, a support-rod electrode, a vacuum chamber, and a pressurized insulating gas tank. The segmented cylindrical ceramic insulator and the guard-ring electrodes were utilized to prevent any damage to the insulator from electrons emitted by the support-rod electrode.


Well-differentiated fetal adenocarcinoma of the lung: cytomorphologic features on fine-needle aspiration with emphasis on use of beta-catenin as a useful diagnostic marker.
Well-differentiated fetal adenocarcinoma (WDFA), also known as low grade adenocarcinoma of the fetal lung type, is a rare pulmonary neoplasm now considered to be a variant of lung adenocarcinoma rather than a type of pulmonary blastoma. Upregulation of the Wnt signaling pathway with subsequent aberrant nuclear/cytoplasmic beta-catenin expression has been recently described in these tumors providing a possible pathogenetic role for this gene in WDFA. We describe the cytomorphologic findings of a case of WDFA in a 36-yr-old female patient and emphasize the diagnostic utility of aberrant nuclear/cytoplasmic expression of beta-catenin as an adjunct to the correct preoperative recognition of this tumor on aspiration cytology.


An Uncommon Presentation of a Scleral Cyst.
Scleral cyst is an unusual, rare clinical condition. Most of the cases reported have described the cyst to occur at the limbus, with or without involvement of the cornea. Posterior scleral cysts have seldom been reported in literature. This case report describes a postequatorial scleral cyst that may mimic a choroidal melanoma. Certain clinical features and swept-source optical coherence tomography are useful for elucidating the location of intraocular lesions anatomically, as well as distinguishing their structural characteristics. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:209-211.].


Antioxidant agents for delaying diabetic kidney disease progression: A systematic review and meta-analysis.
Oxidative stress is a key player in the genesis and worsening of diabetic kidney disease (DKD). We aimed at collecting all available information on possible benefits of chronic antioxidant supplementations on DKD progression. Systematic review and meta-analysis. Adults with DKD (either secondary to type 1 or 2 diabetes mellitus). Cochrane CENTRAL, Ovid-MEDLINE and PubMed were searched for randomized controlled trials (RCTs) or quasi-RCTs without language or follow-up restriction. Any antioxidant supplementation (including but not limited to vitamin A, vitamin C, vitamin E, selenium, zinc, methionine or ubiquinone) alone or in combination. Primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes were change in albuminuria, proteinuria, serum creatinine and renal function. From 13519 potentially relevant citations retrieved, 15 articles referring to 14 full studies (4345 participants) met the inclusion criteria. Antioxidant treatment significantly decreased albuminuria as compared to control (8 studies, 327 participants; SMD: -0.47; 95% CI -0.78, -0.16) but had apparently no tangible effects on renal function (GFR) (3 studies, 85 participants; MD -0.12 ml/min/1.73m2; 95% CI -0.06, 0.01). Evidence of benefits on the other outcomes of interest was inconclusive or lacking. Small sample size and limited number of studies. Scarce information available on hard endpoints (ESKD). High heterogeneity among studies with respect to DKD severity, type and duration of antioxidant therapy. In DKD patients, antioxidants may improve early renal damage. Future studies targeting hard endpoints and with longer follow-up and larger sample size are needed to confirm the usefulness of these agents for retarding DKD progression.


Mammalian Smaug is a translational repressor that forms cytoplasmic foci similar to stress granules.
Cytoplasmic events depending on RNA-binding proteins contribute to the fine-tuning of gene expression. Sterile alpha motif-containing RNA-binding proteins constitute a novel family of post-transcriptional regulators that recognize a specific RNA sequence motif known as Smaug recognition element (SRE). The Drosophila member of this family, dSmaug, triggers the translational repression and deadenylation of maternal mRNAs by independent mechanisms, and the yeast homologue Vts1 stimulates degradation of SRE-containing messengers. Two homologous genes are present in the mammalian genome. Here we showed that hSmaug 1, encoded in human chromosome 14, represses the translation of reporter transcripts carrying SRE motifs. When expressed in fibroblasts, hSmaug 1 forms cytoplasmic granules that contain polyadenylated mRNA and the RNA-binding proteins Staufen, TIAR, TIA-1, and HuR. Smaug 1 foci are distinct from degradation foci. The murine protein mSmaug 1 is expressed in the central nervous system and is abundant in post-synaptic densities, a subcellular region where translation is tightly regulated by synaptic stimulation. Biochemical analysis indicated that mSmaug 1 is present in synaptoneurosomal 20 S particles. These results suggest a role for mammalian Smaug 1 in RNA granule formation and translation regulation in neurons.


Innovation and Exploration of Computer-Aided New Media Translation Course Teaching Mode under the Ecological Environment.
In order to analyze the innovation of computer new media-aided translation course teaching mode under the ecological environment, this paper introduces the CorpTrans system, which analyzes the practical effect of computer-aided translation system applied in the course teaching, verifies the role of the system in computer-aided translation course teaching, and plays an important role in improving students' translation ability. At the same time, starting with the development trend of new media environment, the CorpTrans system is used to innovate the teaching mode of computer-aided translation course. The teaching ecology of the comprehensive new media translation curriculum consists of the interaction between the ecological subject of teaching and the ecological environment of teaching. Through the efforts of both teachers and students, high-quality computer-aided translation courses will contribute to cultivating compound translation talents. The innovation of teaching mode needs to be realized by this system, so as to better meet the requirements of improving the teaching level of translation courses.


Synthetic lapachol derivatives relax guinea-pig ileum by blockade of the voltage-gated calcium channels.
The present study was designed to further evaluate a possible spasmolytic activity of synthetic lapachol derivatives, norlapachol, alpha-norlapachone, beta-norlapachone and hydro-hydroxy-norlapachol (HH-norlapachol), on guinea-pig ileum. In guinea-pig ileum, except for norlapachol, all naphthoquinones inhibited the phasic contractions induced by carbachol or histamine. Even when the ileum was pre-contracted with KCl, carbachol or histamine, all naphthoquinones induced relaxation, suggesting that these naphthoquinones could be acting on the voltage-gated calcium channels (Ca(V)). As the tonic component this contraction is maintained mainly by the opening of the Ca(V), we hypothesized that these naphthoquinones might be acting on these channels. This hypothesis was confirmed by the observation that norlapachol (pD'2 = 4.99), alpha-norlapachone (pD'2 = 4.49), beta-norlapachone (pD'2 = 6.33), and HH-norlapachol (pD'2 = 4.53) antagonized the contractions induced by CaCl2 in depolarizing medium nominally without Ca2+. As beta-norlapachone was the most potent we decided to continue the study of its action mechanism. The fact that this naphthoquinone has inhibited the tonic contractions induced by S-(-)-Bay K8644 [EC50 = (1.6 +/- 0.30) x 10(-5) M] suggests that the Ca2+ channel involved belongs to the type L (Ca(V)1.2). In addition, in the functional level, the spasmolytic effect of beta-norlapachone does not involve participation of free radicals, since its curve of relaxation was unchanged in the presence of glutathione, an antioxidant agent.


Studying Institutional Situational Awareness Through Anonymous Incident Reporting.
The efficacy of anonymous incident reporting (AIR) is critical to creating a culture of safety. Prior studies have sought to establish AIR in a similar manner as aviation, nuclear power, and other industries. However, health care presents unique challenges that differ greatly from these industries. We present a straightforward method using statistical process control to study the progression and efficacy of AIR. This study represents a retrospective review of all anonymous incident reports and surgical critical events from 2012 to 2017 at a single-institution, 500-bed, university-based, metropolitan Veterans Affairs Administration Medical Center located in Texas. This work was approved by the Veterans Administration Quality Board and deemed to be an appropriate quality improvement project. This project did not require institutional review board approval. There was an exponential increase in AIRs in the first 15 months from 1 report per month to 168 reports in the ninth month (1425% increase). The results then plateaued over time (first year: 1017, second year: 1634, and third year: 1938-common-cause variation). A logarithmic regression was performed for progression of AIRs per month yielding the equation y = -7E-13ln(x) + 142.92, Pearson Correlation Coefficient = 0.55, where y represents number of reports and x time by month. The highest number of Critical Incident Tracking Notification System (CITNS) reports was observed early in the self-reporting process and decreased over time (first year: 5, second year: 2, third year: 1, fourth year: 1, and fifth year: 0). The numbers of AIR and CITNS reports were found to be inversely related with a Pearson correlation coefficient of -0.4. Statistical process control can be applied to an institution's AIR program to study progression and situational awareness.


Are suicide terrorists suicidal? A critical assessment of the evidence.
Most of the research on suicide terrorism is conducted in the political science and international relations fields. The prevailing wisdom within this literature is that suicide terrorists are not suicidal. But how good is the evidence for this assumption? Knowing whether suicide terrorists are suicidal has implications for prevention, rehabilitation, and the "softer" side of counterterrorism designed to win minds and hearts. In addition it may deepen our understanding of suicide itself. This article uses a review of existing literature to examine the arguments and evidence for and against the possibility that suicide terrorists could be suicidal in the context of a broad range of explanations for suicide terrorism. Much of the evidence against the possibility that suicide terrorists are suicidal is based on anecdote or faulty assumptions about suicide. Relatively few formal systematic studies of suicidality in suicide terrorists have been conducted. Nonetheless, there is emerging evidence that suicidality may play a role in a significant number of cases. The field needs a more multidimensional approach, more systematic data at the individual level, and greater international cross-disciplinary collaboration. Would-be suicide terrorists (intercepted and arrested on their way to an attack) should be routinely interviewed using standard internationally accepted psychiatric diagnostic interviews as well as suicidality and homicidality rating scales. Psychological autopsies should also be routinely conducted worldwide. Since no one research site can collect all of the information that is needed, the creation of an internationally shared database that focuses on suicide terrorists rather than simply incidents is encouraged.


Zika virus challenges for neuropsychiatry.
Before 2007, Zika virus (ZIKV) was generally considered as an arbovirus of low clinical relevance, causing a mild self-limiting febrile illness in tropical Africa and Southeast Asia. Currently, a large, ongoing outbreak of ZIKV that started in Brazil in 2015 is spreading across the Americas. Virus infection during pregnancy has been potentially linked to congenital malformations, including microcephaly. In addition to congenital malformations, a temporal association between ZIKV infection and an increase in cases of Guillain-Barré syndrome is currently being observed in several countries. The mechanisms underlying these neurological complications are still unknown. Emerging evidence, mainly from in vitro studies, suggests that ZIKV may have direct effects on neuronal cells. The aim of this study was to critically review the literature available regarding the neurobiology of ZIKV and its potential neuropsychiatric manifestations.


Microinversions in mammalian evolution.
We propose an approach for identifying microinversions across different species and show that microinversions provide a source of low-homoplasy evolutionary characters. These characters may be used as "certificates" to verify different branches in a phylogenetic tree, turning the challenging problem of phylogeny reconstruction into a relatively simple algorithmic problem. We estimate that there exist hundreds of thousands of microinversions in genomes of mammals from comparative sequencing projects, an untapped source of new phylogenetic characters.


[Effects of myoblast determining gene and connexin 43 gene on fibroblast differentiation and biological function in rats].
To investigate a change in the differentiation and biological function of the cultured rat fibroblast (FB) transfected by the myoblast determining gene (MyoD) and the connexin 43 (Cx43) gene and to explore the possible mechanism of the MyoD and Cx43 genes on treatment of ischemic heart disease (IHD). The gene cloning technology was used to construct the eukaryotic expressed plasmid vector pLenti6/V5-DEST-MyoD and pLenti6/V5-DEST-Cx43 in which MyoD cDNA or Cx43 cDNA was inserted. The RFL-6 FB cells were transfected with exogenetic MyoD cDNA or Cx43 cDNA via lipofectamine, followed by the Blasticidin (50 microg/ml) selection, according to the lentiviral expression system (ViraPower) protocol. The expression and the biological functions of Myol) and Cx43 in the transfectants were testified by RT-PCR, Western blot, and molecular and immunocytochemical methods. The mophological structure changes of the cells were observed under microscope before and after the transfection. The expression of MyoD and Cx43 was detected in the MyoD and Cx43 genes transfected FB with RT-PCR and Western blot. The immunocytochemical methods indicated the expressions of the MyoD and Cx43 genes, while desmin and alpha-actin were found in these cells. The myotubes were found from the cultures incubated a week in the differentiation medium, in which the transfected cells had a characteristic of the filaments in their cytoplasm and showed a myoblast morphology. MyoD cDNA can induce the cultured FB to differentiate into the myoblasts and Cx43 cDNA can enhance the gap junctional intercellular communication between the cell and the cell. Thus, a further experimental foundation for the therapy of IHD can be provided.


[Antiarrhythmia effects of omega-3 fatty acids. A review].
Omega-3 polyunsaturated fatty acids have been effective in reducing cardiovascular mortality in the recent GISSI-Prevenzione study. In a post-hoc analysis of this study an important observation has been the reduction of sudden cardiac death. The hypothesis that a protection from sudden death occurs because of antiarrhythmic effects of omega-3 fatty acids is supported by studies on cellular and animal models. A few intervention studies before the GISSI-Prevenzione and several retrospective analyses of epidemiological studies, in which nutritional variables connected with the intake of omega-3 fatty acids had been recorded, also support such a hypothesis. This review critically summarizes this type of evidence and indicates current research directions for its further validation.


The β-catenin/TCF-4-LINC01278-miR-1258-Smad2/3 axis promotes hepatocellular carcinoma metastasis.
Hepatocellular carcinoma (HCC) metastasis is largely responsible for HCC-associated recurrence and mortality. We aimed to identify metastasis-related long non-coding RNAs (lncRNAs) to understand the molecular mechanism of HCC metastasis. We first identified that miR-1258 was downregulated in HCC tissues both in The Cancer Genome Atlas (TCGA) and Sun Yat-sen University Cancer Center (SYSUCC) dataset. MiR-1258 expression negatively correlated with recurrence-free survival and overall survival of HCC patients. MiR-1258 overexpression inhibited migration and invasion of HCC cells both in vitro and in vivo, whereas miR-1258 downregulation promoted cell metastasis. Luciferase assays verified direct binding of miR-1258 to Smad2 and Smad3, thereby attenuating TGF-β/Smad signaling. We further established that lncRNA LINC01278 was a negative regulator of miR-1258. In vivo and in vitro assays demonstrated that LINC01278-mediated HCC metastasis was dependent on miR-1258 expression. Furthermore, miR-1258 downregulation in turn increased LINC01278 expression. We also observed that TCF-4 could bind to the LINC01278 promoter site. In addition, LINC01278 downregulation decreased migration and invasion of HCC cells induced by β-catenin and TGF-β1 both in vitro and in vivo. We uncovered a novel mechanism for β-catenin/TCF-4-LINC01278-miR-1258-Smad2/3 feedback loop activation in HCC metastasis, and the study indicated that LINC01278 could serve as a therapeutic target for HCC metastasis.


Electronic state of oxidized nanographene edge with atomically sharp zigzag boundaries.
Combined scanning tunneling microscopy (STM) and density functional theory (DFT) characterizations of the electronic state were performed on the zigzag edge of oxidized nanographene samples. The oxidized zigzag edge with atomically sharp boundaries was prepared by electrochemical oxidation of the graphite surface in aqueous sulfuric acid solution. Bias-dependent STM measurements demonstrated the presence of the edge state at the zigzag edges with local density of states (LDOS) split into two peaks around the Fermi level. Our DFT-based analysis showed that the two-peak structure of the edge state was due to the termination of the zigzag edge by carbonyl functional groups. The LDOS arising from the edge states was slowly dampened in the bulk at the carbonyl-terminated zigzag edges (~1.5 nm). This result is in clear contrast to the strongly localized edge states at hydrogenated zigzag edges in previous reports. The oxygen atoms in the carbonyl functional groups act as additional π sites at the edges; thus, the topology of the π electron network changes from "zigzag" to "Klein" type, leading to drastic modification of the edge states at the oxidized edges.


Effective Chemotherapy of Lung Cancer Using Bovine Serum Albumin-Coated Hydroxyapatite Nanoparticles.
BACKGROUND Successful chemotherapy of lung cancer relies largely on the use of a good drug delivery system (DDS). We successfully constructed a hybrid DDS comprised of hydroxyapatite (HAP) nanoparticles and bovine serum albumin (BSA). MATERIAL AND METHODS The HAP nanoparticles were selected as the core to encapsulate the anticancer drug doxorubicin (DOX), followed by surface modification of BSA as a stabilizer and shielding corona to finally prepare the hybrid DDS (BSA/HAP/DOX). RESULTS The following characterizations revealed that BSA/HAP nanoparticles have high stability, high biocompatibility, and good DOX-loading capability to meet in vivo applications. Moreover, BSA/HAP/DOX can enhance the cellular uptake of drug in A549 cells (lung cancer cells). Most importantly, BSA/HAP had better in vivo tumor targetability than bare HAP nanoparticles, which resulted in stronger anticancer efficacy both in vitro and in vivo than free DOX or HAP/DOX, and greatly decreased the adverse effects of free DOX. CONCLUSIONS Our hybrid DDS shows potential to be applied in more advanced application of cancer therapy.


Differential distribution of actual and surrogate oncotype DX recurrence scores in breast cancer patients by age, menopausal status, race, and body mass index.
The Oncotype DX Recurrence Score (RS) is a widely used prognostic tool for estrogen receptor-positive breast cancer patients. Multiple surrogate models can predict RS with good accuracy. In this study we aimed to determine whether the RS and two surrogate indices were differentially distributed by age, menopausal status, race, and body mass index (BMI). 516 breast cancer cases treated at a single institution were analyzed. Epidemiologic data, RS, tumor size, grade, and biomarker data were abstracted. Breast Cancer Prognostic Score (BCPS) and modified Magee equation 2 were used to calculate surrogate RS. Patients were stratified into different groups based on age, menopausal status, race, BMI, or a combination of strata. Mean and standard deviation were calculated for each group/subgroup. Age below median (< 63) was associated with higher RS, especially in obese and Black patients. RS was also higher in obese and Black patients in the premenopausal subgroup. Black patients had a higher RS compared to White women in the premenopausal and non-obese subgroups. BMI < 30 was associated with higher RS, especially in older, postmenopausal, and Black patients. Some of these observations were replicated by the two surrogate models. The surrogate recurrence scores were higher in the younger age group, in non-obese older/postmenopausal women, and in younger/premenopausal obese individuals. Higher RS was observed in younger and premenopausal breast cancer patients, especially among the Black and obese subgroups, and in non-obese patients, especially among Black and older/postmenopausal women, suggesting more aggressive disease in these subgroups. Some statistical differences could be replicated by both surrogate models, suggesting that they may have utility in breast cancer epidemiology studies that do not have access to Oncotype DX RS or patient outcome data.


Plasmonic Aerogels as a Three-Dimensional Nanoscale Platform for Solar Fuel Photocatalysis.
We use plasmonic Au-TiO2 aerogels as a platform in which to marry synthetically thickened particle-particle junctions in TiO2 aerogel networks to Au∥TiO2 interfaces and then investigate their cooperative influence on photocatalytic hydrogen (H2) generation under both broadband (i.e., UV + visible light) and visible-only excitation. In doing so, we elucidate the dual functions that incorporated Au can play as a water reduction cocatalyst and as a plasmonic sensitizer. We also photodeposit non-plasmonic Pt cocatalyst nanoparticles into our composite aerogels in order to leverage the catalytic water-reducing abilities of Pt. This Au-TiO2/Pt arrangement in three dimensions effectively utilizes conduction-band electrons injected into the TiO2 aerogel network upon exciting the Au SPR at the Au∥TiO2 interface. The extensive nanostructured high surface-area oxide network in the aerogel provides a matrix that spatially separates yet electrochemically connects plasmonic nanoparticle sensitizers and metal nanoparticle catalysts, further enhancing solar-fuels photochemistry. We compare the photocatalytic rates of H2 generation with and without Pt cocatalysts added to Au-TiO2 aerogels and demonstrate electrochemical linkage of the SPR-generated carriers at the Au∥TiO2 interfaces to downfield Pt nanoparticle cocatalysts. Finally, we investigate visible light-stimulated generation of conduction band electrons in Au-TiO2 and TiO2 aerogels using ultrafast visible pump/IR probe spectroscopy. Substantially more electrons are produced at Au-TiO2 aerogels due to the incorporated SPR-active Au nanoparticle, whereas the smaller population of electrons generated at Au-free TiO2 aerogels likely originate at shallow traps in the high surface-area mesoporous aerogel.


Role of ultrasound in the labor ward.
Intrapartum ultrasound is commonly used to evaluate fetal vitality, presentation and status as well as placental location. Health professionals are increasingly using intrapartum ultrasound for advanced applications that have not yet been shown to be effective by controlled research studies, using advanced ultrasound technologies such as bi-dimensional ultrasound, color ultrasound, pulsed Doppler ultrasound and three-dimensional ultrasound. This article reviews the current applications of intrapartum ultrasound and considers which advanced technologies can add to the standard of care in the delivery ward.


Key features of human episodic recollection in the cross-episode retrieval of rat hippocampus representations of space.
Neurophysiological studies focus on memory retrieval as a reproduction of what was experienced and have established that neural discharge is replayed to express memory. However, cognitive psychology has established that recollection is not a verbatim replay of stored information. Recollection is constructive, the product of memory retrieval cues, the information stored in memory, and the subject's state of mind. We discovered key features of constructive recollection embedded in the rat CA1 ensemble discharge during an active avoidance task. Rats learned two task variants, one with the arena stable, the other with it rotating; each variant defined a distinct behavioral episode. During the rotating episode, the ensemble discharge of CA1 principal neurons was dynamically organized to concurrently represent space in two distinct codes. The code for spatial reference frame switched rapidly between representing the rat's current location in either the stationary spatial frame of the room or the rotating frame of the arena. The code for task variant switched less frequently between a representation of the current rotating episode and the stable episode from the rat's past. The characteristics and interplay of these two hippocampal codes revealed three key properties of constructive recollection. (1) Although the ensemble representations of the stable and rotating episodes were distinct, ensemble discharge during rotation occasionally resembled the stable condition, demonstrating cross-episode retrieval of the representation of the remote, stable episode. (2) This cross-episode retrieval at the level of the code for task variant was more likely when the rotating arena was about to match its orientation in the stable episode. (3) The likelihood of cross-episode retrieval was influenced by preretrieval information that was signaled at the level of the code for spatial reference frame. Thus key features of episodic recollection manifest in rat hippocampal representations of space.