Optimal place of a foreign gene in the genome of viral haemorrhagic septicaemia virus (VHSV) for development of VHSV-based viral-vectored vaccines.
As the strength and duration of immune responses can be regulated by the antigen dose, higher expression of foreign antigens in the viral-vectored vaccines would be an important factor for inducing effective immune responses. The aim of this study was to determine the optimal insertion place of a foreign antigen gene in the genome of viral haemorrhagic septicaemia virus (VHSV) for development of VHSV-based viral-vectored vaccines. Recombinant VHSVs (rVHSVs) harbouring the red fluorescent protein (RFP) gene between N and P (rVHSV-A-RFP), P and M (rVHSV-B-RFP), or M and G genes (rVHSV-C-RFP) in the genome were rescued by reverse genetics. Their replication ability and expression level of RFP were compared according to the inserted locations. The viral titres of each rVHSV were not significantly different. However, Epithelioma papulosum cyprini (EPC) cells infected with rVHSV-A-RFP or rVHSV-B-RFP showed clearly higher fluorescence than cells infected with rVHSV-C-RFP. There was no significant difference in RFP expression between cells infected with rVHSV-A-RFP and rVHSV-B-RFP. The present results indicate that insertion of a foreign gene between N and P, or P and M genes of VHSV genome would be advantageous for development of VHSV-based viral-vectored vaccines. The present work is the first report on the optimal location of a foreign gene in VHSV genome for high expression, and the locations identified in this study would be suitable for the development of VHSV-based viral-vectored vaccines.


Sarcomatoid carcinoma of the colon: a case report.
Sarcomatoid carcinoma is a rare biphasic tumor characterized by a combination of malignant epithelial and mesenchymal cells. We report a rare case of sarcomatoid carcinoma of the colon. A 41-yr-old woman was hospitalized with a history of melena. Total colectomy was performed under the impression of colonic carcinoma. Histologically, the tumor was composed of differentiated adenocarcinoma in superficial portion and sarcomatoid spindle cells in deeper portion with a transitional area between the two portions. The sarcomatous areas revealed polygonal and spindle-shaped anaplastic malignant cells arranged in sheet, short fascicular or haphazard pattern. Immunohistochemically, tumor cells showed a positive immunoreaction for cytokeratin, epithelial membrane antigen, and vimentin. The histopathological and immunohistochemical transitions between the adenocarcinoma area and the spindle cell area suggested that the sarcomatous elements originated from the adenocarcinoma during tumor progression.


Atomistic mechanisms for the (1 x 1) <==> hex surface phase transformations of Pt(100).
The atomistic mechanisms and dynamics of the (1 x 1) --> hex surface reconstruction of the clean Pt(100) and its lifting upon CO adsorption have been studied by means of both density functional theory and molecular dynamics simulations based on the modified embedded-atom method. It was found that during the surface reconstruction from the square (1 x 1) to the approximately 20% more dense (quasi)hexagonal phase, the required extra atoms are extracted from the second layer, leaving highly mobile subsurface vacancies, even in the presence of adatom islands or steps. These vacancies will, by surface diffusion, coalesce to form steps. In contrast, during the reverse process--where the hex surface reconstruction is lifted upon adsorption of CO--the roughly 20% excess surface atoms are in a collective manner ejected to form chains of adatoms. In turn, these adatoms coalesce into islands and steps by surface diffusion. A result of the two totally different mechanisms is that the reconstruction process can be concluded not to be the reverse of the deconstruction process.


Long Noncoding RNA CTD-2589M5.4 Inhibits Ovarian Cancer Cell Proliferation, Migration, and Invasion Via Downregulation of the Extracellular Matrix-Receptor Interaction Pathway.
Background: The authors' previous study showed that the long noncoding RNA CTD-2589M5.4 was significantly upregulated in multidrug-resistant ovarian cancer cells. However, the role of CTD-2589M5.4 in the progression of ovarian cancer remains unclear. The purpose of this current study was to illuminate the biological function and possible mechanism of CTD-2589M5.4 in ovarian cancer development. Materials and Methods: The expression of CTD-2589M5.4 was examined via real-time quantitative PCR in primary ovarian cancer tissues (POCTs) and ovarian cancer cell lines. The biological function of CTD-2589M5.4 was analyzed via CCK-8 proliferation, wound healing, transwell, and flow cytometry assays in CTD-2589M5.4-overexpressed/silenced and control ovarian cancer cells. The mechanism of CTD-2589M5.4 function in ovarian cancer progression was analyzed utilizing high-throughput RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes analysis, qRT-PCR, Western blot, and rescue experiments. Results: CTD-2589M5.4 expression was decreased in the POCTs and ovarian cancer cells compared with the normal ovarian tissues (p < 0.05) and normal ovarian epithelial cells (p < 0.05). Overexpression of CTD-2589M5.4 inhibited the proliferation, invasion, and migration of ovarian cancer cells, while knockdown of CTD-2589M5.4 had the opposite effect. Furthermore, a total of 750 and 233 genes were notably upregulated and downregulated, respectively, in the CTD-2589M5.4-overexpressed A2780 cells, while the extracellular matrix (ECM)-receptor interaction pathway was significantly downregulated. In addition, overexpression of fibronectin 1 significantly abrogated the tumor suppressive function of CTD-2589M5.4. Conclusions: This study demonstrated that CTD-2589M5.4 could inhibit ovarian cancer cell proliferation, invasion, and migration, at least partially by way of downregulating the ECM-receptor interaction pathway, therefore providing a potential therapeutic target for the prevention and/or treatment of ovarian cancer.


Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.
The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.


The effects of acute acetaminophen toxicity on hepatic mRNA expression of SOD, CAT, GSH-Px, and levels of peroxynitrite, nitric oxide, reduced glutathione, and malondialdehyde in rabbit.
We investigated the regulation of antioxidant system under acetaminophen (AAP) toxicity. Twelve male New Zealand rabbits were divided into two groups with the following treatments: Group 1 animals were intraperitoneally injected with single saline (control). Group 2 animals were treated with intraperitoneal injection of AAP at a dose of 250 mg/kg body weight. Four hours following the treatments, blood samples were collected and the rabbits were sacrificed to collect liver samples. Hepatocellular damage was evaluated by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as histopathological examinations and immunohistochemical analysis. Tissue-reduced glutathione (GSH), nitric oxide (NO(.)), and malondialdehyde (MDA) levels were also measured. mRNA expression levels of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) were measured by semi-quantitative RT-PCR. It was found that liver GSH was reduced significantly in AAP-treated rabbits (P < 0.05), while MDA and NO(.) levels were increased when they were compared to control (P < 0.05). Blood AST and ALT levels were also increased following AAP treatment (P < 0.05). Hepatocellular degeneration and severe necrosis were detected in histopathological examinations. Increased immunostaining was observed for inducible nitric oxide synthase (iNOS) and nitrotyrosine in the liver. There were no changes in mRNA expression levels of SOD, CAT, and GSH-Px after AAP treatment compared to control group. These results suggest that the expression of these enzymes, which are involved in the antioxidant system, may not be altered after AAP toxicity, although classical toxic changes such as depletion of GSH, hepatocellular necrosis, and increased immunostaining for iNOS and nitrotyrosine were detected.


Isolation of single osteons and osteon lamellae.
Single human osteons were isolated by propagating fractures along their natural boundaries. Furthermore, decalcified osteons were mechanically manipulated to expose their interlamellar interfaces, making possible the study of collagen fibers by means of scanning electron microscopy (SEM). Isolation of single osteons of a wide range of lengths, as described in this paper, makes possible for the first time the study of their mechanical properties in all possible modes. SEM studies of exposed lamellar interfaces reveal that collagen fiber orientations are more complex than previously suggested and suggest further studies in an effort to solve past controversies on collagen fiber orientations in human bone.


Potential for early warning of viral influenza activity in the community by monitoring clinical diagnoses of influenza in hospital emergency departments.
Although syndromic surveillance systems are gaining acceptance as useful tools in public health, doubts remain about whether the anticipated early warning benefits exist. Many assessments of this question do not adequately account for the confounding effects of autocorrelation and trend when comparing surveillance time series and few compare the syndromic data stream against a continuous laboratory-based standard. We used time series methods to assess whether monitoring of daily counts of Emergency Department (ED) visits assigned a clinical diagnosis of influenza could offer earlier warning of increased incidence of viral influenza in the population compared with surveillance of daily counts of positive influenza test results from laboratories. For the five-year period 2001 to 2005, time series were assembled of ED visits assigned a provisional ED diagnosis of influenza and of laboratory-confirmed influenza cases in New South Wales (NSW), Australia. Poisson regression models were fitted to both time series to minimise the confounding effects of trend and autocorrelation and to control for other calendar influences. To assess the relative timeliness of the two series, cross-correlation analysis was performed on the model residuals. Modelling and cross-correlation analysis were repeated for each individual year. Using the full five-year time series, short-term changes in the ED time series were estimated to precede changes in the laboratory series by three days. For individual years, the estimate was between three and 18 days. The time advantage estimated for the individual years 2003-2005 was consistently between three and four days. Monitoring time series of ED visits clinically diagnosed with influenza could potentially provide three days early warning compared with surveillance of laboratory-confirmed influenza. When current laboratory processing and reporting delays are taken into account this time advantage is even greater.


The Past, Present, and Future in Management of Small Renal Masses.
Management of small renal masses (SRMs) is currently evolving due to the increased incidence given the ubiquity of cross-sectional imaging. Diagnosing a mass in the early stages theoretically allows for high rates of cure but simultaneously risks overtreatment. New consensus guidelines and treatment modalities are changing frequently. The multitude of information currently available shall be summarized in this review. This summary will detail the historic surgical treatment of renal cell carcinoma with current innovations, the feasibility and utility of biopsy, the efficacy of ablative techniques, active surveillance, and use of biomarkers. We evaluate how technology may be used in approaching the small renal mass in order to decrease morbidity, while keeping rates of overtreatment to a minimum.


Genome and transcriptome-wide analyses of cellulose synthase gene superfamily in soybean.
The plant cellulose synthase gene superfamily belongs to the category of type-2 glycosyltransferases, and is involved in cellulose and hemicellulose biosynthesis. These enzymes are vital for maintaining cell-wall structural integrity throughout plant life. Here, we identified 78 putative cellulose synthases (CS) in the soybean genome. Phylogenetic analysis against 40 reference Arabidopsis CS genes clustered soybean CSs into seven major groups (CESA, CSL A, B, C, D, E and G), located on 19 chromosomes (except chromosome 18). Soybean CS expansion occurred in 66 duplication events. Additionally, we identified 95 simple sequence repeat makers related to 44 CSs. We next performed digital expression analysis using publically available datasets to understand potential CS functions in soybean. We found that CSs were highly expressed during soybean seed development, a pattern confirmed with an Affymatrix soybean IVT array and validated with RNA-seq profiles. Within CS groups, CESAs had higher relative expression than CSLs. Soybean CS models were designed based on maximum average RPKM values. Gene co-expression networks were developed to explore which CSs could work together in soybean. Finally, RT-PCR analysis confirmed the expression of 15 selected CSs during all four seed developmental stages.


Radiation signature on exposed cells: Relevance in dose estimation.
The radiation is considered as a double edged sword, as its beneficial and detrimental effects have been demonstrated. The potential benefits are being exploited to its maximum by adopting safe handling of radionuclide stipulated by the regulatory agencies. While the occupational workers are monitored by personnel monitoring devices, for general publics, it is not a regular practice. However, it can be achieved by using biomarkers with a potential for the radiation triage and medical management. An ideal biomarker to adopt in those situations should be rapid, specific, sensitive, reproducible, and able to categorize the nature of exposure and could provide a reliable dose estimation irrespective of the time of the exposures. Since cytogenetic markers shown to have many advantages relatively than other markers, the origins of various chromosomal abnormalities induced by ionizing radiations along with dose-response curves generated in the laboratory are presented. Current status of the gold standard dicentric chromosome assay, micronucleus assay, translocation measurement by fluorescence in-situ hybridization and an emerging protein marker the γ-H2AX assay are discussed with our laboratory data. With the wide choice of methods, an appropriate assay can be employed based on the net.


Synthesis of Cerium Dioxide Nanoparticles by Gas/Liquid Pulsed Discharge Plasma in a Slug Flow Reactor.
Cerium dioxide (CeO2) nanoparticles have gained immense attention owing to their use in various applications. Current synthesis methods for CeO2 nanoparticles including hydrothermal and chemical precipitation are time-consuming and require chemical reagents. In order to shorten the reaction time and avoid the use of organic reagents, a new method for CeO2 nanoparticles synthesis in a slug flow system by atmospheric-pressure pulsed discharge plasma was proposed, which provided an easy, efficient, and continuous reaction at room temperature. Cerium nitrate was used as a feed solution, and starch was added as a stabilizer to separate the nucleation and growth processes of the nanoparticles to prevent their aggregation. The system was powered by a high voltage of 10.0 kV (peak-to-peak) from an ac power supply. The products were characterized by transmission electron microscopy (TEM), high-resolution TEM, energy-dispersive X-ray spectroscopy, and UV-vis spectroscopy. The results showed that when a circular capillary glass tube coil was used as the slug flow reactor, the amount of the CeO2 nanoparticles increased compared to the case when a straight glass tube was used. The size also increased from 3.4 to 6.3 nm. The synthesis mechanism of the CeO2 nanoparticles by gas/liquid plasma was finally elucidated.


Noise-induced anomalous diffusion over a periodically modulated saddle.
We study analytically and numerically the anomalous diffusion across periodically modulated parabolic potential within Langevin and Fokker-Planck descriptions. We find that the probability of particles passing over the saddle is affected strikingly by the periodical modulation with average zero bias. Particularly, the initial phase plays an important role in the modulation effect. The effect of the correlation time of external Ornstein-Uhlenbeck noise on dynamical process is also discussed. A reduction in overpassing probability is observed due to finite correlation time.


[Correlation between serum inflammatory cytokine levels and fibrous cap thickness of fibrofatty plaque in coronary culprit lesions].
Objective: To identify the correlation between serum inflammatory cytokine levels including high sensitive C reactive protein (hs-CRP) and lipoprotein associated phospholipase (Lp-PLA2) and the fibrous cap thickness of fibrofatty plaque in coronary culprit lesions. Methods: Clinical data of 117 patients with selective coronary artery angiography diagnosed coronary artery disease admitted to our hospital from January 2015 to January 2016 were retrospective analyzed. According to type of coronary disease, patients were divided into 3 subgroups: SAP group (containing 47 stable angina patients), UAP group (containing 52 unstable angina patients), and NSTEMI group(containing 18 acute non ST segment elevation myocardial infarction patients). Serum hs-CRP and Lp-PLA2 levels were measured before subsequent procedures. The characteristics of the culprit lesions were detected by optical coherence tomogarpgy(OCT) before interventional treatment, and the correlation between hs-CRP and Lp-PLA2 and the fibrous cap thickness of fibrofatty plaque in coronary culprit lesions were analyzed. Results: (1) The serum levels of hs-CRP (2.13(1.04, 4.75)μg/L vs. 1.02(0.60, 1.29)μg/L and 1.30(1.03, 1.96)μg/L, all P<0.05) and Lp-PLA2 ((394.8±61.4)mg/L vs. (140.1±40.4)mg/L and (284.5±93.6)mg/L, all P<0.05) were significantly higher in NSTEMI group than in SAP group and UAP group, and serum levels of hs-CRP and Lp-PLA2 were significantly higher in UAP group than in SAP group (all P<0.05). (2)The fibrous cap thickness of fibrofatty plaque in coronary culprit lesions were smaller in NSTEMI group and UAP group than in SAP group(50(50, 60)μm and 60(50, 90)μm vs. 130(80, 190)μm, all P<0.05), and there was no significantly difference between NSTEMI group and UAP group(P>0.05). Proportion of thin-cap fibroatheroma plaque(82.35%(14/18) vs. 19.15%(9/47) and 63.46%(33/52), all P<0.05), plaque rupture(55.56%(10/18)vs. 6.38%(3/47) and 28.85%(15/52), all P<0.05) and thrombosis(33.33%(6/18) vs. 4.26%(2/47) and 9.26%(5/52), all P<0.05) were significantly higher in NSTEMI group than in SAP group and UAP group. Proportion of calcifiacation in plaque was lower in NSTEMI group than in SAP group (11.11%(2/18)vs. 42.55%(20/47), P<0.05), and there was no significantly difference between NSTEMI group and UAP group(P>0.05). (3) Pearson correlation analysis showed that serum levels of hs-CRP(r=-0.233, P<0.05) and Lp-PLA2(r=-0.465, P<0.01)were negatively correlated with fibrous cap thickness of fibrofatty plaques. Spearman correlation analysis showed that serum levels of hs-CRP were positively correlated with plaque rupture(r=0.409, P<0.01) and thrombosis (r=0.227, P<0.05), and serum levels of Lp-PLA2 were also positively correlated with plaque rupture(r=0.499, P<0.01) and thrombosis(r=0.263, P<0.01). (4)Multiple logistic regression analysis showed that serum levels of Lp-PLA2 at baseline was independently related to thin-cap fibroatheroma plaque(OR=1.017, P<0.01). Conclusions: The serum levels of hs-CRP and Lp-PLA2 in NSTEMI patients are much higher than that in SAP and UAP patients, higher in UAP patients than in SAP patients. Prevalence of thin-cap fibroatheroma plaque, plaque rupture and thrombosis was significantly higher in the NSTEMI patients, while the prevalence of calcification in plaque is more often in SAP patients. Increased serum levels of Lp-PLA2 are independent risk factor of thin-cap fibroatheroma plaque formation.


Utility of STR markers for the molecular diagnosis of a large Brazilian family with Charcot-Marie-Tooth disease.
Charcot-Marie-Tooth type 1A disease (CMT1A) is most frequently caused by a tandem DNA duplication of a 1.4-Mb genomic fragment in the 17p11.2-12 chromosomal region. The disease is probably the product of a dosage effect of the peripheral myelin protein 22 gene located within the duplicated segment. We sought to study the largest reported Brazilian family with suspected diagnosis of CMT1A using eight short tandem repeat microsatellite markers. In addition, we analyzed the informativeness of these markers in the normal Brazilian population. The duplication was found in 12 members of the family. In two patients with CMT1A symptoms, the duplication was not detected, and one asymptomatic subject showed the duplication. D17S2230, D17S9B, D17S2220, D17S2227, D17S9A, and D17S4A markers showed the highest heterozygosity rates, and D17S2228 and D17S2224 markers were the least informative in our analysis.


Comprehensive genetic analysis of cholangiolocellular carcinoma with a coexistent hepatocellular carcinoma-like area and metachronous hepatocellular carcinoma.
The genetic profile of cholangiolocellular carcinoma (CLC) and its origin in relation to hepatocellular carcinoma (HCC) remain unclear. To elucidate the genetic profile of CLC, a comprehensive analysis of genetic mutations was carried out in a case of CLC with an HCC-like focal area and metachronous HCC. Liver tissue was obtained from CLC, a co-existent HCC-like area, and metachronously developed HCC by laser capture microdissection of formalin-fixed paraffin-embedded specimens obtained by hepatectomy. Gene mutational profiles were analyzed comprehensively by next-generation sequencing and digital PCR. Relationships among gene profiles, immunohistochemistry, and clinicopathological findings were investigated. Mutations in EGFR, PTEN, RB1, TP53, and ERBB2 were found in CLC, whereas mutations in KIT, BRAF, PTEN, TP53, and SMAD4 were found in the coexistent HCC-like area. Only the mutation in PTEN has a common Catalogue of Somatic Mutations in Cancer ID in the CLC and coexistent HCC-like area, and is related to the kinase-RAS module. In contrast, no cancer-related mutations were found in the metachronous HCC. No TERT mutations were found in any of the regions by digital PCR. Immunohistochemical staining for p53 was negative in CLC, although ≤10% positive in the coexistent HCC-like area. Immunostaining of C-kit, HER2, PTEN, and SMAD4 were negative. The genomic features of CLC and the focal area of an HCC-like region differ, but are related to the kinase-RAS module. The development of carcinogenesis in the CLC and HCC-like areas in this case might differ, following a common PTEN mutation, although alteration of the kinase-RAS module is the most common molecular event in CLC.


Regulation of wheat seed dormancy by after-ripening is mediated by specific transcriptional switches that induce changes in seed hormone metabolism and signaling.
Treatments that promote dormancy release are often correlated with changes in seed hormone content and/or sensitivity. To understand the molecular mechanisms underlying the role of after-ripening (seed dry storage) in triggering hormone related changes and dormancy decay in wheat (Triticum aestivum), temporal expression patterns of genes related to abscisic acid (ABA), gibberellin (GA), jasmonate and indole acetic acid (IAA) metabolism and signaling, and levels of the respective hormones were examined in dormant and after-ripened seeds in both dry and imbibed states. After-ripening mediated developmental switch from dormancy to germination appears to be associated with declines in seed sensitivity to ABA and IAA, which are mediated by transcriptional repressions of PROTEIN PHOSPHATASE 2C, SNF1-RELATED PROTEIN KINASE2, ABA INSENSITIVE5 and LIPID PHOSPHATE PHOSPHTASE2, and AUXIN RESPONSE FACTOR and RELATED TO UBIQUITIN1 genes. Transcriptomic analysis of wheat seed responsiveness to ABA suggests that ABA inhibits the germination of wheat seeds partly by repressing the transcription of genes related to chromatin assembly and cell wall modification, and activating that of GA catabolic genes. After-ripening induced seed dormancy decay in wheat is also associated with the modulation of seed IAA and jasmonate contents. Transcriptional control of members of the ALLENE OXIDE SYNTHASE, 3-KETOACYL COENZYME A THIOLASE, LIPOXYGENASE and 12-OXOPHYTODIENOATE REDUCTASE gene families appears to regulate seed jasmonate levels. Changes in the expression of GA biosynthesis genes, GA 20-OXIDASE and GA 3-OXIDASE, in response to after-ripening implicate this hormone in enhancing dormancy release and germination. These findings have important implications in the dissection of molecular mechanisms underlying regulation of seed dormancy in cereals.


[Radiation-induced meningioma: the changing pattern of the disease].
In this country radiation-induced meningiomas were usually associated with low-dose irradiation of the scalp of immigrants from North Africa, given as part of the treatment of tinea capitis. An Ashkenazi patient developed meningiomas 15 years after high-dose irradiation for a benign lesion in the parasellar region. The accumulating literature about high-dose radiation-induced meningiomas is reviewed and attention is drawn to the ever increasing number of meningiomas observed in immigrants from the former Soviet Union.


Translocation-excision-deletion-amplification mechanism leading to nonsyntenic coamplification of MYC and ATBF1.
Despite oncogene amplification being a characteristic of many tumor types, the mechanisms leading to amplicon formation have remained largely unresolved. In this study, we used a combinatorial approach of fluorescence in situ hybridization and single-nucleotide polymorphism chip gene copy number analyses to unravel the mechanism leading to nonsyntenic coamplification of MYC and ATBF1 in SJNB-12 cells. To explain our findings, we propose a complex series of events consisting of multiple double-strand breaks, accompanied (or triggered) by the formation of a reciprocal translocation t(8;16), as well as excisions and deletions near the translocation breakpoints. This study provides evidence for a translocation-excision-deletion-amplification sequence of events rather than a breakage-fusion-bridge model, which has been more frequently proposed to explain proto-oncogene amplification. Furthermore, it illustrates the power of presently available tools for detailed analysis of the complex rearrangements that accompany amplicon formation.


Elevation of the index of left ventricular mass during the acute and subacute phase of Kawasaki disease, and its association with indexes of diastolic function.
Our aim was to determine whether the index of left ventricular mass increases during the acute and subacute phase of Kawasaki disease, and to investigate any relationship between this index and clinical and echocardiographic variables. We performed, therefore, a retrospective study of 66 children with Kawasaki disease, having a mean age of 2.85 years, comparing the findings with those obtained from 57 normal controls, having a mean age of 2.99 years. The data from the patients used for comparison was obtained during the acute and subacute phase of the illness, as well as during the phase of convalescence. We performed correlation analysis of the findings during the acute and subacute phase, determining the relationship between the index of left ventricular mass and other variables. The index was higher (p = 0.0461), and the velocity of propagation of left ventricular early diastolic flow was lower (p < 0.0001), during the acute and subacute phase when compared to control values. The index then reduced (p = 0.0001) during the phase of convalescent when compared to the acute and subacute phase. Levels of albumin in the serum (p = 0.0193), peak E velocity (p = 0.0479), and velocity of propagation (p = 0.0360) were found to be related to the index of left ventricular mass. Significant relationships were found between the differences in this index and differences in body weight when findings during the acute and subacute phase were compared to those of the phase of convalescence. The index of left ventricular mass, therefore, is increased during the acute and subacute phase of Kawasaki disease, and is associated with altered diastolic indexes. This elevation may be due to generalized myocardial swelling from acute inflammation and increased vascular permeability. Measuring this index as a potential predictor of diastolic function should be added to studies of cardiac function during the acute and subacute phase of Kawasaki disease.


WISB: Warwick Integrative Synthetic Biology Centre.
Synthetic biology promises to create high-impact solutions to challenges in the areas of biotechnology, human/animal health, the environment, energy, materials and food security. Equally, synthetic biologists create tools and strategies that have the potential to help us answer important fundamental questions in biology. Warwick Integrative Synthetic Biology (WISB) pursues both of these mutually complementary 'build to apply' and 'build to understand' approaches. This is reflected in our research structure, in which a core theme on predictive biosystems engineering develops underpinning understanding as well as next-generation experimental/theoretical tools, and these are then incorporated into three applied themes in which we engineer biosynthetic pathways, microbial communities and microbial effector systems in plants. WISB takes a comprehensive approach to training, education and outreach. For example, WISB is a partner in the EPSRC/BBSRC-funded U.K. Doctoral Training Centre in synthetic biology, we have developed a new undergraduate module in the subject, and we have established five WISB Research Career Development Fellowships to support young group leaders. Research in Ethical, Legal and Societal Aspects (ELSA) of synthetic biology is embedded in our centre activities. WISB has been highly proactive in building an international research and training network that includes partners in Barcelona, Boston, Copenhagen, Madrid, Marburg, São Paulo, Tartu and Valencia.


Phase II evaluation of PALA in patients with refractory metastatic sarcomas.
The efficacy of PALA was evaluated in 22 patients with metastatic soft tissue and bone sarcomas. The 20 evaluable patients had received a median of three prior chemotherapeutic regimens, including an adriamycin combination, to which eight had shown response. PALA was administered at 2-week intervals. Sixteen patients received 6 g/m2 over 1 hour intravenously as their initial dose, while six patients received 5 g/m2. The major side effects were skin rash, stomatitis, diarrhea, nausea, and vomiting. Significant myelosuppression was not seen. Two patients had stabilization of disease for periods of 10 and 13 weeks. At the dose and schedule used in this trial, PALA was not effective against advanced adult sarcoma.


Diaryl azo derivatives as anti-diabetic and antimicrobial agents: synthesis, in vitro, kinetic and docking studies.
In the present study, a series of azo derivatives (TR-1 to TR-9) have been synthesised via the diazo-coupling approach between substituted aromatic amines with phenol or naphthol derivatives. The compounds were evaluated for their therapeutic applications against alpha-glucosidase (anti-diabetic) and pathogenic bacterial strains E. coli (gram-negative), S. aureus (gram-positive), S. aureus (gram-positive) drug-resistant strain, P. aeruginosa (gram-negative), P. aeruginosa (gram-negative) drug-resistant strain and P. vulgaris (gram-negative). The IC50 (µg/mL) of TR-1 was found to be most effective (15.70 ± 1.3 µg/mL) compared to the reference drug acarbose (21.59 ± 1.5 µg/mL), hence, it was further selected for the kinetic studies in order to illustrate the mechanism of inhibition. The enzyme inhibitory kinetics and mode of binding for the most active inhibitor (TR-1) was performed which showed that the compound is a non-competitive inhibitor and effectively inhibits the target enzyme by binding to its binuclear active site reversibly.


[Coupling relationship between water and salt of waters ecosystems in arid zone: a case study in Xinjiang Tarim River basin].
The pollution of waters ecosystems is caused by natural and artificial factors in Tarim River. Temporal and spatial variation of surface runoff is the main reason for changes of coupling relationship between water and salt. In the end of 1950s, mineralization degree was less than 1.0 g.L-1 from the upper reaches to the lower reaches of Tetema Lake in Tarim River. At present, only in July, August and October, mineralization degree is less than 1.0 g.L-1. During the other months, mineralization degree is more than 3.0 g.L-1 in Alaer Lake. In Qiala (the lower reaches of Tarim River), mineralization degree is more than 1.0 g.L-1 except in March. Moreover, mineralization degree is about 5.0 g.L-1 in July and December. It is showed that annual water quality belongs to the fifth seriously polluted water in Alaer, Xinquman and Yingbazha. Meanwhile, annual water quality in Qiala belongs to the fourth polluted water. In a word, water quality state and hydrological chemistry component are the most obviously indicator for coupling relationship between water and salt in Tarim River.


Volume localized spin echo correlation spectroscopy with suppression of 'diagonal' peaks.
Two dimensional homonuclear (1)H correlation spectroscopy is of considerable interest for volume localized spectral studies, both in vivo and in vitro, of biological as well as material objects. The information principally sought from correlation spectra resides in the cross-peaks, which are often masked however by the presence of diagonal peaks in COSY, or 'pseudo-diagonal' peaks at F1=0 in SECSY. It has therefore been a concern to suppress these diagonal or 'pseudo-diagonal' peaks, in order to ensure that cross-peak information is fully discernible. We present here a report of our work on volume localized DIagonal Suppressed Spin Echo Correlation specTroscopy (LDISSECT) and demonstrate its performance in comparison to the standard volume localized SECSY experiment, employing brain metabolite phantoms in a gel. The sequence works in the inhomogeneous, multi-component environment by exploiting the short acquisition time to suppress undesired information by employing an additional rf pulse. A brief description of the pulse sequence, its theory, and simulations are also included, besides experimental benchmarking on two brain metabolite phantoms in gel phase.


[Doppler ultrasound procedures in the diagnosis of occlusive processes of the supra-aortic arteries].
Reported in this paper is experience obtained from application of Doppler sonography to more than 2,000 examinations of patients with suspicion of cerebrovascular insufficiency. Indications for Doppler-type investigation are described together with criteria of Doppler sonography for positive detection of occlusive processes in greater brain-feeding arteries and for adequate assessment of results obtained from vascular surgery. The sensitivity of Doppler sonography amounted to 88.8 per cent and its specificity to 92.9 per cent, as recorded from 117 patients who had been angiographically followed up. Doppler ultrasonography for its high productivity in terms of wide-ranging diagnostic information was found to be the optional method for non-invasive diagnosis of occlusion in supra-aortic arteries, provided absence of contraindications.


Relation between intragastric bile acid concentration and mucosal abnormality in the stomach after vagotomy and gastroenterostomy for duodenal ulcer.
A high incidence of possible premalignant conditions of the gastric mucosa has been reported in the postoperative stomach and it has been suggested that bile plays a role in their pathogenesis. Fifty eight patients who had had a vagotomy and gastrojejunostomy between 1957 and 1967 underwent endoscopy and biopsy. Subsequently, samples of fasting and postprandial gastric juice were taken from all patients for analysis of total bile acid. The patients were divided into three histological groups: group 1 (24 patients) had gastritis or mucosal atrophy but no more than mild dysplasia; group 2 (23 patients) had intestinal metaplasia in one or more biopsies; group 3 (11 patients) had moderate or severe dysplasia in one or more biopsies. Group 2 and group 3 patients had higher fasting intragastric bile acid concentrations than group 1 (p less than 0.01 in both cases). There was no difference between fasting bile acid concentrations in groups 2 and 3. In the postprandial phase groups 2 and 3 also had higher peak intragastric concentrations than group 1 (p less than 0.01 in both cases). Again, there was no significant difference between groups 2 and 3. It is concluded that there is a relation between mucosal abnormality in the postoperative stomach and intragastric bile acid concentration. The possible aetiological link between bile acid and these mucosal abnormalities is discussed.


Perspective projection model for prism-based stereovision.
A perspective projection model for prism-based stereovision was presented in this paper. The prism was considered as a single optical lens. By analyzing each plane individually and then combining them together, an affine transformation matrix which can express the relationship between an object point and its image was derived. Next, the perspective projection model between object point and its image was established. The methods for model parameter calibration, distortion correction and 3D reconstruction were also provided. The proposed method was based on optical geometry and could be used in a multi-ocular prism. Experimental results are presented to demonstrate the reliability and accuracy of our method which could be used in morphological measurement with high precision.


Construction of probe of the plant growth-promoting bacteria Bacillus subtilis useful for fluorescence in situ hybridization.
Strains of Bacillus subtilis are plant growth-promoting bacteria (PGPB) of many crops and are used as inoculants. PGPB colonization is an important trait for success of a PGPB on plants. A specific probe, based on the 16 s rRNA of Bacillus subtilis, was designed and evaluated to distinguishing, by fluorescence in situ hybridization (FISH), between this species and the closely related Bacillus amyloliquefaciens. The selected target for the probe was between nucleotides 465 and 483 of the gene, where three different nucleotides can be identified. The designed probe successfully hybridized with several strains of Bacillus subtilis, but failed to hybridize not only with B. amyloliquefaciens, but also with other strains such as Bacillus altitudinis, Bacillus cereus, Bacillus gibsonii, Bacillus megaterium, Bacillus pumilus; and with the external phylogenetic strains Azospirillum brasilense Cd, Micrococcus sp. and Paenibacillus sp. The results showed the specificity of this molecular probe for B. subtilis.


Escherichia coli with autodisplayed Z-domain of protein A for signal amplification of SPR biosensor.
Generally, an immunoaffinity SPR biosensor detects a target analyte in a sample through highly selective adsorption by using the antigen-antibody interaction. For improving the sensitivity, various kinds of particles have been added to the already bound analytes on the SPR biosensor (sandwich assay). In this work, signal amplification was demonstrated by the expression of the IgG-binding Z-domain of protein A on the outer membrane of Escherichia coli via "Autodisplay". The amount of Z-domain of protein A expressed on the outer membrane was calculated to be 280,000 molecules per cell. In addition, the IgG-binding ability of the expressed protein was characterized using FACS analysis. The signal amplification of the SPR biosensor was performed in the sandwich assay format using a model of horseradish peroxidase (HRP); the limit of detection was determined to be significantly improved from 1 microg/ml to 1 ng/ml. Finally, myoglobin analysis was demonstrated for the medical diagnosis of cardiac diseases. The detection limit was estimated to be improved from 10 ng/ml to <1 ng/ml. These results show that Z-domain-displaying E. coli can be successfully used for the signal amplification of immunoaffinity biosensors, thereby improving the sensitivity and the limit of detection.


Trace Norm Regularized CANDECOMP/PARAFAC Decomposition With Missing Data.
In recent years, low-rank tensor completion (LRTC) problems have received a significant amount of attention in computer vision, data mining, and signal processing. The existing trace norm minimization algorithms for iteratively solving LRTC problems involve multiple singular value decompositions of very large matrices at each iteration. Therefore, they suffer from high computational cost. In this paper, we propose a novel trace norm regularized CANDECOMP/PARAFAC decomposition (TNCP) method for simultaneous tensor decomposition and completion. We first formulate a factor matrix rank minimization model by deducing the relation between the rank of each factor matrix and the mode- n rank of a tensor. Then, we introduce a tractable relaxation of our rank function, and then achieve a convex combination problem of much smaller-scale matrix trace norm minimization. Finally, we develop an efficient algorithm based on alternating direction method of multipliers to solve our problem. The promising experimental results on synthetic and real-world data validate the effectiveness of our TNCP method. Moreover, TNCP is significantly faster than the state-of-the-art methods and scales to larger problems.


Summary of: The relationship between oral health risk and disease status and age, and the significance for general dental practice funding by capitation.
The aim of this paper was to review the oral health and future disease risk scores compiled in the Denplan Excel/Previser Patient Assessment (DEPPA) data base by patient age group, and to consider the significance of these outcomes to general practice funding by capitation payments. Between September 2013 and January 2014 7,787 patient assessments were conducted by about 200 dentists from across the UK using DEPPA. A population study was conducted on this data at all life stages. The composite Denplan Excel Oral Health Score (OHS) element of DEPPA reduced in a linear fashion with increasing age from a mean value of 85.0 in the 17-24 age group to a mean of 72.6 in patients aged over 75 years. Both periodontal health and tooth health aspects declined with age in an almost linear pattern. DEPPA capitation fee code recommendations followed this trend by advising higher fee codes as patients aged. As is the case with general health, these contemporary data suggest that the cost of providing oral healthcare tends to rise significantly with age. Where capitation is used as a method for funding, these costs either need to be passed onto those patients, or a conscious decision made to subsidise older age groups.


A Prospective Observational Study Analyzing the Analgesic Efficacy of Caudal Block and Nerve Stimulator-Guided Pudendal Nerve Block in Children Undergoing Hypospadias Repair.
Hypospadias repair is a common pediatric surgery. While caudal block (CB) is the most widely used procedure for analgesia, pudendal nerve block (PNB) can be utilized as an alternative. We evaluated the postoperative analgesic efficacy of CB and PNB in children undergoing hypospadias repair. In this prospective observational study, we evaluated 101 patients who received standard general anesthesia along with CB or PNB. Postoperative pain score (Face, Legs, Activity, Cry, and Consolability {FLACC} score) along with the total number of analgesic doses and the total amount of analgesic drugs consumed within 24 hours were noted. Time to first rescue analgesia, post-block penile length and midshaft circumference, surgeon satisfaction score, and postoperative complications were also evaluated. Out of 101 patients observed, 50 received CB, and 51 received PNB. At 24-hour interval, the median FLACC score in CB was 6, while in the PNB, it was 4 (p<0.001). None of the patients who were given PNB received more than three doses (p<0.001), and the average consumption of analgesic drugs within 24 hours was significantly higher in CB (38.4±4.28) compared to PNB (21.7±6.33) (p<0.0001). The median time to first rescue analgesia in CB was four hours, while in patients receiving PNB, it was eight hours (p<0.001). The increase in penile volume was significantly higher with CB as compared to PNB (p<0.001). Surgeon satisfaction score was found to be better with PNB (p<0.002). Patients who received PNB had significantly reduced pain scores and analgesic consumption in the first 24 hours post surgery.


An introduction to the electronic waterpipe.
Despite the associated negative health outcomes, waterpipe smoking remains a popular method of tobacco consumption, specifically in young adults. While there have been expanding efforts to decrease waterpipe use, there is a new, non-combustible waterpipe device on the market, the electronic waterpipe (e-waterpipe), that could serve as an alternative to traditional, combustible waterpipe smoking. There is currently no known literature evaluating the e-waterpipe including prevalence of use or its health risks. This mini review defines the e-waterpipe, explains how an e-head is used to construct an e-waterpipe, and describes the various e-head models available for use. The review also discusses implications of e-head use and provides recommendations for future research and regulation.


Big data and ambulatory care: breaking down legal barriers to support effective use.
Big data is heralded as having the potential to revolutionize health care by making large amounts of data available to support care delivery, population health, and patient engagement. Critics argue that big data's transformative potential is inhibited by privacy requirements that restrict health information exchange. However, there are a variety of permissible activities involving use and disclosure of patient information that support care delivery and management. This article presents an overview of the legal framework governing health information, dispels misconceptions about privacy regulations, and highlights how ambulatory care providers in particular can maximize the utility of big data to improve care.


[Volumetric monitoring based on transpulmonary thermodilution in anesthesiology and intensive care].
The review elucidates the technique of transpulmonary thermodilution in volumetric monitoring of critically ill patients. The experimental and clinical studies, now underway, are indicative of a great value of the discussed method for practical medicine. The key parameters of volumetric monitoring comprise Intrathoracic Blood Volume and Extravascular Lung Water as well as a wide range of other derived variables and indices. The approach is highly effective in the mechanical ventilation and inotope/vasopressor support of patients with a high risk of non-cardiogenic or cardiogenic pulmonary edema. The evaluation of volumetric parameters and of invasive monitoring of hemodynamics provide for an excellent guidance in fluid resuscitation in an overwhelming majority of ICU patients. The PiCCO technology of continuous cardiac output (CO) measurements or, the so-called "pulse contour CO" is also under discussion.


In vitro Generation of CRISPR-Cas9 Complexes with Covalently Bound Repair Templates for Genome Editing in Mammalian Cells.
The CRISPR-Cas9 system is a powerful genome-editing tool that promises application for gene editing therapies. The Cas9 nuclease is directed to the DNA by a programmable single guide (sg)RNA, and introduces a site-specific double-stranded break (DSB). In mammalian cells, DSBs are either repaired by non-homologous end joining (NHEJ), generating small insertion/deletion (indel) mutations, or by homology-directed repair (HDR). If ectopic donor templates are provided, the latter mechanism allows editing with single-nucleotide precision. The preference of mammalian cells to repair DSBs by NHEJ rather than HDR, however, limits the potential of CRISPR-Cas9 for applications where precise editing is needed. To enhance the efficiency of DSB repair by HDR from donor templates, we recently engineered a CRISPR-Cas9 system where the template DNA is bound to the Cas9 enzyme. In short, single-stranded oligonucleotides were labeled with O6-benzylguanine (BG), and covalently linked to a Cas9-SNAP-tag fusion protein to form a ribonucleoprotein-DNA (RNPD) complex consisting of the Cas9 nuclease, the sgRNA, and the repair template. Here, we provide a detailed protocol how to generate O6-benzylguanine (BG)-linked DNA repair templates, produce recombinant Cas9-SNAP-tag fusion proteins, in vitro transcribe single guide RNAs, and transfect RNPDs into various mammalian cells.


Magnetic Resonance Assessment of Peritoneal Carcinomatosis: Is There a True Benefit From Diffusion-Weighted Imaging?
To assess the added value of diffusion weighted imaging (DWI) with intermediate (500 s/mm2) and high (1000 s/mm2) b values when combined to conventional contrast-enhanced magnetic resonance imaging (MRI) in identifying peritoneal neoplastic involvement. Twenty-four patients with peritoneal carcinomatosis from gastrointestinal or gynecological tumors were retrospectively evaluated. All patients underwent peritonectomy with hyperthermic intraoperative chemotherapy and 1.5 T MRI including DWI with 500 s/mm2 and 1000 s/mm2 b values within 1 month from surgery. Images were independently reviewed by 2 radiologists with different experience in abdominal MRI in 3 separate reading sessions, the first including conventional MR images alone (T2-weighted, T1-weighted pre- and post gadolinium injection), the second conventional MRI and DWI with a b value of 500 s/mm2 (b 500-DWI), and the third conventional MRI and DWI with a b value of 1000 s/mm2 (b 1000-DWI). Apparent diffusion coefficient maps were included in the DWI analyses. Peritoneal dissemination was assessed in 9 anatomical sites, including right and left subphrenic space, paracolic gutters, small bowel mesentery, greater omentum, gastric-bowel serosa, free peritoneal surfaces, rectosigmoid-colon mesentery, and pelvis. The presence or absence of peritoneal dissemination for each patient and for each site was scored using a 5-point confidence scale. Sensitivity, specificity, and area under the curve (AUC) for identifying per-site peritoneal implants were calculated for each reader at each reading session. Interobserver agreement was evaluated using kappa statistics. For both readers, the sensitivity and AUC values resulting from combined interpretation of conventional MRI and DWI (both b500-DWI and b1000-DWI) were significantly higher than those of conventional MRI alone (P < 0.001). The added value of DWI was greater for the less experienced reader (sensitivity 0.55, specificity 0.73, AUC 0.64 on conventional MRI; sensitivity 0.75, specificity 0.72, AUC 0.74 on b500-DWI; sensitivity 0.87, specificity 0.72, AUC 0.80 on b1000-DWI) than for the more experienced reader (sensitivity 0.63, specificity 0.75, AUC 0.70 on conventional MRI; sensitivity 0.76, specificity 0.77, AUC 0.77 on b500-DWI; sensitivity 0.85, specificity 0.72, AUC 0.79 on b1000-DWI), although the differences between the 2 observers were not statistically significant. Interobserver agreement resulted to be fair (κ = 0.30) when dealing with conventional MRI alone. The addition of b500-DWI and b1000-DWI to conventional MRI allowed to reach a substantial agreement (κ = 0.75). The combined interpretation of high b value DWI and conventional MRI provides increased sensitivity and diagnostic performance in detection of peritoneal carcinomatosis in oncologic patients.


Contributions of metaknowledge to retrieval of natural categories in semantic memory.
Retrieving the answer to a general knowledge question has been shown to involve two metacognitive processes--a feeling-of-knowing that initiates the search of long-term memory and a willingness to continue searching until an answer can be confidently stated. To extend this model, college students were asked to retrieve as many members of 2 natural categories as they could in 1 min. Examination of the points at which they switched categories revealed that they searched longer in categories of higher potency, and they switched earlier when the other category was of higher potency. They also searched the first category longer when they were allowed to switch only once during a trial rather than as often as they wished. It was concluded that feeling-of-knowing maintained search of a category and also contributed to the willingness to continue searching, and the constraint on switching impacted the willingness to continue.


FG nucleoporins feature unique patterns that distinguish them from other IDPs.
FG nucleoporins (FG Nups) are intrinsically disordered proteins and are the putative regulators of nucleocytoplasmic transport. They allow fast, yet selective, transport of molecules through the nuclear pore complex, but the underlying mechanism of nucleocytoplasmic transport is not yet fully discovered. As a result, FG Nups have been the subject of extensive research in the past two decades. Although most studies have been focused on analyzing the conformation and function of FG Nups from a biophysical standpoint, some recent studies have investigated the sequence-function relationship of FG Nups, with a few investigating amino acid sequences of a large number of FG Nups to understand common characteristics that might enable their function. Previously, we identified an evolutionarily conserved feature in FG Nup sequences, which are extended subsequences with low charge density, containing only positive charges, and located toward the N-terminus of FG Nups. We named these patterns longest positive like charge regions (lpLCRs). These patterns are specific to positively charged residues, and negatively charged residues do not demonstrate such a pattern. In this study, we compare FG Nups with other disordered proteins obtained from the DisProt and UniProt database in terms of presence of lpLCRs. Our results show that the lpLCRs are virtually exclusive to FG Nups and are not observed in other disordered proteins. Also, lpLCRs are what differentiate FG Nups from DisProt proteins in terms of charge distribution, meaning that excluding lpLCRs from the sequences of FG Nups make them similar to DisProt proteins in terms of charge distribution. We also previously showed the biophysical effect of lpLCRs in conformation of FG Nups. The results of this study are in line with our previous findings and imply that lpLCRs are virtually exclusive and functionally significant characteristics of FG Nups and nucleocytoplasmic transport.


Health Locus of Control in Parents of Children with Leukemia and Associations with Their Life Perceptions and Depression Symptomatology.
In childhood cancer, parents have an important role in the promotion of their children's wellbeing and in their adoption of a locus of control style towards their children's health. The current study aimed at identifying types of locus of control in parents of children with leukemia and the possible association with depressive symptomatology and current life perception. One hundred and four parents were recruited at the Hematology-Oncology Clinic of the Department of Woman's and Child's Health, University of Padua, one month after a leukemia diagnosis. Participants were Caucasian with a mean age of 37.28 years (SD = 5.89), mostly mothers (87.5%) and with a mean of 12.16 years of education (SD = 3.82). After signing the informed consent, they filled in the Ladder of Life, the Brief Symptom Inventory-18 and the Parental Health Locus of Control (PHLOC) questionnaires. Paired-samples t-test (t = -14.42; df = 103; p = 0.0001) showed that parents of children with leukemia were more inclined to have an external locus of control than an internal one. The hierarchical regression analysis model (R2 = 0.34; F = 4.32; p = 0.0001) identified health professional influence (ß = -0.28; p = 0.004), current life perception (ß = -0.3; p = 0.013) and future life perception (ß = -0.26; p = 0.012) as significant predictors of parental depression. Current life perception was best predicted (R2 = 0.25; F = 3.96; p = 0.01) by the parental influence locus of control style (ß = 0.25; p = 0.03). Improving trust in the medical staff care and strengthening the internal locus of control in parents could be a preventive program to cope with parental depression symptomatology.


Inhibition of pilocarpine-induced aqueous humor flare, hypotony, and miosis by topical administration of anti-inflammatory and anesthetic drugs to dogs.
To investigate the mechanism by which pilocarpine causes increased aqueous humor (AH) flare, hypotony, and miosis in dogs. 6 dogs with normal eyes. Both eyes of each dog were treated topically with a 2% solution of pilocarpine, and 1 eye of each dog was additionally treated with commercially available ophthamic solutions. Breakdown of the blood-aqueous barrier (BAB) was quantitated in each eye, using laser flaremetry to measure AH flare. Intraocular pressure and pupil size were also measured. Pilocarpine caused increased flare from BAB breakdown that was inhibited by the drugs tested. Inhibition (most to least) of BAB breakdown was flurbiprofen more than diclofenac, proparacaine, or suprofen, which were more than 0.125 or 1.0% prednisolone. Inhibition appeared dose-dependent and caused consensual inhibition in the contralateral eye. Intraocular pressure was decreased only in proparacaine-treated eyes and increased in eyes treated with nonsteroidal anti-inflammatory drugs (NSAID). Flurbiprofen and proparacaine were the most effective at blocking miosis. Pilocarpine produced a predictable, reproducible BAB breakdown in dogs. Miosis and increased AH flare were inhibited equally by proparacaine or NSAID, suggesting that these signs were caused by neuropeptide release into the AH from antidromic stimulation, which subsequently triggers prostaglandin production. Hypotony was inhibited only by anti-inflammatory drugs. Proparacaine in combination with pilocarpine would be the best choice for treating dogs with acute glaucoma. Topical administration of NSAID should not be used to treat dogs with acute glaucoma, because they increase intraocular pressure and negate the effects of pilocarpine.


Antioxidant defense system and oxidative status in Antarctic fishes: The sluggish rockcod Notothenia coriiceps versus the active marbled notothen Notothenia rossii.
Adaptive responses of antioxidant defense systems (ADS) to changes in increased levels of activity are critical, especially in Antarctic fishes. The benthopelagic marbled notothen (Notothenia rossii) shows higher spontaneous activity than the benthonic and sluggish rockcod (N. coriiceps). Therefore, we hypothesize that species-related responses of ADS would occur to counteract different rates of reactive oxygen species formation in these two Antarctic fish. Here we evaluated ADS and oxidative damage in tissues (brain, gills, liver and white muscle) of the two Antarctic fish. Despite no significant differences in lipid and protein oxidative damage were observed, we actually found species- and tissue-specific differences in ADS. Gill metallothionein-like proteins (MTLP) and liver reduced glutathione (GSH) concentrations were higher in N. coriiceps than in N. rossii. Brain and gill antioxidant capacity against peroxyl radicals (ACAP); gill enzyme [glutamate-cysteine ligase (GSL), superoxide dismutase (SOD) and catalase (CAT)] activity; liver GCL and SOD activity; and white muscle CAT activity were higher in N. rossii than in N. coriiceps. Therefore, the more active fish (N. rossii) maintains higher activities of enzymes involved in superoxide ions (O2.-) detoxification and GSH production in peripheral tissues (gills, liver and white muscle). This allows the more active fish (N. rossii) to keep levels of lipid and protein oxidative damage similar to those observed in the sluggish fish (N. coriiceps). It is worth noting that the more active fish also shows a higher brain antioxidant capacity, which could involve other non-enzymatic antioxidants like vitamins C and E. In contrast, N. coriiceps shows lower consumption of non-enzymatic antioxidants in peripheral tissues than N. coriiceps. As hypothesized, our results indicate that differences in ADS profiles between fish species are likely related to their habits and metabolic rates. This would imply in different fish abilities to deal with oxidative stress associated with increasing seawater temperature.


The impact of posttraumatic stress disorder on the symptomatology of borderline personality disorder.
Previous findings on the impact of co-occurring posttraumatic stress disorder (PTSD) in patients with borderline personality disorder (BPD) have revealed inconsistencies, which may have been related to small sample sizes or differences in the presence of childhood sexual abuse (CSA). In this study, the potentially aggravating impact of PTSD and the role of CSA were examined in a large cohort of BPD patients. BPD patients with current PTSD (n = 142) were compared to BPD patients without PTSD (n = 225) regarding different BPD features such as non-suicidal self-injury. Further, we examined the potentially confounding role of CSA. BPD patients with PTSD showed elevated affect dysregulation, intrusions, dissociation, history of suicide attempts and self-mutilation compared to those with only BPD. The effects of PTSD on BPD patients regarding dissociation and the history of suicide attempts were at least partially related to CSA. The additional diagnosis of PTSD in BPD patients can aggravate some, but not all BPD features. With respect to dissociation and suicide attempts, at least some of the impact seems to relate to CSA.


Effects of lattice dilution on the nonequilibrium phase transition in the stochastic susceptible-infectious-recovered model.
We investigate how site dilution, as would be introduced by immunization, affects the properties of the active-to-absorbing nonequilibrium phase transition in the paradigmatic susceptible-infectious-recovered (SIR) model on regular cubic lattices. According to the Harris criterion, the critical behavior of the SIR model, which is governed by the universal scaling exponents of the dynamic isotropic percolation (DyIP) universality class, should remain unaltered after introducing impurities. However, when the SIR reactions are simulated for immobile agents on two- and three-dimensional lattices subject to quenched disorder, we observe a wide crossover region characterized by varying effective exponents. Only after a sufficient increase of the lattice sizes does it become clear that the SIR system must transition from that crossover regime before the effective critical exponents asymptotically assume the expected DyIP values. We attribute the appearance of this exceedingly long crossover to a time lag in a complete recovery of small disconnected clusters of susceptible sites, which are apt to be generated when the system is prepared with Poisson-distributed quenched disorder. Finally, we demonstrate that this transient region becomes drastically diminished when we significantly increase the value of the recovery rate or enable diffusive agent mobility through short-range hopping.


A prospective study of tuberculosis and human immunodeficiency virus infection: clinical manifestations and factors associated with survival.
We prospectively studied the effect of human immunodeficiency virus (HIV) infection on the presentation and outcome of tuberculosis. A total of 216 patients with tuberculosis were identified; 162 (75%) of these patients were tested for antibodies to HIV; 92 (57%) were seropositive. The patients who were seropositive for HIV were more likely to be male and Hispanic and to have been homeless or incarcerated. Eighty-one percent of these patients had CD4 lymphocyte counts of < or =200/mm3. The seropositive patients had extrapulmonary tuberculosis more often than did the seronegative patients (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2-4.8). Smears for acid-fast bacilli were positive more often for non-HIV-infected patients with pulmonary tuberculosis (74.5%) than for HIV-infected patients (54.3%) [OR, 2.46; 95% CI, 1.01-6.02]-even those with focal or cavitary disease. A delay in initiating therapy was associated with in-hospital mortality: the median time from admission to the start of treatment was 4 days for patients who survived and 15 days for those who died (P = .02). The median survival was 22.7 months for HIV-infected patients who did not die during the initial hospitalization. Factors independently associated with reduced rates of survival included the severity of immunodeficiency, nonuse of directly observed therapy, infection due to drug-resistant Mycobacterium tuberculosis, and a history of injection drug use.


Methisazone therapy in pediatric vaccinia complications.
Methisazone 40 mg/kg/day was administered orally to six pediatric and one adult patient who contracted vesicular complications affecting the skin or mucocutaneous junctions 3 to 9 days after antismallpox vaccination, and to one elderly man with myeloid leukemia who developed vaccinia necrosum. Therapy was commenced 2 to 10 days after onset of complications and was administered for 3 days. All patients with skin or mucocutaneous complications showed dramatic clinical responses within one day after commencement of antiviral chemotherapy, and complete recovery occurred within one week. Clinical improvement was noted 4 days after therapy was begun in the case of vaccinia necrosum, and recovery occurred after 3 weeks.


[Histochemical findings of and fine structural changes in motor endplates in diseases with neuromuscular transmission abnormalities].
We herein review the histochemical findings and fine structural changes of motor endplates associated with diseases causing neuromuscular transmission abnormalities. In anti-acetylcholine receptor (AChR) antibody-positive myasthenia gravis (MG), type 2 fiber atrophy is observed, and the motor endplates show a reduction in the nerve terminal area, simplification of the postsynaptic membrane, decreased number of acetylcholine receptors, and deposition of immune complexes. In anti-MuSK antibody-positive MG, the fine structure shows a decrease in the postsynaptic membrane length, but the secondary synaptic cleft is preserved. There is no decrease in the number of AChRs, and there are no deposits of immune complexes at the motor endplates. Patients with Lambert-Eaton myasthenic syndrome show type 2 fiber atrophy, their motor endplates show a decrease in both the mean postsynaptic area and postsynaptic membrane length in the brachial biceps muscle. Congenital myasthenic syndrome with episodic apnea is characterized only by small-sized synaptic vesicles; the postsynaptic area is preserved. In subjects with congenital myasthenic syndrome with acetylcholinesterase deficiency, quantitative electron microscopy reveals a significant decrease in the nerve terminal size and presynaptic membrane length; further, the Schwann cell processes extend into the primary synaptic cleft, and partially or completely occlude the presynaptic membrane. The postsynaptic folds are degenerated, and associated with pinocytotic vesicles and labyrinthine membranous networks. Patients with slow-channel congenital myasthenia syndrome show type 1 fiber predominance, and their junctional folds are typically degenerated with widened synaptic space and loss of AChRs. Patients with AChR deficiency syndrome caused by recessive mutations in AChR subunits also show type 1 fiber predominance, and while most junctional folds are normal, some are simplified and have smaller than normal endplates. Rapsin and MuSK mutations cause type 1 fiber predominance, and the small postsynaptic area is associated with AChR decrease.


Compact synchrotron light source of the HSRC.
A 700 MeV synchrotron radiation source optimized in order to be incorporated in the university laboratory is under commissioning at Hiroshima University. The storage ring is of a racetrack type with two long straight sections for installing undulators. The bending field is as strong as 2.7 T, produced by normal-conducting magnet technology, and delivers synchrotron radiation with a critical wavelength of 1.42 nm. The strong magnetic field also enables a low-energy injection scheme to be employed owing to the fast radiation damping. A 150 MeV microtron has been adopted as the injector.


ACE2 and ACE in acute and chronic rejection after human heart transplantation.
The authors sought to evaluate cardiac activity of angiotensin-converting enzyme (ACE) and ACE2 after heart transplantation (HT) and its relation with acute rejection (AR) and chronic allograft vasculopathy (CAV). The renin-angiotensin system is altered in heart failure and HT. However, ACE and ACE2 activities in post-HT acute and chronic rejection have not been previously studied. HT patients (n = 45) were included when appropriate serial endomyocardial biopsies (EMB) and coronary angiography were available for analysis. In 21 patients, three post-HT time points were selected for CAV study in EMB tissue: basal (0-3 wks), second (2-3 months) and third (4-5 months). At 10 years post-HT, CAV was evaluated by coronary angiography (CA) and patients were grouped by degree of CAV: 0-1, non-CAV (n = 15) and 2-3, CAV (n = 6). For the AR study, 28 HT patients with evidence of one EMB rejection at grade 3 and two EMB grade 1A and/or 1B rejections were selected. Post-HT, ACE2 activity was increased in the CAV group, compared to non-CAV. Patients with AR showed increased ACE, but not ACE2, activity. Our results suggest that early post-HT cardiac ACE2 activity may have an important role in CAV development. In contrast, ACE activity was increased in AR. The renin-angiotensin system seems to be altered after HT and strategies to balance the system may be useful.


Reference threshold sound pressure levels for the Welch Allyn AudioScope.
The Welch Allyn AudioScope has been evaluated as an audiometer screening instrument using a threshold, loudness balancing technique. Two sets of eartips have been compared to determine which eartip configuration would yield the most reliable audiometric data. The AudioScope has also been evaluated by the American National Standard Method for Coupler Calibration of Earphones using both sets of eartips, and reference threshold sound pressure levels for the AudioScope were developed by combining the coupler and loudness balance data. The most reliable eartip configuration for audiometric purposes is identified and guidelines for use of the audiometric screening instrument are proposed.


A GRIN3A polymorphism may be associated with glucocorticoid-induced symptomatic osteonecrosis in children with acute lymphoblastic leukemia.
Aim: To evaluate the association between candidate genetic polymorphisms and glucocorticoid-induced osteonecrosis in Arab children treated for acute lymphoblastic leukemia. Methods: A total of 189 children treated for acute lymphoblastic leukemia were genotyped for four SNPs with allele discrimination assays. The incidence and timing of radiologically confirmed symptomatic grade 4 osteonecrosis were classified based on the Ponte di Legno toxicity working group consensus definition. Results: Thirteen children developed grade 4 osteonecrosis (6.8%), of whom 12 received the intermediate/high-risk treatment protocol. GRIN3A variant allele carriers had to stop dexamethasone therapy earlier resulting in significantly shorter duration of dexamethasone treatment (mean [95% CI]: 75.17 [64.28-86.06] vs 85.90 [81.22-90.58] weeks; p = 0.054) and lower cumulative dose (mean [95% CI]: 1118.11 [954.94-1281.29] vs 1341.14 [1264.17-1418.11] mg/m2; p = 0.011). Conclusion: This is the first pharmacogenomics evaluation of the association between GRIN3A variants and glucocorticoid-induced osteonecrosis in Arab children.


Barriers to hearing conservation programs in combat arms occupations.
The Canadian military instituted a hearing conservation program over 45 yr ago. Yet the prevalence of noise-induced hearing loss is escalating. A focus group study involving four combat arms occupations was carried out to probe individuals' knowledge, attitudes, and behaviors relating to hearing loss prevention to find ways to improve compliance. One group each of 4-5 Infantry Soldiers, Artillerymen, Armored Soldiers, and Combat Engineers, with the rank of Warrant Officer, Sergeant, or Master Corporal, and at least 5 yr of service participated. Discussions were led by a Moderator and recorded by an Assistant Moderator. Questions posed related to susceptibility and consequences of hearing loss, benefits and drawback of hearing protection, and preferences. Age range was 28-48 yr and length of service 10-30 yr. Individuals were exposed to noise from weapons, explosives, vehicles, and aircraft. Infantry Soldiers and Artillerymen had confirmed moderate to severe hearing loss. Armored Soldiers and Combat Engineers had not perceived a change in hearing. Main concerns of using hearing protection were interference with detection and localization of auditory warnings, and perception of orders. Devices were often incompatible with other gear and difficult to fit. Good hearing was critical to the occupations studied. Difference in hearing loss among groups was related to type and level of noise exposure. Loss of hearing and/or the use of hearing protection compromised situational awareness, exchange of information, and auditory task performance. Participants favored opportunities to try recommended devices, policies governing use, and sufficient funding to ensure protection for both regular and special forces.


Analysis of thirteen predatory publishers: a trap for eager-to-publish researchers.
To demonstrate a strategy employed by predatory publishers to trap eager-to-publish authors or researchers into submitting their work. This was a case study of 13 potential, possible, or probable predatory scholarly open-access publishers with similar characteristics. Eleven publishers were included from Beall's list and two additional publishers were identified from a Google web search. Each publisher's site was visited and its content analyzed. Publishers publishing biomedical journals were further explored and additional data was collected regarding their volumes, details of publications and editorial-board members. Overall, the look and feel of all 13 publishers was similar including names of publishers, website addresses, homepage content, homepage images, list of journals and subject areas, as if they were copied and pasted. There were discrepancies in article-processing charges within the publishers. None of the publishers identified names in their contact details and primarily included only email addresses. Author instructions were similar across all 13 publishers. Most publishers listed journals of varied subject areas including biomedical journals (12 publishers) covering different geographic locations. Most biomedical journals published none or very few articles. The highest number of articles published by any single biomedical journal was 28. Several editorial-board members were listed across more than one journals, with one member listed 81 times in different 69 journals (i.e. twice in 12 journals). There was a strong reason to believe that predatory publishers may have several publication houses with different names under a single roof to trap authors from different geographic locations.


Low Cycle Fatigue Behavior of Steam Generator Tubes under Axial Loading.
Compared with the fatigue properties of the material (Inconel Alloy 690), the real fatigue lives of tubes are more meaningful in the fatigue design and assessment of steam generator (SG) tube bundles. However, it is almost impossible to get a satisfactory result by conducting fatigue tests on the tube directly. A tube with a uniform and thin wall easily fails near the clamping ends under cyclic loading due to the stress concentration. In this research, a set-up for fatigue tests of real tubes is proposed to overcome the stress concentration. With the set-up, low cycle fatigue tests were conducted in accordance with an existing fatigue design curve for Alloy 690. Strain control mode was applied with fully reversed push⁻pull loading under different strain amplitudes (0.15%, 0.2%, 0.3%, and 0.4%). A favourable result was obtained, and the low cycle fatigue behavior was investigated. The results showed that the fatigue life tested by the real tube was below the strain⁻life curve of Alloy 690 which was fitted by conventional solid specimens. A cyclic hardening behavior was found by the cyclic stress⁻strain curve when compared with the monotonic stress⁻strain curve.


Pd-catalyzed homocoupling reaction of arylboronic acid: insights from density functional theory.
The key step in the mechanism of the Palladium-catalyzed homocoupling of arylboronic acids ArB(OH)(2)(Ar = 4-Z-C(6)H(4) with Z = MeO, H, CN) in the presence of dioxygen, leading to symmetrical biaryls, has been elucidated by using density functional theory. In particular, by starting from the peroxo complex O(2)PdL(2)(L = PPh(3)), generated in the reaction of dioxygen with the Pd(0) catalyst, the fundamental role played by an intermediate formed by coordination of one oxygen atom of the peroxo complex to the oxophilic boron atom of the arylboronic acid has been pointed out. This adduct reacts with a second molecule of arylboronic acid to generate a cis-Ar-Pd(OOB(OH)(2))L(2) complex that can form the stable intermediate trans-Ar-Pd(OH)L(2) (experimentally characterized) through a sequence of hydrolysis and isomerization reactions. All theoretical insights are in agreement and do substantiate the experimentally postulated mechanism. Furthermore, direct comparison of experimental and computed spectroscopic parameters (here, (31)P chemical shifts) allows us to confirm the formation of the intermediate.


Iranian model of decision making to use surrogacy: A grounded theory Study.
Identifying the process of making the decision to use a surrogate mother can create a broad knowledge of this concept. In this grounded theory study, participants were selected through snowball sampling method and obtaining an informed consent, in-depth interviews were conducted face to face and recorded. Then, all the interviews, field notes, and memos were analyzed using Strauss-Corbin 1998 method. Analysis of the statements of the participants boiled down to 487 initial codes, 311 codes, 14 subcategories, and six categories. In the conceptual model of this process, "the hope to have a child" was an influential concept that interacted with other concepts.


Impact of compliance to oral hypoglycemic agents on short-term disability costs in an employer population.
This study evaluated the relationships between compliance with oral hypoglycemic agents and health care/short-term disability costs in a large manufacturing company. The retrospective analysis used an observational cohort drawn from active employees of Ford Motor Company. The study population consisted of 4978 individuals who were continuously eligible for 3 years (between 2001-2007) and who received a prescription for an oral hypoglycemic agent during that time. Medical, pharmacy, and short-term disability claims data were obtained from the University of Michigan Health Management Research Center data warehouse. Pharmacy claims/refill data were used to calculate the proportion of days covered (PDC); an individual was classified as compliant if his/her PDC was ≥80%. Model covariates included age, sex, work type, and Charlson comorbidity scores. The impact of compliance on disability and health care costs was measured by comparing the costs of the compliant with those of the noncompliant during a 1-year follow-up. Among these employees, compliant patients had lower medical, higher pharmacy, and lower short-term disability costs than did the noncompliant. After adjusting for demographics and comorbidity, noncompliance was associated with statistically higher short-term disability costs ($1840 vs. $1161, P<0.0001), longer short-term disability duration, and an increase in short-term disability incidence (21.5% of the noncompliant had a claim compared to 16.0% of the compliant, P<0.0001). These results suggest that medication compliance may be important in curtailing the rise of health care/disability costs in the workplace. Employers concerned with the total costs associated with diabetes should not overlook the impact of compliance on short-term disability.


UDP-Glucose: A Potential Signaling Molecule in Plants?
This perspective paper focuses on the most recent results suggesting a potential role for UDP-Glucose as a signaling molecule in plants. In animals, UDP-Glucose is well-established as an extracellular signaling molecule that is sensed by G-protein coupled receptors, activating several downstream defense mechanisms. Recent studies have shown that abnormal growth occurred in both vegetative and reproductive tissue of plants with reduced UDP-Glucose levels, and this could be rescued by exogenous UDP-Glucose. In plants with increased biomass accumulation, the genes involved in UDP-Glucose production were up-regulated. However, excessive endogenous accumulation of UDP-Glucose induced programmed cell death (PCD), and this could also be obtained by exogenous UDP-Glucose application. Plants with decreased UDP-glucose were insensitive to pathogen induced PCD. We speculate that UDP-Glucose acts as an extracellular signaling molecule in plants, and that it may be perceived as a damage-associated molecular pattern.


Erythromycin inhibits neutrophil chemotaxis in bronchoalveoli of diffuse panbronchiolitis.
The efficacy of low dose long-term erythromycin (EM) therapy in the treatment of chronic lower respiratory tract disease, including diffuse panbronchiolitis (DPB), has been reported, but its therapeutic mechanism is still unclear. In 13 patients receiving oral EM therapy the accumulation of neutrophils in bronchoalveolar lavage (BAL) fluid was significantly reduced (p < 0.05), this reduction corresponds with an improvement in clinical symptoms. We sought to determine whether neutrophil chemotactic activity (NCA) in lavage fluid obtained from these 13 patients with DPB would respond to EM therapy. Pretreatment NCA in all patients was significantly elevated compared with levels in normal healthy nonsmoking volunteers (p < 0.001), and the level was greatly reduced after EM therapy (p < 0.001). In addition, this reduction correlated with increased percentages of neutrophils in the BAL fluid (r = 0.737, p < 0.01). Gel-filtration chromatography was also performed to characterize chemotactic factors. Pre-EM treatment BAL fluid revealed four NCA peaks (about molecular weight 15,000, 8,000, 1,500, and 300 daltons) in the elution profile, and chemotactic activity was reduced in all areas after EM therapy. These findings indicate that NCA in lavage fluid from patients with DPB consists of various components. Although it was not clear which component is predominantly affected, these results indicate that EM may inhibit the migration of neutrophils to inflammatory sites by reducing the intrapulmonary chemotactic gradient, thus, ultimately reducing pulmonary inflammation.


Barriers to Testing and Treatment for Chagas Disease among Latino Immigrants in Georgia.
Background. The lack of testing and treatment of Chagas disease (CD), caused by Trypanosoma cruzi, amongst infected immigrants in the USA increases the risk of serious health complications and transmission (congenital or via blood transfusions). Goal. Our goal was to identify the barriers to testing and treatment of CD and understand the process of seeking healthcare amongst Latino immigrants in Georgia. Methods. In this qualitative study, eleven focus group discussions were conducted with 82 Latino immigrants, including migrant farm workers. Grounded theory was used to collect and analyze the data to develop an inductive conceptual framework to explain the context and process of seeking healthcare for CD amongst this at-risk population. Results. Participants were not aware of CD. Three healthcare seeking behaviors were identified: delaying treatment, using traditional remedies, and using either mainstream or alternative health providers. Behaviors and motivations differed by gender, and the use of licensed medical providers was considered a last resort due to the cost of healthcare, loss of earnings while seeking care, and fear of diagnosis with fatal illness. Discussion. Providing free or low cost services, mobile clinics, and education regarding CD is critical to increase testing and treatment of CD in the US.


Superimposed OER and UOR performances by the interaction of each component in an Fe-Mn electrocatalyst.
The oxygen evolution reaction (OER) and alternative urea oxidation reaction (UOR) are both important half reactions correlated with hydrogen production. Transition metal based catalysts with double metal composition exhibit excellent electrocatalytic performance for the OER or UOR due to their synergetic effect and coupling of different active sites. However, the development of OER/UOR bifunctional electrocatalysts is unsatisfying and the role of each metallic active site in the OER and UOR is still unclear. Herein, we report a Fe-Mn based OER and UOR bifunctional catalyst through a simple one-step electrodeposition method. For the OER, the introduction of Mn improves the conductivity of the catalysts and fine-tunes the electron density of the Fe active sites. For the UOR, both Fe and Mn act as active sites and their coupling effect further improves the UOR activity. The catalyst with the optimal Mn/Fe ratio achieved an overpotential of 237 mV for the OER and a potential of 1.35 V for the UOR at 100 mA cm-2. This study provides a simple synthesis protocol for constructing bifunctional catalysts for green hydrogen production.


Public Confidence in the Health Care System 1 Year After the Start of the Ebola Virus Disease Outbreak - Sierra Leone, July 2015.
Ensuring confidence in the health care system has been a challenge to Ebola virus disease (Ebola) response and recovery efforts in Sierra Leone (1). A national multistage cluster-sampled household survey to assess knowledge, attitudes, and practices (KAP) related to Sierra Leone's health care system was conducted in July 2015. Among 3,564 respondents, 93% were confident that a health care facility could treat suspected Ebola cases, and approximately 90% had confidence in the health system's ability to provide non-Ebola services, including immunizations, antenatal care, and maternity care. Respondents in districts with ongoing Ebola transmission ("active districts") and respondents with higher educational levels reported more confidence in the health care system than did respondents in nonactive districts and respondents with less education. Active districts were the focus of the Ebola response; these districts implemented intensified social mobilization and communication efforts, and established district response centers, Ebola-specific health care facilities, and ambulances. Greater infrastructure and response capacity might have resulted in higher confidence in the health care system in these areas. Respondents ranked Ebola and malaria as the country's most important health issues. Health system recovery efforts in Sierra Leone can build on existing public confidence in the health system.


An Overview of Antiviral Peptides and Rational Biodesign Considerations.
Viral diseases have contributed significantly to worldwide morbidity and mortality throughout history. Despite the existence of therapeutic treatments for many viral infections, antiviral resistance and the threat posed by novel viruses highlight the need for an increased number of effective therapeutics. In addition to small molecule drugs and biologics, antimicrobial peptides (AMPs) represent an emerging class of potential antiviral therapeutics. While AMPs have traditionally been regarded in the context of their antibacterial activities, many AMPs are now known to be antiviral. These antiviral peptides (AVPs) have been shown to target and perturb viral membrane envelopes and inhibit various stages of the viral life cycle, from preattachment inhibition through viral release from infected host cells. Rational design of AMPs has also proven effective in identifying highly active and specific peptides and can aid in the discovery of lead peptides with high therapeutic selectivity. In this review, we highlight AVPs with strong antiviral activity largely curated from a publicly available AMP database. We then compile the sequences present in our AVP database to generate structural predictions of generic AVP motifs. Finally, we cover the rational design approaches available for AVPs taking into account approaches currently used for the rational design of AMPs.


Outbreak of severe myocarditis in England: Havoc by a harmless virus.
The World Health Organization (WHO) has been alerted to a concerning upsurge of severe myocarditis, an inflammatory heart condition, in neonates within Wales and South West England. The myocarditis cases are being intricately associated with enterovirus infection, belonging to the Picornaviridae family. The concerned pathogen poses a significant global disease burden, with an estimated 10 to 15 million symptomatic cases occurring annually in the United States alone. Neonates are particularly vulnerable with children under the age of one accounting for approximately 40% of enterovirus infections. A comprehensive literature search was conducted using various databases including ClinicalTrials, Google Scholar, PubMed, ScienceDirect, MEDLINE, and Ovid Resources. The search strategy included utilizing keywords such as "myocarditis," "Randomized controlled trials (RCTs). Only articles written in English were considered, and selection criteria included relevance to the research objectives, reasonable sample sizes, and robust methodology. In addition to the identified articles, meta-analyses, animal models and studies, and references from the selected articles were also examined to ensure a comprehensive review of the literature. Ten hospitalized neonates, reported in the United Kingdom (UK), with positive PCR tests were reported to have myocarditis, predominantly caused by coxsackieviruses. The current situation in the region has brought global attention. With this study, we hope to draw attention to the critical aspects of the illness and, more crucially, the present strategies required to control the disease outbreak in England. Current European Society of Cardiology (ESC) recommendations for the treatment of acute heart failure apply. Emerging research supports the use of immunosuppressive medication in some circumstances. Patients are advised to avoid aerobic activities for several months after healing. Neonatal enterovirus infections can vary in how they respond to IVIG therapy. The majority of enterovirus infections are self-limited, require no special therapy, and only little supportive care is required. The recent elevation in numbers for reported severe myocarditis in neonates within Wales and South West England, linked to enterovirus infection, poses a significant public health concern. Myocarditis caused by enteroviruses, particularly Group B coxsackieviruses, is associated with significant mortality rates. Diagnosis is supported by non-invasive techniques and cardiac enzyme blood tests. Treatment modalities primarily involve a palliative approach.


Synthesis of di(hetero)aryl sulfides by directly using arylsulfonyl chlorides as a sulfur source.
A new, efficient protocol for the synthesis of di(hetero)aryl sulfides is described. Cheap and easily available arylsulfonyl chlorides as a sulfur source reductively couple with electron-rich (hetero)arenes (e.g., indolizines, indoles, electron-rich benzenes, etc.) in the presence of triphenylphosphine to afford di(hetero)aryl thioethers in good yields.


Breast MR Imaging for Equivocal Mammographic Findings: Help or Hindrance?
Breast magnetic resonance (MR) imaging, because of its extremely high sensitivity in detecting invasive breast cancers, is sometimes used as a diagnostic tool to evaluate equivocal mammographic findings. However, breast MR imaging should never substitute for a complete diagnostic evaluation or for biopsy of suspected, localizable suspicious mammographic lesions, whenever possible. The modality's high cost, in addition to only moderate specificity, mandate that radiologists use it sparingly and with discrimination for problematic mammographic findings. It is rare that the reality or significance of a noncalcified mammographic finding remains equivocal or problematic at diagnostic mammography evaluation, which usually includes targeted ultrasonography (US). There are several reasons for this infrequent occurrence: (a) an asymmetry may persist on diagnostic views but be visible only on craniocaudal or mediolateral oblique projections, precluding three-dimensional localization for US or biopsy, or a lesion may persist on some diagnostic spot views but dissipate or efface on others; (b) uncertainty may exist as to whether apparent change is clinically important or owing to technical factors such as compression or positioning differences; or (c) a lesion may be suspected but biopsy options are limited owing to lack of a US correlate and lesion inaccessibility for stereotactic biopsy, or biopsy of a vague or questionably real lesion has been attempted unsuccessfully. This article will discuss the indications for problem-solving MR imaging for equivocal mammographic findings, present cases illustrating appropriate and inappropriate uses of problem-solving MR imaging, and present false-positive and false-negative cases affecting the specificity of breast MR imaging. (©)RSNA, 2016.


Limitations of Dual-Single Guide RNA CRISPR Strategies for the Treatment of Central Nervous System Genetic Disorders.
Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a toxic gain-of-function CAG expansion in the first exon of the huntingtin (HTT) gene. The monogenic nature of HD makes mutant HTT (mHTT) inactivation a promising therapeutic strategy. Single nucleotide polymorphisms frequently associated with CAG expansion have been explored to selectively inactivate mHTT allele using the CRISPR/Cas9 system. One of such allele-selective approaches consists of excising a region flanking the first exon of mHTT by inducing simultaneous double-strand breaks at upstream and downstream positions of the mHTT exon 1. The removal of the first exon of mHTT deletes the CAG expansion and important transcription regulatory sites, leading to mHTT inactivation. However, the frequency of deletion events is yet to be quantified either in vitro or in vivo. Here, we developed accurate quantitative digital polymerase chain reaction-based assays to assess HTT exon 1 deletion in vitro and in fully humanized HU97/18 mice. Our results demonstrate that dual-single guide RNA (sgRNA) strategies are efficient and that 67% of HTT editing events are leading to exon 1 deletion in HEK293T cells. In contrast, these sgRNA actively cleaved HTT in HU97/18 mice, but most editing events do not lead to exon 1 deletion (10% exon 1 deletion). We also showed that the in vivo editing pattern is not affected by CAG expansion but may potentially be due to the presence of multiple copies of wildtype (wt)/mHTT genes HU97/18 mice as well as the slow kinetics of AAV-mediated CRISPR/Cas9 delivery.


Naloxone administration to patients with acute stroke.
Naloxone, an opiate antagonist, has recently been reported to temporarily reverse neurologic deficits associated with subarachnoid hemorrhage. To determine if this unexpected effect of naloxone might also occur in other forms of cerebrovascular diseases, 13 patients who presented with acute neurologic deficits were administered intravenous naloxone. In 3 of these patients, coincidental improvement in neurologic status was seen. In one patient the improvement was permanent. Ten of the 11 patients with non fatal neurologic damage improved later in their hospital course--7 of them to their pre-admission state. The only side effect noted was the temporally related onset of a single focal seizure in an ethanol intoxicated patient with an intracerebral hemorrhage.