Prediction of real-world functional disability in chronic mental disorders: a comparison of schizophrenia and bipolar disorder.
Schizophrenia and bipolar disorder are associated with multidimensional disability. This study examined differential predictors of functional deficits in the two disorders. Community-dwelling individuals with schizophrenia (N=161) or bipolar disorder (N=130) were assessed with neuropsychological tests, symptom measures, and performance-based social and adaptive (i.e., everyday living skills) functional competence measures as well as three domains of real-world functioning: community and household activities; work skills; and interpersonal relationships. The authors used confirmatory path analysis to find the best-fitting models to examine the direct and indirect (as mediated by competence) prediction of the three domains of real-world functioning. In all models for both groups, neurocognition's relationship with outcomes was largely mediated by competence. Symptoms were negatively associated with outcomes but unassociated with competence, with the exception of depression, which was a direct and mediated (through social competence) predictor in bipolar disorder. In both groups, neurocognition was related to activities directly and through a mediated relationship with adaptive competence. Work skills were directly and indirectly (through mediation with social competence) predicted by neurocognition in schizophrenia and entirely mediated by adaptive and social competence in bipolar disorder. Neurocognition was associated with interpersonal relationships directly in the schizophrenia group and mediated by social competence in both groups. Although there was greater disability in schizophrenia, neurocognition predicted worse functioning in all outcome domains in both disorders. These results support the shared role of neurocognition in bipolar disorder and schizophrenia in producing disability, with predictive differences between disorders in domain-specific effects of symptoms and social and adaptive competence.


Circulating promyelocytes and low levels of CD16 expression on polymorphonuclear leukocytes accompany early-onset periodontitis.
Early-onset periodontitis (EOP) is characterized by rapidly progressive alveolar bone loss, chemotactic defects of neutrophils, and significant familial aggregation. We found immature myeloid lineage cells, defined as promyelocytes, in the peripheral blood in patients with EOP. A hematological examination of peripheral blood cells showed normal reference values regarding cell proportions. Flow cytometry revealed significantly lower expression of CD16, a glycosylphosphatidylinositol (GPI)-anchored protein, on peripheral neutrophils in patients compared with those in age- and sex-matched healthy controls, whereas the levels of CD11a and CD11b expression were similar. The chemotactic response of neutrophils was lower toward not only formyl-methionyl-leucyl-phenylalanine but also complement fragment C5a than that of healthy controls. The expression of another GPI-anchored protein, CD14, was equally expressed by controls and patients. Therefore, the low level of CD16 expression was not due to the incomplete synthesis of the GPI anchor. GPI anchors of CD16 on neutrophils from controls and patients were both partially resistant to phosphatidylinositol-specific phospholipase C. The presence of promyelocytes in peripheral blood, low expression of CD16, and low chemotactic response of neutrophils suggest that patients with EOP have an abnormal maturation system in myeloid lineage cells in the bone marrow, which may be associated with the onset and course of EOP.


Investigation of Plant-Level Volatile Organic Compound Emissions from Chemical Industry Highlights the Importance of Differentiated Control in China.
The chemical industry is a significant source of nonmethane volatile organic compounds (NMVOCs), pivotal precursors to ambient ozone (O3), and secondary organic aerosol (SOA). Despite their importance, precise estimation of these emissions remains challenging, impeding the implementation of NMVOC controls. Here, we present the first comprehensive plant-level assessment of NMVOC emissions from the chemical industry in China, encompassing 3461 plants, 127 products, and 50 NMVOC compounds from 2010 to 2019. Our findings revealed that the chemical industry in China emitted a total of 3105 (interquartile range: 1179-8113) Gg of NMVOCs in 2019, with a few specific products accounting for the majority of the emissions. Generally, plants engaged in chemical fibers production or situated in eastern China pose a greater risk to public health due to their higher formation potentials of O3 and SOA or their proximity to residential areas or both. We demonstrated that targeting these high-risk plants for emission reduction could enhance health benefits by 7-37% per unit of emission reduction on average compared to the current situation. Consequently, this study provides essential insights for developing effective plant-specific NMVOC control strategies within China's chemical industry.


Detection of a divergent Parainfluenza 4 virus in an adult patient with influenza like illness using next-generation sequencing.
Human Parainfluenza viruses are a common cause of both upper and lower respiratory tract infections, particularly in children. Of the four Parainfluenza virus serotypes, Parainfluenza 4 is least well characterised from both the clinical, epidemiological and genetic perspectives. Flocked nose or throat swabs from a previous study investigating viral prevalence in community-based adults suffering from influenza like illness were used as the basis for this study. Samples in which no virus was detected using a 16 viral respiratory pathogen real-time PCR panel were barcoded and pyrosequenced using the Roche 454 GS FLX Titanium chemistry. The sequences were analysed using the VirusHunter bioinformatic pipeline. Sanger sequencing was used to complete the detected Parainfluenza 4 coding region. A variant Parainfluenza 4 subtype b strain (QLD-01) was discovered in an otherwise healthy adult who presented with influenza like illness. Strain QLD-01 shared genomic similarities with both a and b subtypes. The extent of divergence of this genome from the 5 available whole Parainfluenza 4 genomes impacted the predicted binding efficiencies of the majority of published Parainfluenza 4 PCR assays. These findings further support a possible role for Parainfluenza 4 in the aetiology of adult respiratory disease within the community setting, and highlight the caution needed to be used in designing PCR assays from limited sequence information or in using proprietary commercial PCR assays.


α-Tocopherol Polyethylene Glycol 1000 Succinate-Based Cationic Liposome for the Intracellular Delivery of Doxorubicin in MDA-MB-231 Triple-Negative Breast Cancer Cell Line.
Present research work reports the development of doxorubicin (DOX) loaded α-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated cationic liposomes. The developed formulation was evaluated for its anticancer potential and intracellular uptake against the MDA-MB-231 breast cancer cell line. Moreover, hemocompatibility studies were also done on human blood red blood cells for the determination of blood compatibility. The prepared doxorubicin-loaded TPGS liposomes (DOX-LIPO-TPGS) and doxorubicin-loaded cationic liposomes (DOX-LIPO+-TPGS) reveal vesicle size (177.5 ± 2.5 and 201.7 ± 2.3 nm), polydispersity index (0.189 ± 0.01 and 0.218 ± 0.02), zeta potential (-36.9 ± 0.7 and 42 ± 0.9 mv), and % entrapment efficiency (65.88% ± 3.7% and 74.5% ± 3.9%). Furthermore, in vitro, drug release kinetics of the drug alone and drug from formulation shows sustained release behavior of developed formulation with 99.98% in 12 h and 80.98% release of the drug in 72 h, respectively. In addition, cytotoxicity studies and cellular DOX uptake on the MDA-MB-231 breast cancer cell line depict higher cytotoxic and drug uptake potential with better hemocompatibility of DOX-LIPO+-TPGS with respect to DOX. The data from the study revealed that TPGS plays an important role in enhancing the formulation's quality attributes like stability, drug release, cytotoxicity, and hemocompatibility behavior. This may serve that TPGS-coated cationic liposome as a vital candidate for the treatment of cancer and drug delivery in case of breast cancer.


Nanometer-scale siRNA carriers incorporating peptidomimetic oligomers: physical characterization and biological activity.
Synthetic short interfering RNA (siRNA) oligonucleotides can trigger the RNA interference pathway and lead to selective gene silencing. Despite considerable enthusiasm and investment, formidable challenges remain that may deter translating this breakthrough discovery into clinical applications. In particular, the development of efficient, nontoxic, nonimmunogenic methods for delivering siRNA in vivo has proven to be exceptionally challenging. Thorough analysis of the relationship between the structure and function of siRNA carrier systems, both in isolation and in complex with RNA, will facilitate the design of efficient nonviral siRNA delivery vehicles. In this study, we explore the relationship between the physicochemical characteristics and the biological activity of "lipitoid" compounds as potent siRNA delivery vehicles. Lipitoids are cationic peptidomimetic oligomers incorporating a peptoid and a phospholipid moiety. Lipitoids can associate with siRNA oligonucleotides and self-assemble into spherical lipitoid-based nanoparticles (LNPs), with dimensions that are dependent upon the medium and the stoichiometric ratio between the cationic monomers of the lipitoid and anionic siRNA oligonucleotides. The morphology, gene silencing efficiency, and cytotoxicity of the siRNA-loaded LNPs are similarly sensitive to the stoichiometry of the complexes. The medium in which the LNPs are formed affects the assembled cargo particles' characteristics such as particle size, transfection efficiency, and stability. Formation of the LNPs in the biological, serum-free medium OptiMEM resulted in LNPs an order of magnitude larger than LNPs formed in water, and were twice as efficient in siRNA transfection compared to LNPs formed in water. Inhibitor studies were conducted to elucidate the efficiency of lysosomal escape and the uptake mechanism of the siRNA-loaded LNPs. Our results suggest that these lipitoid-based, siRNA-loaded spherical LNPs are internalized through a lipid raft-dependent and dynamin-mediated pathway, circumventing endosomal and lysosomal encapsulation. The lipitoid-siRNA nanospheres proved to be suitable platforms for investigating the critical parameters determining the efficiency of transfection agents, revealing the necessity for conducting characterization studies in biological media. The investigation of the LNP internalization pathway points to an alternative uptake route that bypasses the lysosome, explaining the surprisingly high efficiency of LNPs and suggesting that the uptake mechanism should be probed rather than assumed for the next generation of rationally designed transfection agents.


Circulating oxidized low density lipoprotein levels. A biochemical risk marker for coronary heart disease.
Recent studies have established oxidative modification of low density lipoprotein (LDL) as an important atherogenic factor. We examined the clinical relevance of circulating oxidized LDL (OxLDL) levels in atherosclerotic disease by an enzyme immunoassay with use of specific antibodies against OxLDL (FOH1a/DLH3) and apolipoprotein B. Plasma OxLDL levels were significantly higher in patients with coronary heart disease (n=65) than in control subjects (n=181; 201. 3+/-11.2 versus 112.4+/-3.3 U/dL, respectively; P<0.01). OxLDL levels were not associated with age, sex, total cholesterol, or apolipoprotein B levels in normal control subjects. Our results suggest that circulating OxLDL may be a possible biochemical risk marker for coronary heart disease.


Modification Tadalafil and Macitentan tablets to aerosol.
Aerosolised drugs have been approved for several diseases such as cystic fibrosis and diabetes. Moreover; there are already drugs for pulmonary hypertension in aerosol form already on the market. Two drugs for pulmonary hypertension (Tadalafil and Macitentan) were milled and transformed from tablets to powder. Three different jet-nebulizers with seven different residual cups were combined. Moreover, we used 3 different ultrasound nebulizers with two different release methods. The drug and residual cup designs produce alone or jointly different MMAD diameters. The three large (10 mls) residual cups with the jet-nebulisers produced the smallest aerosol droplets. Both ultrasound nebulisers are capable of producing optimal size aerosol droplets ≤5 μm mmad. These two drugs can be easily administered as aerosol and an vivo clinical study will prove the safety for the airways.


New anticoagulants in critical care settings.
Thromboembolic events commonly occur in critically ill patients, and although they do not consistently present with specific signs and symptoms, they are associated with high morbity and mortality. Antithrombotic agents are the mainstay of the prevention and treatment of venous thromboembolism, and they are also used for stroke prevention in atrial fibrillation, embolism prevention in heart failure, and anticoagulation of prosthetic valves. These drugs have been combined with antiplatelet therapy for the prevention of secondary acute coronary syndrome. Antithrombotic agents such as Aspirin, clopidogrel, vitamin K antagonists and fondaparinux, an indirect Factor Xa inhibitor, are already incorporated into our clinical practice. New small-molecule, selective Factor Xa and thrombin inhibitors that simultaneously inhibit free plasma and clot-associated factor activities have received considerable attention recently. These new oral anticoagulants are in various phases of clinical development. dabigatran, rivaroxaban and apixaban are in more advanced phases of clinical development and are already available in a number of countries. This review article highlights the studies describing the use of these three anticoagulants in an intensive care setting.


Signet ring cell carcinoma arising from a solitary juvenile polyp in the colon.
Juvenile polyps are relatively common polyps that affect predominantly young patients and may occur in isolated, multiple, and/or familial forms. They have been considered to be benign lesions without neoplastic potential, but for patients with multiple juvenile polyposis, the cumulative malignant risk is greater than fifty percents. In patients with a solitary polyp, the risks are minimal, and only a few cases of malignant change from a solitary juvenile polyp have been reported. We describe the case of a twenty one year old female with one solitary juvenile polyp, which contained a signet ring cell carcinoma in the mucosal layer.


Advanced networks and computing in healthcare.
As computing and network capabilities continue to rise, it becomes increasingly important to understand the varied applications for using them to provide healthcare. The objective of this review is to identify key characteristics and attributes of healthcare applications involving the use of advanced computing and communication technologies, drawing upon 45 research and development projects in telemedicine and other aspects of healthcare funded by the National Library of Medicine over the past 12 years. Only projects publishing in the professional literature were included in the review. Four projects did not publish beyond their final reports. In addition, the authors drew on their first-hand experience as project officers, reviewers and monitors of the work. Major themes in the corpus of work were identified, characterizing key attributes of advanced computing and network applications in healthcare. Advanced computing and network applications are relevant to a range of healthcare settings and specialties, but they are most appropriate for solving a narrower range of problems in each. Healthcare projects undertaken primarily to explore potential have also demonstrated effectiveness and depend on the quality of network service as much as bandwidth. Many applications are enabling, making it possible to provide service or conduct research that previously was not possible or to achieve outcomes in addition to those for which projects were undertaken. Most notable are advances in imaging and visualization, collaboration and sense of presence, and mobility in communication and information-resource use.


Long-term treatment with Elamipretide enhances healthy aging phenotypes in mice.
Disruption of metabolic and bioenergetic homeostasis related to mitochondrial dysfunction is a key driver of aging biology. Therefore, targeting mitochondrial function would be a rational approach to slowing aging. Elamipretide (Elam, a.k.a. SS-31) is a peptide known to target mitochondria and suppress mammalian signs of aging. The present study was designed to examine the phenotypic effects of long-term Elam treatment on aging in C57BL/6 mice starting at 18 months of age. Mice were fed regular chow (RC diet) or a diet high in fat and sugar (HF diet) and treated with 3 mg/kg of Elam or saline subcutaneously 5 days per week for 10 months. Physiological performance assessments were conducted at 28 months of age. Elam improved the physical performance of males but not females, while in females Elam improved cognitive performance and enhanced the maintenance of body weight and fat mass. It also improved diastolic function in both males and females, but to a greater extent in males. The HF diet over 10 months had a negative effect on health span, as it increased body fat and decreased muscle strength and heart function, especially in females. Elam enhanced healthy aging and cardiac function in both male and female mice, although the specific effects on function differed between sexes. In females, the treatment led to better cognitive performance and maintenance of body composition, while in males, performance on a rotating rod was preserved. These overall observations have translational implications for considering additional studies using Elam in therapeutic or preventive approaches for aging and age-related diseases.


Does Concurrent Tibial Intramedullary Nailing and Fibular Fixation Increase Rates of Tibial Nonunion? A Matched Cohort Study.
To determine if there is a difference in rates of tibial nonunion in patients undergoing tibial intramedullary (IM) nailing and fibular fixation as compared to a matched cohort undergoing tibial IM nailing alone. Retrospective matched cohort study. Single Level 1 academic trauma center. Consecutive patients 18 years and older with a tibia and fibula fracture treated with tibial IM nailing and fibular fixation who were determined radiographically and clinically healed or had a minimum 1-year follow-up were included. A matched cohort who underwent tibial IM nailing without fibular fixation was used for comparison. Fibular fixation at the time of tibial IM nailing. Tibial nonunion, defined as a persistently symptomatic fracture with no radiographic progression toward healing at 9 months on consecutive radiographs over a 2-month period. One hundred sixty six patients met inclusion criteria for the intervention group. Mean follow-up was 21 months. There was a 12% rate of tibial nonunion. In a matched cohort of 174 patients without fibular fixation there was no significant difference in patient demographics, injury characteristics, infection rates, time to union, postoperative complications, or rates of tibial nonunion. The rate of nonunion in both groups was significantly higher in patients with high energy mechanisms, open fractures, and postoperative infections. Fibular fixation did not impact rates of tibial nonunion. The rate of tibial nonunion in both cohorts is comparable with published rates of tibial nonunion after IM nailing without fibular fixation. Open fractures, high energy mechanism, and postoperative infection are significantly associated with tibial nonunion. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


The Glasgow Face Matching Test.
We describe a new test for unfamiliar face matching, the Glasgow Face Matching Test (GFMT). Viewers are shown pairs of faces, photographed in full-face view but with different cameras, and are asked to make same/different judgments. The full version of the test comprises 168 face pairs, and we also describe a shortened version with 40 pairs. We provide normative data for these tests derived from large subject samples. We also describe associations between the GFMT and other tests of matching and memory. The new test correlates moderately with face memory but more strongly with object matching, a result that is consistent with previous research highlighting a link between object and face matching, specific to unfamiliar faces. The test is available free for scientific use.


The Necessity of Chromatin: A View in Perspective.
Epigenomics has grown exponentially, providing a better understanding of the mechanistic aspects of new and old phenomena originally described through genetics, as well as providing unexpected insights into the way chromatin modulates the genomic information. In this overview, some of the advances are selected for discussion and comment under six topics: (1) histone modifications, (2) weak interactions, (3) interplay with external inputs, (4) the role of RNA molecules, (5) chromatin folding and architecture, and, finally, (6) a view of the essential role of chromatin transactions in regulating the access to genomic DNA.


Prognostic value of intrathecal heme oxygenase-1 concentration in patients with Fisher Grade III aneurysmal subarachnoid hemorrhage.
Experimental studies have demonstrated the crucial role of posthemorrhagic erythrocyte catabolism in the pathogenesis of subarachnoid hemorrhage (SAH). The authors of this study aimed to investigate the prognostic value of a series of CSF biomarkers linked to heme metabolism in SAH patients. Patients with Fisher Grade III aneurysmal SAH undergoing early aneurysm obliteration were enrolled. The levels of heme oxygenase-1 (HO-1), oxyhemoglobin, ferritin, and bilirubin in intrathecal CSF were measured on the 7th day posthemorrhage. The associations of functional outcome with clinical and CSF parameters were analyzed. The study included 41 patients (mean age 59 ± 14 years; 16 male, 25 female), 17 (41.5%) of whom had an unfavorable outcome (Glasgow Outcome Scale score ≤ 3) 3 months after SAH. In terms of the clinical data, age > 60 years, admission World Federation of Neurosurgical Societies Grade ≥ III, and the presence of acute hydrocephalus were independent factors associated with an unfavorable outcome. After adjusting for clinical parameters, a higher level of HO-1 appeared to be the most significant CSF parameter related to an unfavorable outcome among all tested CSF molecules (OR 0.934, 95% CI 0.883-0.989, p = 0.018). Further analysis using a generalized additive model identified a cutoff HO-1 value of 81.2 μM, with higher values predicting unfavorable outcome (82.4% accuracy). The authors propose that the level of intrathecal CSF HO-1 at Day 7 post-SAH can be an effective outcome indicator in patients with Fisher Grade III aneurysmal SAH.


Evaluating the membrane fecal coliform test by using Escherichia coli as the indicator organism.
The fecal coliform membrane filter method (MFC) currently used in water pollution analysis was evaluated by using two strains of Escherichia coli, a known fecal coliform, as the indicator organism. A large relative error in the results obtained with this method was found to be dependent upon the brand of membrane filter employed, the medium, and the temperature of incubation. MFC densities varied between 10 and 60% of the densities determined by means of total bacteria counts and total coliform counts performed at 35 C. Due to the large relative error encountered, the MFC method cannot be recommended as an analytical tool for the laboratory enumeration of E. coli. The results do show that the MFC method can be used at 35 C for enumeration of E. coli and for differential counts of E. coli and Enterobacter aerogenes.


Deep Learning-Based Forgery Attack on Document Images.
With the ongoing popularization of online services, the digital document images have been used in various applications. Meanwhile, there have emerged some deep learning-based text editing algorithms which alter the textual information of an image in an end-to-end fashion. In this work, we present a low-cost document forgery algorithm by the existing deep learning-based technologies to edit practical document images. To achieve this goal, the limitations of existing text editing algorithms towards complicated characters and complex background are addressed by a set of network design strategies. First, the unnecessary confusion in the supervision data is avoided by disentangling the textual and background information in the source images. Second, to capture the structure of some complicated components, the text skeleton is provided as auxiliary information and the continuity in texture is considered explicitly in the loss function. Third, the forgery traces induced by the text editing operation are mitigated by some post-processing operations which consider the distortions from the print-and-scan channel. Quantitative comparisons of the proposed method and the exiting approach have shown the advantages of our design by reducing the about 2/3 reconstruction error measured in MSE, improving reconstruction quality measured in PSNR and in SSIM by 4 dB and 0.21, respectively. Qualitative experiments have confirmed that the reconstruction results of the proposed method are visually better than the existing approach in both complicated characters and complex texture. More importantly, we have demonstrated the performance of the proposed document forgery algorithm under a practical scenario where an attacker is able to alter the textual information in an identity document using only one sample in the target domain. The forged-and-recaptured samples created by the proposed text editing attack and recapturing operation have successfully fooled some existing document authentication systems.


A metabolic perspective on nitric oxide function in melanoma.
Nitric oxide (NO) generated from nitric oxide synthase (NOS) exerts a dichotomous effect in melanoma, suppressing or promoting tumor progression. This dichotomy is thought to depend on the intracellular NO concentration and the cell type in which it is generated. Due to its central role in the metabolism of multiple critical constituents involved in signaling and stress, it is crucial to explore NO's contribution to the metabolic dysfunction of melanoma. This review will discuss many known metabolites linked to NO production in melanoma. We discuss the synthesis of these metabolites, their role in biochemical pathways, and how they alter the biological processes observed in the melanoma tumor microenvironment. The metabolic pathways altered by NO and the corresponding metabolites reinforce its dual role in melanoma and support investigating this effect for potential avenues of therapeutic intervention.


Incremental benefit of maximum-intensity-projection images on observer detection of small pulmonary nodules revealed by multidetector CT.
Our purpose was to assess the incremental effect of maximum-intensity-projection (MIP) image processing on the ability of various observers to detect small (<1 cm in diameter) central and peripheral lung nodules revealed by multidetector CT. We retrospectively identified 25 patients with metastatic disease, each having from two to nine nodules that were 3-9 mm in diameter. Two senior and three junior reviewers interpreted all images on a workstation. The observers first reviewed axial images (3.75-mm collimation, 3-mm reconstruction interval, multidetector acquisition) in cine and sequential fashion and recorded the size, lobe, and central or peripheral (within 1 cm of the edge of lung) location of each nodule. MIP images (10-mm slab, 8-mm interval) were then reviewed, and additional nodules detected were recorded. Final counts were established by consensus. The reviewers found 122 nodules (71 peripheral, 51 central) in the 25 patients. The addition of MIP slabs significantly enhanced reviewer detection of central nodules (p < 0.001) and junior reviewer detection of peripheral nodules (p < 0.001). MIP slabs also reduced the effects of reviewer experience, particularly for peripheral nodules. MIP processing reduces the number of overlooked small nodules, particularly in the central lung. Observer nodule detection remains imperfect even when lesions are clearly depicted on images.


Reuse of wastewater sludge with marine clay as a new resource of construction aggregates.
The disposal of sludge from wastewater treatment presents highly complex problems to any municipality. Most of the sludge disposal methods have varying degrees of environmental impact. Hence, it is necessary to explore potential areas of reuse in order to alleviate sludge disposal problems and to conserve natural resources. Industrial sludge and marine clay are two forms of high-volume wastes. Using these wastes as a resource of raw materials to produce construction aggregates would enable large-scale sludge reuse. The aggregates were produced at various sludge-clay combinations containing 0, 20, 50, 80 and 100% clay contents, respectively. The pelletized aggregates displayed lower particle densities ranged between 1.48 and 2.25 g/cm3, compared to the density of granite at 2.56 g/cm3. Good 28-day concrete compressive strength of 38.5 N/mm2 achieved by the 100% sludge aggregate was comparable to the value of 38.0 N/mm2 achieved of the granite control specimens. The leachate contamination levels from the aggregates after 150 days were found acceptable when used in concrete, indicating insignificant environmental contamination. The heat flow study showed increases in heat flow at the temperatures of 480 degrees C and between 660 degrees C and 900 degrees C, indicating a need for the extension of heating time around these temperatures.


Tracking the behavior of an accidental oil spill and its impacts on the marine environment in the Eastern Mediterranean.
The eastern Mediterranean region is a vital hub for oil transportation and production because of its strategic location between Europe, Asia, and Africa. But its unique attributes, including narrow shipping routes, heavy marine traffic, and proximity to vulnerable ecosystems, render it particularly susceptible to accidental oil spills. In this research, an oil spill detection model, along with bathymetric and oceanographic parameters, was used to track oil spills that occurred at the Syrian Baniyas Station in the Eastern Mediterranean on August 23, 2021. Furthermore, the study employed a pairwise comparison matrix (PWCM) to assess the relative importance of wind speed and direction, water depth, and sea surface temperature (SST) in the dispersion of oil spills. Analysis of Sentinel-1 data obtained prior to, during, and after the incident revealed the accumulation of oil slicks along the Syrian coast from Baniyas to Latakia for up to twenty days. The spilled oil reached the coast of Cyprus six days after the incident. The study determined that wind speed and direction played a critical role in the dispersion of spilled oil, while water depth and SST were comparatively less significant factors in this process. The overall accuracy (OA) and Kappa coefficient (KC) for land, water, and oil slick classes derived from the random forest (RF) algorithm ranged from 90 % to 98 % and from 0.86 to 0.98, respectively. The spread of oil slicks at the incident location was revealed by the decorrelation stretch and band ratios of Sentinel-2 MultiSpectral Instrument (MSI) data. The accidental oil spill could have negative effects on the organic carbon cycle, chlorophyll production, and ecosystem productivity. It is essential to consider the vulnerability of specific regions in the Eastern Mediterranean to oil spills when developing adaptation strategies.


Host limits to accurate human growth hormone production in multiple plant systems.
Human growth hormone (hGH) is not only a valuable recombinant therapeutic protein for hormone deficiency indications, but is also an extensively characterized molecule both from recombinant bacterial systems and as circulating in humans. We describe the characterization of hGH produced in three different plant systems: tobacco cell culture, soy seed, and maize seed. The data indicate highest production in the maize seed system, with continued productivity over multiple generations, and when bred to a new host genotype for improved productivity. Purification indicated significant material of the correct structure from both plant cell culture and maize seed, with maize seed also showing correct activity relative to that produced by Escherichia coli. However, all systems showed some proteolyzed hGH, with data from gel electrophoresis, mass spectrometry, and peptide mapping localizing to a region of the protein also prone to cleavage in some other systems. Together, the data indicate the dependence of recombinant protein accumulation on posttranslational processes in different host systems.


Structural and genetic studies on chicken 7S immunoglobulin allotypes. I. Detection of four heavy chain specificities with a new radioimmunoassay.
A method was developed for the detection of allotypes on intact, radiolabeled 7S immunoglobulin (Ig) which does not involve insolubilized alloantisera. Binding of dinitrophenylated anti-allotype (DAA) antiserum with radiolabeled alloantigen was demonstrated by the addition of rabbit anti-dinitrophenyl antiserum followed by precipitation of complexes with sheep anti-rabbit gamma-globulin antiserum. Dinitrophenylation of alloantiserum up to 8.5 hr had no effect on antibody titer or avidity. Binding inhibition assays with the DAA method detected allotypes on 2 to 5 ng of 7S Ig. Four specificities were detected on 7S Ig heavy (H) chains by binding inhibition with the DAA assay. Specificities CS-1.1 and CS-1.2, located in the Fab fragment, were detected at 3- to 5-fold lower concentrations of reassociated H and light (L) chains than on the isolated H chains. On the basis of regression coefficients calculated from binding inhibition curves, the avidity of isolated H chains was significantly increased following reassociation with L chains, indicating that the conformation of CS-1.1 and CS-1.2 determinants depends in part on H and L chain interactions. In contrast, reassociation of H and L chains did not significantly increase H chain inhibitory activity or avidity for specificities CS-1.3 and CS-1.4.


Medical injection use among adults and adolescents aged 15 to 64 years in Kenya: results from a national survey.
Unsafe medical injections remain a potential route of HIV transmission in Kenya. We used data from a national survey in Kenya to study the magnitude of medical injection use, medication preference, and disposal of medical waste in the community. The Kenya AIDS Indicator Survey 2012 was a nationally representative population-based survey. Among participants aged 15-64 years, data were collected regarding medical injections received in the year preceding the interview; blood samples were collected from participants for HIV testing. Of the 13,673 participants who answered questions on medical injections, 35.9% [95% confidence interval (CI): 34.5 to 37.3] reported receiving ≥1 injection in the past 12 months and 51.2% (95% CI: 49.7 to 52.8) preferred receiving an injection over a pill. Among those who received an injection from a health care provider, 95.9% (95% CI: 95.2 to 96.7) observed him/her open a new injection pack, and 7.4% (95% CI: 6.4 to 8.4) had seen a used syringe or needle near their home or community in the past 12 months. Men who had received ≥1 injection in the past 12 months (adjusted odds ratio, 3.2; 95% CI: 1.2 to 8.9) and women who had received an injection in the past 12 months, not for family planning purposes (adjusted odds ratio, 2.6; 95% CI: 1.2 to 5.5), were significantly more likely to be HIV infected compared with those who had not received medical injection in the past 12 months. Injection preference may contribute to high rates of injections in Kenya. Exposure to unsafe medical waste in the community poses risks for injury and infection. We recommend that community- and facility-based injection safety strategies be integrated in disease prevention programs.


[Quality planning of Family Health Units using Quality Function Deployment (QFD)].
Quality is an indispensible requirement in the health field, and its pursuit is necessary in order to meet demands by a population that is aware of its rights, as part of the essence of good work relations, and to decrease technological costs. Quality thus involves all parties to the process (users and professionals), and is no longer merely an attribute of the health service. This study aimed to verify the possibility of quality planning in the Family Health Units, using Quality Function Deployment (QFD). QFD plans quality according to user satisfaction, involving staff professionals and identifying new approaches to improve work processes. Development of the array, called the House of Quality, is this method's most important characteristics. The results show a similarity between the quality demanded by users and the quality planned by professionals. The current study showed that QFD is an efficient tool for quality planning in public health services.


[The code of ethics and conduct of nursing of the Valencian region: background and content].
TIn order to provide to the nursing professionals in the Valencian Region a code of professional conduct to help them deal with new situations that arise in their daily clinical practice, derived from social changes produced, the Board of Nursing of Valencian Region/ Consejo de Enfermería de la Comunidad Valenciana (CECOVA) approved in May2010, the Code of Ethics and Conduct of Nursing of Valencia. This work is as much about the reasons that led to propel it, and the way they was developed and the most important aspects of your content.


Evaluation of possibilities in identification and susceptibility testing for Candida glabrata clinical isolates with the Integral System Yeast Plus (ISYP).
The aim of this study was to evaluate possibilities of correct identification and susceptibility testing of C. glabrata clinical isolates with Integral System Yeast Plus (ISYP). For species identification, as the reference method, API Candida test and species-specific PCR reactions were used. The potential of antifungal susceptibility testing by the ISYP test was compared with the Sensititre Yeast One. Whilst the reference methods confirmed that the received population (n = 65 isolates) represented only C. glabrata, identification with the ISYP system showed correct data only in the case of 18 strains tested (27.7%). Species identification of the other 47 strains with the ISYP test was not possible at all. Significant differences were also observed for drug susceptibility testing carried out by the ISYP and the Sensititre Yeast One. The highest level of disagreement in classifying strains as resistant or susceptible estimated, as 73.9% and 40.0%, was observed for itraconazole and amphotericin B, respectively. Satisfactory results were only obtained for 5-fluorocytosine with 93.8% agreement between both methods. In our opinion the idea of the ISYP system is certainly good. The combination of identification ability and drug susceptibility testing in one test is very important, especially from a clinical point of view. However, the current version of the ISYP has many disadvantages. We would like to encourage the manufacturer to make an effort and develop a new, more accurate version of the test.


[Comparative study of glucagon and insulin tests for diagnostics of secondary adrenal insufficiency and growth hormone deficiency in children and adolescents].
Diagnostics of growth hormone deficiency (GHD) and secondary adrenal insufficiency (SAI) is based on estimation of peak GH and cortisol concentrations in provocation tests. Russian consensus on diagnostics and treatment of hypopituitarism in children and adolescences recommends to measure GH and cortisol concentrations in every time-point of insulin test (IT). Glucagon test (GT) is discussed in literature as alternative to IT. To estimate the possibility to use provocation GT for diagnostics of SAI and GHD in children and adolescents. We investigated blood and urine cortisol levels, IT, and GT in 20 patients 6.5-17.8 years (Me 13.0 (10.4; 15.3)) after surgery and/or radiology and/or chemical therapy of head and neck tumors; remission for 0.4-7.5 years (Ме 2.1 (1.5; 5.2)). With cut-off point 550 nmol/L sensitivity and specifity of IT was 100% and 60%, GT - 100% and 53% respectively. Minimal cortisol cut-off level for GT with sensitivity 100% was 500 nmol/L, maximal with specifity 100% - 400 nmol/L.Early morning cortisol levels did not exceed 250 nmol/l in 2 patients with SAI; and were above 500 nmol/l in 8 patients without SAI while primary or repeated examination.GHD was reviled by IT in all patients. Maximal GH concentrations in GT and IT did not differ significantly (p>0.05) but GT results of 4 patients exceeded or met cut-off for this test (7 ng/ml).GT was characterized by less severity compared with IT. For diagnostics of SAI by GT we can advise cut-off points of cortisol level 500 (sensitivity 100%, specifty 53%) and 400 nmol/L (sensitivity 80%, specifity 100%). Measuring of cortisol levels in 2-3 early morning blood samples allows to exclude or to suspect SAI in half of patients before tests. GH peaks in GT can exceed similarly data in IT that needs future investigation.


Detection of the recently emerged synthetic cannabinoid 5F-MDMB-PICA in 'legal high' products and human urine samples.
Indole or indazole-based synthetic cannabinoids (SCs) bearing substituents derived from valine or tert-leucine are frequently abused new psychoactive substances (NPS). The emergence of 5F-MDMB-PICA (methyl N-{[1-(5-fluoropentyl)-1H-indol-3-yl]carbonyl}-3-methylvalinate) on the German drug market is a further example of a substance synthesized in the context of scientific research being misused by clandestine laboratories by adding it to 'legal high' products. In this work, we present the detection of 5F-MDMB-PICA in several legal high products by gas chromatography-mass spectrometry (GC-MS) analysis. To detect characteristic metabolites suitable for a proof of 5F-MDMB-PICA consumption by urine analysis, pooled human liver microsome (pHLM) assays were performed and evaluated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF-MS) techniques to generate reference spectra of the in vitro phase I metabolites. The in vivo phase I metabolism was investigated by the analysis of more than 20 authentic human urine specimens and compared to the data received from the pHLM assay. Biotransformation of the 5-fluoropentyl side chain and hydrolysis of the terminal methyl ester bond are main phase I biotransformation steps. Two of the identified main metabolites formed by methyl ester hydrolysis or mono-hydroxylation at the indole ring system were evaluated as suitable urinary biomarkers and discussed regarding the interpretation of analytical findings. Exemplary analysis of one urine sample for 5F-MDMB-PICA phase II metabolites showed that two of the main phase I metabolites are subject to extensive glucuronidation prior to renal excretion. Therefore, conjugate cleavage is reasonable for enhancing sensitivity. Commercially available immunochemical pre-tests for urine proved to be unsuitable for the detection of 5F-MDMB-PICA consumption. Copyright © 2017 John Wiley & Sons, Ltd.


Management of transgender patients in critical care.
As clinicians working in critical care, it is our duty to provide all of our patients with the high-quality care they deserve, regardless of their gender identity. The transgender community continues to suffer discrimination from the media, politicians and general public. As healthcare workers we often pride ourselves on our ability to safely care for all patients. However, there remains a distinct lack of understanding surrounding the care of critically ill transgender patients. This is likely in part because the specific care of transgender patients is not included in the Faculty of Intensive Care Medicine's, Royal College of Anaesthetists', Royal College of Physician's, or Royal College of Emergency Medicine's curriculum. There are several important considerations relevant for transgender patients in critical care including anatomical changes to the airway, alterations to respiratory and cardiovascular physiology and management of hormone therapy. Alongside this, there are simple but important social factors that exist, such as the use of patient pronouns and ensuring admittance to correctly gendered wards. In this review we will address the key points relevant to the care of transgender patients in critical care and provide suggestions on how education on the subject may be improved.


Four Novel d10 Metal-Organic Frameworks Incorporating Amino-Functionalized Carboxylate Ligands: Synthesis, Structures, and Fluorescence Properties.
By employment of amino-functionalized dicarboxylate ligands to react with d10 metal ions, four novel metal-organic frameworks (MOFs) were obtained with the formula of {[Cd(BCPAB)(μ 2-H2O)]} n (1), {[Cd(BDAB)]∙2H2O∙DMF} n (2), {[Zn(BDAB)(BPD)0.5(H2O)]∙2H2O} n (3) and {[Zn(BDAB)(DBPB)0.5(H2O)]∙2H2O} n (4) (H2BCPAB = 2,5-bis(p-carbonylphenyl)-1-aminobenzene; H2BDAB = 1,2-diamino-3,6-bis(4-carboxyphenyl)benzene); BPD = (4,4'-bipyridine); DBPB = (E,E-2,5-dimethoxy-1,4-bis-[2-pyridin-vinyl]-benzene; DMF = N,N-dimethylformamide). Complex 1 is a three-dimensional (3D) framework bearing seh-3,5-Pbca nets with point symbol of {4.62}{4.67.82}. Complex 2 exhibits a 4,4-connected new topology that has never been reported before with point symbol of {42.84}. Complex 3 and 4 are quite similar in structure and both have 3D supramolecular frameworks formed by 6-fold and 8-fold interpenetrated 2D coordination layers. The structures of these complexes were characterized by single crystal X-ray diffraction (SC-XRD), thermal gravimetric analysis (TGA) and powder X-ray diffraction (PXRD) measurements. In addition, the fluorescence properties and the sensing capability of 2-4 were investigated as well and the results indicated that complex 2 could function as sensor for Cu2+ and complex 3 could detect Cu2+ and Ag+ via quenching effect.


Effects of interleukin-1 antagonism on cortisol levels in individuals with obesity: a randomized clinical trial.
Anti-inflammatory treatment with interleukin-1 (IL-1) antagonism decreases both cortisol and adrenocorticotropin hormone (ACTH) levels in individuals with obesity in short term. However, it remains unknown whether these effects persist upon prolonged treatment. In this double-blind, parallel-group trial involving patients with features of the metabolic syndrome, 33 patients were randomly assigned to receive 100 mg of anakinra (recombinant human IL-1 receptor antagonist) subcutaneously twice-daily and 34 patients to receive placebo for 4 weeks. For this analysis, change in cortisol and ACTH levels from baseline to 4 weeks were predefined end points of the trial. The mean age was 54 years, baseline cortisol levels were 314 nmol/L (IQR 241-385) and C-reactive protein (CRP) levels were 3.4 mg/L (IQR 1.7-4.8). Treatment with anakinra led to a significant decrease in cortisol levels at day 1 when compared to placebo with an adjusted between-group difference of 28 nmol/L (95% CI, -7 to -43; P = 0.03). After 4 weeks, the cortisol-lowering effect of anakinra was attenuated and overall was statistically not significant (P = 0.72). Injection-site reactions occurred in 21 patients receiving anakinra and were associated with higher CRP and cortisol levels. IL-1 antagonism decreases cortisol levels in male patients with obesity and chronic low-grade inflammation on the short term. After prolonged treatment, this effect is attenuated, probably due to injection-site reactions (ClinicalTrials.gov, NCT02672592).


Socioeconomic factors and bacillary dysentery risk in Jiangsu Province, China: a spatial investigation using Bayesian hierarchical models.
Bacillary dysentery (BD) is an acute diarrheal disease prevalent in areas affected by socioeconomic disparities. We investigated BD risk and its associations with socioeconomic factors at the county-level in Jiangsu province, China using epidemiological and socioeconomic data from 2011-2014. We fitted four Bayesian hierarchical models with various prior specifications for random effects. As all model comparison criteria values were similar, we presented results from a reparameterized Besag-York-Mollié model, which addressed issues with the identifiability of variance captured by spatial and independent effects. Our model adjusted for year and socioeconomic status showed 18-65% decreased BD risk compared to 2011. We found a high relative risk in the northwestern and southwestern counties. Increasing the percentage of rural households, rural income per capita, health institutions per capita, or hospital beds per capita decreases the relative risk of BD, respectively. Our findings can be used to improve infectious diarrhea surveillance and enhance existing public health interventions.


Effects of Cannabidiol in Inflammation: A Review of Pre-clinical and Clinical Findings.
Cannabidiol (CBD) is the second most abundant component of the plant Cannabis sativa. Currently, CBD is approved for Lennox-Gastaut and Dravet syndrome and newly for tuberous sclerosis complex. However, based on the available data, CBD migth have a broad spectrum of potential therapeutic uses. Therefore, the aim of this review was to summarize the evidence on the effects of CBD on pain and inflammation of various causes. PubMed and Web of Science databases were searched until January 2023. The medical keyword term "cannabidiol" was combined with "pain", "arthritis", and "inflammation". Based on the initial search for these terms, 9, 5, and 5 relevant publications have been selected. Based on the available data, it is not possible to draw a clear conclusion about the effect of CBD to releave pain, because each study used a different route of administration or treatment regimen. The studies also differed in etiopathogenesis of pain (chronic, neuropathic, and possibly inflammatory pain), and in general included only small number of subjects. In case of anti-inflammatory qualities of CBD, its effect on the intestinal system is negligible. On the other hand, positive treatment results were observed in all publications dealing with the effect of CBD on arthritis.


K-ras mutations in colorectal adenocarcinomas and neighbouring transitional mucosa.
The K-ras gene in codons 12 and 13 was investigated using allele-specific polymerase chain reaction in matched normal mucosa (n = 106), transitional mucosa (n = 69) and tumours (n = 149) from 149 patients with colorectal adenocarcinomas. K-ras mutations in codon 12 were detected in 41/149 (28%) of tumours and 4/69 (6%) of transitional mucosa samples, but not in the normal mucosa. Further, mutation rates were increased in younger patients (P = 0.001) and in mucinous carcinomas (50%) compared with well differentiated (17%), moderately differentiated (26%) or poorly differentiated (24%) tumours. Our findings indicate that mucinous carcinoma may represent a distinct genetic entity.


Rapid screening of ascorbic acid, glycoalkaloids, and phenolics in potato using high-performance liquid chromatography.
Evaluation of phenolic metabolism in potato tubers (Solanum tuberosum) would be facilitated by faster analytical methods. A high-throughput HPLC method was developed for the qualitative and quantitative determination in potato of numerous phenolic compounds, the sum of the glycoalkaloids chaconine and solanine, plus ascorbic acid. Following a fast extraction, HPLC run times of 12 min were achieved with the use of a monolithic RP C18 column. UV and MS analyses were used to characterize the phenolic complement in extracts from two white-fleshed varieties. Over 30 compounds were identified, some of which are thought to possess either nutritional value or are involved in plant disease resistance. This method is expected to be useful for germplasm mining and for varietal development programs in which large numbers of lines are generated.


Immunosuppressive Treatment Can Alter Visual Performance in the Royal College of Surgeons Rat.
Immunosuppression is frequently employed to enhance survival of xenografted human cells as part of translational proof-of-concept studies. However, the potential effects of this treatment are easily overlooked. As part of baseline testing in the dark-eyed variant of the dystrophic Royal College of Surgeons (RCS) rat, we documented the time course of retinal degenerative changes versus Long Evans controls using bright field retinal imaging, fluorescein angiography, and histology and examined the impact of immunosuppression on visual function. Rats received either no treatment or systemic immunosuppression with oral cyclosporine A and injectable dexamethasone and subsequently underwent functional evaluation by optomotor response testing and electroretinography (ERG) at multiple intervals from P45 to P180. Immunosuppressed RCS animals demonstrated poorer performance on functional tests than age-matched untreated rats during the earlier stages of degeneration, including significantly lower spatial acuities on optomotor threshold testing and significantly lower b-wave amplitudes on scotopic and photopic ERGs. Retinal imaging documented the progression of degenerative changes in the RCS fundus and histologic evaluation of the RCS retina confirmed progressive thinning of the outer nuclear layer. A standard regimen of cyclosporine A plus dexamethasone, administered to RCS rats, results in demonstrable systemic side effects and depressed scores on behavioral and electrophysiological testing at time points before P90. The source of the functional impairment was not identified. This finding has implications for the interpretation of data generated using this commonly used translational model.


The Heme-Regulated Inhibitor Pathway Modulates Susceptibility of Poor Prognosis B-Lineage Acute Leukemia to BH3-Mimetics.
Antiapoptotic MCL1 is one of the most frequently amplified genes in human cancers and elevated expression confers resistance to many therapeutics including the BH3-mimetic agents ABT-199 and ABT-263. The antimalarial, dihydroartemisinin (DHA) translationally represses MCL-1 and synergizes with BH3-mimetics. To explore how DHA represses MCL-1, a genome-wide CRISPR screen identified that loss of genes in the heme synthesis pathway renders mouse BCR-ABL+ B-ALL cells resistant to DHA-induced death. Mechanistically, DHA disrupts the interaction between heme and the eIF2α kinase heme-regulated inhibitor (HRI) triggering the integrated stress response. Genetic ablation of Eif2ak1, which encodes HRI, blocks MCL-1 repression in response to DHA treatment and represses the synergistic killing of DHA and BH3-mimetics compared with wild-type leukemia. Furthermore, BTdCPU, a small-molecule activator of HRI, similarly triggers MCL-1 repression and synergizes with BH3-mimetics in mouse and human leukemia including both Ph+ and Ph-like B-ALL. Finally, combinatorial treatment of leukemia bearing mice with both BTdCPU and a BH3-mimetic extended survival and repressed MCL-1 in vivo. These findings reveal for the first time that the HRI-dependent cellular heme-sensing pathway can modulate apoptosis in leukemic cells by repressing MCL-1 and increasing their responsiveness to BH3-mimetics. This signaling pathway could represent a generalizable mechanism for repressing MCL-1 expression in malignant cells and sensitizing them to available therapeutics. IMPLICATIONS: The HRI-dependent cellular heme-sensing pathway can modulate apoptotic sensitivity in leukemic cells by repressing antiapoptotic MCL-1 and increasing their responsiveness to BH3-mimetics.


The Relationship Between Gait, Gross Motor Function, and Parental Perceived Outcome in Children With Clubfeet.
Assessment of children treated nonoperatively for idiopathic clubfoot, has primarily focused on the kinematic and kinetic results measured with gait analysis (GA). Excellent results in ankle motion and push-off power during gait have been reported at age 5; however, the assessment of gross motor function, has not been evaluated. The purpose of this study was to look at the relationship between gait measures, Peabody Developmental Motor Scales and parent-perception of their child's outcome [measured with the Pediatric Outcomes Data Collection Instrument (PODCI)]. A total of 81 children with idiopathic clubfoot were seen for both GA and Peabody testing. Children who initially underwent the Ponseti technique (n=29), the French Physical Therapy method (PT) (n=23), and a group of children initially treated nonoperatively, but who required surgical intervention before GA at 5 years of age (n=29) were enrolled. Pearson's correlation coefficient was used to establish significant relationships between gait variables, Peabody, and PODCI scores. Gait data showed that the Ponseti treated feet had significantly greater ankle power than feet treated surgically (P=0.0075). The Peabody results showed that the PT feet had higher stationary (P=0.0332) and overall gross motor quotient percent (GMQ%) scores (P=0.0092) than the surgical feet. No differences were found in PODCI scores. Ankle power was weakly correlated to the GMQ% (r=0.29; P=0.0102); however, the GMQ% showed a strong correlation to the parent report of Global Functioning Scale on the PODCI (r=0.48; P=0.0005). Minimal gait disturbances do not interfere with function or parental assessment of abilities and satisfaction at 5-year follow-up in children with idiopathic clubfeet. Nonoperative correction of clubfeet should be the goal when possible, as the Peabody scores show better function as early as 5 years of age when surgery is not required.


Alumina/epoxy nanocomposite matching layers for high-frequency ultrasound transducer application.
Mismatch of acoustic impedance at the interface between a piezoelectric transducer and the medium to be probed will substantially reduce the amount of ultrasound energy being transmitted into the medium. Therefore, matching layer is a critical component of an ultrasonic transducer. A spin-coating process was used to fabricate alumina/polymer nanocomposite films with alumina volume fractions ranging from 14 to 32%. The particle size of alumina is in the range of 10 to 40 nm. The thicknesses of the matching layer can be controlled by the spinning speed and the concentration of solution. Acoustic impedances of these nanocomposite matching layers are in the range of 2.8 to 5.1 MRayls with different alumina contents, which meet the matching layer requirement. The attenuation of a nanocomposite matching layer with smooth surface is about 15 dB/mm at 40 MHz. The pulse-echo spectrum and frequency spectrum of a high-frequency transducer using this nanocomposite matching layer are reported.


Staged angioplasty versus regular carotid artery stenting in patients with carotid artery stenosis at high risk of hyperperfusion: a randomised clinical trial.
Hyperperfusion (HP) is a devastating complication associated with carotid artery stenting (CAS) or endarterectomy. The efficacy and safety of staged angioplasty (SAP) in patients with CAS at high risk of HP remains unclear. We sought to determine whether SAP is superior to regular CAS in patients with high risk of HP. A randomised, multicentre open-label clinical trial with blinded outcome assessment (STEP) was conducted. Patients with severe carotid stenosis at high risk of HP were randomly assigned (1:1) to the SAP or regular CAS group. The primary endpoint was hyperperfusion syndrome (HPS) and intracerebral haemorrhage (ICH) within 30 days after the procedure. From November 2014 to January 2017, a total of 64 patients were enrolled in 11 centres. 33 patients were allocated to the SAP group and 31 to the regular CAS group. At 30 days, the rate of primary endpoint was 0.0% (0/33) in the SAP group and 9.7% (3/31) in the regular CAS group (absolute risk reduction (ARR), 9.7%; 95% CI -20.1% to 0.7%; p=0.11). As one of the secondary endpoints, the incidence of HP phenomenon (HPP) was lower in the SAP group than the regular CAS group (0.0% vs 22.6%, ARR,-22.6%; 95% CI -36.8% to -10.2%; p=0.04). The rate of HPS and ICH was not significantly lower in SAP group; the extended secondary endpoint of HPP, however, significantly reduced, which suggested that SAP may be a safe and effective carotid revascularisation procedure to prevent HP. NCT02224209.


[Congenital malformations of the abdominal wall].
Congenital malformations of the abdominal wall consist of a combination of a parietal opening and visceral abnormalities. The most frequent are omphalocele and laparoschisis. Embryological analysis of the formation of the abdominal wall distinguishes omphalocele, due to absence of differentiation of the lateral folds of the embryo, from laparoschisis, due to absence of differentiation of the mesenchyma at one point of the somatopleural lining. Clinically, omphalocele consists of an opening of the abdominal wall, lined by a double layer (peritoneum and external layer of the amniotic membrane), which may rupture before birth. Laparoschisis is a true antenatal hernia lying to one side of the umbilical cord. The other abnormalities of the abdominal wall are less common: muscle and purely cutaneous aplasia. The treatment of omphaloceles requires multidisplinary management. Several surgical techniques are used, mainly primary closure and rectomyoplasty. Primary closure of the abdominal wall is only possible in one-half or one-third of cases.


Onset of treelike patterns in negative streamers.
We present analytical and numerical studies of the initial stage of the branching process based on an interface dynamics streamer model in the fully three-dimensional case. This model follows from fundamental considerations on charge production by impact ionization and balance laws, and leads to an equation for the evolution of the interface between ionized and nonionized regions. We compare some experimental patterns with the numerically simulated ones, and give an explicit expression for the growth rate of harmonic modes associated with the perturbation of a symmetrically expanding discharge. By means of full numerical simulation, the splitting and formation of characteristic treelike patterns of electric discharges is observed and described.


Near-infrared inorganic nanomaterial-based nanosystems for photothermal therapy.
The development of robust materials for treating diseases through non-invasive photothermal therapy (PTT) has attracted increasing attention in recent years. Among various types of nanomaterials, inorganic nanomaterials with strong absorption in the near-infrared (NIR) window can be employed as high-efficiency photothermal agents to treat cancer and bacterial infections. In addition, inorganic nanomaterials can be easily combined with other drugs or chemical reagents to construct multifunctional nanomaterials to cascade stimulation responses, enhance therapeutic effects, and perform precise medical treatments. In this review, focusing on the latest developments of inorganic nanomaterials in photothermal therapy, we firstly introduced the light-to-heat conversion mechanism of inorganic nanomaterials. Secondly, we summarized the application of common inorganic nanomaterials, such as metallic nanoparticles, transition metal oxide nanoparticles and two dimensional (2D) nanosheets. In addition, the strategy of developing multifunctional nano-platforms with excellent biocompatibility as well as good targeted capability was also expounded. Finally, challenges and new perspectives for designing effective inorganic nanomaterial-based nanosystems for photothermal assisted therapy were also discussed.


Osteofibrous dysplasia and adamantinoma in children and adolescents: a clinicopathologic reappraisal.
Osteofibrous dysplasia (OFD) and adamantinoma are rare and most commonly arise in the tibia of young individuals. Although OFD has typical histopathologic features, areas resembling OFD have often been noted at the periphery of otherwise classic adamantinomas, and some have suggested that OFD may be either a precursor to or a regressive phase of adamantinoma. The so-called OFD-like adamantinoma encompasses some features of both OFD and adamantinoma. We studied the clinical, imaging, histopathologic, immunohistochemical, ultrastructural, and molecular features of 16 OFD and 8 adamantinomas (5 OFD-like and 3 classic) in an attempt to further define their morphology, clinical course, and relationship. Patients with OFD were generally younger than those with adamantinoma. Osteoblastic and osteoclastic activity was more prominent in OFD than in OFD-like adamantinoma. In addition to the inconspicuous small clusters of epithelial cells in OFD-like adamantinoma, isolated keratin-positive cells with a unique ultrastructural hybrid fibroblastic-epithelial phenotype were found in the stroma of all OFD and OFD-like adamantinomas. Fluorescence in situ hybridization analysis revealed trisomies 7, 8, and/or 12 in the spindle cell stroma of OFD, OFD-like, and classic adamantinoma, supporting a neoplastic origin of OFD and a common histogenesis for all 3 lesions. Trisomies were not observed in osteoblasts or osteoclasts suggesting that the osseous component is reactive and non-neoplastic. Of the 11 OFD patients with follow-up (median, 4.5 y), all 3 who underwent incisional biopsy had persistent, nonprogressive disease and 2 of 8 who underwent curettage or wide excision had recurrence; none developed adamantinoma. All 6 adamantinoma patients with follow-up (3 classic and 3 OFD-like) were treated with wide excision. One with classic adamantinoma died of pulmonary metastases 9 years after presentation; the other 5 were free of disease with a median follow-up of 12 years. None of the classic adamantinomas evolved into OFD-like adamantinoma or OFD. Although the histopathology, immunohistochemistry, ultrastructure, and cytogenetics indicate that these lesions are closely related, our data and the literature suggest that only classic adamantinoma has malignant potential. OFD, OFD-like adamantinoma, and classic adamantinoma appear to show a progressive complexity of cytogenetic aberrations, perhaps indicative of a multistep neoplastic transformation.


[Therapeutic and prophylactic care of disabled children under conditions of a pediatric outpatient clinic].
The volume and type of treatment and prophylactic care rendered on an outpatient basis to children during a year is assessed based on a sampling from files of 2083 disabled children living in a large industrial city Ufa. In contrast to the entire population of children, each disabled child receives more visits from doctors at home and visits the health center more often. The majority of visits to the health center are for treatment and diagnosis and for consultations. Local doctors are visited mainly for prevention. The activity of local nurses responsible for follow-up of disabled children is low.


Effect of hilar nerve denervation on breathing and arterial PCO2 during CO2 inhalation.
We determined the effects of denervating the hilar branches (HND) of the vagus nerves on breathing and arterial PCO2 (PaCO2) in awake ponies during eupnea and when inspired PCO2 (PICO2) was increased to 14, 28, and 42 Torr. In five carotid chemoreceptor-intact ponies, breathing frequency (f) was less, whereas tidal volume (VT), inspiratory time (TI), and ratio of TI to total cycle time (TT) were greater 2-4 wk after HND than before HND. HND per se did not significantly affect PaCO2 at any level of PICO2, and the minute ventilation (VE)-PaCO2 response curve was not significantly altered by HND. Finally, the attenuation of a thermal tachypnea by elevated PICO2 was not altered by HND. Accordingly, in carotid chemoreceptor-intact ponies, the only HND effect on breathing was the change in pattern classically observed with attenuated lung volume feedback. There was no evidence suggestive of a PCO2-H+ sensory mechanism influencing VE, f, VT, or PaCO2. In ponies that had the carotid chemoreceptors denervated (CBD) 3 yr earlier, HND also decreased f, increased VT, TI, and TT, but did not alter the slope of the VE-PaCO2 response curve. However, at all levels of elevated PICO2, the arterial hypercapnia that had persistently been attenuated, since CBD was restored to normal by HND. The data suggest that during CO2 inhalation in CBD ponies a hilar-innervated mechanism influences PaCO2 by reducing physiological dead space to increase alveolar ventilation.


Labouring women who used a birthing pool in obstetric units in Italy: prospective observational study.
For women at low risk of childbirth complications, water immersion during labour is a care option in many high income countries. Our aims were (a) to describe maternal characteristics, intrapartum events, interventions, maternal and neonatal outcomes for all women who used a birthing pool during labour who either had a waterbirth or left the pool and had a landbirth, and for the subgroup of women who had a waterbirth in 19 obstetric units, and (b) to compare maternal characteristics, intrapartum events, interventions, and maternal and neonatal outcomes for women who used a birthing pool with a control group of women who did not use a birthing pool for whom we prospectively collected data in a single centre. Prospective observational study in 19 Italian obstetric units 2002-2005. Participants were: (a) 2,505 women in labour using a birthing pool in 19 obstetric units; and (b) 114 women in labour using a birthing pool and 459 women who did not use a birthing pool in one obstetric unit. Descriptive statistics were calculated for the sample as a whole and, separately, for those women who gave birth in water. Categorical data were compared using Chi square statistics and continuous data by T-tests. Overall, 95.6% of women using a birthing pool had a spontaneous vertex delivery, 63.9% of which occurred in water. Half of nulliparas and three quarters of multiparas delivered in water. Adverse maternal and neonatal outcomes were rare. There were two cases of umbilical cord snap with waterbirth. Compared with controls, significantly more women who used a birthing pool adopted an upright birth position, had hands off delivery technique, and a physiological third stage. Significantly fewer nulliparas had an episiotomy, and more had a second degree perineal tear, with no evidence of a difference for extensive perineal tears. Birthing pool use was associated with spontaneous vaginal birth. The increase in second degree tears was balanced by fewer episiotomies. Undue umbilical cord traction should be avoided during waterbirth.


Consumption of plant sterols in Belgium: estimated intakes and sources of naturally occurring plant sterols and β-carotene.
The objective of the present study was to assess the intake of naturally occurring plant sterols and β-carotene via the overall diet of Belgian pre-school children and adults. Two different Belgian food consumption databases were used: (1) one with consumption data of pre-school children (2·5-6·5 years old) and (2) one with consumption data of adults ( ≥ 15 years old). These consumption data were combined with a newly developed database containing the plant sterol and β-carotene content in all relevant food items based on international food composition databases and scientific literature. The results show that Flemish pre-school children have a median plant sterol intake of 172 (interquartile range (IQR) = 47) and 184 (IQR = 52) mg/d for girls and boys, respectively. Their median β-carotene intake was 1857 (IQR = 1250) μg/d, without significant difference between girls and boys. Belgian women and men have a median plant sterol intake of 218 (IQR = 113) and 280 (IQR = 158) mg/d, respectively, and a median β-carotene intake of 2086 (IQR = 1254) μg/d (not significantly different between the sexes). The main food source of naturally occurring plant sterols was bread and other cereal products. For β-carotene, the main food source was vegetables.


Angiotensin II-stimulated nitric oxide release from porcine pulmonary endothelium is mediated by angiotensin IV.
In this study, a nitric oxide (NO) sensor was used to examine the ability of angiotensin II (AngII), AngIV, and bradykinin (Bk) to stimulate NO release from porcine pulmonary artery (PPAE) and porcine aortic endothelial (PAE) cells and to explore the mechanism of the AngII-stimulated NO release. Physiologic concentrations of AngII, but not Bk, caused release of NO from PPAE cells. In contrast, Bk, but not AngII, stimulated NO release from PAE cells. AngIII-stimulated NO release from PPAE cells required extracellular L-arginine and was inhibited by L-nitro-arginine methyl ester. AT1 and AT2 receptor inhibition had no affect on AngII-mediated NO release or activation of NO synthase (NOS). AngIV, an AngII metabolite with binding sites that are pharmacologically distinct from the classic AngII receptors, stimulated considerably greater NO release and greater endothelial-type constitutive NOS activity than the same amount of AngII. The AngIV receptor antagonist, divalinal AngIV, blocked both AngII- and AngIV-mediated NO release as well as NOS activation. The results demonstrate that AngIV and the AngIV receptor are responsible, at least in part, for AngII-stimulated NO release and the associated endothelium-dependent vasorelaxation. Furthermore, these results suggest that differences exist in both AngII- and Bk-mediated NO release between PPAE and PAE cells, which may reflect important differences in response to these hormones between vascular beds.


Efficacy trial of a selective prevention program targeting both eating disorders and obesity among female college students: 1- and 2-year follow-up effects.
Evaluate the effects of a prevention program targeting both eating disorders and obesity at 1- and 2-year follow-ups. Female college students at risk for these outcomes because of body image concerns (N = 398) were randomized to the Healthy Weight 2 group-based 4-hr prevention program, which promotes lasting healthy improvements to dietary intake and physical activity and nutrition science health behavior change principles, or an educational brochure control condition. Intervention participants showed significantly less body dissatisfaction and eating disorder symptoms and lower eating disorder onset through 2-year follow-up versus controls, but the former 2 effects were small. There were no main effects for body mass index (BMI), depressive symptoms, dieting, caloric intake, physical activity, or obesity onset. Moderator analyses revealed stronger eating disorder symptom effects for youths with initially elevated symptoms and lower pressure to be thin, stronger BMI effects for youths with initially elevated symptoms and BMI scores, and weaker eating disorder symptom effects for youths with initially elevated pressure to be thin. The 60% reduction in eating disorder onset over the 2-year follow-up was clinically significant and a novel effect for a prevention program, but the main effects on continuous outcomes were small, suggesting that adding nutrition science principles weakened the intervention efficacy. Effects on both eating disorder symptoms and BMI were greater for those with elevated eating disorder symptoms and BMI at pretest, implying that it might be useful to target these individuals in future trials.


Predicted structural similarities of the DNA binding domains of c-Myc and endonuclease Eco RI.
The c-Myc oncoprotein belongs to a family of proteins whose DNA binding domains contain a basic region-helix-loop-helix (bHLH) motif. Systematic mutagenesis of c-Myc revealed that dimerized bHLH motifs formed a parallel four-helix bundle with the amino termini of helices 1 and 2 directed toward the inner and outer nucleotides of the DNA binding site, respectively. Both the basic region and the carboxyl-terminal end of the loop contributed to DNA binding specificity. The DNA binding domain of c-Myc may therefore be structurally similar to that of restriction endonuclease Eco RI.


High-throughput screening of triplex DNA binders from complicated samples by 96-well pate format in conjunction with peak area-fading UHPLC-Orbitrap MS.
Conventional strategies for the screening of DNA triplex binders cannot be used for complicated samples, such as ligand libraries created by combinatorial chemistry or from natural product extracts. In the current study, an ultra-high-performance liquid chromatography coupled with an Orbitrap mass spectrometry (UHPLC-Orbitrap-MS)-based approach, which we call peak area-fading (PAF) UHPLC-Orbitrap-MS and was designed for just such a purpose, is reported. The triplex DNA modified 96-well plate and the single stranded oligonucleotide modified 96-well plate (as control) were incubated with ligand libraries, and the unbound ligands were directly determined via UHPLC-ESI-MS. The binders were detected through the decrease (fading) in the peak areas compared to those of the control group. Several factors, such as incubation time, incubation temperature, and buffer, which might affect the binding affinity and reproducibility, were optimized. The potential of the approach was examined using the extracts of Rhizoma Coptidis and Phellodendron chinense Schneid cortexe. The triplex DNA-binding capabilities of the five components (epiberberine, coptisine, jatrorrhizine, berberrubine, and columbamine) were found for the first time, indicating their efficiency for the analysis of complicated samples. In contrast to our previous study, which suffered from a serious drawback of poor reproducibility, this method is more robust and more suitable for high-throughput measurements, opening a new experimental strategy in assessing large libraries of potential drug candidates that work by forming a drug/DNA complex.


The relation between self-efficacy in patients with chronic obstructive pulmonary disease and caregiver burden.
The study was conducted to examine the relation between self-efficacy in patients with chronic obstructive pulmonary disease (COPD) and caregiver burden. This descriptive, cross-sectional study included 200 patients with stage II and III COPD presenting to hospital between June and November in 2017 and their caregivers. Data were gathered with a questionnaire, COPD Assessment Test and COPD Self-Efficacy Scale from the patients. A questionnaire and Caregiver Burden Scale was used to collect data from the caregivers. Obtained data were analysed with the descriptive statistics numbers, percentages, mean, median and standard deviation. Spearman's correlation analysis was utilised to examine the relation between paired groups. The mean age of the patients with COPD was 63.53 years and 51.1% of the patients were female. The mean age of the caregivers was 48.88 ± 14.09 years. 54.4% of the caregivers were aged 40-60 years, and 59.9% of the caregivers were female. The mean score was 26.97 ± 5.25 for COPD Assessment Test and 2.32 ± 0.43 for COPD Self-Efficacy Scale. Of all the caregivers, 64.8% had mild caregiving burden and 18.1% had moderate caregiving burden. The mean score for Caregiver Burden Scale had a significant, moderate relation with the mean score for the subscale physical effort in COPD Self-Efficacy Scale (r = -0.42; p < 0.01) and had a significant, weak, negative relation with the mean total score for COPD Self-Efficacy Scale and the mean scores for its subscales. There was a significant, moderate, positive relation between the mean scores for Caregiver Burden and COPD Assessment Test (r = 0.51; p < 0.001) and a significant, negative relation between the scores for COPD Self-Efficacy Scale and its subscales and the scores for CAT (r = -0.26 - r = -0.52; p < 0.05). As self-efficacy in COPD patients increases, their health and daily lives are affected less by COPD and caregiver burden decreases.


Cyberbiosecurity Challenges of Pathogen Genome Databases.
Pathogen detection, identification, and tracking is shifting from non-molecular methods, DNA fingerprinting methods, and single gene methods to methods relying on whole genomes. Viral Ebola and influenza genome data are being used for real-time tracking, while food-borne bacterial pathogen outbreaks and hospital outbreaks are investigated using whole genomes in the UK, Canada, the USA and the other countries. Also, plant pathogen genomes are starting to be used to investigate plant disease epidemics such as the wheat blast outbreak in Bangladesh. While these genome-based approaches provide never-seen advantages over all previous approaches with regard to public health and biosecurity, they also come with new vulnerabilities and risks with regard to cybersecurity. The more we rely on genome databases, the more likely these databases will become targets for cyber-attacks to interfere with public health and biosecurity systems by compromising their integrity, taking them hostage, or manipulating the data they contain. Also, while there is the potential to collect pathogen genomic data from infected individuals or agricultural and food products during disease outbreaks to improve disease modeling and forecast, how to protect the privacy of individuals, growers, and retailers is another major cyberbiosecurity challenge. As data become linkable to other data sources, individuals and groups become identifiable and potential malicious activities targeting those identified become feasible. Here, we define a number of potential cybersecurity weaknesses in today's pathogen genome databases to raise awareness, and we provide potential solutions to strengthen cyberbiosecurity during the development of the next generation of pathogen genome databases.


Efficacy of Four Nematicides Against the Reproduction and Development of Pinewood Nematode, Bursaphelenchus xylophilus.
To understand the efficacy of emamectin benzoate, avermectin, milbemectin, and thiacloprid on the reproduction and development of Bursaphelenchus xylophilus, seven parameters, namely population growth, fecundity, egg hatchability, larval lethality, percent larval development, body size, and sexual ratio, were investigated using sublethal (LC20) doses of these compounds in the laboratory. Emamectin benzoate treatment led to a significant suppression in population size, brood size, and percent larval development with 411, 3.50, and 49.63%, respectively, compared to 20850, 24.33, and 61.43% for the negative control. The embryonic and larval lethality increased obviously from 12.47% and 13.70% to 51.37% and 75.30%, respectively. In addition, the body length was also significantly reduced for both males and females in the emamectin benzoate treatment. Avermectin and milbemectin were also effective in suppressing population growth by increasing larval lethality and reducing larval development, although they did not affect either brood size or embryonic lethality. Body length for both male and female worms was increased by avermectin. Thiacloprid caused no adverse reproductive effects, although it suppressed larval development. Sexual ratio was not affected by any of these four nematicides. Our results indicate that emamectin benzoate, milbemectin, and avermectin are effective against the reproduction of B. xylophilus. We think these three nematicides can be useful for the control of pine wilt disease.


Premature Birth and Developmental Programming: Mechanisms of Resilience and Vulnerability.
The third trimester of pregnancy represents a sensitive phase for infant brain plasticity when a series of fast-developing cellular events (synaptogenesis, neuronal migration, and myelination) regulates the development of neural circuits. Throughout this dynamic period of growth and development, the human brain is susceptible to stress. Preterm infants are born with an immature brain and are, while admitted to the neonatal intensive care unit, precociously exposed to stressful procedures. Postnatal stress may contribute to altered programming of the brain, including key systems such as the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. These neurobiological systems are promising markers for the etiology of several affective and social psychopathologies. As preterm birth interferes with early development of stress-regulatory systems, early interventions might strengthen resilience factors and might help reduce the detrimental effects of chronic stress exposure. Here we will review the impact of stress following premature birth on the programming of neurobiological systems and discuss possible stress-related neural circuits and pathways involved in resilience and vulnerability. Finally, we discuss opportunities for early intervention and future studies.


Hereditary telangiectasia manifested as gastrointestinal bleeding without external visible telangiectasia.
Gastrointestinal bleeding is one of the most common problems confronting the physician. In most instances, the source of the bleeding is easily identified, e.g., peptic ulcer disease, bleeding esophageal varices or a colonic lesion. Recurrent gastrointestinal bleeding, however, represents one of the major enigmas confronting the practicing physician. The patient experiences intermittent episodes of weakness, easy fatigability and anemia with occult blood in the stool. Multiple barium radiographic examinations and often endoscopy and exploratory laparotomy are unrevealing as to the etiology of the bleeding. We have had occasion to investigate three such patients. Multiple evaluations of these individuals did not reveal the source of the bleeding until many years later--Rendu-Osler-Weber Disease (ROW). At the time of their evaluations these patients did not reveal the usual telangiectatic areas present on the skin and oral mucous membrane. The diagnosis was suggested by the presence of multiple gastric mucosal telangiectasia identified by gastroscopic examination. This report emphasizes the need for thorough endoscopic evaluation of patients with gastrointestinal bleeding and describes the gastroscopic findings that indicated hereditary telangiectasia as the probable source of bleeding from the gastrointestinal tract.


Effects of chronic widespread pain on the health status and quality of life of women after breast cancer surgery.
Most research and treatment of post-breast cancer chronic pain has focused on local or regional pain problems in the operated area. The purpose of this pilot study was to compare and contrast the pain characteristics, symptom impact, health status, and quality of life of post-breast cancer surgery women with regional chronic pain versus those with widespread chronic pain. A cross-sectional, descriptive design compared two groups of women with chronic pain that began after surgery: regional pain (n = 11) and widespread pain (n = 12). Demographics, characteristics of the surgery, as well as standardized questionnaires that measured pain (Brief Pain Inventory (BPI), Short Form McGill Pain Questionnaire (MPQ-SF)), disease impact (Fibromyalgia Impact Questionnaire (FIQ), Functional Assessment of Cancer Therapy-Breast (FACT-B)), health status (Medical Outcomes Short Form (SF-36)) and quality of life (Quality of Life Scale (QOLS)) were gathered. There were no significant differences between the groups on any demographic or type of surgery variable. A majority of both groups described their pain as aching, tender, and sharp on the MPQ-SF. On the BPI, intensity of pain and pain interference were significantly higher in the widespread pain group. Differences between the two groups reached statistical significance on the FIQ total score as well as the FACT-B physical well-being, emotional well-being and breast concerns subscales. The SF-36 physical function, physical role, and body pain subscales were significantly lower in the widespread pain group. QOLS scores were lower in the widespread pain group, but did not reach statistical significance. This preliminary work suggests that the women in this study who experienced widespread pain after breast cancer surgery had significantly more severity of pain, pain impact and lower physical health status than those with regional pain.


Mesenchymal stem cells induce an inflammatory response after intravenous infusion.
Mesenchymal stem cells (MSCs) have potent immunosuppressive effects in vitro and are considered as a therapeutic option for autoimmune disease and organ transplantation. While MSCs show beneficial effects on immune disease progression and transplant survival in animal models, the immunomodulatory mechanisms involved are largely unknown. In the present study, we show that intravenously infused C57BL/6- green fluorescent protein (GFP) MSCs home to the lungs in C57BL/6 recipient mice and induce an inflammatory response. This response was characterized by increased mRNA expression of monocyte chemoattractant protein-1 (MCP1), IL1-β, and TNF-α and an increase in macrophages in lung tissue 2 h after MSC infusion. Simultaneously, serum levels of proinflammatory IL6, CXCL1, and MCP1 protein increased, demonstrating systemic immune activation after MSC infusion. In liver tissue, no C57BL/6-GFP MSCs were detected, but MCP1 and TNF-α mRNA levels peaked 4 h after MSC infusion. The expression of the anti-inflammatory cytokines TGF-β, IL4, and IL10 was only marginally affected. Nevertheless, 3 days after MSC infusion, animals developed a milder inflammatory response to lipopolysaccharides. Our results suggest that the in vivo immunomodulatory effects of MSCs originate from an inflammatory response that is induced by the infusion of MSCs, which is followed by a phase of reduced immune reactivity.


Controller design and consonantal contrast coding using a multi-finger tactual display.
This paper presents the design and evaluation of a new controller for a multi-finger tactual display in speech communication. A two-degree-of-freedom controller consisting of a feedback controller and a prefilter and its application in a consonant contrasting experiment are presented. The feedback controller provides stable, fast, and robust response of the fingerpad interface and the prefilter shapes the frequency-response of the closed-loop system to match with the human detection-threshold function. The controller is subsequently used in a speech communication system that extracts spectral features from recorded speech signals and presents them as vibrational-motional waveforms to three digits on a receiver's left hand. Performance from a consonantal contrast test suggests that participants are able to identify tactual cues necessary for discriminating consonants in the initial position of consonant-vowel-consonant (CVC) segments. The average sensitivity indices for contrasting voicing, place, and manner features are 3.5, 2.7, and 3.4, respectively. The results show that the consonantal features can be successfully transmitted by utilizing a broad range of the kinesthetic-cutaneous sensory system. The present study also demonstrates the validity of designing controllers that take into account not only the electromechanical properties of the hardware, but the sensory characteristics of the human user.


Endovascular management of acute postprocedural flow diverting stent thrombosis.
Postprocedural thrombosis is a rare complication after flow diverting stent (FD) implantation for aneurysm treatment with few reported cases in the literature. Management strategies and outcomes associated with this complication have not been reported. A multicenter retrospective series of cases of acute postprocedural FD thrombosis were compiled and prevalence was calculated based on procedural volumes over a 7 year period. Acute postprocedural FD thrombosis was defined as the development of neurologic deficit with angiographic imaging demonstrating acute thrombus within the index FD stent at least 2 hours following completion of the implantation procedure. A total of 10 cases of postprocedural thrombosis were identified at five participating centers among a total of 768 patients treated (prevalence 1.3%). Thrombosis occurred a median of 5.5 days after implantation (range 0-83 days). 9/10 patients underwent emergent angiography with intent to perform endovascular reperfusion. A variety of different endovascular treatments were used, including aspiration thrombectomy, retrievable stent thrombectomy, balloon angioplasty, and intra-arterial thrombolytic infusion, without any procedural complications. There were no instances of FD migration, stent kinking, or aneurysm rupture. 90% of patients achieved Thrombolysis in Cerebral Infarction 2B or greater revascularization. Favorable clinical outcomes (modified Rankin Scale score of 0-2) at 3 months were achieved in 88% of patients. Acute postprocedural thrombosis of an FD is a rare complication that occurs in approximately 1-2% of patients after aneurysm treatment. Patients presenting with acute postprocedural FD thrombosis should be aggressively managed using large vessel occlusion thrombectomy techniques, as good angiographic and clinical outcomes are possible.


FIRST BRAZILIAN CONSENSUS ON MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 1: PRE-TREATMENT EVALUATION.
Liver metastases of colorectal cancer are frequent and potentially fatal event in the evolution of patients with these tumors. In this module, was contextualized the clinical situations and parameterized epidemiological data and results of the various treatment modalities established. Was realized deep discussion on detecting and staging metastatic colorectal cancer, as well as employment of imaging methods in the evaluation of response to instituted systemic therapy. The next step was based on the definition of which patients would have their metastases considered resectable and how to expand the amount of patients elegible for modalities with curative intent. Were presented clinical, pathological and molecular prognostic factors, validated to be taken into account in clinical practice.


Ion exchange tumor targeting: a new approach.
Connective tissues are distinguished by the types, concentrations, and organizations of material in the extracellular matrix. Many physiological functions are determined largely by the nature and organization of the extracellular components. The components are characterized by their content and distribution of charged, mostly anionic groups. The distinct roles played by the charges are sometimes modeled by analogy to the transport theory of ion exchange resins. The intent of this study was to investigate whether the properties of the tumor matrix could be used for selective, charge-dependent accumulation of charge-modified dextran. Ten patients with diagnosed superficial urinary bladder carcinoma were included in the study. They received intravesical instillations of technetium-99m-labeled charge-modified dextran derivatives (approximately 0.1-1 mg; approximately 50 MBq in saline; 30-min incubation). After treatment and resection, samples were taken from normal and diseased tissue. The result clearly demonstrated a charge-dependent difference in the quotient of radioactive uptake in tumor tissue: normal tissue. Instillations of cationic dextran yielded a high quotient, up to 3000. Normal tissue had background activity. Anionic dextran yielded a low quotient, 1.8-2, with increased background (i.e. uptake in normal tissue). Neutral dextran gave a quotient of up to 90. No radioactivity could be detected in blood. The tumors in this study apparently displayed cation-exchanging properties. We will continue this investigation and determine whether this is a general property of bladder carcinomas and whether other carcinomas display ion exchange properties. If this is the case, the finding could have important implications for the local treatment of several cancers.


Recognition of base-pairing by DNA polymerases during nucleotide incorporation: the properties of the mutagenic nucleotide dPTP alphaS.
The highly mutagenic nucleoside dP (6-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,4-dihydro-6H,8H-pyrimido[4,5-c][1,2]oxazin-2-one) is a bicyclic analogue of N4-methoxy-2'-deoxycytidine. It exists as a mixture of its imino and amino tautomers in solution with a ratio of about 10:1 based on its tautomeric constant. The bicyclic nature of the heterocycle P restrains the amino substituent in an anti conformation and permits effective Watson-Crick base-pairing using either tautomer. The specificity of incorporation of dP by the 3'-5'-exonuclease-free Klenow fragment of DNA polymerase I (exo-free Klenow) has been studied using the 5'-(1-thio)triphosphate dPTP alphaS in combination with phosphorothioate-specific sequencing of the DNA products. The method provides a convenient qualitative assay for studying nucleotide incorporation and reveals for the first time a potential role for the minor tautomeric forms of the natural DNA bases in base misinsertion (substitution mutagenesis) during replication.


Insight into Protein-Polymer Conjugate Relaxation Dynamics: The Importance of Polymer Grafting.
The bio and chemical physics of protein-polymer conjugates are related to parameters that characterize each component. With this work, it is intended to feature the dynamical properties of the protein-polymer conjugate myoglobin (Mb)-poly(ethyl ethylene phosphate), in the ps and ns time scales, in order to understand the respective roles of the protein and of the polymer size in the dynamics of the conjugate. Elastic and quasi-elastic neutron scattering is performed on completely hydrogenated samples with variable number of polymer chains covalently attached to the protein. The role of the polymer length in the protein solvation and internal dynamics is investigated using two conjugates formed by polymers of different molecular weight. It is confirmed that the flexibility of the complex increases with the number of grafted polymer chains and that a sharp dynamical transition appears when either grafting density or polymer molecular weight are high. It is shown that protein size is crucial for the polymer structural organization and interaction on the protein surface and it is established that the glass properties of the polymer change upon conjugation. The results give a better insight of the equivalence of the polymer coating and the role of water on the surface of proteins.